(Optionally: A. Container is labeled - __. The specimen is received in formalin and consists of ) 1 fragment(s) of pink-tan tissue with a vaguely recognizable mucosal surface. The tissue measures __ cm. (The surgical margin is inked black. The specimen is bisected and entirely submitted for microscopic examination in one cassette.)
Microscopic evaluation
Anatomic/Histologic location
Describe mucosa as squamous (or ectocervical), endocervical (generally mucinous and glandular) or transformation zone mucosa.
A cervical biopsy may contain nabothian cysts, which are single or multiple cysts that contain mucin, lined by a single layer of columnar, cuboidal to flat cells with variable amounts of mucinous cytoplasm and small, basal, round to oval nuclei with fine chromatin, without conspicuous nucleoli or mitotic activity.[1]
The anatomic level of the transformation zone varies:[2] Type 1: Completely ectocervical (common under hormonal influence). Type 2: Endocervical component but fully visible (common before puberty). Type 3: Endocervical component, not fully visible (common after menopause).
Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain.[5]
Example report
Endocervix, curettings: Fragments of squamous and endocervical glandular epithelium without significant histopathologic changes. Negative for dysplasia.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑International Federation for Cervical Pathology and Colposcopy (IFCPC) classification. References: -. Transformation zone (TZ) and cervical excision types. Royal College of Pathologists of Australasia. - Jordan, J.; Arbyn, M.; Martin-Hirsch, P.; Schenck, U.; Baldauf, J-J.; Da Silva, D.; Anttila, A.; Nieminen, P.; et al. (2008). "European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1
". Cytopathology19 (6): 342–354. doi:10.1111/j.1365-2303.2008.00623.x. ISSN0956-5507. PMID 19040546.
↑Khaled J. Alkhateeb, M.B.B.S., Ziyan T. Salih, M.D.. HSIL / CIN II / CIN III. PathologyOutlines. Topic Completed: 29 March 2021. Minor changes: 9 February 2022
↑Anissa Ben Amor.. Cervical Ectropion. StatPearls, National Center for Biotechnology Information. Last Update: November 14, 2021. - This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
Image sources
Cervical cone
Unless otherwise specified, the primary focus is any cervical neoplasia.
If the cone is more than 1 cm long, take transverse slices from the top of the cone and towards the ectocervix, and stop when approximately 1 cm of the ectocervical portion of the cone remains.
Cut the portion into radial or sagittal slices. Sagittal slices are made perpendicularly to the portion surface, and should be divided into at least the four quadrants.[note 1][1]
In cases where the cone is small and fragmented, try to orient the preparations and divide them if possible to obtain sagittal slices.[1]
The anatomic level of the transformation zone varies:[2] Type 1: Completely ectocervical (common under hormonal influence). Type 2: Endocervical component but fully visible (common before puberty). Type 3: Endocervical component, not fully visible (common after menopause).
Cervical dysplasia
edit
Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours.[3]
File:Cervix quadrants and directions.svgLocations of non-radicality should be reported in relation to tissue markings (such as needles), or in terms of quadrants or corresponding to a clock face, based on the patient being in supine position.
Look whether there is normal epithelium on each side of all slices where neoplasia is seen, and when the epithelium is missing in any direction, consider ordering additional serial sections or step sections.
HPV changes
Also look koilocytic changes of human papillomavirus (HPV), with such cells typically displaying:
Nuclear enlargement (two to three times normal size).
Irregularity of the nuclear membrane contour, creating a wrinkled or raisinoid appearance.
A darker than normal staining pattern in the nucleus, known as hyperchromasia.
Endometrial polyp (without atypia), with a thick-walled blood vessel in middle - typical of endometrial polyps. Glands are may be cystic but have unremarkable linings.
Endometrial polyp (without atypia), with tubal metaplasia (black arrow, showing ciliated epithelium) and a thick-walled blood vessel (white arrow). The stroma is hemorrhagic in this case.
Atypia (mainly seen as signs of endometrial intraepithelial neoplasia (EIN), which has the following criteria:[6] - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.
Endometrial adenocarcinoma[7] arising in an endometrial polyp. These are most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[8]
Subserosal pedunculated uterine leiomyomas may present as endometrial polyps. They typically show smooth muscle in a fascicular pattern[9]Further information: Smooth muscle tumor
Reporting
Most importantly:
Benign versus malignant (or presence or absence of atypia.)
((The size of the polyp.))
((The type of epithelium at both the surface and gland coverings.))
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 1.01.11.21.31.41.51.61.7Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26.
↑International Federation for Cervical Pathology and Colposcopy (IFCPC) classification. References: -. Transformation zone (TZ) and cervical excision types. Royal College of Pathologists of Australasia. - Jordan, J.; Arbyn, M.; Martin-Hirsch, P.; Schenck, U.; Baldauf, J-J.; Da Silva, D.; Anttila, A.; Nieminen, P.; et al. (2008). "European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1
". Cytopathology19 (6): 342–354. doi:10.1111/j.1365-2303.2008.00623.x. ISSN0956-5507. PMID 19040546.
↑Khaled J. Alkhateeb, M.B.B.S., Ziyan T. Salih, M.D.. HSIL / CIN II / CIN III. PathologyOutlines. Topic Completed: 29 March 2021. Minor changes: 9 February 2022
↑Anissa Ben Amor.. Cervical Ectropion. StatPearls, National Center for Biotechnology Information. Last Update: November 14, 2021. - This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
↑Owings, Richard A.; Quick, Charles M. (2014). "Endometrial Intraepithelial Neoplasia
". Archives of Pathology & Laboratory Medicine138 (4): 484–491. doi:10.5858/arpa.2012-0709-RA. ISSN1543-2165.
↑Stewart, Colin J.R.; Crum, Christopher P.; McCluggage, W. Glenn; Park, Kay J.; Rutgers, Joanne K.; Oliva, Esther; Malpica, Anais; Parkash, Vinita; et al. (2019). "Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites
". International Journal of Gynecological Pathology38: S75–S92. doi:10.1097/PGP.0000000000000553. ISSN0277-1691. - "Figures - available via license: Creative Commons Attribution 4.0 International"
↑Rabban, Joseph T.; Gilks, C. Blake; Malpica, Anais; Matias-Guiu, Xavier; Mittal, Khush; Mutter, George L.; Oliva, Esther; Parkash, Vinita; et al. (2019). "Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas
". International Journal of Gynecological Pathology38: S25–S39. doi:10.1097/PGP.0000000000000512. ISSN0277-1691.
Postmenopausal (atrophic) endometrium: Thin epithelium, and scattered glands lined by columnar cells with small inactive nuclei, supported by a dense fibrous stroma of spindle cells. (H&E stain)
The phases of endometrium through the menstrual cycle:
Secretory endometrium: Prominent glands (G), which have a dilated lumen and an irregular outer border stretching down into the basal compartment. In the luminal (functional) layer immune cells are readily detected (most of these are likely to be macrophages and uterine natural killer (uNK) cells), as are areas of decidualised fibroblasts (DEC) close to arterioles. (H&E stain)
If you want to specify the phase by day, then it's more accurate to state it as days past ovulation where applicable, since the follicular phase may vary substantially.
Endometrial intraepithelial neoplasia (EIN), has the following criteria:[2] - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.
Endometrial adenocarcinoma[3], most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[4]
Microscopy report
Example in a normal case:
(Endometrial curettings: Benign proliferative endometrium and endocervical mucosa without significant histopathologic changes.) Negative for neoplasia ((or viral cytopathic changes)).
2 longitudinal sections through ecto/endocervix (1 anterior and 1 posterior)
2 longitudinal sections through upper endocervix/lower uterine segment (1 anterior and 1 posterior), immediately adjacent to the sections taken from the cervix
4 full-thickness representative sections of endomyometrium (2 anterior and 2 posterior)
Transversely section the remaining anterior and posterior endomyometrium (~1 cm thick). Submit the entire endometrium from the lower uterine segment to the fundus, maintaining orientation.
Submit entire fimbriae (longitudinally sectioned) and 2 representative cross-sections on each side.
Endometrial intraepithelial neoplasia (EIN), has the following criteria:[2] - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.
Endometrial adenocarcinoma[7], most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[4]
Reporting
Most importantly:
Presence or absence of atypia.
Hysterectomy
For a freshly received uterus, generally gross it fresh to include either opening it up (small specimen, no suspected malignancy seen) and/or serial sectioning, in order to let the formalin penetrate it properly. Ensure the endometrium is immersed in the formalin (such as having the serosa oriented upwards).
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Other legend
<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page
Gross processing
Gross examination
For orientation:
The round ligament lies anterior to the tubes and ovaries.[8]
The peritoneum extends further down along the cervix posteriorly than anteriorly.[9] Its ends bluntly posteriorly and sharply anteriorly.[9]
When received the same day as the surgery, perform the following steps at least to serial sectioning before putting (back) in formalin, preferably with paper towels between slices, so that it fixes properly:[8]
(Remove the adnexa.[8]Weigh the uterus without the adnexa.)
Perform a general inspection
Measure the 3 dimensions, including the cervix. (Also measure the length of the cervix, the maximum diameter of the cervix, and the width of the cervical os.)
(Ink the surgical margin of the cervix for orientation, such as black on the posterior side.)
Open the uterus by transmural radial cuts on both sides of the uterine cavity.[note 1] The cavity is sometimes be squeezed or rolled around a leiomyoma, and you'll you have to improvise and perhaps go around the leiomyoma to open the cavity properly.
(Even the absence of) any smooth muscle tumor. Further information: Smooth muscle tumor
Example
(A. Labeled - __. The specimen is received in formalin and consists of a resected) uterus with cervix [and bilateral fallopian tubes and ovaries]. The uterus and cervix measure __ ((cm superior to inferior)) x __ ((cm cornu to cornu)) x __ cm ((anterior to posterior,)) and weighs ___ grams. The serosa is [tan-pink and smooth]. The cervix measures ___ cm in diameter and ___ cm in length. The ectocervical mucosa is [tan-pink and smooth] and the cervical os[ is patent] and measures ___ cm in diameter. The specimen is bisected in the coronal plane. The endocervical canal is [patent and displays a tan-pink smooth mucosa]. The endometrial cavity is [triangular] and is lined by[ smooth] endometrium measuring [0.1] cm in average thickness. The myometrium measures up to ___ cm in thickness.[
- It displays __ intramural leiomyomata measuring up to __ cm in greatest diameter.
] The right ovary measures ___ cm and has a [tan-pink and smooth] capsule. Cut sections show [no gross lesions]. The right fallopian tube measures ___ cm in length and ___ cm in average diameter. The serosa [is tan-pink and smooth]. Cut sections reveal a small patent lumen and no gross lesions. The left ovary measures ___ cm and has a [tan-pink and smooth] capsule. Cut sections show [no gross lesions].The left fallopian tube measures ___ cm in length and ___ cm in average diameter. The serosa [is tan-pink and smooth]. Cut sections reveal a small patent lumen and no gross lesions. Representative sections are submitted for microscopic examination in ___ cassettes.
Slices for microscopy
Applicable in bleeding disorders, pain, leiomyoma and endometrial hyperplasia:[8]
One, (two - at 6 and 12 o'clock), ((or four)) cross-sections from any accompanying ectocervix/endocervix (aiming to include the transformation zone). In subtotal extirpation, a cross-section is taken from the lower resection border.
((A transverse slice through the endocervix, possibly divided into two.))
Endometrium and myometrium, by one slice from the front and one from the back wall of the corpus.
{{Any mucosal parts with macroscopically abnormal appearance, including polyps.}}
{{For any area suspicious for malignancy, submit a full cross-section of the uterine wall that includes the serosa. Use multiple contiguous cassettes if needed.}}
Postmenopausal (atrophic) endometrium: Thin epithelium, and scattered glands lined by columnar cells with small inactive nuclei, supported by a dense fibrous stroma of spindle cells. (H&E stain)
The phases of endometrium through the menstrual cycle:
Secretory endometrium: Prominent glands (G), which have a dilated lumen and an irregular outer border stretching down into the basal compartment. In the luminal (functional) layer immune cells are readily detected (most of these are likely to be macrophages and uterine natural killer (uNK) cells), as are areas of decidualised fibroblasts (DEC) close to arterioles. (H&E stain)
If you want to specify the phase by day, then it's more accurate to state it as days past ovulation where applicable, since the follicular phase may vary substantially.
Endometrial intraepithelial neoplasia (EIN), has the following criteria:[2] - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.
Endometrial adenocarcinoma[15], most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[4]
Uterus, cervix, bilateral tubes and ovaries, abdominal hysterectomy and bilateral salpingo-oophorectomy:
Benign cervix.
Benign inactive endometrium.
{{Leiomyomata and adenomyosis.}}
Benign ovaries.
Benign fallopian tubes.
Negative for malignancy.
Microscopy of hysterectomy shows ecto and endocervix without atypia. The glands have columnar epithelium without atypia.
In the uterine cavity, there is endometrial mucosa with ordinary thickness and regularly arranged endometrial glands. (Optionally: Description of likely menstrual phase.) Sharp delimitation between endometrium and myometrium. The myometrium contains no focal changes. No evidence of malignancy.
Endometrial intraepithelial neoplasia
Uterus, cervix, bilateral tubes and ovaries, hysterectomy and bilateral salpingo-oophorectomy:
Endometrial intraepithelial neoplasia; entire endometrial/myometrial junction submitted for microscopic exam.
When finding fibroids (spherical tumors with whorled pattern, which in the uterus can be presumed to be smooth muscle tumors), examine and describe:[8]
Location. If in the uterus:
Intramural/submucosal/subserosal (see image)
(Posterior/anterior/right or left lateral.)
Number of tumors, if multiple. May be described simply as "multiple".
Size (may be described as "up to ___ cm in greatest dimension".
(Presence or absence of any hemorrhage or necrosis.)
((Demarcation))
Selection
In case of hysterectomy, submit pieces from all fibroids >5 cm in diameter.[8]
Submit any macroscopically abnormal parts of the fibroids (hemorrhagic, necrotic, brittle or softening areas, and areas with blurry delimitation).[8]
For fibroids that are significantly calcified, a gross-only description as a calcified fibroid is generally sufficient, without the need to decalcify it to dissect it or sample from it.[note 3]
Microscopic examination
Distinguish leiomyoma (benign) from leiomyosarcoma (malignant) by looking at the latter's criteria:[16]
Marked cellular atypia
Mitoses: > 10 mitoses/10 high power fields
Necrosis
Diagnosis of conventional leiomyosarcoma requires 2 of these 3 histologic features.[16]
Polyp lined by a single layer of columnar epithelium consistent with endometrium. The interior consists of smooth muscles in a whorled pattern. No atypia. The finding is consistent with a pedunculated submucosal leiomyoma.
Intrauterine device
Gross processing
These are generally just visually described, with no samples for microscopic examination. Example report:
File:Copper IUD.jpg T-shaped item with metal-coated arms and stem (Optionally: consistent with an intrauterine device with copper), with attached threads measuring 6.5 cm each.
Products of conception
Gross processing
Look up the gestational age of the pregnancy.
Look for fetal tissue (fetus, fetal membranes or chorionic villi). They are generally easier to distinguish from decidua (which is maternal tissue) when fragments are put in clear fluid and shaken, with chorionic villi having a consistency like orange pulp, whereas decidua is more rubbery. The fluid may be formalin if no sample for genetic workup is needed. If chorionic villi are found, no lengthy search is needed for other kinds of fetal tissue, just a quick look for obvious ones. Membranous material is less reliable, and may still indicate further sampling. Inspect any found fetal tissue for gross anomalies. If found, submit one piece of the fetus and one piece of the placenta.[19]
Fresh chorionic villi in a term placenta for comparison, being more granular.
If fetal parts are not visually found, search for diagnostic placental tissue, which is soft and shaggy or spongy (as opposed to membranous, which is likely to be decidua or blood clots).[19]
If no fetal or placental tissue is found, all presented tissue generally needs to be submitted.
(If transported or processed together with other cases, put any chorionic villi in thin-mesh cassettes or tissue bags to limit contamination).[note 4]
Gross report
(Labeled - products of conception.) The specimen (is received <<fresh / in formalin>>) and consists of multiple fragments of soft tan-pink decidua, blood clots and amniotic sac measuring about 5 cc in aggregate. The intact amniotic sac measures 2.3 cm in greatest dimension. Fetal tissue is identified within the amniotic sac, measuring 1.0 cm in crown-rump length. Representative sections are submitted for microscopic examination (in 1 cassette).
Microscopy
The most important is to detect the presence of chorionic villi.
Products of conception, with chorionic villi (arrow) among decidualized endometrium
((Products of conception:)) Products of conception, including immature chorionic villi, corresponding to first trimester pregnancy. ((Spontaneous abortion, clinically.))
((Products of conception:)) Fragments of focally necrotic decidua and implantation site, consistent with intrauterine products of conception. Negative for chorionic villi.
(Look in the history for any intra-fallopian coils (Essure devices).)[note 5]
For sterilization
Measure length and average diameter of each tube
Serially section at 3-4 mm intervals,[21] or 2-3 mm if suspected malignant (including BRCA mutation).[22] Submit
Submit 1 (or 3) circumferential transverse sections. If the specimen is only a segment of the tube of less than <5mm((, ink the surgical cut surfaces and)) submit all tissue.[21]
Example gross report:
(A. Labeled - __. The specimen is received in formalin and consists of) two fimbriated segments of fallopian tube measuring __ cm in length and __ cm in average diameter. On sectioning, each displays a patent lumen. No gross abnormalities are identified. The tubes are unoriented. The specimen is serially cross-sectioned and representative sections are submitted for microscopic examination in two cassettes.
Microscopic examination
File:Histopathology of edematous fallopian tubes.jpgFallopian tubes may be substantially edematous and congested, which can generally be attributed to surgery, in which case it does not need mention in the report.
Ensure there is at least one full cross-section from each tube, and take further samples otherwise.
Check for patency of the lumen.
Tumor
The most common tumor of the fallopian tubes is adenomatoid tumor:[23]
High magnification of the same case, showing the typical[23] features of tubular spaces of varying size composed of flattened cells resembling endothelium.
Reporting
Example of a normal report in sterilization:
(Right and left fallopian tubes, ((laparoscopic)) bilateral salpingectomy:) Complete cross-sections of histologically unremarkable fallopian tubes.
When included in a uterus specimen, normal tubes and ovaries may simply be mentioned as:
Bilateral fallopian tubes and ovaries, unremarkable.
When done for ectopic pregnancy, report any rupture, either from the gross report or from microscopy, for example:
Benign ruptured fallopian tube with ectopic products of conception, including degenerated immature chorionic villi and implantation site with fresh hemorrhage.
In the US, the cut goes from side to side, through the cervix and uterine cavity, keeping the anterior and posterior halves attached by a relatively thin connection left at the fundus. It is done by cutting with scissors with the blunt end in the cervix and then uterine cavity, or by a blade guided on each side by the shanks of a pair of forceps inserted through the cervix.
In Sweden, the uterus is usually opened at the front in the midline, optionally with an incision towards each corner.
It can be done by scissors, or by inserting a probe or forceps to guide a long blade.
↑The first example is used in Connecticut, and the second example is used in Sweden.
↑When a fibroid has calcifications it has been there a long time, and can be assumed to be benign.
↑For a case with intra-fallopian coils in the medical records, an inability to find them on gross processing must be noted in order to raise the possibility of coil expulsion.
↑ 2.02.12.2Owings, Richard A.; Quick, Charles M. (2014). "Endometrial Intraepithelial Neoplasia
". Archives of Pathology & Laboratory Medicine138 (4): 484–491. doi:10.5858/arpa.2012-0709-RA. ISSN1543-2165.
↑Stewart, Colin J.R.; Crum, Christopher P.; McCluggage, W. Glenn; Park, Kay J.; Rutgers, Joanne K.; Oliva, Esther; Malpica, Anais; Parkash, Vinita; et al. (2019). "Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites
". International Journal of Gynecological Pathology38: S75–S92. doi:10.1097/PGP.0000000000000553. ISSN0277-1691. - "Figures - available via license: Creative Commons Attribution 4.0 International"
↑ 4.04.14.2Rabban, Joseph T.; Gilks, C. Blake; Malpica, Anais; Matias-Guiu, Xavier; Mittal, Khush; Mutter, George L.; Oliva, Esther; Parkash, Vinita; et al. (2019). "Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas
". International Journal of Gynecological Pathology38: S25–S39. doi:10.1097/PGP.0000000000000512. ISSN0277-1691.
↑Nicole Cipriani (2020-06-22). Gross Pathology Manual. The University of Chicago Department of Pathology.
↑Stewart, Colin J.R.; Crum, Christopher P.; McCluggage, W. Glenn; Park, Kay J.; Rutgers, Joanne K.; Oliva, Esther; Malpica, Anais; Parkash, Vinita; et al. (2019). "Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites
". International Journal of Gynecological Pathology38: S75–S92. doi:10.1097/PGP.0000000000000553. ISSN0277-1691. - "Figures - available via license: Creative Commons Attribution 4.0 International"
↑Nicole Cipriani (2020-06-22). Gross Pathology Manual. The University of Chicago Department of Pathology.
↑Khaled J. Alkhateeb, M.B.B.S., Ziyan T. Salih, M.D.. HSIL / CIN II / CIN III. PathologyOutlines. Topic Completed: 29 March 2021. Minor changes: 9 February 2022
↑Anissa Ben Amor.. Cervical Ectropion. StatPearls, National Center for Biotechnology Information. Last Update: November 14, 2021. - This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
↑Stewart, Colin J.R.; Crum, Christopher P.; McCluggage, W. Glenn; Park, Kay J.; Rutgers, Joanne K.; Oliva, Esther; Malpica, Anais; Parkash, Vinita; et al. (2019). "Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites
". International Journal of Gynecological Pathology38: S75–S92. doi:10.1097/PGP.0000000000000553. ISSN0277-1691. - "Figures - available via license: Creative Commons Attribution 4.0 International"
↑Crum, Christopher P.; Mckeon, Frank D.; Xian, Wa (2012). "The Oviduct and Ovarian Cancer
". Clinical Obstetrics and Gynecology55 (1): 24–35. doi:10.1097/GRF.0b013e31824b1725. ISSN0009-9201.
The ovary is cut in the longitudinal plane (through the "long axis").
Ovaries, including those with cysts, are almost never inked.
Gross report
Template:
(A. Labeled - __. The specimen is received in formalin and consists of) an ovary measuring ___. The ovarian capsule is tan-pink and smooth. Cut sections reveal solid, white and whorled parenchyma, and no gross lesions. Representative sections are submitted for microscopic examination in __ cassettes.
Apart from any obvious tumor, also look for signet ring cells, which is a major feature of metastatic tumors to the ovary.
Placenta
Gross processing
Determine the shape of the placenta
Look for any accessory lobes
Determine the completeness of placental membranes, opacity, color and consistency (slimy/slippery?)
Determine the point of rupture from nearest margin
Note where the membranes are inserted
Examine the umbilical cord
Measure the distance between the insertion point and the nearest placental margin
Measure the cord length and give proximal and distal diameter. In placental pathology, the proximal umbilical cord refers to the segment closest to the placenta, and distal is the segment closest to the fetus.[note 1]
Count the number of vessels away from the insertion
Weigh the trimmed disk, after having trimmed away the cord and membranes, and after having removed excess amounts of loose retroplacental blood clots over the maternal surface.
Examine the fetal surface (chorionic plate):
Note its color, in particular if it is green (often faint and tan-green, brown-green to yellow-green (which indicates meconium staining).
Look for any pathologies including granular excrescences, subchorionic fibrin or subamniotic hemorrhage
Look at the integrity and extent of the vasculature, including any traumatic damage. Also palpate the vasculature for any thrombosis. If a thrombus is grossly found for a live birth, the baby may have thrombosis, so the finding must immediately be reported to the clinician in care of the baby.
Examine the maternal surface (basal plate) for completeness, adherent blood clots, depressions, calcifications and fibrin
Take a membrane roll and cord sections, before sectioning the placenta
With the fetal surface down on the cutting board, cut the placenta at 1cm intervals so that it can be reconstructed.
Placental tissue after cutting, here showing severe intervillositis, with dark red and soggy tissue.
Palpate the parencyhmal sections for areas of induration.
Note the color of the parenchyma and describe any pale areas, cysts, thrombi, increased fibrin, calcifications and infarcts. For possible infarcts, estimate the total amount of infarcted tissue as a percentage of the placental volume. Infarction is clinically significant if it involves at least 5-10% of the placental volume.
If you see a true knot (rather than "false knots" which are merely bulges or protuberances that may look like knots), report whether the diameter of the cord is significantly different before versus after the knot (which is a sign of constriction caused by the knot).
Tissue selection
Distal (toward fetus) membrane roll and cross section of distal cord. It should include the area of rupture.
Proximal (toward placenta) membrane roll and cross section of proximal cord ( 2-3 cm from insertion). They should include membranes up to the chorionic plate.
A membrane roll is created by cutting a strip, about 3 cm wide, of membrane, from the rupture site to the placental insertion. Hold the edge with forceps and roll it around the forceps, and then cut a transverse section of the roll. Cord sections should be no thicker than 4mm.
Placental section including fetal surface ( full thickness if possible)
Placental section including maternal surface (full thickness if possible)
Any lesions or abnormalities
Avoid taking placental sections near the margin. (If transported or processed together with other cases, put the placental in thin-mesh cassettes or tissue bags to limit contamination).[note 2]
Example report:
Container A. Labeled "bladder tumor". The specimen is received in formalin and consists of multiple fragments of tan-gray, friable soft tissue measuring about __ x __ x __ cm in aggregate. The specimen is entirely submitted for microscopic examination in __ cassettes.
(A. Labeled with patient's name and medical record number. The specimen is received fresh and consists of a) placenta with attached membranes and umbilical cord. The membranes are tan-red( with a marginal insertion. The site of rupture is __ cm from the nearest placental margin. There is no accessory lobe.) The trimmed placental weight is __ gramsTemplate:Comprehensive-begin-Corresponding to the __th percentile for the gestational age)). The placental disc measures __ cm and varies in thickness from __ to __ cm. The umbilical cord is tan-pink and eccentrically inserted(, __ cm from the nearest placental margin, and measures __ cm in length, __ cm in proximal diameter and __ cm in distal diameter.) Cut sections of the cord reveal three blood vessels. The fetal surface is blue-pink, smooth with normal vasculature and << minimal / moderate / major>> subchorionic fibrin deposition. The maternal surface is complete with <<minimal / moderate / major>> physiologic calcifications. Sectioning reveals a red, spongy, homogenous parenchyma without gross lesions. (Representative sections are submitted for microscopic examination in 4 cassettes.)
KEY OF SECTIONS (example):
1- distal membranes and umbilical cord
2- proximal membranes and umbilical cord
3- placental section including fetal surface
4- placental section including maternal surface
Microscopic examination
Look for inflammation, especially by the fetal surface in the intervillous spaces and around the fetal blood vessels.
Acute subchorionic intervillositis, with neutrophils (annotated) in Langhan’s layer of fibrinoid (by the fetal surface, at the base of a chorionic villus, seen at top right).
On the other hand, a small amount of intervillous neutrophils by the fetal surface like this is insignificant.
Acute choriodeciduitis, with neutrophils seen in the chorion and decidua.
At least if there is a suspicion of meconium in the amniotic fluid (from clinical history and/or the gross exam), look for the following histopathologic signs of it:[5]
Increased syncytial knotting of chorionic villi, with two knots pointed out. Causes include both hypoxia and hyperoxia.[7]
Microscopy report
Generally, also include major gross findings, such as an area of placental abruption.
Example of normal report:
(Placenta, <<vaginal/Caesarean>> delivery:) Third trimester placenta with term villous histology. Placental weight (__ gm), at __th percentile for gestational age. Membranes without significant histopathologic changes((, negative for chorioamnionitis)). Trivascular umbilical cord, with no significant histopathologic changes((, negative for funisitis)).
Mild to moderate inflammation in the decidua alone can be ignored (as it is most commonly a physiological response and doesn't have a clinical significance for the fetus).
Example in a twin placenta:
Twin placenta, Caesarean section:
Third trimester dichorionic, diamniotic twin placenta.
Villous morphology histologically appropriate for gestational age.
Placental weight approximately 25th percentile for gestational age.
Tumors of the vulva are staged as per the AJCC, 8th Ed:[9]
Primary tumor (T)
TNM
FIGO
Criteria
TX
Primary tumor cannot be assessed
T0
No evidence of a primary tumor
Tisa
Carcinoma in situ (preinvasive)
T1a
IA
Lesions ≤2 cm, confined to the vulva or perineum and with stromal invasion ≤1 mmb
T1b
IB
Lesions >2 cm or any size with stromal invasion >1 mm, confined to the vulva or perineum
T2
II
Tumor of any size with extension to adjacent perineal structures (distal third of the urethra, distal third of the vagina, anal involvement)
T3
IVA
Tumor of any size with extension to any of the following proximal two thirds of the urethra, proximal two thirds of the vagina, bladder mucosa, or rectal mucosa or fixed to pelvic bone
Regional lymph nodes (N)
TNM
FIGO
Criteria
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
1 or 2 regional (inguinofemoral) lymph nodes with the following features (see N1a, N1b)
N1a
IIIA
1 or 2 lymph node metastases, each < 5 mm
N1b
IIIA
1 regional lymph node metastasis ≥5 mm
N2
Regional (inguinofemoral) lymph nodes with the following features (see N2a, N2b, N2c)
N2a
IIIB
3 or more lymph node metastases, each < 5 mm
N2b
IIIB
2 or more regional lymph node metastases ≥5 mm
N2c
IIIC
Regional lymph node metastasis with extracapsular spread
N3
IVA
Fixed or ulcerated regional lymph node metastasis
Distant metastasis (M)
TNM
FIGO
Criteria
M0
No distant metastasis
M1
IVB
Distant metastasis (including to pelvic lymph nodes)
Cervical cytology
Clinical information
It is not necessary to look through more than readily available reports from previous cervical cytologies.
Magnification
While being fairly new to cervical cytology, preferably start looking at a high magnification such as 20x objective (with 10x eye piece). For suspicious findings, you may magnify up to maximum. On the other hand, once the pattern feels repetitive you can try switching to a slightly lower magnification such as 10x.
Adequacy
Adequacy should always be stated, either as "Satisfactory" or "Unsatisfactory". For estimating the number of cells, determine the following:
The area of your field of view at high power (see the Evaluation chapter)
The total size of the relevant area on the microscope slide. A ThinPrep is about 360 mm2.
Look at 10 representative high power fields (HPFs) within that area, and calculate the average number of cells per high power field.
HPF example on a ThinPrep (about 360 mm2). If 10 fields gives a total of 40 cells, it will be 4 cells per HPF. The area of this field is 0.23 mm2. Therefore, total cellularity is estimated to be: 4 cells * 360mm2 / 0.23mm2 = 6260 cells.
You may count 10 fields either across the slide, or 5 fields in each direction.[10]
Total number of cells = Average number of cells per HPF *
Total size of area HPF area
Conventional smear cellularity should be at least 8,000 cells. Liquid-based cytology cellularity should be at least 5,000 cells. Also a conventional smear is inadequate if >75% of cells are obscured by blood, exudate or air-drying artefact.[10]
Eventually you will be able to tell when most cases are adequate or inadequate without performing a detailed calculation.
State whether the endocervical/transformation zone is present or absent. Count an endocervical component as present if there are 10 or more endocervical or squamous metaplastic cells.[11]
Endocervical cells can be viewed from the side as nuclear polarity (margination towards the same side as others) in a “picket-fence” configuration.
Sheets of endocervical cells have a honeycomb pattern.
In patients with previous hysterectomy, simply report glandular or squamous metaplastic cells as such, rather than stating the presence of a transformation zone, since they are likely vaginal in origin in such patients.[12]
Very common findings
For reporting, acute inflammation should be a background of ample dispersed neutrophils, and not only aggregates of neutrophils with cells or mucus.
Vaginal squamous cell with normal vaginal flora versus bacterial vaginosis on Pap stain. Normal vaginal flora (left) is predominantly rod-shaped Lactobacilli, whereas in bacterial vaginosis (right) there are clue cells, covered in bacteria. A significant amount of clue cells can be reported as "Shift in vaginal flora suggestive of bacterial vaginosis".
Squamous atypia, seen mainly as cells with increased nucleus/cytoplasm ratio, nuclear hyperchromasia and irregular nuclear outline.
If the slide has been previously marked by a cytotechnologist or other previewer, grade the marked cells first. Then, you only need to look for worse findings on the rest of the slide.
Low-grade squamous intraepithelial lesion (LSIL), here compared to an unremarkable intermediate squamous cell.
High-grade squamous intraepithelial lesion (HSIL), showing even more prominent features, and decreased cytoplasm, causing a high nuclear/cytoplasmic ratio.
LSIL and changes consistent with human papillomavirus (HPV), which is the presence of koilocytes, which show perinuclear cavitation, binucleation, nuclear hyperchromasia, and nuclear enlargement.
File:Cytopathology of nonkeratinizing squamous cell carcinoma.pngCytopathology of squamous cell carcinoma, nonkeratinizing variant, with typical features.[14] Pap stain. Necrotic debris (dirty background) is a feature that generally makes a HSIL case "suspicious for invasive squamous cell carcinoma".[15] In contrast to the more distinct keratinizing variant, these findings are overall less specific, and most can be seen in other cancers such as adenocarcinoma as well (which, however, tends to have fine chromatin)[16]
Distinguish HPV-changes from glycogenated squamous cells. Glycogen confers a yellowish color to the cytoplasm. It can look like the perinuclear cavitation of koilocytes, but has more rounded edges.
Clinical implication
If you are uncertain of the degree of dysplasia, it can be useful to look up how much difference it will likely make for the management of the patient. You may make an Internet search for the management of abnormal cervical screening in your region (such as The ASCCP tool for management in the US). A change from close follow-up to colposcopy is not that big of a deal, but if one of the alternatives will lead to a diagnostic excision, make sure that the case is looked upon by commensurate expertise.
Report
Example in a normal case:
Cervical/endocervical ThinPrep:
Negative for intraepithelial lesion or malignancy (NILM).
Male reproductive system
Phimosis
Gross processing
Generally sample one or two representative sections in a cassette, in addition to sections of any grossly visible lesions.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
If the lesion was pigmented on gross examination, evaluate as a dark skin focality. If not:
Look for atypical cells, possibly by scrolling through the epidermis at intermediate magnification and then through the dermis at a lower magnification. If atypical cells are found, look for:
Main differential diagnoses and their characteristics:[22]
Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread.
Actinic keratosis: Atypical keratinocytes that do not span the full thickness of the epidermis (or, in Bowenoid variant, are less disordered with less nuclear atypia and crowding).
Keratoacanthoma: Symmetrical and circumscribed proliferation of keratinocytes, with central horn plug, with epidermis that extends over the tumor. It can be regarded as a highly differentiated SCC.
Crush artifacts: Needles used to orient the skin sample may create crush artifacts (black arrow) mimicking cellular atypia with mainly hypereosinophilia and nuclear pleomorphism. Image also shows folding artifacts (white arrows).
Verrucous squamous cell carcinoma[note 5]: Exophytic squamous proliferation with marked papillomatosis and low atypia and the presence of koilocyte-like changes. Found in head and neck locations, as well as in the genitalia and sole of the foot.
A melanoma may have relatively plentiful eosinophilic cytoplasm, and be seemingly continuous with the squamous epithelium (at left in image), thus resembling a squamous cell carcinoma. However, the nesting of cells at right in the image is more characteristic of a melanoma.
Metastasis: Personal medical history of the patient, nodular proliferation without connection to epidermis, immunohistochemical evaluation. Squamous-cell carcinoma metastasis from lungs to the skin is pictured.
In case of skin cancer, determine whether the peripheral/radial and deep margins are clear, close or continuous.[23][note 7] A close margin has various definitions for different malignancies, but for basal-cell carcinoma and cutaneous squamous cell carcinoma it is defined as being closer than 1 mm from the edge (but yet non-continuous with it),[23][24] but 2-3 mm for melanoma.[25]
Previous biopsy
(At least if there is a known previous biopsy, look for changes that are consistent with a biopsy site, to confirm that it was taken from the excised area.) Such changes in the skin include:
Preferably see specific article on the condition at hand, if available.
Optionally, the presence of a keratinized squamous epithelium.
Any abnormalities, generally preceded by location in terms of epidermal, dermal or more specific layers thereof.
If malignant:
Degree of differentiation
Radicality, mainly into either of the following: edit
>___ mm (Definitions vary for the distance as per Further workup of malignant findings above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
<___ mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.[23]
Continuous with margin: "Not radically excised at (location)."
For skin shave biopsies, non-radicality may be reported as: "Extending to base and peripheral edges of biopsy" (as they may not be regarded as "margins" on a biopsy).
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑- Buschke–Löwenstein tumor is an alternative name for verrucous squamous cell carcinoma in the ano-genital region. - Carcinoma cuniculatum is a characteristic form of verrucous squamous cell carcinoma on the sole.
↑Inverted follicular keratosis is generally thought to be a rare variant of seborrheic keratosis, but this position is not universally accepted. - Karadag, AyseSerap; Ozlu, Emin; Uzuncakmak, TugbaKevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant (2016). "Inverted follicular keratosis successfully treated with imiquimod
". Indian Dermatology Online Journal7 (3): 177. doi:10.4103/2229-5178.182354. ISSN2229-5178.
↑"Peripheral" or "radial" margins are preferred rather than "lateral", since a "lateral" margin may be interpreted as opposite to the "medial margin".
↑Pellerito, John; Polak, Joseph F. (2012). Introduction to Vascular Ultrasonography (6th ed.). Elsevier Health Sciences. p. 559. ISBN 978-1-4557-3766-6.
↑Chen, Yukun; Zhang, Zhuomin; Wu, Chenyan; Davaasuren, Dolzodmaa; Goldstein, Jeffery A.; Gernand, Alison D.; Wang, James Z. (2020). "AI-PLAX: AI-based placental assessment and examination using photos
". Computerized Medical Imaging and Graphics84: 101744. doi:10.1016/j.compmedimag.2020.101744. ISSN08956111. - Fig 5- available via license: Creative Commons Attribution 4.0 International.
↑Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee (2015). "Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance
". American Journal of Obstetrics and Gynecology213 (4): S29–S52. doi:10.1016/j.ajog.2015.08.040. ISSN00029378.
↑Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC961218414. - For access, see the Secrets chapter of Patholines. - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
↑Cibas, Edmund S.; Ducatman, Barbara S. (2021). Cytology : diagnostic principles and clinical correlates. Philadelphia, PA. p. 9. ISBN 978-0-323-63637-7. OCLC1138033641.
↑- Image annotated by Mikael Häggström - Reference for entries: Gulisa Turashvili, M.D., Ph.D.. Cervix - Squamous cell carcinoma and variants. Pathology Outlines. Last author update: 24 September 2020. Last staff update: 4 April 2022. - Source image from National Cancer Institute (Public Domain)
↑- Image annotated by Mikael Häggström - Reference for entries: Gulisa Turashvili, M.D., Ph.D.. Cervix - Squamous cell carcinoma and variants. Pathology Outlines. Last author update: 24 September 2020. Last staff update: 4 April 2022. - Source image by Ravi Mehrotra, Anurag Gupta, Mamta Singh and Rahela Ibrahim (Creative Commons Attribution 2.0 Generic license.)
↑Clemmensen, Ole J.; Krogh, John; Petri, Michael (1988). "The Histologic Spectrum of Prepuces from Patients with Phimosis
". The American Journal of Dermatopathology10 (2): 104–108. doi:10.1097/00000372-198804000-00002. ISSN0193-1091.
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑Initially copied from: Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update
". Biomedicines5 (4): 71. doi:10.3390/biomedicines5040071. ISSN2227-9059. "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)."
↑1 mm as cutoff for close margin: Brodie M Elliott, Benjamin R Douglass, Daniel McConnell, Blair Johnson, Christopher Harmston (2018-12-14). New Zealand Medical Journal.
↑Page 406 in: Klaus J. Busam, Richard A Scolyer, Pedram Gerami (2018). Pathology of Melanocytic Tumors. Elsevier Health Sciences. ISBN 9780323508681.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
Broadly consists of determining the following:
Whether it is basal-cell carcinoma or a differential diagnosis.
Aggressiveness pattern
Radicality
Optionally, further subtyping of basal-cell carcinoma can be made.
Hair follicle tissue may be superficial, resembling a superficial basal-cell carcinoma.
The edges of hair follicle cells may resemble palisades, but are less pronounced, and are generally more diffusely delineated compared to surroundings.
Squamous-cell carcinoma
Squamous-cell carcinoma of the skin is generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations.
Yet, a high prevalence means a relatively high incidence of borderline cases. In such cases, look particularly at the surface and attempt to classify as either of the following:
Basal-cell carcinoma with squamous cell metaplasia or metatypical (squamoid) basal-cell carcinoma. It is basal-cell carcinoma with subepidermal (but no intraepidermal) areas resembling squamous-cell carcinoma.
Basaloid squamous-cell carcinoma, in this case showing a biplastic pattern with basaloid elements associated with both conventional dysplastic squamous surface (arrow heads) and conventional squamous cell carcinoma (arrow).[4]
In unclear cases, the most useful immunohistochemistry marker appears to be MOC-31, which essentially always stains metatypical basal-cell carcinomas but not basaloid squamous-cell carcinomas.[5]UEA-1 appears to be the second most useful marker, staining almost all basaloid squamous-cell carcinomas but only a few metatypical basal-cell carcinomas.[5]
Adenoid cystic carcinoma: Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts
Trichoepithelioma:[note 3] Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-)
Merkel cell carcinoma: Cells arranged in a diffuse, trabecular and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-)
Aggressiveness
Aggressiveness can be classified as low-level aggressive, moderately aggressive and highly aggressive, based mainly the cohesion of cancer cells, but also upon other histopathologic subtypes:
Nodular. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC.[6] It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts.[6] Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions.[6] Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions.[6]
Micronodular pattern: Small and closely spaced nests.
Radicality
Determine if there are basal-cell formations continuous with resection margins, or if they are closer or farther than 1 mm from the closest edge.[10] If closer, measure the distance.
If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells.
Aggressiveness pattern, at least if highly aggressive.
Radicality, mainly into either of the following: edit
>1 mm (as per Radicality above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
<1 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.[10]
Continuous with margin: "Not radically excised at (location)."
Optionally, subtype of basal-cell carcinoma
Example:
File:Non-radical basal-cell cancer.jpg (Skin excision with stratified squamous keratinized epithelium, where the dermis contains) moderately aggressive basal-cell carcinoma, not radically excised at the right margin.[note 4]
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑Desmoplastic tricoepithelioma is particularly similar to basal-cell carcinoma.
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑ 3.03.1Sunjaya, Anthony Paulo; Sunjaya, Angela Felicia; Tan, Sukmawati Tansil (2017). "The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell Carcinoma
". Journal of Skin Cancer2017: 1–10. doi:10.1155/2017/2692604. ISSN2090-2905.
↑El-Mofty, SK. (2014). "Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas
". Medicina Oral Patología Oral y Cirugia Bucal: e377–e385. doi:10.4317/medoral.20184. ISSN16986946. License: CC BY 2.5
↑ 5.05.1Webb, David V.; Mentrikoski, Mark J.; Verduin, Lindsey; Brill, Louis B.; Wick, Mark R. (2015). "Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal
". Annals of Diagnostic Pathology19 (2): 70–75. doi:10.1016/j.anndiagpath.2015.01.004. ISSN10929134.
↑ 6.06.16.26.36.4Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update
". Biomedicines5 (4): 71. doi:10.3390/biomedicines5040071. ISSN2227-9059.
↑Inskip, Mike; Magee, Jill (2015). "Microcystic adnexal carcinoma of the cheek—a case report with dermatoscopy and dermatopathology
". Dermatology Practical & Conceptual5 (1). doi:10.5826/dpc.0501a07. ISSN21609381.
↑Yonan, Yousif; Maly, Connor; DiCaudo, David; Mangold, Aaron; Pittelkow, Mark; Swanson, David (2019). "Dermoscopic Description of Fibroepithelioma of Pinkus with Negative Network
". Dermatology Practical & Conceptual: 246–247. doi:10.5826/dpc.0903a23. ISSN2160-9381. Creative Commons Attribution License
↑East, Ellen; Fullen, Douglas R.; Arps, David; Patel, Rajiv M.; Palanisamy, Nallasivam; Carskadon, Shannon; Harms, Paul W. (2016). "Morpheaform Basal Cell Carcinomas With Areas of Predominantly Single-Cell Pattern of Infiltration
". The American Journal of Dermatopathology38 (10): 744–750. doi:10.1097/DAD.0000000000000541. ISSN0193-1091.
Lesions of actinic keratosis are typically ill-marginated, erythematous, scaling, and rough papules or patches. These will typically be found in areas displaying other signs of solar damage, such as atrophy, uneven pigmentation, and telangiectasias.[1]
Tissue selection
Tissue selection from suspected malignant skin lesions, by lesion size:[2][note 2]
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
Evaluation mainly consists of:
Establishing a diagnosis of actinic keratosis rather than differential diagnoses:
Error creating thumbnail: Normal skin (left) and actinic keratosis (right) with the defining characteristic of atypical basal keratinocytes that does not involve the full thickness of the epidermis.File:Micrograph of actinic keratosis - low magnification.jpg1(a). Actinic keratosis at low magnification, showing discontinuous parakeratosis (as the dysplastic process spares adnexal structures, including sebaceous glands. This specimen also demonstrates dense dermal elastosis).[1]
By definition, actinic keratosis is confined to foci within the epidermis.[1] it also generally has:[1]
Aggregates of atypical, pleomorphic keratinocytes which show nuclear atypia, dyskeratosis, and loss of polarity.
Hyperkeratosis and parakeratosis, the latter overlying the abnormal cells in the epidermis. Due to the sparing of segments of the epithelium overlying adnexal structures, a characteristic pattern of alternating orthokeratosis and parakeratosis, referred to as the “flag-sign,” can often be seen (Figure 1(a)).
Atypical keratinocytes will not span the full thickness of the epidermis (Figure 1(b)), although those in the basal cell layer will frequently extend into the granular and cornified layers. The exception to this criterion is the Bowenoid variant of actinic keratosis, which resembles cutaneous squamous-cell carcinomain situ (Bowen's disease) but is less disordered with less nuclear atypia and crowding.
A more basophilic basal layer than normal, which is generally thought to be a consequence of the close crowding of atypical keratinocytes (Figure 1(b)).
Some cases will also show basal layer degeneration and the formation of Civatte bodies (Figure 1(c)), the result of a lichenoid infiltrate with irregular acanthosis. This can be distinguished from lichenoid dermatitis by the presence of keratinocyte atypia.
Dermoepidermal junction irregularities, with small round buds at the basal cell layer that will protrude slightly into the upper papillary dermis (Figure 1(d)).
There is almost always an associated solar elastosis in the dermis, and a lack thereof can often be sufficient to prompt reconsideration of the diagnosis.
1(d). A more established lesion of actinic keratosis demonstrating nearly full thickness keratinocyte dysplasia and prominent budding of the basal layer into the superficial dermis.[1]
Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread.
Actinic keratosis: Atypical keratinocytes that do not span the full thickness of the epidermis (or, in Bowenoid variant, are less disordered with less nuclear atypia and crowding).
Keratoacanthoma: Symmetrical and circumscribed proliferation of keratinocytes, with central horn plug, with epidermis that extends over the tumor. It can be regarded as a highly differentiated SCC.
Crush artifacts: Needles used to orient the skin sample may create crush artifacts (black arrow) mimicking cellular atypia with mainly hypereosinophilia and nuclear pleomorphism. Image also shows folding artifacts (white arrows).
Verrucous squamous cell carcinoma[note 3]: Exophytic squamous proliferation with marked papillomatosis and low atypia and the presence of koilocyte-like changes. Found in head and neck locations, as well as in the genitalia and sole of the foot.
A melanoma may have relatively plentiful eosinophilic cytoplasm, and be seemingly continuous with the squamous epithelium (at left in image), thus resembling a squamous cell carcinoma. However, the nesting of cells at right in the image is more characteristic of a melanoma.
Metastasis: Personal medical history of the patient, nodular proliferation without connection to epidermis, immunohistochemical evaluation. Squamous-cell carcinoma metastasis from lungs to the skin is pictured.
Clinical clues
Biopsy from sun exposed area (including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp).[1]
File:Histopathology of actinic keratosis with moderate atypia.jpg (Skin excision with squamous stratified epithelium with moderate) atypia in the basal epidermis (, with enlarged and dark cell nuclei as well as slightly disrupted cell arrangements.) No evidence of malignancy.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑- Buschke–Löwenstein tumor is an alternative name for verrucous squamous cell carcinoma in the ano-genital region. - Carcinoma cuniculatum is a characteristic form of verrucous squamous cell carcinoma on the sole.
↑Inverted follicular keratosis is generally thought to be a rare variant of seborrheic keratosis, but this position is not universally accepted. - Karadag, AyseSerap; Ozlu, Emin; Uzuncakmak, TugbaKevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant (2016). "Inverted follicular keratosis successfully treated with imiquimod
". Indian Dermatology Online Journal7 (3): 177. doi:10.4103/2229-5178.182354. ISSN2229-5178.
↑ 1.01.11.21.31.41.51.61.71.8Initially largely copied from: Yanofsky, Valerie R.; Mercer, Stephen E.; Phelps, Robert G. (2011). "Histopathological Variants of Cutaneous Squamous Cell Carcinoma: A Review
". Journal of Skin Cancer2011: 1–13. doi:10.1155/2011/210813. ISSN2090-2905. -"This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited."
↑There are many variants for the processing of skin excisions. These examples use aspects from the following sources:
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑Initially copied from: Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update
". Biomedicines5 (4): 71. doi:10.3390/biomedicines5040071. ISSN2227-9059. "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)."
Squamous cell carcinoma in situ (essentially synonymous with Bowen’s disease) often presents as an erythematous, well-demarcated, scaly patch or plaque, with a fairly irregular border. They occasionally present as dark skin focalities, especially when found in the genital region and the nails.[1]
Invasive SCC typically has ill-marginated, erythematous, scaling, and rough papules or patches.[1]
Tissue selection
Tissue selection from suspected malignant skin lesions, by lesion size:[2][note 2]
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
Evaluation consists of:
Determining whether it is a SCC rather than a differential diagnosis.
Distinguishing a SCC in situ from an invasive SCC
Radicality, and if radical, determine the least distance to a margin.
Malignant keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or “windblown” appearance.
In situ
In SCC in situ (Bowen’s disease) the epidermis will show:
Atypia spanning the full thickness of the epidermis, being the main finding.[1]
Marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC.
Typical squamous-cell carcinoma cells are large with abundant eosinophilic cytoplasm and large, often vesicular, nuclei.[3]
In contrast to actinic keratosis, the basal epidermal layer in SCC in situ is frequently spared, and will show little to no visible atypia. Additionally, SCC in situ will almost always involve both the interfollicular and adjacent follicular epithelium and adnexal structures.[1]
Overlap of squamous-cell and basal-cell carcinoma
Basal-cell carcinoma is generally distinguishable by for example relatively less cytoplasm, palisading, cleft formations and absence of horn cyst formation.
Yet, a high prevalence means a relatively high incidence of borderline cases. In such cases, look particularly at the surface and attempt to classify as either of the following:
Basal-cell carcinoma with squamous cell metaplasia or metatypical (squamoid) basal-cell carcinoma. It is basal-cell carcinoma with subepidermal (but no intraepidermal) areas resembling squamous-cell carcinoma.
Basaloid squamous-cell carcinoma, in this case showing a biplastic pattern with basaloid elements associated with both conventional dysplastic squamous surface (arrow heads) and conventional squamous cell carcinoma (arrow).[4]
In unclear cases, the most useful immunohistochemistry marker appears to be MOC-31, which essentially always stains metatypical basal-cell carcinomas but not basaloid squamous-cell carcinomas.[5]UEA-1 appears to be the second most useful marker, staining almost all basaloid squamous-cell carcinomas but only a few metatypical basal-cell carcinomas.[5]
Clinical clues
Biopsy from sun exposed area (including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp).[1]
Superficially invasive squamous cell carcinoma (SCCSI). These lesions often do not show the marked pleomorphism and atypical nuclei of SCC in situ, but demonstrate early keratinocyte invasion of the dermis.[1]
Invasive nests with characteristic large celled centers. Ulceration (at left) is common in invasive SCC.
This infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate.[1]
Radicality
Determine whether the distances between atypical cells are more or less than 1 mm from the deep and radial edges. If less than 1 mm, quantify the distance.[6]
Well-differentiated (and yet invasive) SCC, showing prominent keratinization and may form “pearllike” structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated SCC has slightly enlarged, hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible.[1]
Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous cell carcinoma. The dysplastic cells here infiltrate in cords through the dermis. Poorly differentiated SCC has greatly enlarged, pleomorphic nuclei demonstrating a high degree of atypia and frequent mitoses.[1]
Poorly differentiated clear-cell squamous cell carcinoma. For this type of SCC, immunostains will likely be required to classify it unless other areas of the tumor show obvious squamous cell features such as seen here (keratinization in center).
Perineural or vascular invasion
In SCC, look for any perineural invasion,[note 3] and at least a quick glance for any vascular invasion.
Vascular invasion: the arrow indicates a small cluster of atypical squamous cells in a small vessel.[1]
Perineural invasion is defined as tumor in close proximity to nerve and involving at least 33% of its circumference or tumor cells within any of the three layers of the nerve sheath (epineurium, perineurium and endoneurium).[7] First look along the border of the tumor, followed by surrounding tissue, and if still not found, look through the rest of the tumor area as well.[1]
Staging
The AJCC, 8th Ed., does not include any staging system for skin SCC, except for tumors of the vulva.[8]
Optionally: Grading
Multiple variables can be combined to classify a SCC as low or high grade:
Radicality, mainly into either of the following: edit
>1 mm (as per Radicality above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
<1 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]."[6] Numbers are generally given at an exactness of 0.1 mm.
Continuous with margin: "Not radically excised at (location)."
((You may also add a synoptic report (see examples):))
Examples
Squamous cell carcinoma in situ:
Error creating thumbnail: ((Skin excision with squamous epithelium with))(central parakeratosis. The epidermis is thickened and exhibits disturbed stratification. )All cell layers show atypical epithelial cells with polymorphic and partially hyperchromatic nuclei. The basement membrane is intact. Clear margins. ((There is elastosis and inflammatory cells in the dermis.))
Invasive squamous cell carcinoma:
(Skin, right breast, excision:) Invasive keratinizing squamous cell carcinoma, well differentiated, measuring 1.7 cm in greatest dimension. Surgical margins are negative for carcinoma. (Negative for lymphovascular and perineural invasion.) ((Solar elastosis.))
((Example synoptic report:))
Procedure: Skin excision.
Tumor site: Scalp
Tumor laterality: Right
Tumor focality: Unifocal
Tumor size: 1.6 x 1.4 cm
Tumor depth of invasion: 0.3 cm
Histologic type: Squamous cell carcinoma
Histologic grade: Moderately differentiated
Specimen margins: Uninvolved by invasive tumor.
Lymphovascular invasion: Not identified
Perineural invasion: Not identified
Regional lymph nodes: No lymph nodes submitted or found.
Regional Lymph Nodes: pNX: Regional lymph nodes cannot be assessed
Additional pathologic findings: Actinic keratosis
Example microscopic description of invasive squamous cell carcinoma:
Squamous epithelium, with central ulceration, surrounded by hyperkeratosis. In this area in the dermis there are infiltrative nests of epithelioid cells with nuclear pleomorphism and <sparse / moderate / abundant> keratin formation.
Lesion not visible: At least one additional radicality slice towards the tips, up to the entire specimen.[11]
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑ 3.03.1Presence or absence of perineural invasion in squamous-cell carcinoma affects whether adjuvant radiotherapy will be used.
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑El-Mofty, SK. (2014). "Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas
". Medicina Oral Patología Oral y Cirugia Bucal: e377–e385. doi:10.4317/medoral.20184. ISSN16986946. License: CC BY 2.5
↑ 5.05.1Webb, David V.; Mentrikoski, Mark J.; Verduin, Lindsey; Brill, Louis B.; Wick, Mark R. (2015). "Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal
". Annals of Diagnostic Pathology19 (2): 70–75. doi:10.1016/j.anndiagpath.2015.01.004. ISSN10929134.
↑ 6.06.11 mm as cutoff for close margin: Brodie M Elliott, Benjamin R Douglass, Daniel McConnell, Blair Johnson, Christopher Harmston (2018-12-14). New Zealand Medical Journal.
↑Strowd, Roy (2021). Neuro-oncology for the clinical neurologist. Philadelphia, PA: Elsevier. ISBN 978-0-323-69494-0. OCLC1220993756.
↑Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC961218414. - For access, see the Secrets chapter of Patholines. - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
↑Anjelica Hodgson, M.D., Carlos Parra-Herran, M.D.. p16. Pathology Outlines. Last author update: 1 July 2017. Last staff update: 20 July 2022
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
In suspected but not certain nevus or melanoma in situ, generally perform immunohistochemistry with SOX10, whereby melanocyte proliferation and nuclear pleomorphism is easier to see.[note 5]
Invasive melanoma of the skin has features melanoma in situ, but also has dermal involvement of atypical melanocytes with cytologic atypia and no maturation.[6]
Further workup
Upon a diagnosis of melanoma in situ, evaluate its margins. Optionally, attempt to determine the histopathologic type and amount of cytoplasmic pigmentation:
Margins
If melanoma, determine if the distance to any margin is greater or lesser than 2-3 mm.
2 mm is used as a cutoff for sharply demarcated, small, superficially spreading or nevoid melanomas.[7]
3 mm is used for ill-defined lentigo maligna melanoma in situ.[7]
If lesser, quantify the distance.
If margins are difficult to determine, consider immunohistochemistry with SOX10 to better visualize melanoma nests.[note 5]
Histopathologic type
Main types of melanoma in situ are:
Type
Features
Micrograph
Superficial spreading melanoma in situ
Melanoma cells with nest formation along the dermo-epidermal junction.
Radicality,[10] mainly into either of the following: edit
>2 or 3 mm (as per Further workup above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
<2 or 3 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.
Continuous with margin: "Not radically excised at (location)."
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑Lentiginous proliferation is proliferation along the basal layer of the epidermis
↑Histological regression is one or more areas within a tumor in which neoplastic cells have disappeared or decreased in number. In this case, this means complete or partial disappearance from areas of the dermis (and occasionally from the epidermis), which have been replaced by fibrosis, accompanied by melanophages, new blood vessels, and a variable degree of inflammation. - Ribero, Simone; Gualano, Maria Rosaria; Osella-Abate, Simona; Scaioli, Giacomo; Bert, Fabrizio; Sanlorenzo, Martina; Balagna, Elena; Fierro, Maria Teresa; et al. (2015). "Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status
". JAMA Dermatology151 (12): 1301. doi:10.1001/jamadermatol.2015.2235. ISSN2168-6068.
↑ 5.05.1SOX10 stains cell nuclei of melanocytes. - Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; et al. (2015). "Sox10—A Marker for Not Only Schwannian and Melanocytic Neoplasms But Also Myoepithelial Cell Tumors of Soft Tissue
". The American Journal of Surgical Pathology39 (6): 826–835. doi:10.1097/PAS.0000000000000398. ISSN0147-5185.
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑ 7.07.1Measurements used to classify a melanoma as radical: Page 406 in: Klaus J. Busam, Richard A Scolyer, Pedram Gerami (2018). Pathology of Melanocytic Tumors. Elsevier Health Sciences. ISBN 9780323508681.
↑Error on call to Template:cite web: Parameters url and title must be specifiedHon A/Prof Amanda Oakley (2011). . DermNet NZ.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Histological regression is one or more areas within a tumor in which neoplastic cells have disappeared or decreased in number. In this case, it means complete or partial disappearance of neoplastic cells from areas of the dermis (and occasionally from the epidermis), which have been replaced by fibrosis, accompanied by melanophages, new blood vessels, and a variable degree of inflammation.[7]
In suspected but not certain nevus or melanoma, generally perform immunohistochemistry with SOX10 (which stains cell nuclei of melanocytes), whereby melanocyte proliferation and nuclear pleomorphism is easier to see:[8]
Determine if the distance to any margin is greater or lesser than 3 mm.[10] If a margin is closer, measure it at an exactness of 0.1 mm.
If margins are difficult to determine, consider immunohistochemistry with SOX10 (staining the nuclei of melanocytes), to better visualize melanoma nests.[11]
Depth and ulceration
For invasive melanoma, measure the depth and whether there is ulceration or not, so as to be able to classify the T stage (following table by AJCC, 8th edition):[12]
T Category
Thickness
Ulceration status
TX: primary tumor thickness cannot be assessed (e.g., diagnosis by curettage)
Not applicable
Not applicable
T0: no evidence of primary tumor (e.g., unknown primary or completely regressed melanoma)
Not applicable
Not applicable
Tis (melanoma in situ)
Not applicable
Not applicable
T1
≤1.0 mm
Unknown or unspecified
T1a
<0.8 mm
Without ulceration
T1b
<0.8 mm
With ulceration
0.8–1.0 mm
With or without ulceration
T2
>1.0–2.0 mm
Unknown or unspecified
T2a
>1.0–2.0 mm
Without ulceration
T2b
>1.0–2.0 mm
With ulceration
T3
>2.0‐4.0 mm
Unknown or unspecified
T3a
>2.0–4.0 mm
Without ulceration
T3b
>2.0–4.0 mm
With ulceration
T4
>4.0 mm
Unknown or unspecified
T4a
>4.0 mm
Without ulceration
T4b
>4.0 mm
With ulceration
Histopathologic type
If needing to evaluate, the main types of invasive melanoma are:[13]
Type
Features
Relative incidence (in comparison to all melanomas)[13]
Photograph
Micrograph
Superficial spreading melanoma
Melanoma cells with nest formation along the dermo-epidermal junction.
If negative on H&E stain, generally use immunohistochemistry for melanoma markers (such as a combination of melan-A and HMB-45) to exclude micrometastasis:
histological regression, with complete or partial disappearance from areas of the dermis (and occasionally from the epidermis), which have been replaced by fibrosis, accompanied by melanophages, new blood vessels, and a variable degree of inflammation.[18]
Radicality,[19] mainly into either of the following: edit
>3 mm : "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
<3 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.
Continuous with margin: "Not radically excised at (location)."
Depth or most distant invasion of melanoma cells.[19]
Ulceration or not, and maximum dimension if present
Stage as per AJCC
Clark's level
Histopathologic type
Mitotic rate, as amount per mm2
Significant signs of regression
Cytoplasmic pigmentation
Melanoma cell shapes
US example
Skin, mid upper back, excision:
Malignant melanoma, nodular type, Clark level IV, Breslow thickness 10mm. Surgical margins are negative for melanoma.
See synoptic report.
SYNOPTIC REPORT:
Specimen
Procedure: Excision
Specimen Laterality: Midline
Tumor
Tumor Site: Skin of trunk
Histologic Type: Nodular melanoma
Maximum Tumor (Breslow) Thickness (Millimeters): 10 mm
Macroscopic Satellite Nodule(s): Not identified
Ulceration: Present
Extent of Ulceration (Millimeters): 12 mm
Anatomic (Clark) Level: IV (Melanoma invades reticular dermis)
Mitotic Rate: 18 mitoses / mm2
Microsatellite(s): Not identified
Lymphovascular Invasion: Not identified
Neurotropism: Not identified
Tumor-Infiltrating Lymphocytes: Present, nonbrisk
Tumor Regression: Not identified
Margins
Peripheral Margins: Negative for invasive melanoma
Distance of Invasive Melanoma from Closest Peripheral Margin (Millimeters): 5 mm
Location: 3 o'clock and 9 o'clock
Status of melanoma in situ at peripheral margins: Negative for melanoma in situ
Distance of melanoma in situ from closest peripheral margin (millimeters): Cannot be determined - Ulcerated surface and no in-situ noted in the remaining surface
Location: Lateral
Deep Margin: Negative for invasive melanoma
Distance of Invasive Melanoma from Deep Margin (Millimeters): 2 mm
Status of Melanoma in situ at Deep Margin: Negative for melanoma in situ
Distance of Melanoma in situ from Deep Margin (Millimeters): Cannot be determined (negative for melanoma in situ)
Lymph Nodes
Regional Lymph Nodes: No lymph nodes submitted or found
Sun-damaged skin with central diffusely delimited proliferation of melanocytic cells having polymorphic cell nuclei, distinct nucleoli and uneven light brown pigmentation. An area of pagetoid migration is seen. There is ulceration of a smaller area. The radial margin is over 3.0 mm and the deep margin is 2.0 mm.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The excision example shows a superficial basal cell carcinoma.
↑ 3.03.1Clark's level is not included in United States AJCC guidelines, but is mandatory for melanomas in Sweden. -. Breslow Depth and Clark Level. Melanoma Research Alliance. Retrieved on 2020-02-13. - . Bilaga 6. Kvalitetsbilaga för patologi (KVAST-bilaga). Regionala Cancercentrum i Samverkan, guidelines by Swedish Society of Pathology. Retrieved on 2020-02-13.
Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26. - For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑ 6.06.16.26.3Husain, Ehab A; Mein, Charles; Pozo, Lucia; Blanes, Alfredo; Diaz-Cano, Salvador J (2011). "Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi
". Modern Pathology24 (4): 471–486. doi:10.1038/modpathol.2010.143. ISSN0893-3952.
↑Ribero, Simone; Gualano, Maria Rosaria; Osella-Abate, Simona; Scaioli, Giacomo; Bert, Fabrizio; Sanlorenzo, Martina; Balagna, Elena; Fierro, Maria Teresa; et al. (2015). "Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status
". JAMA Dermatology151 (12): 1301. doi:10.1001/jamadermatol.2015.2235. ISSN2168-6068.
↑Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; et al. (2015). "Sox10—A Marker for Not Only Schwannian and Melanocytic Neoplasms But Also Myoepithelial Cell Tumors of Soft Tissue
". The American Journal of Surgical Pathology39 (6): 826–835. doi:10.1097/PAS.0000000000000398. ISSN0147-5185.
↑Definition of "thin margin": Wolf, Y.; Balicer, R.D.; Amir, A.; Feinmesser, M.; Hauben, D.J. (2001). "The vertical dimension in the surgical treatment of cutaneous malignant melanoma – how deep is deep?
". European Journal of Plastic Surgery24 (2): 74–77. doi:10.1007/s002380100225. ISSN0930-343X.
↑Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; et al. (2015). "Sox10—A Marker for Not Only Schwannian and Melanocytic Neoplasms But Also Myoepithelial Cell Tumors of Soft Tissue
". The American Journal of Surgical Pathology39 (6): 826–835. doi:10.1097/PAS.0000000000000398. ISSN0147-5185.
↑ 12.012.1Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC961218414. - For access, see the Secrets chapter of Patholines. - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
↑Michael Xiong; Ahmad Charifa; Chih Shan J. Chen.. Cancer, Lentigo Maligna Melanoma. StatPearls, National Center for Biotechnology Information. Last Update: May 18, 2019.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Staining
3 H&E sections and one section with periodic acid Schiff (PAS)[note 2][1]
If suspected bacterial and fungal microorganisms, consider Gram stain and Gomori methenamine silver stain.[1]
Microscopic evaluation
One approach is to classify into mainly either of the following, primarily based on depth of involvement:[1]
Epidermis, papillary dermis, and superficial vascular plexus:
Vesiculobullous lesions
Pustular dermatosis
Non vesicullobullous, non-pustular
With epidermal changes
Without epidermal changes. These characteristically have a superficial perivascular inflammatory infiltrate, and can be classified by type of cell infiltrate:[1]
Lymphocytic (most common)
Lymphoeosinophilic
Lymphoplasmacytic
Mast cell
Lymphohistiocytic
Neutrophilic
No visible pathology
Continue in corresponding section:
Non vesicullobullous, non-pustular lesions with epidermal changes
Spongiotic dermatitis
It is characterized by epithelial intercellular edema.[1]
Focal, usually mild, spongiosis with overlying scale crust, with a few neutrophils
The crust is often centered on a follicle
The papillary dermis is generally mildly edematous
Dilated blood vessels in the superficial vascular plexus
Mild superficial perivascular infiltrate of lymphocytes, histiocytes and occasional neutrophils. There is some exocytosis of inflammatory cells but not as prominent as in nummular dermatitis
In addition to above, an unspecific spongiotic dermatitis can be consistent with nummular dermatitis, dyshidrotic dermatitis, Id reaction, dermatophytosis, miliaria, Gianotti-Crosti syndrome and pityriasis rosea.[1][note 3]
Vacuolar alteration of various severity, from focal or diffuse vacuolation of the basal keratinocytes (grade I), to separation at the dermoepidermal junction (grade III)
An interface dermatitis with vacuolar alteration, not otherwise specified, may be caused by viral exanthems, phototoxic dermatitis, acute radiation dermatitis, erythema dyschromicum perstans, lupus erythematosus and dermatomyositis.[1]
In the papillary dermis: a confluent, band-like, dense inflammation of mainly small lymphocytes and a few histiocytes, along or hugging the dermoepidermal junction.
Often vacuolar degeneration of basal keratinocytes and apoptotic bodies (colloid or Civatte bodies).
Lichen planus
Irregular epidermal hyperplasia with a jagged “sawtooth” appearance, compact hyperkeratosis or orthokeratosis, foci of wedge-shaped hypergranulosis, basilar vacuolar degeneration, slight spongiosis in the spinous layer, and squamatization. The dermal papillae between the elongated rete ridges are frequently dome shaped. Necrotic keratinocytes can be observed in the basal layer of the epidermis and at the dermal-epidermal junction. Eosinophilic remnants of anucleate apoptotic basal cells may also be found in the dermis and are referred to as “colloid or civatte bodies”. Whickham striae are usually seen in the areas of hypergranulosis. Vacuolar degeneration at the basal layer may be noted leading to focal subepidermal clefts (Max Joseph spaces). Squamatization occurs as a result of maturation and flattening of cells in the basal layer. It happens in areas of marked hypergranulosis with prominence of the sawtooth pattern of rete ridges. Wedge-shaped hypergranulosis can occur in the eccrine ducts (acrosyringia) or hair follicles (acrotrichia). In the hypertrophic subtype, the associated hyperkeratosis, parakeratosis, hypergranulosis, papillomatosis, acanthosis, and hyperplasia markedly increased with thicker collagen bundles forming in the dermis. Moreover, the rete ridges are more elongated and rounded as opposed to the typical sawtooth pattern. In atrophic LP, loss of the rete ridges and dermal fibrosis is prominent. In vesiculobullous LP, the disease progression is quicker. Hence, some of the distinctive features such as hyperkeratosis, hypergranulosis, or dense lymphocytic dermal-epidermal infiltrate may not be present. LP lesion may resolve with residual hyperpigmentation caused by a persistent increase in the number of melanophages in the papillary dermis.[9]
Can virtually be indistinguishable from cutaneous LP both clinically and histopathologically.
Typically, lesions have a photodistribution in the absence of oral mucosal involvement.[9]
Characteristically parakeratosis, a dermal eosinophilic infiltrate, and a perivascular lymphocytic infiltrate affecting the reticular dermis.
Epidermal changes are less common in lichenoid drug eruptions when compared to classic lichen planus. However, a higher concentration of necrotic keratinocyte and eosinophils in the infiltrate can be helpful in distinguishing lichenoid drug reaction from cutaneous lichen planus. A lengthy interval between the commencement of drug therapy and the onset of lesions does not exclude a diagnosis of lichenoid drug reaction. Resolution of the lesions often occurs within weeks to months after discontinuation of the offending drug.[9]
Localized granulomatous lymphohistiocytic infiltrate in an expanded dermal papilla.
Thinning of overlying epidermis and downward extension of the rete ridges at the lateral margin of the infiltrate, resulting in a typical "claw clutching a ball" appearance.[10]
Interface dermatitis with lichenoid inflammation, not otherwise specified, can be caused by lichen planus-like keratosis, lichenoid actinic keratosis, lichenoid lupus erythematosus, lichenoid GVHD (chronic GVHD), pigmented purpuric dermatosis, pityriasis rosea, and pityriasis lichenoides chronica.[1] Unusual conditions that can be associated with a lichenoid inflammatory cell infiltrate are HIV dermatitis, syphilis, mycosis fungoides, urticaria pigmentosa, and post-inflammatory hyperpigmentation.[1] In cases of post-inflammatory hyperpigmentation, it is important to exclude potentially harmful mimics such as a regressed melanocytic lesion or lichenoid pigmented actinic keratosis.[1]
Psoriaform dermatitis
Examining multiple deeper levels is recommended if initial cuts do not correlate well with the clinical history.[1]
Often: Thinning of epidermal cells overlying the tips of dermal papillae (suprapapillary plates), and dilated, tortuous blood vessels within these papillae
Further histopathologic diagnosis is performed by the following parameters:
Perivascular location. Mast cells are relatively sparse, potentially demonstrated with special stains, preferably tryptase stain. Extravasated erythrocytes are present in about 50% of the cases. No vasculitis.[14]
File:Micrograph of urticaria.jpg Dermal edema [solid arrows in (A,B)] and a sparse superficial predominantly perivascular and interstitial infiltrate of lymphocytes and eosinophils without signs of vasculitis (dashed arrow).[15]
A lesion with superficial lymphocytic infiltrate without additional histopathologic characteristics can be due to for example drug reactions and insect bites.[1][note 3]
Perivascular location. Mast cells are relatively sparse, potentially demonstrated with special stains, preferably tryptase stain. Extravasated erythrocytes are present in about 50% of the cases. No vasculitis.[14]
File:Micrograph of urticaria.jpg Dermal edema (solid arrows) and a sparse superficial predominantly perivascular and interstitial infiltrate of lymphocytes and eosinophils (dashed arrow)
Image at right shows influx of inflammatory cells including eosinophils and neutrophils in the dermis (solid arrow) and blister cavity (dashed arrows), and deposition of fibrin (asterisks).[19] However, the diagnosis of bullous pemphigoid consist of at least 2 positive results out of 3 criteria:[20]
Pruritus and/or predominant cutaneous blisters
Linear IgG and/or C3c deposits (in an n- serrated pattern) by direct immunofluorescence microscopy (DIF)
Positive epidermal side staining by indirect immunofluorescence microscopy on human salt-split skin (IIF SSS) on a serum sample.
A lesion with superficial lymphoeosinophilic infiltrate without additional histopathologic characteristics can be due to for example drug reactions and insect bites.[1][note 3]
Typically enlarged, dilated capillaries and venules located in the upper dermis, angulated telangiectasias, perivascular and perifollicular lymphocytic infiltration, and superficial dermal edema.[21]
Typically a superficial and deep perivascular lymphocytic infiltrate.[23] Plasma cells are typically located at the periphery of the lesion, whereas eosinophils are in the center.[23]
The patch stage typically shows irregular proliferation of jagged vascular channels in the dermis below an integral epidermis. The so-called promontory sign is sometimes found in patch stage lesions and denotes vascular spaces surrounding pre-existing blood (see image).[24]
A lesion with superficial lymphoplasmacytic infiltrate without additional histopathologic characteristics can be due to for example trauma, ulceration, scar and early cutaneous connective tissue diseases.[1][note 3]
These include bacterial infections including leprosy, and the sample should therefore be stained with Ziel-Neelsen, acid fast stains, Gomori methenamine silver, PAS, and Fite stains.[1] If negative, an unspecific lymphohistocytic dermatosis may be caused by drug reactions and viral infections.[1][note 3]
Granulomatous inflammation
Further information: Granulomatous skin inflammation
Granulomatous inflammation is defined by the presence of mononuclear leukocytes, specifically histiocytes, appearing as epithelioid cells with round to oval nuclei, often with irregular contours and abundant granular eosinophilic cytoplasm with indistinct cell borders. They may also coalesce to form multinucleated giant cells.[25]
Subepidermal vesicles and blisters associated with accumulation of neutrophils at the papillary tips.[26]
Sometimes presence of eosinophils, giving an appearance similar to bullous pemphigoid.[26]
The histopathology is unspecific in approximately 35%–40% of the cases,[26] and direct immunofluorescence is needed, showing deposition of IgA in the papillary dermis in a granular or fibrillar pattern.[27]
In a referral with a rash or other suspicion of dermatitis, but no visible pathology is seen, generally do a fungal stain, as fungal infections may have no visible pathology on H&E stain.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑PAS is for evaluation of the epidermal basement membrane, blood vessels, and the presence of fungal organisms
↑ 3.003.013.023.033.043.053.063.073.083.093.10In "not otherwise specified" cases, a description of the findings attained so far is generally enough as a diagnosis, but may mention when it can be consistent with a diagnosis that is clinically suspected according to the referral. A more comprehensive approach is to include a comment such as the following: "Differential diagnosis for this condition include: ____, ____ and ____. Clinical correlation is recommended.
↑Parakeratotic mounds at the edge of follicular ostia.
↑Pigmented purpuric dermatitis of Gougerot and Blum particularly have a tendency for lichenoid infiltrate.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑ 6.06.16.26.36.46.5Unless else specified in boxes, reference is: Alsaad, K O (2005). "My approach to superficial inflammatory dermatoses
". Journal of Clinical Pathology58 (12): 1233–1241. doi:10.1136/jcp.2005.027151. ISSN0021-9746.
↑Lisa K Pappas-Taffer. Lichen Sclerosus. Medscape. Updated: May 17, 2018
↑Shenoi, SD; Balachandran, C; Mehta, VandanaRai; Salim, T (2005). "Lichen amyloidosus: A study of clinical, histopathologic and immunofluorescence findings in 30 cases
". Indian Journal of Dermatology, Venereology and Leprology71 (3): 166. doi:10.4103/0378-6323.16230. ISSN0378-6323.
↑"Diagnosis and classification of psoriasis
". Autoimmunity Reviews13 (4–5): 490–5. January 2014. doi:10.1016/j.autrev.2014.01.008. PMID 24434359.
↑ 14.014.114.214.314.414.514.6Barzilai, Aviv; Sagi, Lior; Baum, Sharon; Trau, Henri; Schvimer, Michael; Barshack, Iris; Solomon, Michal (2017). "The Histopathology of Urticaria Revisited—Clinical Pathological Study
". The American Journal of Dermatopathology39 (10): 753–759. doi:10.1097/DAD.0000000000000786. ISSN0193-1091.
↑Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey (2018). "Complement Activation in Inflammatory Skin Diseases
". Frontiers in Immunology9. doi:10.3389/fimmu.2018.00639. ISSN1664-3224.
↑Guarner, J.; Brandt, M. E. (2011). "Histopathologic Diagnosis of Fungal Infections in the 21st Century
". Clinical Microbiology Reviews24 (2): 247–280. doi:10.1128/CMR.00053-10. ISSN0893-8512.
↑ 23.023.1Wilson, Thomas C.; Legler, Allison; Madison, Kathi C.; Fairley, Janet A.; Swick, Brian L. (2012). "Erythema Migrans
". The American Journal of Dermatopathology34 (8): 834–837. doi:10.1097/DAD.0b013e31825879be. ISSN0193-1091.
↑Soyer, H. Peter; Jakob, Lena; Metzler, Gisela; Chen, Ko-Ming; Garbe, Claus (2011). "Non-AIDS Associated Kaposi's Sarcoma: Clinical Features and Treatment Outcome
". PLoS ONE6 (4): e18397. doi:10.1371/journal.pone.0018397. ISSN1932-6203.
↑Shah, Kabeer K.; Pritt, Bobbi S.; Alexander, Mariam P. (2017). "Histopathologic review of granulomatous inflammation
". Journal of Clinical Tuberculosis and Other Mycobacterial Diseases7: 1–12. doi:10.1016/j.jctube.2017.02.001. ISSN24055794.
↑ 26.026.126.2Antiga, Emiliano; Caproni, Marzia (2015). "The diagnosis and treatment of dermatitis herpetiformis
". Clinical, Cosmetic and Investigational Dermatology: 257. doi:10.2147/CCID.S69127. ISSN1178-7015.
↑Huma A. Mirza; Amani Gharbi; William Gossman.. Dermatitis Herpetiformis. StatPearls at National Center for Biotechnology Information. Last Update: July 11, 2019.
↑Saleem, Maryam; Iftikhar, Hassaan (2019). "Linear IgA Disease: A Rare Complication of Vancomycin
". Cureus. doi:10.7759/cureus.4848. ISSN2168-8184.
↑Casarin Costa, Jose Ricardo; Virgens, Anangelica Rodrigues; de Oliveira Mestre, Luisa; Dias, Natasha Favoretto; Samorano, Luciana Paula; Valente, Neusa Yuriko Sakai; Festa Neto, Cyro (2017). "Sweet Syndrome: Clinical Features, Histopathology, and Associations of 83 Cases
". Journal of Cutaneous Medicine and Surgery21 (3): 211–216. doi:10.1177/1203475417690719. ISSN1203-4754.
↑Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey (2018). "Complement Activation in Inflammatory Skin Diseases
". Frontiers in Immunology9. doi:10.3389/fimmu.2018.00639. ISSN1664-3224.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
The primary objective is to determine the location, and then the most likely cell type of the aberration:
Ulceration: On the outer ear, consider chondrodermatitis nodularis chronica helicis (pictured): With the ulceration surrounded by acanthosis and parakeratosis.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
↑Sato, Toshitsugu; Tanaka, Masaru (2014). "Linear sebaceous hyperplasia on the chest
". Dermatology Practical & Conceptual. doi:10.5826/dpc.0401a16. ISSN21609381.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Microscopic evaluation
File:Histopathology of a keloid.jpgA keloid is characterized by wide bands of collagen with large, brightly eosinophilic, glassy fibers, parallel to fibroblasts and myofibroblasts.
Tongue-like advancing edge underneath normal-appearing epidermis and papillary dermis
Yes
No
Horizontal cellular fibrous band in the upper reticular dermis
Yes
No
Prominent fascia-like fibrous band
Yes
No
Reporting
Example report:
Skin, left earlobe, excision: - Keloid
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.
Further information: Gross processing of skin excisions
Tongue-like advancing edge underneath normal-appearing epidermis and papillary dermis
Yes
No
Horizontal cellular fibrous band in the upper reticular dermis
Yes
No
Prominent fascia-like fibrous band
Yes
No
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
. Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23. - For microtomy of the most central side at the lesion
". Ochsner J5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen. - It also shows an example of circular coverage, with equal coverage distance in all four directions. - The entire specimen may be submitted if the risk of malignancy is high.
A progressive atherosclerotic lesion: Pathological intima thickening (A) has some extracellular lipid (EL) present deep in the lesion without true necrosis.[1]
Histopathology of plaque components in atherosclerosis: (A) Intraplaque neovasculature (arrows); (B) intraplaque hemorrhage; (C) large areas of calcification seen as purple morula; (D) lumen thrombus (arrowhead); stained with hematoxylin and eosin (H&E); (E) macrophage infiltration; stained with CD68 antibodies.[1]
Cross-sections collapse more or less after cutting, and estimations of the maximum percentage of stenosis should be made as imagined on an expanded blood vessel, as: 1-(lumen area)/(atherosclerosis area). In this case, there is 45-50% stenosis.
File:Histopathology of giant cell arteritis.pngEvaluate for giant cell arteritis at least upon request. It is characterized by a granulomatous inflammation of arteries with discontinuous and fragmented internal elastic lamina.[2]
Microscopy report
Classify any atherosclerosis as mild, moderate or severe.
If cross-sections were made, state the maximum percentage of stenosis for each artery.
Example:
Sections of the three main coronary arteries reveal << mild / moderate / severe>> atherosclerosis, with approximately __%, __% and __% stenosis of the left anterior descending, left circumflex coronary artery and right coronary artery, respectively.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 1.01.11.21.31.4Yang, Wen Jie; Fisher, Mark; Zheng, Lu; Niu, Chun Bo; Paganini-Hill, Annlia; Zhao, Hai Lu; Xu, Yun; Wong, Ka Sing; et al. (2017). "Histological Characteristics of Intracranial Atherosclerosis in a Chinese Population: A Postmortem Study
". Frontiers in Neurology8. doi:10.3389/fneur.2017.00488. ISSN1664-2295.
Look for presence of fibroblasts or myofibroblasts, conferring a diagnosis of an organizing thrombus.
Reporting
Example:
Right profunda femoris artery clot, excision: Organizing thrombus.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Picture from:Pantanowitz, Liron; Duke, Wayne H (2008). "Intravascular lesions of the hand
". Diagnostic Pathology3 (1): 24. doi:10.1186/1746-1596-3-24. ISSN1746-1596. - "Figure- available via license: Creative Commons Attribution 2.0 Generic"
File:Arterial aneurysm.jpgCross-section of an arterial aneurysm, showing most of the area consisting of organized mural thrombus (tan-brown area).
Gross processing
Describe the shape (generally either fusiform or saccular).
Measure the length and diameter
Make several cross-sections and look for any dissection in the wall.
Gross report
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
(( A. Labeled -left upper extremity aneurysm. The specimen is received in formalin and consists of a segment of)) fusiformly dilated vessel measuring 11.5 cm in length and the diameter is 6.5 (x 6.5 cm). Upon sectioning, <<most \ (( __ %))>> of the area is occupied by tan-yellow to tan-red non-homogenous surface, consistent with an organized mural thrombus. (No visible wall dissection.)
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
Preferably make a touch prep for polarized light microscopy. At least if urate crystals are not initially detected, take sections to be put in 100% alcohol and tell the histology lab to prepare it as per gout protocol.[note 2] With characteristic crystals on a touch prep, sections may possibly be submitted in formalin.[note 2]
Microscopy evaluation
On a touch prep, look for needle-shaped crystals of urate. On polarized light, these will have negative birefriengence.
Uric acid crystals in polarized light, showing negative birefringence, with yellow color when aligned parallel to the axis of the red compensator, and blue when aligned perpendicularly to it.[1]
In contrast, pseudogout, also called calcium pyrophosphate dihydrate (CPPD) crystal deposition disease) displays rhombus-shaped or parallelogram-shaped crystals with negative birefringence.
To look for crystals in a regular light microscope, look without condenser (right image) if possible, wherein crystal outlines are more clear than with condenser (left image). CPPD crystals are depicted.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
In uncertain cases, the following immunohistochemistry markers are usually helpful:
CD34, indicating a solitary fibrous tumor
S100, indicating a neural or nerve sheath tumor (see section below)
Desmin, indicating a muscular tumor (skeletal muscle or Smooth muscle tumor, latter also positive on SMA)[1]
Beta catenin, indicating fibromatosis
At least in case of enlarged atypical nuclei, consider sarcoma as a differential diagnosis, and if unsure, have a low threshold for consulting with people with expertise in the matter, as the visual difference between benign and malignant spindle cells is relatively subtle. Relevant stains may include MDM2 and CDK4 for liposarcoma,[2] as well as desmin and SMA for Leiomyosarcoma.[1]
Main features of liposarcoma:[3] - Spindle cells with enlarged, hyperchromatic nuclei. - Apparently univacuolated adipocytes (may look normal). - Lipoblasts (multivacuolated), but neither necessary nor sufficient for diagnosis.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Gross processing
Perform consecutive slicing of the entire specimen.
Look for signs of liposarcoma: Mainly by firm volumes.[1] Color varies from yellow to white (and firm) depending on the proportion of adipocytic, fibrous and/or myxoid content.[2] Areas of fat necrosis are common in larger lesions. Rarely, infiltrative growth is seen.[2]
Submit slices from any suspicious parts, or at least one representative slice from the specimen.[3] (A more comprehensive practice is to submit 1 section per centimeter, and 2 sections per cassette.[4])
Liposarcoma: Tumor section reveals brownish-yellowish areas, hemorrhagic and calcific zones.
Gross report
Color
Even absence of hemorrhage or necrosis.
Example:
Mass ((weighing 121 grams)) and measuring 10 x 6,5 x 3,5 cm. ((The surgical margin is intact.)) Cut sections show homogenous yellow color, with no hemorrhage or necrosis. ((The specimen is serially sectioned, and representative sections are submitted for microscopic examination in __ cassettes.))
Lipoma: lobules of mature white adipose tissue divided by delicate and inconspicuous fibrous septa containing thin-walled capillary-sized vessels. Still, look close at the fibrous septa:
An atypical lipomatous tumor (also termed well-differentiated liposarcoma), lipoma-like subtype. At low magnification, the majority of the tumor essentially has the look of benign mature adipocytes (except for mildly increased variation in lipid droplet sizes), but high magnification of a fibrous band shows spindle cells with enlarged, hyperchromatic nuclei. Another clue for liposarcoma is a higher variability of lipid droplet sizes.
Fibrolipoma is a lipoma with focal areas of large amounts of fibrous tissue. A sclerotic lipoma is one step further: a predominantly fibrous lesion with focal areas of fat.[5] If unsure of degree of fibrosis: Simply report as lipoma.
Main features of liposarcoma:[7] - Spindle cells with enlarged, hyperchromatic nuclei. - Apparently univacuolated adipocytes (may look normal). - Lipoblasts, but is neither necessary nor sufficient for diagnosis.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Fixation
Generally 10% neutral buffered formalin.
Gross processing
A gross inspection is almost always enough, and tissue generally does not need to be submitted except in unique circumstances.[1] ((Still you may submit 1 cassette of one or more representative sections for an inguinal hernia sac in a patient aged up to 16 years of age, or in case of hernia sacs from other regions than inguinal.))
Gross report
((A. Labeled - ___. The specimen is received in formalin and consists of)) __ fragment(s) of pink-tan fibromembranous tissue, measuring ___ cm in greatest dimension and ___ cm in greatest thickness. The surfaces are smooth. There are no sections submitted for microscopic examination. (Representative sections are submitted for microscopic examination in __ cassettes.)
In case of a gross only examination, the microscopic report may still be given as a formality:
Right inguinal region, herniorrhaphy: Hernia sac, gross examination only.
When microscopy slides of the case are available, you may screen the sample at low magnification to rule out obvious pathology:
Umbilical hernia sac, hernia repair: Connective tissue lined by mesothelium, consistent with hernia sac.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
All the following are odontogenic cyst, and in case of inability to specify further, may be simply diagnosed as such:
Cyst type
Lining epithelium
Other characteristics
Image
Periapical (radicular) cyst
Stratified squamous epithelium of variable thickness, except when originating in a maxillary sinus where there is respiratory epithelium (pseudostratified ciliated columnar epithelium).[1]
A fibrous capsule of varying thickness, with chronic inflammatory cells, wherein a plasma cells may be abundant.[1]
May demonstrate exocytosis, spongiosis, and/or hyperplasia
May be discontinuous in part and range in thickness from 1 to 50 cell layers, but usually 6 - 20 cell layers
In early cysts, the epithelial lining tend to be proliferative and arcading, with an intense inflammation.
Established cysts tend to rather have fairly regular lining with a higher degree of differentiation, resembling a simple stratified squamous epithelium
Cyst lumen may demonstrate fluid and cellular debris.[5]
All types above can occasionally have scattered mucous or ciliated cells, as well as Rushton bodies, which are amorphic, eosinophilic, linear to crescent-shaped bodies in the cyst epithelium.[4][1][2][5]
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 4.04.1Tsesis, I; Rosen, E; Dubinsky, L; Buchner, A; Vered, M (2016). "Metaplastic changes in the epithelium of radicular cysts: A series of 711 cases
". Journal of Clinical and Experimental Dentistry: 0–0. doi:10.4317/jced.52846. ISSN19895488. - "Fig 2- available via license: Creative Commons Attribution 2.5 Generic"
Verrucous squamous cell carcinoma (images are from penis).
If uncertain, perform immunohistochemistry for Ki67 and p53.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Initially copied from: Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update
". Biomedicines5 (4): 71. doi:10.3390/biomedicines5040071. ISSN2227-9059. "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)."
First look at the requisition form ((and in the medical records)) for the following suspicions:
Suspected infection: Confirm that a sample has been taken for microbiology. If not, take a sample from within the specimen when you gross it.
Possible lymphoma: Make a touch prep and take sample(s) for flow cytometry. If you have bilateral tonsils, and they look grossly similar, you may combine a small sample of each tonsil into one container for flow cytometry.
Suspected tumor: Ink the external surfaces before sectioning. Otherwise inking is not needed. Further information: Tumor
Inspect the tonsils for any significant gross focal changes. A representative section of the grossly most abnormal part from each tonsil is generally enough.
Example gross report
((A. Labeled - ___. The specimen is received in formalin and consists of)) one rubbery, ovoid, pink-tan tonsil(s) measuring ____. The mucosal surfaces are unremarkable. On sectioning, the tissue is tan-white and homogenous, with no gross lesions. (Representative sections are submitted for microscopic examination in __ cassettes.)
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
Pleomorphic adenoma (Pap stain). It can usually be diagnosed by its typical fibrillary stroma (mesenchyme). Stromal cell nuclei are small. Myoepithelial cells are usually the predominant cell type, and can have various shapes but are usually more elongated than epithelial cells. Epithelial cells may have prominent nucleoli.[3]
Warthin's tumor, with typical cellular features (and relatively uncommon binucleated cells).[4] Pap stain. For a diagnosis, you should see sheets of oncocytes and a mixed population of lymphocytes.[5]
Reporting=
Example report:
Right parotid mass, biopsy: – Pleomorphic adenoma.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 1.01.1Steve C Lee, MD, PhD. Salivary Gland Neoplasms. Medscape. Updated: Jan 13, 2021}} Diagrams by Mikael Häggström, MD
↑Image by Mikael Häggström, MD. Reference for description: Bin Xu, M.D., Ph.D.. Pleomorphic adenoma. Pathology Outlines. Last author update: 30 July 2021. Last staff update: 6 February 2023
↑Image by Mikael Häggström, MD. Reference for description: Bin Xu, M.D., Ph.D.. Pleomorphic adenoma. Last author update: 30 July 2021. Last staff update: 5 August 2021
Sharply dissect the thyroid from the cartilage, starting at the posterior end of each lobe & working forward. Do not cut the isthmus. Try to find parathyroids.
Gross processing of thyroidectomy
Weigh.[2] Up to 30 g versus over 30 g grams is an accepted cutoff between normal and increased weight of the thyroid gland.[3]
Measure each lobe and isthmus in 3 dimensions, respectively.[2]
Ink outer surface,[2] at least if malignancy is suspected.[4]
Hemithyroidecomy (lobe + isthmus) or lobectomy, including completion thyroidectomies: Use separate colors over the cut surface and the outer “capsular” or "peripheral" surface.
Thyroid hyperplasia: Variable sized dilated follicles with flattened to hyperplastic epithelium. May form nodules, but without any significant capsule. Architecture resembles normal thyroid, but may be somewhat hypercellular.[6]
Thyroid follicular adenoma, being architecturally and cytologically different from surrounding gland, and being completely enveloped by thin fibrous capsule (if not being encapsulated, mainly consider thyroid carcinoma if atypical cells, otherwise nodular hyperplasia with dominant nodule, the latter especially if there are hyperplastic changes elsewhere in gland).[7] Hyperfunctioning follicular adenoma typically shows follicles with papillary infoldings and bubbly, pale colloid with peripheral scalloping (a). Non-hyperfunctioning adenomas with papillary hyperplasia usually show a more predominantly papillary pattern without vacuolated cytoplasm and scalloping colloid (b).[8]
Hürthle cell adenoma, typically consisting of cells with large size, distinct cell borders, deeply eosinophilic and granular cytoplasm, large nucleus with prominent nucleolus, and complete loss of cell polarity.[10]
Follicular thyroid carcinoma, resembling follicular cells, and typically do not display the nuclear features of papillary thyroid carcinoma mentioned above. Distinction from adenoma requires invasion of adjacent thyroid parenchyma, capsule (complete penetration) and/or blood vessels (in or beyond the capsule).[12]
A minimum number of 6 clusters with 10 cells each has been arbitrary established to assume adequacy for a definitive diagnosis.[13] The presence of characteristic cells may still confer a definitive diagnosis, but otherwise, the report will simply state inadequate number of cells.
Clusters of benign follicular epithelial cells and colloid. Findings are consistent with a benign hyperplastic nodule. (Bethesda category II)
III
Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (follicular or lymphoid cells with atypical features)
Thyroid aspiration, right mid pole:
Clusters of atypical follicular cells of undetermined significance (Bethesda category III).
Look for microfollicles, which are flat groups of follicular cells, each having less than 15 follicular cells arranged in a circle that is at least two thirds complete.[16][image 1] They indicate a follicular neoplasm.
Thyroid spherules, on the other hand, are benign features. A spherule may mimic a microfollicle, but has a more smooth, round, ball-like contour, and even spacing of the follicular cell nuclei.[17]
Cytopathology suspicious for Hürthle cell neoplasm (Bethesda category IV), Pap stain. However, it cannot distinguish Hürthle cell adenoma from Hürthle cell carcinoma, which requires histopathologic sections to see transcapsular or vascular invasion. Hürthle cell hyperplasia (as seen in Hashimoto's thyroiditis) may show moderate variation in nuclear sizes and prominent nucleoli, but further findings favoring Hürthle cell neoplasm include a large number of Hürthle cells, and discohesiveness.[18]
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Shamim, A; Monira, K; Manowara, B; Sabiha, M; Alim, A; Nurunnabi, ASM (1970). "Weight of the Human Thyroid Gland A Postmortem Study
". Bangladesh Journal of Medical Science9 (1): 44–48. doi:10.3329/bjms.v9i1.5230. ISSN2076-0299. - In turn citing: Langer P. Discussion about the limit between normal thyroid and goiter: mini review. Endocrine regulations. 1999 March; 33(1): 39-45.
↑Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26.
↑. THYROID. Royal College of pathologists of Australia. Retrieved on 2019-12-17.
↑Image by Mikael Häggström, MD. Reference for findings: Rachel Jug, M.B.B.Ch., B.A.O., David Poller, M.D., Xiaoyin "Sara" Jiang, M.D.. NIFTP. Pathology Outlines. Last author update: 10 May 2018
↑Michael, Claire W.; Pang, Yijun; Pu, Robert T.; Hasteh, Farnaz; Griffith, Kent A. (2007). "Cellular adequacy for thyroid aspirates prepared by ThinPrep: How many cells are needed?
". Diagnostic Cytopathology35 (12): 792–797. doi:10.1002/dc.20768. ISSN87551039.
Respiratory epithelial shedding in a small bronchus. If present, look for vascular leakage, mucus hypersecretion and/or widespread airway narrowing, together indicating asthma.[1]
Pulmonary mucormycosis, seen as non-septated and broad-branching, and sometimes branching at right angles (black arrow).[3]
For fungi not conforming to the two main forms above, a general pathologist may attempt to get input by readily available expertise locally, but if it cannot be readily speciated, then it's generally acceptable to simply report as fungi present.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Madea, B (2014). Handbook of forensic medicine. Hoboken, N.J: Wiley-Blackwell. ISBN 978-1-118-57062-3. OCLC872114659.
↑Error on call to Template:cite web: Parameters url and title must be specified. . Wellcome Collection. Retrieved on 2024-02-21. License: CC0 1.0 Universal
Medical imaging provides a major clue as to whether a lung tumor is benign or malignant, where lesions smaller than 2 cm are likely to be benign, whereas lesions larger than 2 cm are malignant (that is, lung cancer) in 85% of cases.[1]
Benign tumors
Subsequently distribution of benign tumors and lung cancers, respectively, are as follows:[1]
Whereas large cell carcinoma is more often histologically distinct, adenocarcinoma and SCC may look alike. In such cases, an immunohistochemistry panel of TTF1, CK5/6, and p63 can be used to distinguish the two.[6][7]
In case of adenocarcinoma, in order to distinguish primary lung cancer from a gastrointestinal metastasis, the best panel, in addition to CK7 and TTF-1, may be CDX2 and/or GPA33 plus MUC2, or all of the following GI markers: CDH17, CDX2, CK20, GPA33, MUC2, and SATB2 with four positive GI markers supporting metastasis.[8]
Further workup
edit For primary lung non-small cell carcinoma (NSCLC) stages IB - IV (such as being more than 3 cm in size), generally perform full next generation sequencing panel (DNA and RNA) with PDL-1 immunostaining. For an advanced stage NSCLC that is not a candidate for biopsy or re-biopsy, a viable alternative is “liquid biopsy” on peripheral blood for circulating tumor DNA.[9]
↑Image by Mikael Häggström, MD. Source for findings: Caroline I.M. Underwood, M.D., Carolyn Glass, M.D., Ph.D.. Lung - Small cell carcinoma. Pathology Outlines. Last author update: 20 September 2022}}
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Other legend
<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page
Intraoperative consultation
Perform:
Tumor microscopy on frozen sectioning if there is intermediate risk of cancer (if frozen section does not show cancer, the surgeon may not need to perform lymph node dissection)
Margin assessment: A gross distance from tumor to the parenchymal is generally sufficient, unless a suspected malignancy is close enough to confer a significant risk of extension to the margin, in which case the closest parenchymal margin should be frozen en face[note 2]. For lobectomies, generally perform frozen section on the bronchial and vascular margin en face[note 2].
Describe pleural surface, including color, and any presence of granularity, adhesions, retraction, or tumor.
Palpate for any tumors.
Ink the surgical margin and cut it away just below any sutures or staples. If the margin is substantially stapled (and their removal would be either too tissue-damaging or otherwise inconvenient), ink and use another section of the tissue underneath it for frozen sectioning.
In intraoperative consultations use a section that is presumably closest to a tumor for frozen sectioning, with the tissue en face[note 2], for radicality. This is generally enough to report intraoperatively to the surgeon, unless otherwise requested.
((Sample the entire surgical margin for standard processing.))
Cut open the bronchi of the specimen with a pair of scissors, as far as they can fit within the lumina. Attempt to cut so as to be able to take a section that includes both any tumor and nearest bronchus. Palpate for tumors intermittently. Describe the cut surface, including color and consistency, and any focal lesions.
Turn the specimen to the side with least cuts so far, and serially section it. Palpate for tumors intermittently.
Initial measurements when triaging fresh lobectomies
Size of lobe in 3 dimenstions
Size of tumor (in 3 dimensions)
(Weight)
Distance from tumor to closest parenchymal, bronchial and vascular margins
Measure tumor size as a maximum diameter (or 3 dimensions)
Determine location: Which lobe if applicable, and if it is peripheral, central or hilar.
Margin length to pleura and hilum/surgical margin.
Any involvement of major bronchi or blood vessels.
Describe any lymph nodes, including location, range of sizes and appearance of cut surface.
Tissue selection
File:Margins of a lobectomy.jpgVascular (inked yellow), bronchial (inked blue) and parenchymal (inked black) margins of a lobectomy, showing staple line of bronchial margin being removed with scissors to allow for tissue selection.
1 from bronchial and vascular margins, en face[note 2], if present, ((differentially inked))
1 from nearest parenchymal margin, en face
Sections of any tumor
Any other focal change
1 from random non-neoplastic lung tissue
Gross report
((A. Labeled - ___. The specimen is received fresh for intraoperative consultation and consists of)) of a right upper lobe of lung which measures __ x __ x __ cm (and weighs __ g). The specimen includes a bronchial stump measuring __ cm in length and __ cm in diameter, which grossly appears unremarkable. The pleural surface is mottled tan-pink {{and slightly puckered on the __ aspect}}. There is a staple line representing the parenchymal margin measuring __ cm in length. The stapled margin is inked black. (On opening the bronchial tree, the mucosa is tan and smooth and the lumens are patent. The blood vessels are opened to reveal no blood clot or tumor.) {{Cut section show an irregular, gray-tan, rubbery firm mass measuring __ x __ x __ cm. The tumor is located __ cm from the bronchial and vascular margin and __ cm from the nearest surgical margin. The tumor abuts smaller bronchi and vessels.}} The remaining parenchyma is pink and spongy. (No lymph nodes are identified in the peribronchial region.) (Representative sections are submitted for microscopic examination in __ cassettes.)
Squamous cell carcinoma involving a subsegmental bronchus with distal chronic obstructive pneumonia. The tumor is seen as a rounded nodule, approximately 2 cm in diameter, proximal to a more irregular focus of chronic obstructive pneumonia with fibrosis.
Look mainly for carcinoma. Further information: Lung tumor
Microscopy report
Lung synoptic reports contain information (number and station) on all lymph nodes received per accession. For example, if Parts A-D are mediastinal nodes (8 in total) and Part E is a lobectomy containing 2 additional peribronchial nodes, the synoptic report for Part E should document all 10 nodes, for example:
A. Lymph node, station 1:
Negative for carcinoma. (0/1, 2 etc)
B. Lymph node, station 2:
Negative for carcinoma. (0/1, 2 etc)
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 2.02.12.22.3En face means that the section is tangential to the region of interest (such as a lesion) of a specimen. Further information: Gross_processing#Cutting
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Gross processing
If suspected lymphoma, before putting tissue in formalin, ensure that tissue is preserved in appropriate media for any special tests (usually flow cytometry). Further information: Lymphoma
In samples with tumors, slice through all included fat while palpating and looking for lymph nodes, and submit all that are found.
For lymph nodes taken for potential breast cancer metastasis, find out and report the procurement time and the time when put in formalin.[note 2]
Gross procedure
Measure the dimensions. For a lymph node with minimal surrounding fatty tissue, measure the greatest dimension (or 3 dimensions). For specimens with substantial amount of fatty tissue, measure the specimen in 3 dimensions, and measure the greatest dimension seen for individual lymph nodes therein after serial sectioning.
Find as many lymph nodes as you can in a specimen. Good locations to start include the presumed lymphatic drainage directions from a tumor, as well as when following the lymphatic directions from the vascular margins of a specimen. Serially section fatty tissue into slices that are thin enough to be palpated for small ovoid resistances. If you still have trouble finding enough lymph nodes, put fatty tissue in a vinegar and acetic acid solution made for the purpose of turning lymph nodes pale/white as well as making them more firm for palpation. Colon tumors are sometimes tattooed during endoscopy, and in such cases the tatoo ink often stains lymph nodes as well.
Lymph node in partially inked mesorectal fat after a night in acetic acid.
Section lymph nodes if needed. Lymph nodes less than 5 mm may be submitted whole, while larger lymph nodes may be sectioned at 2-3 mm intervals.[1]
Generally do not submit multiple sectioned lymph nodes in the same cassette, to allow exact counting of the number of involved lymph nodes on microscopy. If you will nevertheless submit multiple bisected lymph nodes in the same cassette, ink each lymph node differently.
File:Touch prep on a lymph node.jpgMaking a "touch prep": Press a glass slide against the cut surface of the lymph node, apply cytologic fixative solution immediately and stain with H&E.
If suspected lymphoma, such as an enlarged lymph node without any adjacent tumor or another almost certain cause, make a touch prep. Also, take a small fresh sample for flow cytometry:
For flow cytometry, aim for a tissue size of approximately 5 mm3. Put it in specific flow cytometry preservative medium (such as RPMI), and ensure it gets to the flow cytometry lab. If it is after normal hours and there is no one to ask to find such medium, you can put the specimen in normal sterile saline (enough to cover the tissue) in a fridge (2-8°C) until the next morning.[2] If you receive multiple lymph nodes for flow cytometry, still only sample one (unless the referral asks for separate flow cytometry studies, or there is a given history of one lymph node having high uptake and another having low uptake on PET scanning).
Urgency
The processing of lymph nodes is preferably rushed when the H&E stain will determine whether immunohistochemistry will be performed, especially when a lymph node is submitted together with a separate specimen that may be solved without immunostains. This rushing allows you to have the immunostained slides by a similar time as the rest of the case.[3] Examples of cases that are preferably rushed for such reasons include those that may be stained by CK AE1/AE3 in order to visualize otherwise occult lymph node involvement if you don't see any involvement on the H&E stain, mainly in cases when one or more sentinel lymph nodes are submitted together with any of the following:
Rushing is not necessary for non-sentinel lymph nodes.
Gross report
Individual lymph node, example
((A. Labeled - ___. The specimen is received in formalin and consists of)) __ fragment(s) of soft pink-tan tissue, measuring __ cm in greatest dimension (or __ x __ x __(. (Representative sections are submitted for microscopic examination in __ cassettes.)
Multiple lymph nodes
((A. Labeled - ___. The specimen is received fresh and consists of)) 2 irregular fragments of yellow-tan fatty and fibrous soft tissue measuring __ and ___ cm in greatest dimension. Within the adipose tissue are multiple tan-brown lymph nodes measuring up to __ cm in greatest dimension. The cut surfaces display no gross lesions. The lymph nodes are entirely submitted for microscopic examination (in 10 cassettes). KEY TO SECTIONS:
A1–A3– one lymph node, serially section
A4-A5– one lymph node, serially sectioned
A6– one lymph node, bisected
A7– one lymph node, bisected
A8– two lymph nodes, each bisected, differentially inked
A9– one lymph node, bisected
A10– multiple lymph nodes.
Additional information
If potential breast cancer metastasis: The specimen was procured at __ AM/PM on (date), 2020. The specimen was placed in formalin at __ AM/PM on (date), 2020.
If lymphoma workup: A touch prep is made, and a minor part of the specimen is submitted for flow cytometry. The remainder of the specimen is submitted for microscopic examination in one cassette.
Microscopic examination
Defining a lymph node
For counting lymph nodes, each should have a discernible capsule around lymphoid cells. Also count larger free-standing lymphoid aggregates. However, the definition of what constitutes a lymph node is largely subjective.[4] Also strive to keep a consistency with the gross description. In addition, any cancer involvement is in itself a relative indication of being a lymph node.
General screening
Look for:
Whatever pathology is indicated by the referral, or findings in other submitted specimens.
Enlargement, as preferably measured during grossing, but can possibly be made on the microscopy slide. If present, see separate section below.
Metastases: generally first look around the edges with intermediate magnification, and low mag in the middle, since cancer metastases usually occur at edges (as in this case). For suspected urothelial cancers, however, look closely throughout the node, as they have a tendency to show up anywhere in lymph nodes.
Granulomas (non-necrotizing granuloma pictured). If seen generally perform staining for acid-fast bacilli, and GMS stain for fungi.
Microscopy of enlarged lymph nodes
Look at any other slides for the same case first, in order to find any pathology that may be reflected in in the lymph nodes as well, mainly cancer metastasis or reactive lymph nodes from inflammation.
Look primarily at the overall architecture, with main findings being:
Follicular hyperplasia: Indicates mainly follicular hyperplasia of a reactive lymph node (pictured) or follicular lymphoma. Further information: Follicular hyperplasia
Dilated sinuses. The most cellular expansion is sinus histiocytosis (pictured). If it appears as such, look for a signet ring appearance, which may be a signet ring carcinoma or melanoma. If unsure, use immunostains for CD68, cytokeratin, S100 and mucin.[5]
Paracortical hyperplasia: Paracortical hyperplasia of a reactive lymph node shows expansion of paracortical areas by a mixed infiltrate, often having a mottled appearance, and it usually has a concomitant reactive follicular hyperplasia.[6] A T-cell lymphoma should be suspected if there is obliteration or marked diminution of the B-cell cortical region, or highly irregular or hyperchromatic nuclei.[6]
Unspecific hyperplasia: An unspecific pattern of lymph node enlargement, without atypical cells, in the lymphatic drainage direction from an inflamed area, may simply be diagnosed as "benign reactive lymph node".
Workup of cancerous lymph nodes
If cancer is detected in a lymph node:
Attempt to specify a specific cancer diagnosis'. If the patient has a known carcinoma or sarcoma etc, it is generally enough to confirm that it is consistent with a metastasis thereof.
Measure the size of involvement.
Look for extranodal extension.
Reporting
A non-involved lymph node in a patient with cancer can be reported for example as:
Sentinel lymph node #1, left axilla, (excision): One benign lymph node((, negative for malignancy (0/1))).
Cancerous lymph nodes with patients with known consistent cancer primary can be reported as metastatic,, such as:
Sentinel lymph node #2, left axilla, (excision): Macrometastatic carcinoma involving one of one (1/1) lymph node. Metastatic carcinoma measures 0.4 cm in greatest dimension. (Negative for extranodal extension).
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑The duration that a specimen has been without formalin affects mainly the reliability of estreogen and progesteron receptor testing: - Pekmezci, Melike; Szpaderska, Anna; Osipo, Clodia; Erşahin, Çağatay (2012). "The Effect of Cold Ischemia Time and/or Formalin Fixation on Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Results in Breast Carcinoma
". Pathology Research International2012: 1–7. doi:10.1155/2012/947041. ISSN2090-8091.
Generally 10% neutral buffered formalin.
Non–formalin-fixed tissue may be needed for tests such as microbiological analysis or copper quantification studies.[1]
Gross processing in autopsy
((Measure the distance from the liver edge to the right costal margin.))
Inspect the color and texture of the surfaces, including external and cut surfaces. Potential pathologies:
The liver surface is <<smooth ((and glistening)) {{/deformed by small and large nodules}}((, and is <<light tan / dark brown>> in color)). << Normal/ {{/ firm}} consistency. Cut surface[note 2] is normal / << (shows normal homogeneous brown parenchyma) / {{Yellowish color, indicating steatosis}} / {{dark nutmeg similar paths, indicating congestion}}. (No focal changes.)((The liver edge is _cm below the right costal margin.))
A general screening includes (with further information in sections below):
Looking at the referral/requisition form (and looking at the medical records) for particular conditions to look for or evaluate. (Perform a severity grading of previously known liver diseases.)
Commonly, this includes to quantify any cirrhosis, at least if the patient had alcohol abuse.
Steatosis is also common.
Signs of acute liver failure.
Signs of malignancy. If a tumor is found: Further information: Liver tumor
Signs of congestive hepatopathy (indicating heart failure).
Signs of inflammation at least around the portal triads.
Note the presence of microvesicular steatosis, as it is usually more harmful. It shows foamy hepatocytes (two annotated by arrows), as opposed to the more common macrovesicular steatosis (insert).
Shock liver, showing its hallmark[4] pathologic finding centrilobular necrosis but viable periportal hepatocytes. The necrotic hepatocytes are seen as slightly more eosinophilic (red) and discohesive.
File:Histopathology of congestive hepatopathy.jpgHistopathology of congestive hepatopathy, with sinusoidal dilation in zone 3. As the severity of the lesion increases, the sinusoids around the central vein become distended with extravasated red cells and there is adjacent hepatocyte plate atrophy.[6]
Acute hepatic congestion shows dilated sinusoidal capillaries predominantly in zone 3 of the hepatic acinus.[7]
Typical findings of chronic hepatic congestion are atrophy of hepatocytes in zone 3, perisinusoidal edema, thrombosis and hemorrhage. Chronic congestion typically displays perivenous and perisinusoidal fibrosis, with fibrous septa that bridge central hepatic veins. In contrast, other causes of distortion and cirrhosis typically have fibrous septa predominantly between portal triads. However, nonalcoholic steatohepatitis also may show perisinusoidal fibrosis in early stages; in later stages, the fibrosis tends to be in the portal triad. Cirrhosis develops in the final stages of congestive hepatopathy. Regenerating hepatocytes tend to grow in a sleevelike pattern along portal tracts, resulting in a nodular liver with preserved portal triads and obliterated or fibrosed hepatic veins, a pattern called "reverse lobulation". This pattern can also be seen in venous obstruction due to Budd-Chiari syndrome.[8]
Hepatocyte lipofuscin alone is of no real pathologic importance and does not warrant a mention in the report.[9]
Report
Presence of any liver disease
(Quantification of its severity.)
((Even absence of hepatitis, malignancy, congestive hepatopathy and/or steatosis.))
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑"Cut surface shows..." may alternatively be expressed as "On sectioning, the parenchyma is..."
"This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license"
↑ 2.02.1Standard reference range: Molina, D. Kimberley; DiMaio, Vincent J.M. (2012). "Normal Organ Weights in Men
". The American Journal of Forensic Medicine and Pathology33 (4): 368–372. doi:10.1097/PAF.0b013e31823d29ad. ISSN0195-7910.
↑ 3.03.1Standard reference range: Molina, D. Kimberley; DiMaio, Vincent J. M. (2015). "Normal Organ Weights in Women
". The American Journal of Forensic Medicine and Pathology36 (3): 182–187. doi:10.1097/PAF.0000000000000175. ISSN0195-7910.
↑Xue, Ran; Zhu, Yueke; Liu, Hui; Meng, Qinghua (2019). "The clinical parameters for the diagnosis of hepatitis B virus related acute-on-chronic liver failure with sepsis
". Scientific Reports9 (1). doi:10.1038/s41598-019-38866-3. ISSN2045-2322. -"This article is licensed under a Creative Commons Attribution 4.0 International License"
↑Shah, Shailja C.; Sass, David A. (2015). "“Cardiac Hepatopathy”: A Review of Liver Dysfunction in Heart Failure
". Liver Research - Open Journal1 (1): 1–10. doi:10.17140/LROJ-1-101. ISSN23794038. -"This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0),"
↑Wells, Michael L.; Fenstad, Eric R.; Poterucha, Joseph T.; Hough, David M.; Young, Phillip M.; Araoz, Philip A.; Ehman, Richard L.; Venkatesh, Sudhakar K. (2016). "Imaging Findings of Congestive Hepatopathy
". RadioGraphics36 (4): 1024–1037. doi:10.1148/rg.2016150207. ISSN0271-5333.
File:Histopathology of a bile duct hamartoma, high magnification.jpgA bile duct hamartoma is also very common.[2] This image shows typical features:[3] - Small to medium sized, irregularly shaped bile ducts lined by bland cuboidal epithelium (may also be flattened). - Prominent intervening collagenous stroma. - Bile ducts containing eosinophilic debris (may also contain inspissated bile)
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Table 37.2 in: Sternberg, Stephen (2012). Sternberg's diagnostic surgical pathology. Place of publication not identified: LWW. ISBN 978-1-4511-5289-0. OCLC953861627.
↑Figure 7 from Bioulac-Sage, Paulette; Sempoux, Christine; Possenti, Laurent; Frulio, Nora; Laumonier, Hervé; Laurent, Christophe; Chiche, Laurence; Frédéric Blanc, Jean; et al. (2013). "Pathological Diagnosis of Hepatocellular Cellular Adenoma according to the Clinical Context
". International Journal of Hepatology2013: 1–13. doi:10.1155/2013/253261. ISSN2090-3448. - Attribution 3.0 Unported (CC BY 3.0) license
Adrenal cortical necrosis. Hemorrhage, fibrin thrombi and short postmortem interval indicate ante-mortem necrosis, otherwise it can be regarded as a postmortem change.[2]
(Adrenal glands are ordinarily configured and with no definable focal changes on cut surfaces.)
((The adrenals are normal in size, shape and consistency, with a weight of __ grams on the right and __ grams on the left. The cortices are orange with <normal / increased / decreased thickness>. The medullae are <grey / autolyzed>.))
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑O'Hare, A. Munro Neville, Michael J. (1982). The Human Adrenal Cortex Pathology and Biology – An Integrated Approach. Springer London. pp. Chapter 4: Structure of the adult cortex. ISBN 9781447113171.
↑Page 120 in: Rutty, Guy (2001). Essentials of autopsy practice. London New York: Springer. ISBN 978-1-85233-541-0. OCLC44769560.
The most common adrenal tumors are adrenocortical adenomas and carcinomas. These are most commonly distinguished by the Weiss system,[2] as follows:[3]
Zona fasciculata versus adrenocortical adenoma. An adrenocortical adenoma typically has mild changes in comparison, including larger cells with larger and more pleomorphic nuclei with more coarse chromatin. H&E stain. [image 1]
Author:Mikael Häggström[note 1]
When sent to the pathology department, these are generally sent for stone analysis to determine the chemical composition.
Gross processing
Abide by local practices for what container to use and where to leave stone specimens. Generally submit the entire specimen, or as much as you can conveniently fit in the container.
Example report:
The specimen is received dry and consists of __ irregular fragment(s) of {{tan}} calculus measuring up to __ cm in maximum dimension. The entire specimen is submitted for spectrographic analysis.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Wang, Cuiping; Sun, Yang; Wu, Huanwen; Zhao, Dachun; Chen, Jie (2014). "Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers
". Histopathology64 (4): 567–576. doi:10.1111/his.12283. ISSN03090167.
↑ 3.03.13.2Aye, Than Than; Myint, Phone; Myint, Kyar Nyo Soe (2015). "Adrenocortical Oncocytoma Presenting with Gynaecomastia
". Journal of the ASEAN Federation of Endocrine Societies30 (1): 27–30. doi:10.15605/jafes.030.01.08. ISSN08571074.
Pancreatic lipomatosis is a common finding. This case shows moderate to severe lipomatosis, with mainly interlobular but also scattered intralobular fatty infiltration. Reporting is optional in at least mild to moderate cases.
Stages of pancreatic intraepithelial neoplasia.[2]
Notes
↑Upper limit is calculated as mean plus 2 standard deviations.
↑The pancreas may also be cut in the longitudinal plane.
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Kin, Tatsuya; Murdoch, Travis B.; Shapiro, A. M. James; Lakey, Jonathan R. T. (2017). "Estimation of Pancreas Weight from Donor Variables
". Cell Transplantation15 (2): 181–185. doi:10.3727/000000006783982133. ISSN0963-6897.
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Gross processing
Inspect
Measure
Serially section in 3-4 mm wide slices.
Example gross report:
(Labeled: ___. The specimen is received in formalin and consists of an) << opaque / translucent>> corneal disc measuring __ cm in diameter and __ cm in thickness. The specimen is serially sectioned and entirely submitted for microscopic examination in one cassette.
Microscopic examination
File:Histopathology of corneal acute and chronic inflammation.jpgCorneal subepithelial acute inflammation, seen as the presence of neutrophils, as well as chronic inflammation, seen as plasma cells and lymphocytes. There is an associated neovascularization. Bowman's membrane is disrupted. The findings are non-specific.
Look for integrity of Bowman's and Descemet's membranes.
For corneal opacities, look for the most common causes, which generally manifest as:[9]
(Right eye cornea, excision: Cornea with) patchy acute and chronic inflammation, nonspecific, with disrupted Bowman's membrane and associated neovascularization.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Image by Mikael Häggström, MD. Reference for features: Pooja Navale, M.D., Omid Savari, M.D., Joseph F. Tomashefski, Jr., M.D., Monika Vyas, M.D.. Solid pseudopapillary neoplasm. Last author update: 4 March 2022
↑Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC961218414. - For access, see the Secrets chapter of Patholines. - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
File:Histopathology of a nasal polyp.jpgBenign nasal/sinonasal polyp (not otherwise specified), consisting of hyperplastic edematous connective tissue with some seromucous glands and inflammation (mostly neutrophils and eosinophils), surrounded by respiratory or squamous epithelium.[1] It can be termed inflammatory nasal/sinonasal polyp when inflammation is more pronounced.
Squamous papilloma, with acanthosis and hyperkerratosis.
In case of significant inflammation:
Take at least one high magnification look to confirm that it is mixed and that lymphocytes are not atypical (otherwise, consult hematopathology, particularly whether it could be a lymphoma, notably extranodal NK/T cell lymphoma, nasal type.
(Classify as acute (with neutrophils) versus chronic (lymphocytes, eosinophils and/or plasma cells). Also look at any bone fragments for osteomyelitis.) Further information: Osteomyelitis
Extranodal NK/T cell lymphoma, nasal type.[2] These lymphoma cells are typically monotonous, with folded nuclei, indistinct nucleoli and moderate amount of cytoplasm.[3]
Reporting
Example:
Right and left sinus contents, excisions: Benign respiratory mucosa with chronic inflammation. Bone without significant histopathologic changes.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Mario L. Marques-Piubelli, M.D., Carlos A. Torres-Cabala, M.D., Roberto N. Miranda, M.D.. Extranodal NK / T cell lymphoma, nasal type. Pathology Outlines. Last author update: 5 January 2021. Last staff update: 14 October 2021
Weight of the parathyroid gland or fragment thereof. Generally, there should not be any subjective description of "enlarged" or similar.[note 2]
Presence of parathyroid tissue upon frozen section. In particular, exclude sampling from the thyroid. It is not necessary to specify any particular parathyroid pathology on intraoperative consultation (which in case of hyperparathyroidism relies on imaging and intraoperative parathyroid hormone levels rather than the histopathology)[1].
Autopsy
Optionally for a comprehensive autopsy, or where there is suspicion of parathyroid pathology, an effort is made to find the parathyroid glands, and inspect them for general or focal hyper-/neoplasia.
Microscopic evaluation
The main conditions to look for and distinguish are:
Parathyroid hyperplasia: Typically involves all 4 glands with diffuse enlargement.[2]
Parathyroid adenoma: Typically nodular growth with compressed rim of normal tissue.[2]
Either is indicated by a decreased amount of intra-gland adipose tissue, and increased weight. A weight of 35-160 mg is above average but not in itself "enlarged" in the absence of other findings.[note 2]
Parathyroid chief cell hyperplasia: An increase in the parenchymal cell mass,as a result of the proliferation of chief cells, oncocytes, and transitional oncocytes in multiple parathyroid glands.[3]
A. Left inferior parathyroid, excision: 24 mg of parathyroid tissue.
C. Right superior parathyroid, excision: 14 mg of parathyroid tissue.
Whenever possible, make a single report for multiple fragments from the same location. Example of final report, including additional fragments from the same locations:
A,B. Left inferior parathyroid gland, excision: Hypercellular parathyroid gland (121 mg aggregate weight), consistent with parathyroid hyperplasia.
C,D. Right superior parathyroid gland, excision: Parathyroid gland (94 mg aggregate weight) without significant histopathologic changes.
E. Left superior parathyroid gland, excision: Hypercellular parathyroid gland (142 mg aggregate weight), consistent with parathyroid hyperplasia.
F. Right inferior parathyroid gland, excision: Hypercellular parathyroid gland (85 mg aggregate weight), consistent with parathyroid hyperplasia.
Normal example in autopsy:
Sections show <<1, 2, 3, 4>> parathyroid glands with no focal changes or signs of hyperplasia.
Usually performed as a transuretral resection of the bladder (TURB).
Gross reporting of transurethral resections
Generally submit all material. (It may be sufficient to submit representative sections that include the muscular layer, if grossly identified. Yet, many departments require submission of the entire specimen regardless, so if unsure, that is the safe choice.)
If transported or processed together with other cases, put the samples in thin-mesh cassettes or tissue bags to limit contamination.[note 3]
Example report:
Container A. Labeled "bladder tumor". The specimen is received in formalin and consists of multiple fragments of tan-gray, friable soft tissue measuring about __ x __ x __ cm in aggregate. The specimen is entirely submitted for microscopic examination in __ cassettes.
Microscopy
Mainly look for urothelial carcinoma (also called transitional cell carcinoma), which constitutes 95% of bladder cancers.[4]
In contrast, an inverted urothelial papilloma has smooth surface with minimal to absent exophytic component, is well circumscribed with smooth base, and has no obvious infiltration and no/minimal cytologic atypia.[5]
Radiation cystitis with atypical stromal cells (“radiation fibroblasts”), edema and inflammation. Check whether the patient has received radiation before making the diagnosis.
Edema (clear spaces of both the lamina propria and cytoplasm of multiple urothelial cells), which is non-specific.
Notes
↑ 1.01.1For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 2.02.1The average weight of each parathyroid gland is about 30 mg in men and 35 mg in women,A but with a great variability: 90% of normal parathyroid glands weight less than 100g, and 96% less than 160g.B Thus, by weight alone, a pathologists generally can't tell whether a parathyroid is enlarged, or whether it is of its normal weight, such as being one of the 4% that are normally over 160g. - A. Johnson, S J (1 April 2005). "Best Practice No 183: Examination of parathyroid gland specimens
". Journal of Clinical Pathology58 (4): 338–342. doi:10.1136/jcp.2002.002550. PMID 15790694. - B. Yao, Kathy; Singer, Frederick R.; Roth, Sanford I.; Sassoon, Aaron; Ye, Cynthia; Giuliano, Armando E. (2004). "Weight of Normal Parathyroid Glands in Patients with Parathyroid Adenomas
". The Journal of Clinical Endocrinology & Metabolism89 (7): 3208–3213. doi:10.1210/jc.2003-031184. ISSN0021-972X.
↑Piciucchi, Sara; Barone, Domenico; Gavelli, Giampaolo; Dubini, Alessandra; Oboldi, Devil; Matteuci, Federica (2012). "Primary Hyperparathyroidism: Imaging to Pathology
". Journal of Clinical Imaging Science2: 59. doi:10.4103/2156-7514.102053. ISSN2156-7514. - This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Reactive urothelial changes, Pap stain, showing urothelial cells with enlarged nuclei but a nucleus-cytoplasm ratio of less than 0.5. There are bacteria, as well as an inflammatory response of neutrophils, providing a cause for the changes. Can be reported as "Benign urothelial cells, neutrophils and bacteria".
The N/C ratios apply to the finding of any cells meeting the criteria, and not the average among atypical cells (in the majority of obviously positive cases, N/C/ratio averages 0.5).[2] When there are obvious features of malignancy, there is no need to hunt for cells that fulfil all criteria to make such diagnosis.[2]
Fibrovascular cores weakly indicate a urothelial neoplasm, but can be present in all Paris System categories.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
Split the digit longitudinally, either in the midline or at the closest margin between any ulcer and the soft tissue margin.
Let the tissue fix in formalin and then use a relatively strong decalcifying agent, usually at least 5-6 hours.
Tissue selection
Sections for microscopy are taken as follows:
For amputations disarticulated at the joint:
Perpendicular sections of the articular cartilage and adjacent bone. State which bone in key of sections.
For amputations resected by cutting across bone:
Ink the bone at the proximal margin, submit perpendicular section of bony margin.
Gangrene and/or suspected osteomyelitis:
Submit cross sections of each bone with associated ulcer and/or gangrene if appropriate, generally sagittal/longitudinal. Attempt to include the longitudinal distance from potential osteomyelitis to the proximal bony/cartilaginous margin.
Skin and soft tissues at proximal margin.
If margin is close to gangrene: perpendicular sections
If you receive a separate thin or discoid bone slice, it is generally an additional bone margin. Preferably, have this decalcified and processed promptly, so that it may be used to make a preliminary report as to whether it is involved even before the main specimen is processed.
Finger with en face soft tissue margins because of no proximity to gangrene.
At least if osteomyelitis is suspected, ink all proximal (and/)or distal cut surfaces (differentially) of each slice, so that the pieces can be oriented, and the distance between osteomyelitis and the surgical margin can be estimated. The exception is where pieces can most definitely be anatomically oriented, such as the presence of a nail distally.
Gross report
Example:
(A. Labeled - ___. The specimen is received in formalin and consists of an amputated toe/finger.) The digit measures ___ cm in length and ___ cm in average diameter. The digit is resected ___ [[location]]. {{The proximal ___ cm of the specimen is not covered by skin and soft tissue.}} The skin and soft tissue margins appear <viable / necrotic>. The skin surface of the digit appears ___ {{and displays an (ulcerated/necrotic/gangrenous) lesion, cm from the cutaneous margin}}. The nail is <color/thickened/absent/necrotic>. The soft tissue surgical margin is inked blue [[for example]], and the <<bony surgical / cartilaginous>> margin of the ___ [[specific bone involved]] is inked green [[for example]]. On cut sections, the bone subjacent to the ulcer shows no gross abnormalities. Representative sections are submitted for microscopic examination in ___ cassettes following decalcification. Key to sections:
Longitudinal section through distal phalanx
Longitudinal section through proximal phalanx, including <<bony surgical / cartilaginous>> margin
Skin and soft tissues at proximal margin, submitted en face
Significant pathologies at the margins, such as necrosis of soft tissue margins as shown with neutrophil involvement.
Microscopic report
Example:
(A. Left third toe, amputation:) Toe with ulcer, gangrene and osteomyelitis. Osteomyelitis involves the distal phalanx, middle phalanx and proximal phalanx. Osteomyelitis is 2.0 cm from the proximal articular surface of the proximal phalanx. (The skin and soft tissue at the surgical margin appear viable.)
Bone
Grossing
To submit slides for microscopy, generally gross as follows:
Split the bone in the plane of interest for microscopy slides.
Fix the bone in formalin.
Perform decalcification of the specimen. First, generally take at least a small piece to be kept separately in formalin, in case the main specimen becomes necrotic, so that you have at least one more chance to decalcify it more lightly. If the order and/or history is suspicious for metastasis, try to sample a part of the specimen that is soft enough to not need decalcification (to avoid the risk that decalcification will impair later immunohistochemistry or other testing).
Acute osteomyelitis: Numerous neutrophils in the stroma.
Metastasis
Highly suspicious prostate adenocarcinoma metastasis can be confirmed with NKX1, TTF1 and CDX2.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑En face means that the section is tangential to the region of interest (such as a lesion) of a specimen. Further information: Gross_processing#Cutting
Look for cellular expansions, which in the anterior pituitary confers a loss of normal cellular heterogeneity.
If present, distinguish it as hyperplasia or neoplasia. If uncertain, by using reticulin immunohistochemistry, hyperplasia will show a preserved reticulin meshwork, whereas pituitary adenomas have disruption of it.[1]
For adenomas, unless otherwise indicated by the medical history, will generally by definition be of the silent type. Basophilic or acidophilic staining may give a clue about the subtype, but immunohistochemistry is generally required.
Normal cellular heterogeneity of the anterior pituitary. Nuclear pleomorphism, like the large nucleus of the chromophobe, is a normal finding in this location.
A silent gonadotroph pituitary adenoma which is in this case is eosinophilic (contrary to normal, basophilic, gonadotroph cells).[3]
Microscopy report
In normal autopsy:
Adenohypophysis and neurohypophysis with no focal changes.
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Al-Brahim, N Y Y; Asa, S L (2006). "My approach to pathology of the pituitary gland
". Journal of Clinical Pathology59 (12): 1245–1253. doi:10.1136/jcp.2005.031187. ISSN0021-9746.
↑Drummond, Juliana; Roncaroli, Federico; Grossman, Ashley B; Korbonits, Márta (2019). "Clinical and Pathological Aspects of Silent Pituitary Adenomas
". The Journal of Clinical Endocrinology & Metabolism104 (7): 2473–2489. doi:10.1210/jc.2018-00688. ISSN0021-972X. - "This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/)"
↑Gaballa, Salem; Lindsay, Jane; AlJaf, Avan; Hlaing, Kyaw M; Patel, Kashyap (2020). "Acute Unilateral Oculomotor Nerve Palsy as the Initial Presenting Sign of Nonfunctioning Apoplectic Gonadotroph Adenoma
". Cureus. doi:10.7759/cureus.8819. ISSN2168-8184. - "This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0"
Memorization-worthy:[note 2] For the most likely types of cases and/or questions that you may be responsible for, know where to find local policies and procedures, and have a good idea of whom to ask for further advice. Make sure you have access and/or contact details for whenever and wherever you are likely to need them.
Preferably have at least a quick look at policies and procedures so that you have an idea of what kind of answers you will find there when needed.
Blood bank
Author:Mikael Häggström[note 1]
If you expect to get questions regarding blood products, get a copy of the local cutoffs for approving transfusions of red blood cells, platelets and plasma, and keep it so that you can quickly look it up when needed.
Always consider if a blood product should be given as per a local precaution protocol (usually including regular check-ups of the patient).
Specific questions or requests
Generalized dosage in adults:
Plasma: Generally 10-15 ml/kg, and results in approximately 25-30% plasma volume replacement. Detailed calculation
Cryoprecipitate: 1 unit for every 7-10kg of body weight. 10 units generally replaces 100-150 mg/dl. Detailed calculation
Notes
↑ 1.01.1For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Further information on what is memorization-worthy or not: Learning pathology
Upon direct testing by adding antibodies against A, B and/or Rh to patient blood, agglutination means that the patient has the antigen tested. Upon indirect testing by adding A or B antigen to patient plasma, agglutination means absence of the antigen in the patient (and thus the patient produces antibodies against it).
Identification of non-ABO antibodies
In the antibody screening procedure, an individual's plasma is added to a panel of two or three sets of red blood cells which have been chosen to express most clinically significant blood group antigens. Agglutination of the screening cells by the plasma, with or without the addition of anti-human globulin, indicates that an unexpected blood group antibody is present. If this occurs, further testing using more cells (usually 10–11) is necessary to identify the antibody. By examining the antigen profiles of the red blood cells the person's plasma reacts with, it is possible to determine the antibody's identity as follows:
The image above shows the interpretation of an antibody panel used to detect antibodies towards the most relevant blood group antigens. Each row represents "reference" or "control" red blood cells of donors which have known antigen compositions and are ABO group O. A + means that the antigen is present on the reference red blood cells, and 0 means it is absent; nt means "not tested". The "result" column to the right displays reactivity when mixing reference red blood cells with plasma from the patient in 3 different phases: room temperature, 37°C and AHG (with anti-human globulin, by the indirect antiglobulin test).[1]
Step 1; Annotated in blue: starting to exclude antigens without reaction in all 3 phases; looking at the first reference cell row with no reaction (0 in column at right, in this case cell donor 2), and excluding (here marked by X) each present antigen where the other pair is either practically non-existent (such as for D) or 0 (presence is homozygous, in this case homozygous c). When both pairs are + (heterozygous cases), they are both excluded (here marked by X), except for C/c, E/e, Duffy, Kidd and MNS antigens (where antibodies of the patient may still react towards blood cells with homozygous antigen expression, because homozygous expression results in a higher dosage of the antigen).[2] Thus, in this case, E/e is not excluded in this row, while K/k is, as well as Jsb (regardless of what Jsa would have shown).[note 2]
Step 2: Annotated in brown: Going to the next reference cell row with a negative reaction (in this case cell donor 4), and repeating for each antigen type that is not already excluded.
Step 3: Annotated in purple. Repeating the same for each reference cell row with negative reaction.
Step 4: Discounting antigens that were absent in all or almost all reactive cases (here marked with \). These are often antigens with low prevalence, and while there is a possibility of such antibodies being produced, they are generally not the type that is responsible for the reactivity at hand.
Step 5: Comparing the remaining possible antigens for a most likely culprit (in this case Fya), and selectively ruling out significant differential antigens, such as with the shown additional donor cell type that is known to not contain Fya but contains C and Jka.
In this case, the antibody panel shows that anti-Fya antibodies are present. This indicates that donor blood typed to be negative for the Fya antigen must be used. Still, if a subsequent cross-matching shows reactivity, additional testing should be done against previously discounted antigens (in this case potentially E, K, Kpa and/or Lua).[1]
When multiple antibodies are present, or when an antibody is directed against a high-frequency antigen, the normal antibody panel procedure may not provide a conclusive identification. In these cases, hemagglutination inhibition can be used, wherein a neutralizing substance cancels out a specific antigen.[2] Alternatively, the plasma may be incubated with cells of known antigen profiles in order to remove a specific antibody (a process termed adsorption); or the cells can be treated with enzymes such as ficain or papain which inhibit the reactivity of some blood group antibodies and enhance others (see table below).
Clinical implication
The following is a simplified classification for the main anti-erythrocyte antibodies, using mneumonics for the main involved antigen groups:
Anti-A/B antibodies: These will cause immediate hemolytic transfusion reaction if the red blood cells do not have compatible antigens, even if there is no previous exposure to the antigens. Therefore, blood transfusions must always be ABO compatible.
"Kickers"-class antibodies: Antibodies against Kidd, Kell, Rh, S and Duffy group antigens. These have a significant risk of causing hemolytic transfusion reactions when present, and therefore, patients with kickers-class antibodies should receive blood that is negative for the antigen, except for very critical situations where there is no time to find compatible blood.[3] Kickers-class antibodies generally need a previous exposure to the antigen to form, with transfusion reactions being possible upon subsequent transfusions.[2] Some patients first test positive and later test negative for a kickers-class antibody, but such patients must still be transfused with antigen-negative blood regardless.[4] They are generally of the IgG subtype, and are generally most active at 37°C. They can potentially cross the placenta and cause hemolytic disease of the newborn. They generally show increased reactivity against homozygously expressed antigens compared to heterozygously expressed ones (as mentioned in Step 1 above).
"Limply"-class antibodies: Antibodies against Lutheran, Ii, M/N, P1, Lewis group antigens. These almost never cause clinically significant transfusion reactions (but anti-Ii antibodies are usually the type that causes cold agglutinin disease,[5] a form of autoimmune hemolytic anemia).[2] Hence, there is generally no need to find blood that is negative for the antigen for a limply-class positive patient. These antibodies are generally naturally occurring, that is, they don't require a previous exposure to the antigen to form. They are generally of the IgM class, and are generally not reactive at body temperature, but rather most active at room temperature and below.[6] They generally pose no significant risk of hemolytic disease of the newborn (as IgM class antibodies do not cross the placenta).
Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems:[2]
ABO
Rh
Kell
Duffy
Kidd
Lutheran
MNS
Lewis
P
Ii
Most common in immediate hemolytic transfusion reactions
A
Yes
Fya
Jka
Most common in delayed hemolytic transfusion reactions
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Besides from C/c, E/e, Duffy, Kidd and MNS, clinically significant dosage effects is rare but not impossible for other antigens, which thus may still be considered if subsequent cross-matching is reactive.
↑ 2.02.12.22.32.42.5Mais, Daniel (2014). Quick compendium of clinical pathology. United States: American Society for Clinical Pathology Press. ISBN 978-0-89189-615-9. OCLC895712380.
↑Pamela P. Goodell, Lynne Uhl, Monique Mohammed, Amy A. Powers (2010). "Risk of Hemolytic Transfusion Reactions Following Emergency-Release RBC Transfusion
". American Journal of Clinical Pathology134 (2). doi:10.1309/AJCP9OFJN7FLTXDB.
↑ 7.07.1Hill, Ben C.; Hanna, Courtney A.; Adamski, Jill; Pham, Huy P.; Marques, Marisa B.; Williams, Lance A. (2017). "Ficin-Treated Red Cells Help Identify Clinically Significant Alloantibodies Masked as Reactions of Undetermined Specificity in Gel Microtubes
". Laboratory Medicine48 (1): 24–28. doi:10.1093/labmed/lmw062. ISSN0007-5027. PMID 28007780.
Author:Mikael Häggström[note 1]
The Kleihauer–Betke test stains fetal red blood cells (cells containing HbF) dark reddish-pink, while adult red blood cells will be white to light pink.
Collection
EDTA-containing-tube.
Criteria for fetal cells
File:KB stain, annotated.jpgKB stain with green marks at cells counted as fetal (HbF) cells, and red marks at incompletely colored cells at top and a too small cell at right.
To count, a fetal blood cell should be:
Stained more than approximately half of what is seen in control.
Not be nucleated or too big (white blood cell are generally also stained).
Not be too small.
Semi-quantification
This is done for Rh-positive mothers to estimate the severity of a suspected feto-maternal hemorrhage, which can be suspected by various clinical findings (including neonatal anemia, stillbirth, intrauterine growth restriction, hydrops fetalis, decreased or absent fetal movements, non-reassuring fetal heart rate tracing, sinusoidal fetal tracing, and fetal tachyarrythmias, placenta previa with bleeding, and placental abruption)[1].
10HPFs (in 40x) are scanned, and fetal RBCs are counted (cells per 10 HPFs, not average per HPF), and classified as:
0 - Negative
1 - Rare
2-5 - Few
6-10 - Moderate
>10 - Abundant
Quantification
This is done for Rh-negative mothers to estimate the number of Rho(D) immune globulin vials to administer.
2000 cells are counted, in order to give a percentage calculated as:
Alternatively, an acceptable estimation of at least 2000 cells can be done by using a micrograph (or a microscopy grid) to estimate the mean number of cells in a certain area, and using the same mean to estimate the number of cells in equally sized areas:
1. Count cells (both adult and fetal) until reaching 100 cells (including each cell in square by square if using a microscopy grid). Take note of how large micrograph area (or how many grid squares) were counted (here designated as x amount), and how many fetal RBCs were counted.
2. Pick another random location (you may randomize again if it is of a significantly different cell density, but do not let your decision be influenced by the number of fetal RBCs in the area or near its edge). Count the total number of cells in the same area size (or same x number of squares), and how many of them are fetal RBCs.
3. Pick another location again, and count the number of cells in the same area size, and how many of them are fetal RBCs.
If a count of 200-300 cells only shows 0 or 1 fetal RBC, there only needs to be 1 vial of 300 micrograms Rho(D) immune globulin, and the rest of the steps in this section can be skipped.
Standard deviation
Count cells in following number of areas
Up to 6
3
7
4
8
5
9
6-7
10
8
11
10
12
12
Calculate how much the count for the second and third areas deviated from 100, and take the average thereof, which will be used as standard deviation.[note 2] If the standard deviation is higher than 12, count a total of 2000 cells regardless of areas and calculate as per formula above, and the rest of the steps can be skipped.
Use the table at right to estimate how many areas in total you need to count in order to have a mean number of cells per area with an acceptable confidence interval.
4. After having counted the needed number of areas, calculate the average of the number of cells per area (or per x number of squares), and assume that number for the rest of the counting.
5. Divide 2000 by the number of cells per area, and round that up to know the number of areas you need to perform the next step on in order to presumably have a total of 2000 cells (including previously counted areas).
6. In those additional areas, only count the number of fetal cells per area (or x number of squares), and add that to the fetal cells from previous areas.
100 cells are counted, and their area is marked with a rectangle.
A new location is randomly chosen, and inside the same rectangular area, 94 cells are counted. This is a deviation 6 cells compared to the first count.
A third area of the same size yields a count of 108 cells, deviating 8 from 100. The standard deviation used[note 2] is therefore the mean of 6 and 8, which is 7. As per the table, one more area needs to be counted.
The third area yields 110 cells. The average number of cells per area is now calculated as the mean of 100, 94, 108 and 110, which is 103.
With an average of 103 cells per area, the number of areas needed to presumably include at least 2000 cells in our case is another 16.
The sum of all fetal RBCs in all areas in this example is 45. The presumable total cell count is 103 * 20 = 2060. Thus:
Fetal RBCs (given in%) = 45 / 2060 * 100 = 2.2%
Calculation of number of vials
Assuming that a vial of 300 micrograms of Rho(D) immune globulin will protect against 30 mL of fetal blood, the number of vials needed to compensate for the fetal-maternal transfusion is calculated as following, rounded up,[2] or rounded to the closest full number and then adding 1.[3]
Number of vials = Fetal RBCs in% * 1.7
For example, with 2.2% fetal RBCs, the number of vials would be 4[2] or 5[3].
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 2.02.1Technically, the standard deviation would be calculated as the average deviation from the mean of all areas, but the simplified calculation used in this resource can be regarded to be close enough for practical purposes.
↑ 2.02.1Diann M. Krywko. Kleihauer Betke Test. StatPearls, National Center for Biotechnology Information. Last update: Last Update: January 20, 2020.
↑ 3.03.1Practice at Danbury Hospital, Danbury, Connecticut, New England.
Image sources
Peripheral blood smear
Author:Mikael Häggström[note 1]
Look at and comment separately on white blood cells, red blood cells and platelets. You generally don't need to aim for a perfect report, because for most purposes, a peripheral smear is a relatively simple screening test, and clinicians may opt to perform for example flow cytometry and/or a bone marrow biopsy if they want a better evaluation.
Comprehensiveness
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Other legend
<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page
Oil immersion microscopy
This is preferred for light microscopy of peripheral blood smears in order to achieve a very high magnification. First use low or medium power to center on suspicious cells, or where red or white blood cells are best appreciated. Put a drop of immersion oil on the location and switch to the immersion objective. Then, whenever there's oil on a slide, always think twice before switching between objectives so as to avoid getting oil on any of your dry objectives (which is a bit tedious to clean off).
Red blood cells
Automated values
When available, automatic quantification of mean corpuscular volume (MCV) and red blood cell (RBC) distribution width (RDW), usually as part of CBC panel, generally decides whether you will call the sample "normocytic" versus "microcytic"/"macrocytic" and/or "anisocytotic", even if it is not clearly visible in the microscope. If automated values are not available, compare RBC sizes to lymphocyte nuclei, which should normally be the same size. If mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are normal, but you still see multiple RBCs with central pallor greater than 50% of the diameter, you can report it as "Increased central pallor", and you may add "indicating iron deficiency" if it is compatible with the clinical history.
Burr cells are distinguished from spur cells by having more equally distributed and rounded projections. They are usually artifactual. However, they may also be caused by renal insufficiency, so if this is present, a report may include "Occasional/Multiple echinocytes, consistent with renal insufficiency".
If malaria is suspected, also make a thick blood film.
Platelets
If CBC is performed, use count to determine whether platelets are "normal in number" or whether there is "thrombocytopenia" or "thrombocytosis". If no CBC, count platelets within a high power oil immersed field, which should normally be 8 to 20.
Large platelets are those with a diameter greater than 4 microns. Giant platelets are those with a diameter greater than 7 microns (larger than a normal red blood cell).[3] Example report:
Numerous large and giant platelets(, suggesting an increased platelet turnover)(( such as in immune thrombocytopenic purpura. They may also be present in myeloproliferative neoplasms, myelodysplasia, and some congenital thrombocytopenia syndromes, including Bernard-Soulier syndrome and MYH9-related disorders.[3]))
In thrombocytopenia from automatic counting, look in particular for:
Clumping of platelets (which can cause a falsely low automatic platelet count). If present, check with the lab if it was sent in EDTA (which may cause artefactual clumping) and ask to have a blood sample sent in sodium citrate instead. Also, look for satellitosis (platelets attached around white blood cells).
Blast cells, generally having large nucleus, immature chromatin, a prominent nucleolus, scant cytoplasm and few or no cytoplasmic granules. This example has an Auer rod (to the left of the nucleus). Further information: Suspected blasts on peripheral blood smear
Hypersegmented neutrophils. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.[4]
In patients with known chronic lymphocytic leukemia, estimate the percentage of prolymphocytes, which are medium-sized lymphocytes with prominent nucleoli.[5] A percentage of less than 5% can be reported as such.
When smudge cells constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.[6] A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.
Normochromic normocytic red blood cells. Red blood cells show <normal morphology / anisopoikilocytosis with occasional ___>. [[If thrombocytopenia, also add "Schistocytes are not significantly increased" if applicable.]]
{{Leukocytosis with neutrophilia / lymphocytosis.}} White blood cells show no left shift or blasts.
Platelets show no evidence of clumping, and show normal granularity.
(Causes of the above findings include ___.)
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑ 3.03.1Teresa Scordino (2016-12-02). Giant platelets. American Society of Hematology.
↑Glassy, Eric (1998). Color atlas of hematology : an illustrated field guide based on proficiency testing. Northfield, Ill: College of American Patholgists. ISBN 978-0-930304-66-9. OCLC40976106.
↑Nozaka, Hiroyuki; Kushibiki, Mihoko; Kamata, Kosuke; Yamagata, Kazufumi (2023). "Classifying Microscopic Images of Reactive Lymphocytosis Using Two-Step Tandem AI Models
". Applied Sciences13 (9): 5296. doi:10.3390/app13095296. "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."
In a platelet aggregation study, the aggregation process is started by different agonists (ADP, epinephrine etc.) and the aggregation pattern can usually conform into any of the following patterns:
Platelet aggregation function by disorders and agonists
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Jiang, L.; Xu, C.; Yu, S.; Liu, P.; Luo, D.; Zhou, Q.; Gao, C.; Hu, H. (2013). "A critical role of thrombin/PAR-1 in ADP-induced platelet secretion and the second wave of aggregation
". Journal of Thrombosis and Haemostasis11 (5): 930–940. doi:10.1111/jth.12168. ISSN15387933. PMID 23406164.
↑ 2.02.12.22.32.4Borhany, Munira; Pahore, Zaen; ul Qadr, Zeeshan; Rehan, Muhammad; Naz, Arshi; Khan, Asif; Ansari, Saqib; Farzana, Tasneem; et al. (2010). "Bleeding disorders in the tribe: result of consanguineous in breeding
". Orphanet Journal of Rare Diseases5 (1). doi:10.1186/1750-1172-5-23. ISSN1750-1172.
File:Trilineage hematopoiesis, annotated.jpgBone marrow aspirate showing normal "trilineage hematopoiesis": - Myelomonocytic cells: an eosinophil myelocyte marked - Erythroid cells: an orthochromatic erythroblast marked - Megakaryocytic cells.
Autopsy
Using pliers or similar tool, squeeze some bone marrow from a rib.
Microscopic evaluation
Confirm trilineage hematopoiesis (see image).
Look for apparent cellular atypia or decrease of cellular diversity.
Report
Example in a normal case:
Bone marrow from rib (or other location if applicable): Trilineage hematopoiesis. There is no evidence of malignancy.
Bone marrow biopsy
Gross processing
Ensure that the biopsy is properly fixed (generally at least 2 hours).
Measure length and diameter of each fragment.
If the biopsy is received in a zinc-containing fixative, rinse it for about 2 minutes, such as placing the cassette in a container under running water (and block any sink enough so that the cassette won't float away).
File:Histopathology of bone marrow with insufficient decalcification.jpgHistopathology of bone marrow with insufficient decalcification, wherein the bony trabeculae may get pushed by the microtome blade and plow away the cells of interest as displayed. To compensate, thicker sections may be taken, also making evaluation harder.
Put in decalcifying solution, preferably using a type that is optimal for performing subsequent immunohistochemistry. Generally decalcify the specimen for about 15 minutes initially, and palpate the specimen to check whether it is still firm. If it is, decalcify another 5-10 minutes and check again. Rather have it a little bit too soft than a little bit too firm. Be careful to follow grossing guidelines for bone marrows, since even a small aberration in the processing is likely to be noticed as creating artifacts.
Gross report example
The specimen is received in AZF solution and consists of __ core needle bone marrow biopsy fragment(s) measuring __ cm in length and 0.2 cm in diameter. The specimen is entirely submitted for microscopic examination in one cassette following decalcification.
Microscopic evaluation
Evaluate the following:
Bone marrow aspirate
Find a location where bone marrow cells can be seen individually, preferably with minimal peripheral blood among them. Sometimes it is between trabeculae and sometimes it is in the surrounding area. Perform a differential count by counting 500 cells[1] and dividing the numbers by 5 to get their percentages. Don't count cells that don't have a cytoplasm or nucleus. If you receive several slides, count about the same number of cells from each slide, but don't count cells from slides where the cell types are more indistinct.
Myeloid/erythroid ratio, usually defined as the ratio between the number of neutrophil granulocytes and precursors versus the number of erythroblasts. Depending on source, the lower limit of the normal range for this ratio bone marrow aspirate smears in adults is 1 to 2, and the upper limit is 5 to 8.[2] In histologic sections, the normal range is 1.5 – 3.0.[2] Some hematologists also include eosinophils, basophils and monocytes, as well as their precursors, in the myeloid number, but this has only a minor effect on the M:E ratio in normal individuals.[2] Still, if you are to calculate the value for a senior, check their preference first.
In a bone marrow count, nucleated red blood cells count into the total percentage of cells (but does not count into percentage of white blood cells in peripheral blood).
Bone marrow biopsy, H&E stain
Adequacy: There should preferably be 5 intertrabecular spaces.
Cellularity: This is a rather rough estimation of the area of hematopoietic cells divided by the area of all intertrabecular matter, which otherwise mainly consists of fat cells and a small interstitial space. Areas of bone, hemorrhage or artifacts are not counted. In patients 20-80 years, the percentage should be about 100 minus age, such as 40% in a 60 year old patient.
Thrombopoiesis: There are normally about 3 megakaryocytes per 40x field.
Look for any granuloma or cancer metastasis
Bone marrow biopsy, other stains
Generally including:
File:Ring sideroblast.jpgRing sideroblast, defined by five or more perinuclear iron granules that encompass at least 1/3 of the nuclear circumference.[3]
Iron stain: Look at approximately 100 cells and semi-quantify the presence of any ring sideroblasts.
Reticulin to grade the amount of fibrosis.
CD3 and CD20 to highlight T and B cells, respectively.
Microscopic report
Example template:
On this resource, the following formatting is used for comprehensiveness:
Minimal depth
(Moderate depth)
((Comprehensive))
Other legend
<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page
SOURCE:
Bone marrow aspirate and biopsy
CLINICAL INFORMATION:
{{Lymphocytosis / Pancytopenia / Anemia etc }}
DIAGNOSIS: PERIPHERAL BLOOD:
{{Lymphocytosis / Pancytopenia / Anemia etc }}
BONE MARROW, {{POSTERIOR ILIAC CREST,}} ASPIRATE AND BIOPSY:
{{Chronic/Acute lymphocytic/myeloid leukemia.}}
See description and comment.
GROSS DESCRIPTION:
[[As per gross report above.]]
MICROSCOPIC DESCRIPTION:
PERIPHERAL SMEAR:
WBC:__ x103/ul
RBC:__ x106/ul
HGB:__ g/dl
HCT:__ %
MCV:__ fl
MCHC:__ g/dl
RDW-CV:__ %
PLT:__ x103/ul
RETIC:__ %
DIFFERENTIAL(%):
NEUTR/BANDS:_
LYMPHS:_
MONOS:_
EOS:_
BASOS:_
BLASTS:_
MYELOS:_
METAS:_
NRBCS/100WBCS:_
PLASMA CELLS:_
MORPHOLOGY:
Red Blood Cells: No significant abnormality.
White Blood Cells: No significant abnormality.
Platelets: No significant abnormality.
BONE MARROW ASPIRATE:
Left / RIGHT / UNDESIGNATED SITE
CELLULARITY ESTIMATE: Adequate. / Hypocellular and hemodilute. / Hypercellular. /
Too few cells for morphologic evaluation.
MARROW DIFFERENTIAL
Erythroblasts: __%
Blasts: __%
Neutrophils/precursors: __%
Eosinophils: __%
Basophils: __%
Lymphocytes: __%
Monocytes: __%
Plasma Cells: __%
M:E ratio: __:__
ERYTHROPOIESIS: Maturing.
GRANULOPOIESIS: Maturing.
MEGAKARYOCYTES: Present.
LYMPHOCYTES: Mature.
PLASMA CELLS: Rare without atypia.
BONE MARROW TOUCH PREPARATION:
_
BONE MARROW BIOPSY:
Left / RIGHT / UNDESIGNATED SITE
SPECIMEN ADEQUACY:
Satisfactory. / Limited. / Unsatisfactory.
CELLULARITY:_
_%: Normocellular / Hypercellular / Hypocellular for age. / Variable ( _ %- _ %, overall _ %) / Cannot assess cellularity due to small biopsy. {{With aspirative artifact.}}
Decalcified bone marrow biopsy demonstrates ____________________
BM Erythropoiesis
_
BM Cellularity
_
BM Megakaryocytes
_
BM Myelopoiesis
_
BONE MARROW IRON STAIN:
Storage iron _/4 on aspirate smear with / without ring sideroblasts.
SPECIAL STAINS:
Reticulin Stain: ___ reticulin fibrosis (_+/3+)
FLOW CYTOMETRY:
No immunophenotypic evidence for abnormal myeloid maturation, an increase in blasts, or a lymphoproliferative disorder (see attached report).
COMMENT:
{{Cytogenetic study and next generation sequencing panel for myeloid neoplasm are pending.}}
An estimation of the time of death is made by postmortem changes of the body. A very approximate rule of thumb for estimating the postmortem interval is as follows:[4]
↑ 1.01.1For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
↑Salama M, Teruya-Feldstein J, Kremyankaya M. Atlas of Diagnostic Hematology. Philadelphia, PA: Elsevier; 2021.
↑Senior, T (2018). Forensic ecogenomics : the application of microbial ecology analyses in forensic contexts. London, United Kingdom San Diego, CA: Academic Press. ISBN 978-0-12-809360-3. OCLC1023028365.
Image sources
↑Image(s) by: Mikael Häggström et al. - using source images from multiple authors (full list is located at image page in Wikimedia Commons. Attribution 4.0 International license
The most useful goal is arguably to become a subspecialist in a particular field within pathology, for which you can be a go-to person when other pathologists need help, and at the same time maintaining basic skills in handling general pathology, at least for the most common conditions where you are expected to practice. In either case, it is important to be able to extend beyond your comfort zone when needed, and at least try to solve cases that fall outside the official subspecialties of the pathologists at hand, even if you may need to search for someone to consult you for the case.
Judge subspecialties primarily by their presumed everyday work, and how well it fits with your personal strengths and weaknesses. As much as possible, base your evaluation on real life exposure to the practice, and put only minimal weight on how interesting the theoretical literature thereof is.
To some degree, consider whether you will want to live and work in (or commute to) a larger city (with more demand to dedicate yourself to a narrow-scoped subspecialty), or a relatively smaller town (with an increased demand for broader or otherwise generally needed subspecialties, mainly surgical pathology and cytopathology but mostly also hematopathology).
Notes
↑For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
Strive to always begin with the real life situation in which the point you want to teach is relevant for improving the management of a patient. If you can't think of a situation where something would relevant, generally don't teach it. Also, present them with all pertinent information that you can readily look up or ask from fellow trainees.
If possible, teach by giving students tasks from real cases and present to you what they would do. Until you know a student better, assume that the person is uneducated enough to need to ask or look up how to do something, but at the same time smart enough to only study what is needed to perform the task, so a greater responsibility means a greater need to study.
When making MCQs, keep the presentation brief, with only little irrelevant and/or misleading information. Everyday pathology work offers enough practice in finding the relevant information among medical records, lab results etc.
Only expect memorization to what is memorization-worthy (see the Learning pathology chapter). Memorized does not mean teach-worthy; just because you've memorized something yourself doesn't automatically mean it's worthy of memorization for others.
.jpg)
![A third area of the same size yields a count of 108 cells, deviating 8 from 100. The standard deviation used[note 2] is therefore the mean of 6 and 8, which is 7. As per the table, one more area needs to be counted.](/File:KB_stain_-_calculation_of_same_area_2.jpg)
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![A cervical biopsy may contain nabothian cysts, which are single or multiple cysts that contain mucin, lined by a single layer of columnar, cuboidal to flat cells with variable amounts of mucinous cytoplasm and small, basal, round to oval nuclei with fine chromatin, without conspicuous nucleoli or mitotic activity.[1]](/index.php?title=Special:Upload&wpDestFile=Histology_of_nabothian_cysts_on_cervical_biopsy.jpg){kind=link}
![The anatomic level of the transformation zone varies:[2] Type 1: Completely ectocervical (common under hormonal influence). Type 2: Endocervical component but fully visible (common before puberty). Type 3: Endocervical component, not fully visible (common after menopause).](/index.php?title=Special:Upload&wpDestFile=Transformation_zone_types.png){kind=link}
![Spectrum from normal to high grade SIL.[4]](/index.php?title=Special:Upload&wpDestFile=Spectrum_of_SIL_cervical_dysplasia.png){kind=link}
![Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain.[5]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_endocervical_polyp.jpg){kind=link}
![Myometrium (smooth muscle cells) versus endometrial stroma (more cellular) versus endometrial polyp stroma (more collagenous).[image 1]](/index.php?title=Special:Upload&wpDestFile=Myometrium_versus_endometrial_stroma_versus_endometrial_polyp_stroma.jpg){kind=link}
![Atypia (mainly seen as signs of endometrial intraepithelial neoplasia (EIN), which has the following criteria:[6] - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_endometrial_intraepithelial_neoplasia_(EIN).jpg){kind=link}
![Endometrial adenocarcinoma[7] arising in an endometrial polyp. These are most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[8]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_Serous_carcinoma_arising_in_endometrial_polyp.jpg){kind=link}
![Subserosal pedunculated uterine leiomyomas may present as endometrial polyps. They typically show smooth muscle in a fascicular pattern[9] Further information: Smooth muscle tumor](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_a_leiomyoma_with_fascicular_growth.jpg){kind=link}
![Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_complex_hyperplasia_without_atypia.jpg){kind=link}
![Endometrial adenocarcinoma[3], most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.[4]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_low-grade_(FIGO_grade_1)_endometrial_endometrioid_adenocarcinoma.png){kind=link}
_(2556674506).jpg){kind=link}
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![Leiomyosarcoma: Variable atypia, often with cytoplasmic vacuoles at both ends of nuclei, and frequent mitoses.[18]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_leiomyosarcoma.jpg){kind=link}
![High magnification of the same case, showing the typical[23] features of tubular spaces of varying size composed of flattened cells resembling endothelium.](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_an_adenomatoid_tumor_of_the_fallopian_tube,_intermediate_magnification.jpg){kind=link}
![Acute chorioamnionitis, with neutrophils in the chorion. Also seen are fibrin thrombi, which indicate a severe fetal inflammatory response.[4]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_chorioamnionitis.jpg){kind=link}
![Calcifications, are normal in term placentas. Report if seen in a placenta younger than 36 weeks of gestational age.[6]](/index.php?title=Special:Upload&wpDestFile=Histology_of_calcification_of_a_term_placenta.jpg){kind=link}
![Increased syncytial knotting of chorionic villi, with two knots pointed out. Causes include both hypoxia and hyperoxia.[7]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_placenta_with_increased_syncytial_knotting_of_chorionic_villi,_annotated.jpg){kind=link}
_of_vulva.jpg){kind=link}
![You may count 10 fields either across the slide, or 5 fields in each direction.[10]](/index.php?title=Special:Upload&wpDestFile=Adequacy_counting_for_cervical_Pap_tests.png){kind=link}
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_(9392112063).jpg){kind=link}
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![Cytopathology of squamous cell carcinoma, keratinizing variant, with typical features.[13] Pap stain.](/index.php?title=Special:Upload&wpDestFile=Cytopathology_of_keratinizing_squamous_cell_carcinoma.png){kind=link}
![[image 1]](/index.php?title=Special:Upload&wpDestFile=Histology_of_vas_deferens.jpg){kind=link}
![[20]](/index.php?title=Special:Upload&wpDestFile=Vas_deferens.jpg){kind=link}
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![Basaloid squamous-cell carcinoma, in this case showing a biplastic pattern with basaloid elements associated with both conventional dysplastic squamous surface (arrow heads) and conventional squamous cell carcinoma (arrow).[4]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_basaloid_squamous_cell_carcinoma.png){kind=link}
![Microcystic adnexal carcinoma: Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases)[7], CEA+, EMA+](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_microcystic_adnexal_carcinoma_-_superficial_follicular_keratin-filled_cysts_-_infiltrative_aggregates.jpg){kind=link}
![Trichoepithelioma:[note 3] Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-)](/index.php?title=Special:Upload&wpDestFile=Trichoepithelioma_(1338537528).jpg){kind=link}
![Nodular. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC.[6] It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts.[6] Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions.[6] Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions.[6]](/index.php?title=Special:Upload&wpDestFile=Low-level_aggressive_basal-cell_carcinoma.jpg){kind=link}
![Fibroepitheliomatous pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma[8]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_basal-cell_carcinoma_with_fibroepitheliomatous_pattern.jpg){kind=link}
![Cicatricial or morphoeic pattern: Narrow strands and nests of basaloid cells, typically with sharp edges, surrounded by dense sclerotic stroma.[9]](/index.php?title=Special:Upload&wpDestFile=Morpheaform_basal-cell_carcinoma.jpg){kind=link}
![1(b). Early actinic keratosis with keratinocyte dysplasia confined to the lower third of the epidermis.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_early_actinic_keratosis.jpg){kind=link}
![1(d). A more established lesion of actinic keratosis demonstrating nearly full thickness keratinocyte dysplasia and prominent budding of the basal layer into the superficial dermis.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_established_actinic_keratosis.jpg){kind=link}
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![High magnification, demonstrating an intact basement membrane.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_squamous_cell_carcinoma_in_situ_-_400x.jpg){kind=link}
![High magnification demonstrates the pleomorphism of the invading keratinocytes.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_invasive_squamous_cell_carcinoma_-_200x.jpg){kind=link}
![Well-differentiated (and yet invasive) SCC, showing prominent keratinization and may form “pearllike” structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated SCC has slightly enlarged, hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_well-differentiated_and_invasive_squamous-cell_carcinoma.jpg){kind=link}
![Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_moderately_differentiated_and_invasive_squamous-cell_carcinoma.jpg){kind=link}
![Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous cell carcinoma. The dysplastic cells here infiltrate in cords through the dermis. Poorly differentiated SCC has greatly enlarged, pleomorphic nuclei demonstrating a high degree of atypia and frequent mitoses.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_clear-cell_squamous-cell_carcinoma.jpg){kind=link}
![Perineural invasion: the arrow indicates a large peripheral nerve that has been surrounded by tumor cells.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_squamous-cell_carcinoma_with_perineural_invasion.jpg){kind=link}
![Vascular invasion: the arrow indicates a small cluster of atypical squamous cells in a small vessel.[1]](/index.php?title=Special:Upload&wpDestFile=Micrograph_of_squamous-cell_carcinoma_with_vascular_invasion.jpg){kind=link}
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_on_the_soles_of_the_feet._Plantar_lesions-CDC.jpg){kind=link}
![Sebaceous hyperplasia: Increased volume of multiple, mature sebaceous lobules attached central dilated ducts in the upper dermis.[2]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_sebaceous_hyperplasia.jpg){kind=link}
![Hypertrophic scar: Replacement of the papillary and reticular dermis by scar tissue with prominent vertically oriented blood vessels.[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_a_hypertrophic_scar,_medium_magnification.jpg){kind=link}
![Histopathology of pre-atherosclerotic intimal lesions: Intimal thickening (A) consists mainly of smooth muscle cells in a proteoglycan-rich matrix. Intimal xanthoma (B) displays intimal thickening with isolated foam cells (arrows).[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_pre-atherosclerotic_intimal_lesions.jpg){kind=link}
![A progressive atherosclerotic lesion: Pathological intima thickening (A) has some extracellular lipid (EL) present deep in the lesion without true necrosis.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_progressive_atherosclerotic_lesion_with_extracellular_lipid.jpg){kind=link}
![Progressive lesion: A fibrous cap atheroma has a well-formed necrotic core (NC) containing lipids with an overlying thick fibrous cap (FC).[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_progressive_atherosclerotic_lesion_with_fibrous_cap_and_necrotic_core.jpg){kind=link}
![Progressive lesion: Fibrocalcific plaques are heavily calcified lesions with or without a necrotic core.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_a_fibrocalcific_atheroma.jpg){kind=link}
![Histopathology of plaque components in atherosclerosis: (A) Intraplaque neovasculature (arrows); (B) intraplaque hemorrhage; (C) large areas of calcification seen as purple morula; (D) lumen thrombus (arrowhead); stained with hematoxylin and eosin (H&E); (E) macrophage infiltration; stained with CD68 antibodies.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_plaque_components_in_atherosclerosis.jpg){kind=link}
![Uric acid crystals in polarized light, showing negative birefringence, with yellow color when aligned parallel to the axis of the red compensator, and blue when aligned perpendicularly to it.[1]](/index.php?title=Special:Upload&wpDestFile=Birefringence_microscopy_of_gout,_annotated.jpg){kind=link}
![Main features of liposarcoma:[3] - Spindle cells with enlarged, hyperchromatic nuclei. - Apparently univacuolated adipocytes (may look normal). - Lipoblasts (multivacuolated), but neither necessary nor sufficient for diagnosis.](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_liposarcoma,_annotated.jpg){kind=link}
![Fibrolipoma is a lipoma with focal areas of large amounts of fibrous tissue. A sclerotic lipoma is one step further: a predominantly fibrous lesion with focal areas of fat.[5] If unsure of degree of fibrosis: Simply report as lipoma.](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_a_fibrolipoma.jpg){kind=link}
![Angiolipoma is a lipoma with abundant capillaries, with hyaline or fibrin (pictured) thrombi.[6]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_angiolipoma.jpg){kind=link}
![Myxoid liposarcoma: Hypercellular solid sheets of cells lying back to back, with round cells or primitive cytomorphology.[8]](/index.php?title=Special:Upload&wpDestFile=Myxoid_liposarcoma_(16105753363).jpg){kind=link}
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![Cholesterol clefts: Indicates of a periapical (radicular) cyst[1] or an inflamed dentigerous cyst[2].](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_cholesterol_clefts_of_a_periapical_cyst_of_the_jaw.jpg){kind=link}
![Relative incidence of parotid tumors.[1]](/index.php?title=Special:Upload&wpDestFile=Relative_incidence_of_parotid_tumors.png){kind=link}
![Relative incidence of submandibular tumors.[1]](/index.php?title=Special:Upload&wpDestFile=Relative_incidence_of_submandibular_tumors.png){kind=link}
![Pleomorphic adenoma (also called benign mixed tumor), H&E stain.[2]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_pleomorphic_adenoma.png){kind=link}
![Pleomorphic adenoma (Pap stain). It can usually be diagnosed by its typical fibrillary stroma (mesenchyme). Stromal cell nuclei are small. Myoepithelial cells are usually the predominant cell type, and can have various shapes but are usually more elongated than epithelial cells. Epithelial cells may have prominent nucleoli.[3]](/index.php?title=Special:Upload&wpDestFile=Cytopathology_of_pleomorphic_adenoma.png){kind=link}
![Warthin's tumor, with typical cellular features (and relatively uncommon binucleated cells).[4] Pap stain. For a diagnosis, you should see sheets of oncocytes and a mixed population of lymphocytes.[5]](/index.php?title=Special:Upload&wpDestFile=Cytopathology_of_Warthin%27s_tumor.jpg){kind=link}
![Thyroid hyperplasia: Variable sized dilated follicles with flattened to hyperplastic epithelium. May form nodules, but without any significant capsule. Architecture resembles normal thyroid, but may be somewhat hypercellular.[6]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_nodular_hyperplasia_of_the_thyroid.png){kind=link}
![Thyroid follicular adenoma, being architecturally and cytologically different from surrounding gland, and being completely enveloped by thin fibrous capsule (if not being encapsulated, mainly consider thyroid carcinoma if atypical cells, otherwise nodular hyperplasia with dominant nodule, the latter especially if there are hyperplastic changes elsewhere in gland).[7] Hyperfunctioning follicular adenoma typically shows follicles with papillary infoldings and bubbly, pale colloid with peripheral scalloping (a). Non-hyperfunctioning adenomas with papillary hyperplasia usually show a more predominantly papillary pattern without vacuolated cytoplasm and scalloping colloid (b).[8]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_hyperfunctioning_and_non-hyperfunctioning_thyroid_follicular_adenoma.jpg){kind=link}
![NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features): [9]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_NIFTP.png){kind=link}
![Hürthle cell adenoma, typically consisting of cells with large size, distinct cell borders, deeply eosinophilic and granular cytoplasm, large nucleus with prominent nucleolus, and complete loss of cell polarity.[10]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_a_H%C3%BCrthle_cell_adenoma.jpg){kind=link}
![Follicular thyroid carcinoma, resembling follicular cells, and typically do not display the nuclear features of papillary thyroid carcinoma mentioned above. Distinction from adenoma requires invasion of adjacent thyroid parenchyma, capsule (complete penetration) and/or blood vessels (in or beyond the capsule).[12]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_follicular_thyroid_carcinoma.png){kind=link}
![Relative incidences of histopathologic diagnoses of solitary thyroid nodules that have undergone fine needle aspiration.[15]](/index.php?title=Special:Upload&wpDestFile=Relative_incidences_of_histopathologic_diagnoses_of_solitary_thyroid_nodules.png){kind=link}
![Look for microfollicles, which are flat groups of follicular cells, each having less than 15 follicular cells arranged in a circle that is at least two thirds complete.[16][image 1] They indicate a follicular neoplasm.](/index.php?title=Special:Upload&wpDestFile=Cytology_of_microfollicles.jpg){kind=link}
![Thyroid spherules, on the other hand, are benign features. A spherule may mimic a microfollicle, but has a more smooth, round, ball-like contour, and even spacing of the follicular cell nuclei.[17]](/index.php?title=Special:Upload&wpDestFile=Cytology_of_thyroid_spherule.jpg){kind=link}
![Cytopathology suspicious for Hürthle cell neoplasm (Bethesda category IV), Pap stain. However, it cannot distinguish Hürthle cell adenoma from Hürthle cell carcinoma, which requires histopathologic sections to see transcapsular or vascular invasion. Hürthle cell hyperplasia (as seen in Hashimoto's thyroiditis) may show moderate variation in nuclear sizes and prominent nucleoli, but further findings favoring Hürthle cell neoplasm include a large number of Hürthle cells, and discohesiveness.[18]](/index.php?title=Special:Upload&wpDestFile=Cytopathology_suspicious_for_H%C3%BCrthle_cell_neoplasm,_annotated.png){kind=link}
![Respiratory epithelial shedding in a small bronchus. If present, look for vascular leakage, mucus hypersecretion and/or widespread airway narrowing, together indicating asthma.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_respiratory_epithelial_shedding.jpg){kind=link}
![Pulmonary aspergillosis, seen as acutely branching septated hyphae.[2]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_pulmonary_aspergillosis.jpg){kind=link}
![Pulmonary mucormycosis, seen as non-septated and broad-branching, and sometimes branching at right angles (black arrow).[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_pulmonary_mucormycosis.jpg){kind=link}
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![Squamous-cell carcinoma (SCC) of the lung. Typical squamous-cell carcinoma cells are large with abundant eosinophilic cytoplasm and large, often vesicular, nuclei.[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_squamous-cell_carcinoma_of_the_lung.jpg){kind=link}
![Small-cell carcinoma, with typical findings.[4]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_small_cell_carcinoma,_annotated.png){kind=link}
![Dilated sinuses. The most cellular expansion is sinus histiocytosis (pictured). If it appears as such, look for a signet ring appearance, which may be a signet ring carcinoma or melanoma. If unsure, use immunostains for CD68, cytokeratin, S100 and mucin.[5]](/index.php?title=Special:Upload&wpDestFile=Sinus_histiocytosis_(intermediate_magnification).jpg){kind=link}
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![Steatohepatitis with mild fibrosis (van Gieson's stain).[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_steatohepatitis_with_mild_fibrosis_in_the_form_of_fibrous_expansion_(van_Gieson).jpg){kind=link}
![Histopathology of steatohepatitis with moderate fibrosis (van Gieson's stain).[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_steatohepatitis_with_moderate_fibrosis,_with_thin_fibrous_bridges_(van_Gieson).jpg){kind=link}
![Lobular disarray and associated lymphocytic inflammation, acidophil acidophil body formation (arrow) and bilirubinostasis, suggesting acute hepatitis.[1]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_acute_hepatitis.jpg){kind=link}
![Shock liver, showing its hallmark[4] pathologic finding centrilobular necrosis but viable periportal hepatocytes. The necrotic hepatocytes are seen as slightly more eosinophilic (red) and discohesive.](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_shock_liver_(intermediate_magnification),_annotated.jpg){kind=link}
![Massive hepatic necrosis: Liver cell dropout, residual hepatocytes and intact portal tract pattern.[5]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_massive_hepatic_necrosis_in_hepatitis_B.jpg){kind=link}
![Hepatocyte lipofuscin alone is of no real pathologic importance and does not warrant a mention in the report.[9]](/index.php?title=Special:Upload&wpDestFile=Histology_of_hepatocyte_lipofuscin.jpg){kind=link}
![Liver tumor types by relative incidence in adults in the United States.[4]](/index.php?title=Special:Upload&wpDestFile=Liver_tumor_types_in_adults_by_relative_incidence.png){kind=link}
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![Hepatocellular adenoma (inflammatory type pictured) may have minor atypia.[5]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_inflammatory_hepatocellular_adenoma.jpg){kind=link}
![Adrenal cortical necrosis. Hemorrhage, fibrin thrombi and short postmortem interval indicate ante-mortem necrosis, otherwise it can be regarded as a postmortem change.[2]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_adrenal_cortical_necrosis.jpg){kind=link}
![Zona fasciculata versus adrenocortical adenoma. An adrenocortical adenoma typically has mild changes in comparison, including larger cells with larger and more pleomorphic nuclei with more coarse chromatin. H&E stain. [image 1]](/index.php?title=Special:Upload&wpDestFile=Zona_fasciculata_versus_adrenocortical_adenoma.jpg){kind=link}
![Adrenocortical adenoma with focal high grade nuclear atypia.[5]](/index.php?title=Special:Upload&wpDestFile=Adrenocortical_adenoma_with_focal_high_grade_nuclear_atypia.jpg){kind=link}
![Adrenocortical adenoma with focal necrosis[5]](/index.php?title=Special:Upload&wpDestFile=Adrenocortical_adenoma_with_focal_necrosis.jpg){kind=link}
![Stages of pancreatic intraepithelial neoplasia.[2]](/index.php?title=Special:Upload&wpDestFile=Progression_of_pancreatic_intraepithelial_neoplasia.png){kind=link}
![Relative incidences of various pancreatic neoplasm.[2]](/index.php?title=Special:Upload&wpDestFile=Relative_incidence_of_pancreatic_neoplasms.png){kind=link}
![Extranodal NK/T cell lymphoma, nasal type.[2] These lymphoma cells are typically monotonous, with folded nuclei, indistinct nucleoli and moderate amount of cytoplasm.[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_extranodal_NK-T_cell_lymphoma,_nasal_type.png){kind=link}
![Parathyroid chief cell hyperplasia: An increase in the parenchymal cell mass,as a result of the proliferation of chief cells, oncocytes, and transitional oncocytes in multiple parathyroid glands.[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_parathyroid_chief_cell_hyperplasia.jpg){kind=link}
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![In contrast, an inverted urothelial papilloma has smooth surface with minimal to absent exophytic component, is well circumscribed with smooth base, and has no obvious infiltration and no/minimal cytologic atypia.[5]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_inverted_urothelial_papilloma,_high_magnification.jpg){kind=link}
![High-grade urothelial carcinoma. Cytologic diagnosis of high-grade urothelial carcinoma requires > 10 cells with high N/C ratio, irregular chromatin pattern and hyperchromatic nuclei (Pap stain).[1]](/index.php?title=Special:Upload&wpDestFile=HIgh-Grade_Urothelial_Carcinoma_(28263697589).jpg){kind=link}
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![Incidences of silent pituitary adenomas.[2]](/index.php?title=Special:Upload&wpDestFile=Pie_chart_of_incidences_of_silent_pituitary_adenomas.png){kind=link}
![A silent gonadotroph pituitary adenoma which is in this case is eosinophilic (contrary to normal, basophilic, gonadotroph cells).[3]](/index.php?title=Special:Upload&wpDestFile=Histopathology_of_eosinophilic_silent_gonadotroph_pituitary_adenoma.jpg){kind=link}
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![Hypersegmented neutrophils. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.[4]](/index.php?title=Special:Upload&wpDestFile=Hypersegmented_neutrophil.jpg){kind=link}
![In patients with known chronic lymphocytic leukemia, estimate the percentage of prolymphocytes, which are medium-sized lymphocytes with prominent nucleoli.[5] A percentage of less than 5% can be reported as such.](/index.php?title=Special:Upload&wpDestFile=Prolymphocyte_in_peripheral_blood_smear.png){kind=link}
![When smudge cells constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.[6] A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.](/index.php?title=Special:Upload&wpDestFile=Smudge_cell_in_a_peripheral_blood_smear.jpg){kind=link}
![Timeline of postmortem changes.[image 1]](/index.php?title=Special:Upload&wpDestFile=Postmortem_interval_changes_(stages_of_death).png){kind=link}
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