Starting pathology (Repro and skin)

Cervical biopsy

Author: Mikael Häggström
This article includes endocervical curettage (ECC).

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

• Minimal depth
• (Moderate depth)
• ((Comprehensive))

Fixation

Generally 10% neutral buffered formalin.

  See also: General notes on fixation

Gross processing

Example report:

(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. Squamous (or ectocervical) mucosa at left and endocervical (mucinous) mucosa at right, in an example with abrupt transition. Squamous (or ectocervical) mucosa at left and endocervical (mucinous) mucosa at right, in an example with abrupt transition. Transformation zone mucosa, consisting of a mix of stratified squamous epithelium and mucinous glands, in an example with gradual transition. Transformation zone mucosa, consisting of a mix of stratified squamous epithelium and mucinous glands, in an example with gradual transition. Endocervical mucosa, with mucinous columnar epithelium and mucinous glands. H&E stain Endocervical mucosa, with mucinous columnar epithelium and mucinous glands. H&E stain However, the endocervical mucosa may appear columnar and non-mucinous. However, the endocervical mucosa may appear columnar and non-mucinous. 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] 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. 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). The anatomic level of the transformation zone varies: 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). If you see fragments of non-mucinous epithelium and glands, it is likely endometrial, so evaluate it like an endometrial curetting. If you see fragments of non-mucinous epithelium and glands, it is likely endometrial, so evaluate it like an endometrial curetting. Pathologies Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours. Spectrum from normal to high grade SIL.[4] Spectrum from normal to high grade SIL. Further information: Cervical dysplasia Other common findings: Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain.[5] Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain. Example report Endocervix, curettings: Fragments of squamous and endocervical glandular epithelium without significant histopathologic changes. Negative for dysplasia. Notes Main page Main page of Patholines References Image sources Cervical cone Unless otherwise specified, the primary focus is any cervical neoplasia. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing Measure length, as well as the transverse and sagittal diameter of the ectocervical surface. Optionally, weight the sample. Note the symmetry of the sample, and the position of the cervical canal. Note whether the circumference is complete. If not, and the directions are indicated on the cone, determine the approximate position of the defect. Cones excised by knife should be inked on the excision surfaces. Those excised by laser do not need inking. Selection and trimming File:Gross preparation of cervical cone.svg 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. In cases where the cone is small and fragmented, try to orient the preparations and divide them if possible to obtain sagittal slices.   See also: General notes on gross processing   Microscopic evaluation Anatomic/Histologic location Describe mucosa as squamous (or ectocervical), endocervical (generally mucinous and glandular) and/or transformation zone mucosa. Squamous (or ectocervical) mucosa at left and endocervical (mucinous) mucosa at right, in an example with abrupt transition. Squamous (or ectocervical) mucosa at left and endocervical (mucinous) mucosa at right, in an example with abrupt transition. Transformation zone mucosa, consisting of a mix of stratified squamous epithelium and mucinous glands, in an example with gradual transition. Transformation zone mucosa, consisting of a mix of stratified squamous epithelium and mucinous glands, in an example with gradual transition. Endocervical mucosa, with mucinous columnar epithelium and mucinous glands. H&E stain Endocervical mucosa, with mucinous columnar epithelium and mucinous glands. H&E stain 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). The anatomic level of the transformation zone varies: 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 Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours. Spectrum from normal to high grade SIL.[4] Spectrum from normal to high grade SIL. Further information: Cervical dysplasia Radicality File:Cervix quadrants and directions.svg Locations 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. Perinuclear cytoplasmic vacuolization ("nuclear halo"). Other findings Other common findings: Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain.[5] Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain. Microscopy report If a neoplasia is found, the report should include: The histolopathological type and degree of differentiation Location and extent Radicality File:Histopathology of CIN 3.jpg High-grade squamous intraepithelial lesion (CIN-2), present at 3:00 to 12:00. All margins of excision are negative for CIN-2. Example report in a normal case: Cervix at transformation zone without significant histopathologic changes. Negative for neoplasia/carcinoma. Endometrial polyp Author: Mikael Häggström Comprehensiveness On this resource, the following formatting is used for comprehensiveness: Minimal depth (Moderate depth) ((Comprehensive)) Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Microscopic evaluation The main objectives are: Making a diagnosis of endometrioid polyp. An endometrial polyp may be diagnosed in the presence of 2 of the following 3: Thick-walled vessels Collagenous stroma Epithelium on at least 3 sides Look for signs of atypia or malignancy. 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 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. 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. Myometrium (smooth muscle cells) versus endometrial stroma (more cellular) versus endometrial polyp stroma (more collagenous).[image 1] Myometrium (smooth muscle cells) versus endometrial stroma (more cellular) versus endometrial polyp stroma (more collagenous). 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. Atypia (mainly seen as signs of endometrial intraepithelial neoplasia (EIN), which has the following criteria: - 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] Endometrial adenocarcinoma 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. Subserosal pedunculated uterine leiomyomas may present as endometrial polyps. They typically show smooth muscle in a fascicular pattern[9] Further information: Smooth muscle tumor Subserosal pedunculated uterine leiomyomas may present as endometrial polyps. They typically show smooth muscle in a fascicular pattern 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.)) Example of a minimal report: Benign endometrial polyp.   See also: General notes on reporting Notes Main page Main page of Patholines References Image sources Endometrial curettings Gross processing Generally submit all tissue for microscopy, even larger volumes. Look for products of conception if indicated from referral and/or history Microscopic evaluation Describe the anatomic/histologic type of epithelium. Look mainly for: Endometrial hyperplasia, atypa and/or malignancy. Products of conception if indicated from referral and/or history If a polyp is mentioned in the history or referral, also evaluate as endometrial polyp. Anatomic/histologic epithelium type (Determine the type or phase of the endometrium:) File:Histology of endocervix.jpg In contrast, endocervical mucosa typically consists of mucinous columnar epithelium and mucinous glands. Evaluate this like a cervical biopsy or cervical cone. The most superficial layer of the endometrium usually consists of a simple columnar epithelium. The most superficial layer of the endometrium usually consists of a simple columnar epithelium. 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) 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: Proliferative endometrium: long curving glands (G) and some stromal edema (H&E stain) Proliferative endometrium: long curving glands (G) and some stromal edema (H&E stain) 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) 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. Hyperplasia, atypa and/or malignancy Look for signs of atypia or malignancy: Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia.[1] Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia. 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 intraepithelial neoplasia (EIN), has the following criteria: - 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] Endometrial adenocarcinoma, 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. 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)). Endometrial thickening Hysterectomy sampling A regular hysterectomy grossing is performed, but with the following sampling: 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. Microscopic evaluation Look for signs of atypia or malignancy: Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia.[6] Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia. 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 intraepithelial neoplasia (EIN), has the following criteria: - 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] Endometrial adenocarcinoma, 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. 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).   See also: General notes on fixation 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 Gross processing Gross examination For orientation: The round ligament lies anterior to the tubes and ovaries. The peritoneum extends further down along the cervix posteriorly than anteriorly. Its ends bluntly posteriorly and sharply anteriorly. 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: (Remove the adnexa. 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. 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. Inspect the mucosa. If any polyps: Further information: Endometrial polyp If more extensive tumor, gross as per endometrial cancer Serially section through almost the entire depth of the myometrium at approximately 1 cm intervals, still keeping the specimen together. Measure the thickness of the mucosa and myometrium Inspect the myometrium. If any tumor: Further information: Smooth muscle tumor Smooth muscle tumor (in this case leiomyoma). Smooth muscle tumor (in this case leiomyoma). Gross pathology of extensive adenomyosis, contrasted to normal myometrium at bottom in right image. Gross pathology of extensive adenomyosis, contrasted to normal myometrium at bottom in right image. Gross report Applicable in bleeding disorders, pain, leiomyoma and endometrial hyperplasia: Components: (Shape of uterus and adnex) Measurements Mucosa, such as smooth or irregular. (Even the absence of) any polyps. Further information: Endometrial polyp Mucosal and endometrial thickness. Further information: Endometrial thickening (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: Submit: 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.}} {{Samples from all smooth muscle tumors >5 cm in diameter.}} Further information: Smooth muscle tumor A specific sampling scheme is used in: Endometrial thickening See also: Fallopian tube Ovary Microscopic evaluation Look for signs of malignancy: Myometrium tumors: Further information: Smooth muscle tumor Polyps: Further information: Endometrial polyp Endometrial thickening: Further information: Endometrial thickening Cervix Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours. Spectrum from normal to high grade SIL.[12] Spectrum from normal to high grade SIL. Further information: Cervical dysplasia Other common findings: Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Acute cervicitis, having a largely neutrophilic intra-epithelial infiltrate. Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Chronic cervicitis, displaying mononuclear inflammatory cells. When clearly forming follicles as shown it can be called follicular cervicitis Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain.[13] Endocervical polyp: With endocervical epithelium and glands (mucinous columnar linings), edematous stroma and clear congestion. H&E stain. Uterine body (Determine the type or phase of the endometrium:) File:Histology of endocervix.jpg In contrast, endocervical mucosa typically consists of mucinous columnar epithelium and mucinous glands. Evaluate this like a cervical biopsy or cervical cone. The most superficial layer of the endometrium usually consists of a simple columnar epithelium. The most superficial layer of the endometrium usually consists of a simple columnar epithelium. 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) 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: Proliferative endometrium: long curving glands (G) and some stromal edema (H&E stain) Proliferative endometrium: long curving glands (G) and some stromal edema (H&E stain) 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) 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. Main pathologic findings Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia.[14] Endometrial hyperplasia: Cystically dilated endometrial glands lined by a single layer of columnar epithelium, without atypia. 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 intraepithelial neoplasia (EIN), has the following criteria: - 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] Endometrial adenocarcinoma, 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. Adenomyosis (endometrial glands in the myometrium). Look at these at high magnification to exclude dysplasia, as for endometrium. Adenomyosis (endometrial glands in the myometrium). Look at these at high magnification to exclude dysplasia, as for endometrium. Smooth muscle tumor (usually fascicular pattern)[image 1] Smooth muscle tumor (usually fascicular pattern) Microscopy report Examples of reports: Normal cases 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. Benign lower uterine segment. Benign bilateral tubes and ovaries. Smooth muscle tumor File:Leiomyoma.jpg Smooth muscle tumor (in this case leiomyoma). Gross processing Gross examination File:Fibroid locations.jpg Fibroid locations. When finding fibroids (spherical tumors with whorled pattern, which in the uterus can be presumed to be smooth muscle tumors), examine and describe: 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. Submit any macroscopically abnormal parts of the fibroids (hemorrhagic, necrotic, brittle or softening areas, and areas with blurry delimitation). 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. Microscopic examination Distinguish leiomyoma (benign) from leiomyosarcoma (malignant) by looking at the latter's criteria: Marked cellular atypia Mitoses: > 10 mitoses/10 high power fields Necrosis Diagnosis of conventional leiomyosarcoma requires 2 of these 3 histologic features. Leiomyomas typically show smooth muscle in a fascicular pattern (arrows point at fascicles).[17][image 1] Leiomyomas typically show smooth muscle in a fascicular pattern (arrows point at fascicles). Leiomyoma, with areas where the cellularity is relatively lower (left) and higher (right). Leiomyoma, with areas where the cellularity is relatively lower (left) and higher (right). Leiomyoma with nuclear pleomorphism, yet within benign limits. Leiomyoma with nuclear pleomorphism, yet within benign limits. Epithelioid leiomyoma Epithelioid leiomyoma Leiomyoma with palisading pattern Leiomyoma with palisading pattern Leiomyosarcoma: Variable atypia, often with cytoplasmic vacuoles at both ends of nuclei, and frequent mitoses.[18] Leiomyosarcoma: Variable atypia, often with cytoplasmic vacuoles at both ends of nuclei, and frequent mitoses. Epithelioid leiomyosarcoma Epithelioid leiomyosarcoma Further information: Evaluation of tumors Microscopic report Report: Microscopic findings, including any visible linings Diagnosis or most probable one Any linings or borders. Example, for a cervical polyp: File:Histopathology of uterine leiomyoma.jpg File:Uterine leiomyoma with lining.jpg 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. Fresh chorionic villi (arrows), surrounded by decidua, at 10 weeks of gestational age. Fresh chorionic villi (arrows), surrounded by decidua, at 10 weeks of gestational age. Chorionic villi (arrow) become more characteristic when held in fluid, having a fibrillary shape Chorionic villi (arrow) become more characteristic when held in fluid, having a fibrillary shape Fresh chorionic villi (left) compared to decidua (right). Fresh chorionic villi (left) compared to decidua (right). Chorionic villi become more pale when fixed in formalin. Chorionic villi become more pale when fixed in formalin. Macropathology of fixed umbilical cord, amnion and chorionic villi at 7-13 weeks of gestational age Macropathology of fixed umbilical cord, amnion and chorionic villi at 7-13 weeks of gestational age Fresh chorionic villi in a term placenta for comparison, being more granular. 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). 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). 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 Immature chorionic villi, having loose stroma and few capillaries. Immature chorionic villi, having loose stroma and few capillaries. Necrotic chorionic villi in a tubal pregnancy. Necrotic chorionic villi in a tubal pregnancy. Scantly cellular decidua may look like chorionic villi, but lack the thick trophoblastic lining. Scantly cellular decidua may look like chorionic villi, but lack the thick trophoblastic lining. In the absence of chorionic villi, look for implantation site intermediate trophoblasts (ISITs): ISITs, having relatively large and dark nuclei. ISITs, having relatively large and dark nuclei. Histology of decidua for comparison, having smaller and brighter nuclei. Histology of decidua for comparison, having smaller and brighter nuclei. In the absence of both chorionic villi and ISITs, preferably perform cytokeratin immunostaining of each tissue sample, such as CAM5.2. In the absence of chorionic villi and ISITs even after staining, call the clinician, since there may be an ectopic pregnancy. Microscopy report Examples: File:Histopathology of chorionic villi at gestational age of 9 weeks.jpg ((Products of conception:)) Products of conception, including immature chorionic villi, corresponding to first trimester pregnancy. ((Spontaneous abortion, clinically.)) File:Histology of implantation site intermediate trophoblasts.jpg ((Products of conception:)) Fragments of focally necrotic decidua and implantation site, consistent with intrauterine products of conception. Negative for chorionic villi. Fallopian tube Gross processing File:Gross pathology of paratubal cysts.jpg Paratubal cysts can be ignored if incidentally found. (Look in the history for any intra-fallopian coils (Essure devices).) For sterilization Measure length and average diameter of each tube Serially section at 3-4 mm intervals, or 2-3 mm if suspected malignant (including BRCA mutation). 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. 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.jpg Fallopian 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: An adenomatoid tumor of the fallopian tube, low magnification, displaying infiltrative-like borders. An adenomatoid tumor of the fallopian tube, low magnification, displaying infiltrative-like borders. High magnification of the same case, showing the typical[23] features of tubular spaces of varying size composed of flattened cells resembling endothelium. High magnification of the same case, showing the typical 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. File:Histopathology of an ectopic pregnancy in a fallopian tube.jpg Histopathology of an ectopic pregnancy in a fallopian tube, with chorionic villi and implantation site changes Further information: Products of conception . 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. Further information: Products of conception Notes Main page Main page of Patholines References Image sources Ovary Gross processing File:Long and short axis.png "Long" and "short" axis. 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. Microscopic examination File:Gross pathology and histopathology of signet ring cell carcinoma metastasis to the ovary.jpg Signet ring cell carcinoma metastasis to the ovary, also called Krukenberg tumor: Gross pathology (top, cross-section at right) and histopathology at low and high magnification. 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. 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. Making a fetal membrane roll. Making a fetal membrane roll. Placental tissue after cutting, here showing severe intervillositis, with dark red and soggy tissue. 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. File:Gross pathology of placental disorders.jpg Gross pathology of placental disorders. 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). 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. Gross report File:Placenta weight by gestational age.svg Placenta weight by gestational age. Example in a normal case: (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). 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. Umbilical cord: Acute phlebitis and funisitis (inflammation of a vein and the connective tissue, respectively) with neutrophils. Umbilical cord: Acute phlebitis and funisitis (inflammation of a vein and the connective tissue, respectively) with neutrophils. Acute chorioamnionitis, with neutrophils in the chorion. Also seen are fibrin thrombi, which indicate a severe fetal inflammatory response.[4] Acute chorioamnionitis, with neutrophils in the chorion. Also seen are fibrin thrombi, which indicate a severe fetal inflammatory response. Acute choriodeciduitis, with neutrophils seen in the chorion and decidua. 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: The pigment-laden macrophages are presumably meconium-laden "meconiophages", the pathologic diagnosis can be termed "meconium histocytosis" The pigment-laden macrophages are presumably meconium-laden "meconiophages", the pathologic diagnosis can be termed "meconium histocytosis" Other relatively common findings Calcifications, are normal in term placentas. Report if seen in a placenta younger than 36 weeks of gestational age.[6] Calcifications, are normal in term placentas. Report if seen in a placenta younger than 36 weeks of gestational age. Villous fibrinoid necrosis. Only needs mention when severe ((or moderate)). Villous fibrinoid necrosis. Only needs mention when severe ((or moderate)). Chorangiosis, an abundance of blood vessels within the chorionic villi. Chorangiosis, an abundance of blood vessels within the chorionic villi. Increased syncytial knotting of chorionic villi, with two knots pointed out. Causes include both hypoxia and hyperoxia.[7] Increased syncytial knotting of chorionic villi, with two knots pointed out. Causes include both hypoxia and hyperoxia. 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. Two three-vessel umbilical cords. Negative for chorioamnionitis and funisitis. Vulva Gross processing Generally as per skin. Microscopic examination File:Histopathology of high-grade squamous intraepithelial lesion (HSIL) of vulva.jpg Histopathology of high-grade squamous intraepithelial lesion (HSIL) of vulva (left in image) with full thickness dysplasia, compared to normal epithelium at right. Mainly look for squamous vulvar intraepithelial lesions: Low-grade squamous intraepithelial lesion (LSIL): Acanthosis, papillomatosis, and/or atypical koilocytosis in upper layers Usually mild atypia and mitoses, limited to the lower third of stratum spinosum and basale Binucleated epithelial cells High-grade squamous intraepithelial lesion (HSIL): Enlarged atypical nuclei and mitoses involving middle and upper third of the epithelium. Also telling are atypical mitoses and/or extension in hair follicles and skin appendages. Squamous cell carcinoma (SCC) of the skin. Staging of vulvar cancer Tumors of the vulva are staged as per the AJCC, 8th Ed: 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] You may count 10 fields either across the slide, or 5 fields in each direction. 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. Eventually you will be able to tell when most cases are adequate or inadequate without performing a detailed calculation. Transformation zone presence File:Cytology of cervical squamous metaplasia.png Squamous metaplasia also counts as endocervix. Typical features are annotated. Pap stain. 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. Endocervical cells can be viewed from the side as nuclear polarity (margination towards the same side as others) in a “picket-fence” configuration. 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. 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". 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". Candida, seen as pseudohyphae. Candida, seen as pseudohyphae. Main conditions to exclude or confirm 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. Atypical squamous cells of undetermined significance (ASCUS), with only few slightly atypical cells Atypical squamous cells of undetermined significance (ASCUS), with only few slightly atypical cells Low-grade squamous intraepithelial lesion (LSIL), here compared to an unremarkable intermediate squamous cell. 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. Cytopathology of squamous cell carcinoma, keratinizing variant, with typical features.[13] Pap stain. Cytopathology of squamous cell carcinoma, keratinizing variant, with typical features. Pap stain. LSIL and changes consistent with human papillomavirus (HPV), which is the presence of koilocytes, which show perinuclear cavitation, binucleation, nuclear hyperchromasia, and nuclear enlargement. 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.png Cytopathology of squamous cell carcinoma, nonkeratinizing variant, with typical features. Pap stain. Necrotic debris (dirty background) is a feature that generally makes a HSIL case "suspicious for invasive squamous cell carcinoma". 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) 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. 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.   See also: General notes on gross processing Microscopic evaluation Look for: Signs of lichen sclerosus Epithelial hyperplasia, dysplasia, or early invasive carcinoma. Optionally, note any sclerosis and/or fibrosis. Reporting Description of objective findings, and any suspected underlying disease. Presence or absence of dysplasia. Vas deferens Gross processing in sterilization In sterilization: Measure length and diameter. Serially section Submit 2 cross sections measuring 5 mm in length. Communicate to the histology lab to section the specimen as tubular structures, in order to get proper cross-sections. Microscopic examination in sterilization Confirm that there is a complete cross-section from each side. Example images of normal vas deferens: [image 1] [20] Report Example report: Right and left vas deferens segments, excisions: Complete cross-sections of vasa deferentia without significant histopathologic changes. Skin Suspected malignant skin excisions Author: Mikael Häggström Suspected malignant skin excisions: Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Common targets If directly suspected from the referral, see: Melanoma Melanoma in situ Invasive melanoma of the skin Basal-cell carcinoma Squamous-cell carcinoma of the skin Gross processing Gross examination Note: Color Well-defined or diffuse border Size Any elevation See separate article in case of dark skin focalities Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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: Similarity to epidermal basal cells, evaluate as suspected basal-cell carcinoma Basal-cell carcinoma Basal-cell carcinoma Similarity to squamous cells: See below: Squamous cell-like skin proliferations: Differential diagnosis Main differential diagnoses and their characteristics: Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis. Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis. 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). 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. 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). 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). Adnexal carcinomas: Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Adnexal carcinomas: Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Adenosquamous carcinoma: Mixed glandular and squamous differentiation. Adenosquamous carcinoma: Mixed glandular and squamous differentiation. Verruca vulgaris: Marked hyperkeratosis and papillomatosis. Rete ridges slope inward at the borders of the lesion. Verruca vulgaris: Marked hyperkeratosis and papillomatosis. Rete ridges slope inward at the borders of the lesion. 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. Verrucous squamous cell carcinoma: 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. Inverted follicular keratosis:[note 6]: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Inverted follicular keratosis:: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Bowenoid papulosis: Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. Bowenoid papulosis: Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. 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. 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. 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. General benign imitators of skin malignancy Granulomatous skin inflammation often contains giant cells that may appear atypical. Granulomatous skin inflammation often contains giant cells that may appear atypical. Further workup of malignant findings In case of skin cancer, determine whether the peripheral/radial and deep margins are clear, close or continuous. 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), but 2-3 mm for melanoma. 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: Granulation tissue in more fresh biopsies Dense collagen Fibrosis with vertical blood vessels Fibrosis that replaces solar elastosis Reporting 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: >___ 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. 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). Perineural or vascular invasion if present. Notes Main page Main page of Patholines References Image sources Basal-cell carcinoma Author: Mikael Häggström File:Basal Cell Carcinoma, Nodular Pattern (6032028849).jpg Nodular basal-cell carcinoma. Basal-cell carcinoma (BCC): Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing Gross examination Note: Color Well-defined or diffuse border Size Any elevation Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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. Characteristics Nests of cells appearing similar to epidermal basal cells, and are usually well differentiated.[2] Nests of cells appearing similar to epidermal basal cells, and are usually well differentiated. Palisading is a typical feature. Palisading is a typical feature. Cleft formation is fairly specific, but may not be seen in smaller nests. Cleft formation is fairly specific, but may not be seen in smaller nests. File:Histopathology of a pigmented basal-cell carcinoma.jpg Basal-cell carcinomas may be pigmented as shown (but consider the possibility of melanoma in such cases). In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells. Differential diagnoses Main histological differential diagnoses of basal cell carcinoma: Hair follicles Hair follicles: Peripheral sections may look like nests, but do not display atypia, and nuclei are smaller. Hair follicles: Peripheral sections may look like nests, but do not display atypia, and nuclei are smaller. Also, hair follicles generally display more distinct features when looking at adjacent levels. Also, hair follicles generally display more distinct features when looking at adjacent levels. Hair follicle tissue may be superficial, resembling a superficial basal-cell carcinoma. 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. 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] 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). 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. 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. Others Trichoblastoma: Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies. Trichoblastoma: Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies. Adenoid cystic carcinoma: Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts Adenoid cystic carcinoma: Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts Microcystic adnexal carcinoma: Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases)[7], CEA+, EMA+ Microcystic adnexal carcinoma: Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases), CEA+, EMA+ 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-) Trichoepithelioma: 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-) 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: Low-level aggressive patterns 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] Nodular. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC. It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts. 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. Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions. Superficial Superficial Fibroepitheliomatous pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma[8] Fibroepitheliomatous pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma Moderately aggressive pattern Moderate cohesion Moderate cohesion Highly aggressive patterns Cicatricial or morphoeic pattern: Narrow strands and nests of basaloid cells, typically with sharp edges, surrounded by dense sclerotic stroma.[9] Cicatricial or morphoeic pattern: Narrow strands and nests of basaloid cells, typically with sharp edges, surrounded by dense sclerotic stroma. Micronodular pattern: Small and closely spaced nests. 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. If closer, measure the distance. If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells. File:BCC with squamous cell metaplasia with HE and BerEP4 staining.jpg Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4. Further information: Evaluation of tumors Reporting Aggressiveness pattern, at least if highly aggressive. Radicality, mainly into either of the following: >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. 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.   See also: General notes on reporting Notes Main page Main page of Patholines References Image sources Actinic keratosis Authors: Mikael Häggström; Authors of integrated Creative Commons article Actinic keratosis may present as suspected malignant skin excisions. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing File:Actinic keratosis of the scalp.jpg Multiple lesions of actinic keratosis on the scalp. Gross examination Note: Color Well-defined or diffuse border Size Any elevation 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. Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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: Excluding any presence of cutaneous squamous cell carcinoma in the lesion. Characteristics File:Histopathology of actinic keratosis.jpg 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.jpg 1(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). By definition, actinic keratosis is confined to foci within the epidermis. it also generally has: 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 carcinoma in 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(b). Early actinic keratosis with keratinocyte dysplasia confined to the lower third of the epidermis.[1] 1(b). Early actinic keratosis with keratinocyte dysplasia confined to the lower third of the epidermis. Civatte body (in a case in lichen planus). Civatte body (in a case in lichen planus). 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] 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. Squamous cell-like skin proliferations: Differential diagnosis Main differential diagnoses and their characteristics: Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis. Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis. 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). 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. 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). 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). Adnexal carcinomas: Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Adnexal carcinomas: Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Adenosquamous carcinoma: Mixed glandular and squamous differentiation. Adenosquamous carcinoma: Mixed glandular and squamous differentiation. Verruca vulgaris: Marked hyperkeratosis and papillomatosis. Rete ridges slope inward at the borders of the lesion. Verruca vulgaris: Marked hyperkeratosis and papillomatosis. Rete ridges slope inward at the borders of the lesion. 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. Verrucous squamous cell carcinoma: 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. Inverted follicular keratosis:[note 4]: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Inverted follicular keratosis:: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Bowenoid papulosis: Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. Bowenoid papulosis: Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. 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. 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. 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). Generally middle-aged or older individuals. Further workup Once a diagnosis of actinic keratosis is established, optionally characterize the degree of atypia into either mild, moderate or severe. File:Histopathology of actinic keratosis with moderate atypia.jpg Actinic keratosis with moderate atypia, spanning approximately half of stratum spinosum. Histopathology report Objective findings A diagnosis of actinic keratosis Optionally: The degree of atypia. Even absence of evidence of malignancy. Example for the case in "Further workup": 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.   See also: General notes on reporting Notes Main page Main page of Patholines References Image sources Squamous-cell carcinoma of the skin Authors: Mikael Häggström; Authors of integrated Creative Commons article Squamous-cell carcinoma (SCC) of the skin may present as suspected malignant skin excisions. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing File:Bowen's disease (crop).jpg Squamous cell carcinoma in situ. File:Squamous cell carcinoma crop.jpg SCC with scaling and ulceration. If re-excision, see separate section at bottom. Gross examination Note: Color Well-defined or diffuse border Size Any elevation 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. Invasive SCC typically has ill-marginated, erythematous, scaling, and rough papules or patches. Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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. Characteristics File:Micrograph of squamous cell carcinoma in situ - 100x.jpg Squamous cell carcinoma in situ, showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis. File:Histopathology of squamous-cell carcinoma.png Main characteristics of squamous-cell carcinoma regardless of location. 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. Hyperkeratosis and parakeratosis. 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. Two types of multinucleated cells may be seen: Multinucleated giant cells Dyskeratotic cells engulfed in the cytoplasm of keratinocytes. Occasionally, cells of the upper epidermis will undergo vacuolization. There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis. File:Histopathology of squamous cell carcinoma in situ.jpg Atypia spanning the full thickness of the epidermis is enough in this case for the diagnosis of SCC in situ. There is also a lymphohistiocytic infiltrate. 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. 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. 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] 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). 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. 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. Clinical clues Biopsy from sun exposed area (including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp). Generally middle-aged or older individuals. In situ versus invasive In situ (Bowen's disease) Intact basement membrane. High magnification, demonstrating an intact basement membrane.[1] High magnification, demonstrating an intact basement membrane. Invasive SCC Invasive SCC is defined by dermal infiltration. 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] 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. High magnification demonstrates the pleomorphism of the invading keratinocytes.[1] High magnification demonstrates the pleomorphism of the invading keratinocytes. Invasive nests with characteristic large celled centers. Ulceration (at left) is common in invasive SCC. 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. 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. Degree of differentiation This is applicable to invasive SCC. 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] 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. Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation.[1] Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation. 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, 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. 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). 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, and at least a quick glance for any vascular invasion. Perineural invasion: the arrow indicates a large peripheral nerve that has been surrounded by tumor cells.[1] Perineural invasion: the arrow indicates a large peripheral nerve that has been surrounded by tumor cells. Vascular invasion: the arrow indicates a small cluster of atypical squamous cells in a small vessel.[1] Vascular invasion: the arrow indicates a small cluster of atypical squamous cells in a small vessel. 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). 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. Staging The AJCC, 8th Ed., does not include any staging system for skin SCC, except for tumors of the vulva. Optionally: Grading Multiple variables can be combined to classify a SCC as low or high grade: Low-Grade SCC High-Grade SCC Well to moderately differentiated: intercellular bridges and keratin pearls Tumor cells arranged in solid or sheet-like patterns Association with solar damage and precursor actinic keratosis Diameter less than 2 cm Depth less than 2 mm Poorly differentiated: clear-cell, sarcomatoid, or single cell features Presence of infiltrating individual tumor cells Arising de novo or in site of prior injury (ulcer, burn scar, or osteomyleitis) Perineural and/or perivascular invasion Diameter greater than 2 cm Depth greater than 2 mm Further work-up In vulvar squamous cell carcinoma, generally perform p16 immunohistochemistry, which is considered a surrogate marker for oncogenic HPV infection. Microscopy report On this resource, the following formatting is used for comprehensiveness: Minimal depth (Moderate depth) ((Comprehensive)) Components of the report: Diagnosis of squamous-cell carcinoma Whether it is in situ or invasive. If invasive: Degree of differentiation. (High or low grade.) Even absence of perineural invasion ((Even absence of or vascular invasion.)) Radicality, mainly into either of the following: >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. Continuous with margin: "Not radically excised at (location)." Staging is only applicable for the head and neck (lip, ear, face, scalp and neck - see staging at Medscape) and vulva (see staging at cancer.net). ((You may also add a synoptic report (see examples):)) Examples Squamous cell carcinoma in situ: File:Micrograph of squamous cell carcinoma in situ - 100x.jpg ((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. Pathologic Stage Classification (pTNM, AJCC 8th Edition): Primary Tumor: pT1 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.   See also: General notes on reporting Re-excisions Gross processing File:Tissue selection from skin re-excisions.png ((Submit the entire specimen, or)) depending on radicality of previous excision: Previously radical (including thin margins): Submit at least one central section across the surgical scar. Previously non-radical: Visible lesion: Submit the entire scar. Lesion not visible: At least one additional radicality slice towards the tips, up to the entire specimen. Notes Main page Main page of Patholines References Image sources Melanoma in situ Author: Mikael Häggström Melanoma of the skin generally presents as a dark skin focality and/or a suspected malignant skin excision. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing Gross examination Note: Color Well-defined or diffuse border Size Any elevation Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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 Differential diagnoses Distinguish mainly from dysplastic nevus and invasive melanoma of the skin: Dysplastic nevus Comparison of congenital pattern nevus, dysplastic nevus and suspected melanoma   Parameter Non-atypical congenital pattern Low-grade dysplastic nevus High-grade dysplastic nevus Suspected melanoma in situ Mild dysplasia Moderate dysplasia Severe dysplasia Macroscopic Lateral circumscription Sharp Slightly diminished Moderate Poor File:Excised melanoma in situ.jpg Symmetry Good Often broken Rare Structural (Low mag.) Delimitation Rarely diffuse Sometimes diffuse Often diffuse Lentiginous proliferation Yes, along with rete pegs Yes, along with and focally between rete pegs Yes, along with and focally between rete pegs Yes partially continuous, multilayered File:Histopathology of lentigo maligna.jpg Bridging Rarely Often Confluent nests Rarely Sometimes Often Often widespread Pigment distribution Regular Irregular Suprabasal presence (less than most superficial third of subcorneal epidermis) Occasionally centrally No or rarely Occasionally centrally Yes, multifocal Pagetoid migration including superficial third of subcorneal epidermis No No Yes, in a maximum of 2 HPF centrally, but not peripherally Yes, multifocal and/or in periphery File:Pagetoid peripherally to a melanoma in situ (crop).jpg Peripheral. Extended rete pegs Ocassional Yes, regular Yes, varying Yes, often irregular Varying, flattened Concentric fibrosis Regressive Yes Occasional Lamellar fibrosis Rarely Often Often pronounced Occasional Lymphocytic infiltrate Mild, perivascular Mild or moderate, perivascular Varying Varying Suprapapillary plate involvement No Usually no Often Yes Cellular (high mag.) Image File:Compound nevus with moderate atypia.jpg Junctional extension Unusual Usual Extensive Nuclear size Age-related Small Medium Large Medium or large. Pleomorphic Nuclear pleomorphism Slight Prominent Chromatin pattern Uniform Condensed Partically expanded Expanded, coarse in some cells Expanded, hyperchromatic, coarse. Usually granular. Nucleoli Age-related Small Medium Large Usually large Mitoses Few superficial Superficial and deep Histological regression Usually Usually not Percentage of atypical melanocytes <10% About 10 - 50% about 50-90% Usually> 90% Intradermal melanocytic atypia No Rarely, in superficial part Can be detected in superficial part Intradermal melanocyte maturation Yes Yes, can be partial Yes, can be partial Variable 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. SOX10 immunohistochemistry of a junctional nevus, with atypical melanocytic proliferation, seen mainly in hair follicles. SOX10 immunohistochemistry of a junctional nevus, with atypical melanocytic proliferation, seen mainly in hair follicles. SOX10 immunohistochemistry of lentigo maligna, showing an increased number of melanocytes along stratum basale, and nuclear pleumorphism. SOX10 immunohistochemistry of lentigo maligna, showing an increased number of melanocytes along stratum basale, and nuclear pleumorphism. Further information: Evaluation of suspected malignancies Invasive melanoma of the skin Invasive melanoma of the skin has features melanoma in situ, but also has dermal involvement of atypical melanocytes with cytologic atypia and no maturation. 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. 3 mm is used for ill-defined lentigo maligna melanoma in situ. If lesser, quantify the distance. If margins are difficult to determine, consider immunohistochemistry with SOX10 to better visualize melanoma nests. 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. File:Histopathology of superficial spreading melanoma.jpg Lentigo maligna Linear spread of atypical epidermal melanocytes along stratum basale. File:Histopathology of lentigo maligna.jpg Acral lentiginous melanoma in situ Continuous proliferation of atypical melanocytes at the dermoepidermal junction. File:Histopathology of acral lentiginous melanoma in situ, intermediate magnification.jpg Report Most important entries: Melanoma area dimensions (width x width) Radicality, mainly into either of the following: >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)."   See also: General notes on reporting Notes Main page Main page of Patholines References Image sources Invasive melanoma of the skin Author: Mikael Häggström Melanoma of the skin generally presents as a dark skin focality. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing Gross examination Note: Color Well-defined or diffuse border Size Any elevation Tissue selection Tissue selection from suspected malignant skin lesions, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with suspected malignant lesion.png File:Tissue selection from skin excision 4-8 mm with suspected malignant lesion.png File:Tissue selection from skin excision 9-15 mm with suspected malignant lesion.png 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 Differential diagnoses Melanoma in situ, where melanoma cells are limited to the epidermis.[2] Melanoma in situ, where melanoma cells are limited to the epidermis. Dermal nevus Comparison of dermal nevus and suspected invasive melanoma   Parameter Non-dysplastic dermal nevus Low-grade dysplastic dermal nevus High-grade dysplastic dermal nevus Suspected invasive melanoma Mild dysplasia Moderate dysplasia Severe dysplasia Macroscopic Lateral circumscription Sharp Slightly diminished Moderate Poor File:Excised melanoma in situ.jpg Symmetry Good Often broken Rare Structural (Low mag.) Micrograph File:Histopathology of non-dysplastic dermal nevus, low magnification.jpg File:Histopathology of invasive acral lentiginous melanoma.jpg Delimitation Rarely diffuse Sometimes diffuse Often diffuse Confluent nests Rarely Sometimes Often Often widespread Pigment distribution Regular Irregular Concentric fibrosis Regressive (see below table) Yes Occasional Lamellar fibrosis Rarely Often Often pronounced Occasional Lymphocytic infiltrate Mild, perivascular Mild or moderate, perivascular Varying Varying Cellular (high mag.) Micrographs File:Histopathology of dermal nevus, high magnification.jpg File:Histopathology of invasive melanoma, high magnification.jpg Nuclear size Small Medium Large Medium or large. Pleomorphic Nuclear pleomorphism Slight superficial Slight Prominent Chromatin pattern Uniform Condensed Partically expanded Expanded, coarse in some cells Expanded, hyperchromatic, coarse. Usually granular. Nucleoli Small Medium Large Usually large Mitoses Few superficial Superficial and deep Histological regression (see below table) Usually Usually not Percentage of atypical melanocytes <10% About 10 - 50% about 50-90% Usually> 90% 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. 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: SOX10 showing dermal nevus nests. SOX10 showing dermal nevus nests. Further workup In case a diagnosis of invasive melanoma of the skin can be made, the following are generally mandatory: Margins Depth Any ulceration Histopathologic type. Presence of mitoses in the intradermal component. The following aspects are mandatory in some regions: Clark's level (not mandatory in the US) Margins Determine if the distance to any margin is greater or lesser than 3 mm. 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. 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): 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: Type Features Relative incidence (in comparison to all melanomas) Photograph Micrograph Superficial spreading melanoma Melanoma cells with nest formation along the dermo-epidermal junction. 70% File:Superficial spreading melanoma in situ on dermoscopy.jpg File:Histopathology of superficial spreading melanoma.jpg Nodular melanoma Grows relatively more in depth than in width. 15% - 20% File:Photography of nodular melanoma.jpg File:Histopathology of nodular melanoma.jpg Lentigo maligna melanoma Atypical epidermal melanocytes as well as invasion into the dermis. 5% - 10% File:Photograph of lentigo maligna melanoma.jpg File:Histopathology of lentigo maligna melanoma.jpg Acral lentiginous melanoma Continuous proliferation of atypical melanocytes at the dermoepidermal junction. 7% - 10% File:Photography of a large acral lentiginous melanoma.jpg File:Histopathology of invasive acral lentiginous melanoma.jpg Clark's level File:Epidermis, papillary dermis and reticular dermis.png Skin layers. If needing to evaluate, Clark's levels are: Level 1: Melanoma confined to the epidermis (melanoma in situ) Level 2: Invasion into the papillary dermis Level 3: Invasion to the junction of the papillary and reticular dermis Level 4: Invasion into the reticular dermis Level 5: Invasion into subcutaneous tissue. Tumor‐infiltrating Lymphocytes (TILs) Classify as either of the following: Absent TIL infiltrate: no lymphocytes present or, if present, they do not interact with tumor cells. Non-brisk TIL infiltrate: focal areas of lymphocytic infiltration in the tumor. Brisk TIL infiltrate: TIL infiltration of the entire base of the tumor, or diffuse permeation of the tumor. Lymph nodes File:Histopathology of capsular nevus.png Cells that stain for melan-A but are nevus-like may be a capsular nevus 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: Melanoma micrometastases on melan-A stain. Melanoma micrometastases on melan-A stain. Other parameters Optionally, the following parameters can be given: File:Cytoplasmic pigmentation of neoplastic melanocytes.jpg File:Melanoma cell shapes.jpg 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. Further information: Evaluation of tumors Report Report when evaluated (as per mandatory vs. optional in Further workup above): Melanoma area dimensions (width x width) Radicality, mainly into either of the following: >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. 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 Pathologic Stage Classification (pTNM, AJCC 8th Edition) Primary Tumor (pT):  pT4b Regional Lymph Nodes (pN):  pNX European example 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. Free margin: Yes Margin in mm: 2.0 mm Tumor depth: 1.2 mm Ulceration: Yes Stage: T2b Clark's level: IV Histopathologic type: Superficial spreading melanoma Presence of mitoses: Yes Significant signs of regression: No   See also: General notes on reporting Notes Main page Main page of Patholines References Image sources Dermatitis Author: Mikael Häggström Scope: This article deals with skin conditions where inflammation is the main finding, excluding suspected malignant skin excisions (where inflammation is often a concurrent finding). Sampling For punch biopsies, a size of 4 mm is preferred for most inflammatory dermatoses. Panniculitis or cutaneous lymphoproliferative disorders: 6 mm punch biopsy or skin excision. A superficial or shave biopsy is regarded as insufficient. Fixation Generally 10% neutral buffered formalin. Suspected immunologic disease: Fixation for immunofluorescence, with for example Michel's solution. For details, see immunofluorescense of skin tissues   See also: General notes on fixation Gross processing Gross pathology processing of skin lesions with benign appearance, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with well-defined lesion.png File:Tissue selection from skin excision 4-8 mm with well-defined lesion.png File:Tissue selection from skin excision 9-15 mm with well-defined lesion.png 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) If suspected bacterial and fungal microorganisms, consider Gram stain and Gomori methenamine silver stain. Microscopic evaluation One approach is to classify into mainly either of the following, primarily based on depth of involvement: 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: 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. Characteristics Micrograph Photograph Acute Subacute Chronic Generally/Not otherwise specified Typical findings: Variable degree of epidermal spongiosis and vesicle formation, filled with proteinaceous fluid containing lymphocytes and histiocytes. Usually superficial dermal edema with perivascular lymphocytic infiltrate, with exocytosis. No acanthosis or parakeratosis. Typical findings: Mild to moderate spongiosis and exocytosis of inflammatory cells Irregular acanthosis and parakeratosis. Superficial dermal perivascular lymphohistiocytic infiltrate Swelling of endothelial cells Papillary dermal edema are present Typical findings: The spongiosis is mild to absent Pronounced irregular acanthosis, hyperkeratosis, and parakeratosis Minimal dermal inflammation and exocytosis of inflammatory cells are present. Possibly fibrosis of papillary dermis PAS stain is essential to exclude fungal infection. File:Micrograph of subacute spongiotic dermatitis.jpg Subacute Allergic/contact dermatitis or atopic dermatitis As above. Eosinophils may be present in the dermis and epidermis (eosinophilic spongiosis). File:Spongiotic dermatitis from drug allergy.jpg Allergic dermatitis File:Eczema (14100950936).jpg Atopic dermatitis Seborrheic dermatitis Typical findings: 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 Typical findings: Psoriasiform hyperplasia, initially slight, with mild spongiosis Usually numerous yeast-like organisms in the surface keratin Same changes as seen in acute stage. Typical findings: More pronounced psoriasiform hyperplasia Only minimal spongiosis Presence of scaling crusts in a folliculocentric distribution, distinguishes from psoriasis. File:Seborrhoeic dermatitis example.jpg 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. Interface dermatitis These are sorted into either: Interface dermatitis with vacuolar change Interface dermatitis with lichenoid inflammation Interface dermatitis with vacuolar change Causes of vacuolar interface dermatitis Main conditions Characteristics Micrograph Photograph Generally/Not otherwise specified Typical findings, called "vacuolar interface dermatitis": Mild inflammatory cell infiltrate along the dermoepidermal junction (black arrow in image) Vacuolization within the basal keratinocytes (white arrow in image) Often necrotic, predominantly basal, individual keratinocytes, manifesting as colloid or Civatte bodies File:Vacuolar interface dermatitis, annotated.jpg Acute graft-versus-host-disease Vacuolar alteration of various severity, from focal or diffuse vacuolation of the basal keratinocytes (grade I), to separation at the dermoepidermal junction (grade III) Involvement of the hair follicle Rarely eosinophils File:Micrographs of grades of skin graft-versus-host-disease.jpg Allergic drug reaction Rarely involvement of hair follicles. Frequently eosinophils File:Spongiotic dermatitis from drug allergy.jpg Lichen sclerosus Hyperkeratosis, atrophic epidermis, sclerosis of dermis and dermal lymphocytes. File:Micrograph of lichen sclerosus.jpg Erythema multiforme Lupus erythematosis Typical findings in systemic lupus erythematosus: Fibrinoid necrosis at the dermoepidermal junction Liquefactive degeneration and atrophy of the epidermis Mucin deposition in the reticular dermis Edema, small hemorrhages Mild and mainly lymphocytic infiltrate in the upper dermis Fibrinoid material in the dermis around capillary blood vessels, on collagen and in the interstitium In non-bullous cases, perivascular and interstitial neutrophils are sometimes present in the upper dermis, with damage to blood vessels File:Histopathology of systemic lupus erythematosus.jpg File:Butterfly rash of lupus erythematosus.jpg 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. Further information: Vacuolar interface dermatitis Interface dermatitis with lichenoid inflammation Main conditions Characteristics Micrograph Photograph Generally/Not otherwise specified Typical findings: 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. File:Histopathology of lichen planus.jpg File:Lichen planus 1.jpg Lichenoid drug reaction Can virtually be indistinguishable from cutaneous LP both clinically and histopathologically. Typically, lesions have a photodistribution in the absence of oral mucosal involvement. 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. File:Histopathology of lichenoid drug reaction.jpg Lichen nitidus 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. File:Histopathology of lichen nitidus.jpg File:Photography of lichen nitidus.jpg Lichen amyloidosus Presence of amyloid, possibly with direct immunofluorescence and Congo red staining. File:Histopathology of lichen amyloidosis with Congo red.jpg Congo red. 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. Unusual conditions that can be associated with a lichenoid inflammatory cell infiltrate are HIV dermatitis, syphilis, mycosis fungoides, urticaria pigmentosa, and post-inflammatory hyperpigmentation. 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. Psoriaform dermatitis Examining multiple deeper levels is recommended if initial cuts do not correlate well with the clinical history. Psoriaform dermatitis typically displays: Regular epidermal hyperplasia, elongation of the rete ridges, hyperkeratosis, and parakeratosis. Usually:A superficial perivascular inflammatory infiltrate 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: Psoriasiform dermatitis Condition Hyperkeratosis Parakeratosis Acanthosis Suprapapillary plate Spinous cell layer changes Other distinctive feature Micrograph Psoriasis Present Diffuse Regular Thin Increased mitoses; minimal spongiosis Clubbed rete pegs Microabscesses Thin or absent granular cell layer File:Micrograph of psoriasis vulgaris.jpg Psoriasiform drug reaction Present Focal Regular and irregular Normal or thick Spongiosis; eosinophilic infiltrate Basal cell layer with inflammatory cells; Civatte bodies Chronic allergic/contact and atopic dermatitis Present Focal; crust may be present Irregular Normal or thick Spongiosis; eosinophilic infiltrate Fungal infection Compact Focal; crust may be present Irregular Normal or thick Occasional neutrophiles; Lichen simplex chronicus Present Focal; thick crust Regular or irregular Thin or thick ±minimal inflammatory infiltrate Thickened granular cell layer Scabies Present Focal or diffuse Irregular Normal or thick Inflammatory infiltrate; eosinophilic spongiosis Seborrheic dermatitis and HIV dermatitis Present Focal Irregular Normal or thick Spongiosis; lymphocytic and neutrophilic infiltrate Pityriasis rubra pilaris Compact Shoulder parakeratosis; alternating orthokeratosis and parakeratosis Regular or irregular Normal or thick Spongiosis; lymphocytic infiltrate; rare acantholysis Pityriasis rosea Present Focal Irregular Normal or thick Small foci of spongiosis; lymphocytic infiltrate Occasional necrotic keratinocytes of basal layer Syphilis Present Focal Regular or irregular Normal or thick Lymphocytes and neutrophils Basal layer interface change Pityriasis lichenoides chronica Present Caps of parakeratosis Irregular Normal Mild spongiosis, lymphocytic infiltrate; necrotic keratinocytes Necrotic keratinocytes of basal layer Mycosis fungoides Present Focal Regular or irregular Normal Minimal or no spongiosis; ±Pautrier microabscess Atypical lymphoid cells lining the dermo–epidermal junction File:Histopathology of Pautrier microabscesses.jpg Pautrier microabscesses Non vesicullobullous, non-pustular lesions without epidermal changes Lymphocytic infiltrate Main conditions Characteristics Micrograph Photograph Urticaria, lymphocyte predominant 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. 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). File:Urticaria near navel.jpg Fungal skin infection Often visible fungus. Other signs depend on fungus species. Pigmented purpuric dermatosis Perivascular infiltrate, but may involve the dermis, further away from blood vessels. Sometimes tendency for lichenoid infiltrate Mild vascular damage, mainly endothelial swelling and focal karyorrhectic debris. Red blood cell extravasation. The epidermis may be normal or may exhibit spongiosis, focal parakeratosis, exocytosis and/or vacuolar change. File:Histopathology of Schamberg disease.jpg File:Schambergdisease-26male.png Erythema annulare centrifugum Superficial types: Mild spongiosis, parakeratosis and microvesiculation. "Coat-sleeve anomaly": tight lymphohistiocytic infiltrate surrounding superficial vessels Deep lesions: Sharply demarcated perivascular mononuclear cell infiltrate in middle to deep dermis File:Micrograph of erythema annulare centrifugum.jpg File:Erythema annulare centrifugum on arms and legs.jpg Not otherwise specified A lesion with superficial lymphocytic infiltrate without additional histopathologic characteristics can be due to for example drug reactions and insect bites. Lymphoeosinophilic infiltrate Main conditions Characteristics Micrograph Photograph Urticaria, lymphocyte predominant 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. File:Micrograph of urticaria.jpg Dermal edema (solid arrows) and a sparse superficial predominantly perivascular and interstitial infiltrate of lymphocytes and eosinophils (dashed arrow) File:Urticaria near navel.jpg Prevesicular stage of bullous pemphigoid 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). However, the diagnosis of bullous pemphigoid consist of at least 2 positive results out of 3 criteria: 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. File:Micrograph of infiltrate in bullous pemphigoid.jpg Not otherwise specified A lesion with superficial lymphoeosinophilic infiltrate without additional histopathologic characteristics can be due to for example drug reactions and insect bites. Lymphoplasmacytic infiltrate Main conditions Characteristics Micrograph Photograph Rosacea Typically enlarged, dilated capillaries and venules located in the upper dermis, angulated telangiectasias, perivascular and perifollicular lymphocytic infiltration, and superficial dermal edema. File:Micrograph of rosacea.jpg File:Rosacea.jpg Secondary syphilis Various, but often one or a combination of: Psoriasiform hyperplasia with superficial neutrophils Lichenoid tissue reaction, epidermal apoptosis and exocytosis of neutrophils Superficial and deep chronic infiltrate in the dermis Often numerous plasma cells in about 1/3 of cases Often endothelial swelling. File:Micrograph of secondary syphilis, HE.jpg File:Secondary stage syphilis sores (lesions) on the soles of the feet. Plantar lesions-CDC.jpg Erythema migrans Typically a superficial and deep perivascular lymphocytic infiltrate. Plasma cells are typically located at the periphery of the lesion, whereas eosinophils are in the center. File:Erythema migrans - erythematous rash in Lyme disease - PHIL 9875.jpg Kaposi’s sarcoma in patch stage 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). vessels File:Micrograph of promontory sign of kaposi's sarcoma.jpg File:Patch stage Kaposi's sarcoma.jpg Not otherwise specified 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. Mastocytosis Main conditions Characteristics Micrograph Photograph Urticaria pigmentosa Mastocytosis with a clinical picture of darkish spots. File:Histopathology of urticaria pigmentosa.jpg File:Urticaria pigmentosa lesions on a child.jpg Not otherwise specified Includes the rare disease of primary mastocytosis. Lymphohistiocytic infiltrate File:Histopathology of leprosy.jpg Leprosy 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. If negative, an unspecific lymphohistocytic dermatosis may be caused by drug reactions and viral infections. 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. Foreign body: Suture granuloma, with multinucleated giant cells surrounding (grey) suture material. Foreign body: Suture granuloma, with multinucleated giant cells surrounding (grey) suture material. Neutrophilic infiltrate Main conditions Characteristics Micrograph Photograph Urticaria, neutrophil predominant Interstitial location Relatively dense infiltrate 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. File:Micrograph of neutrophilic urticarial dermatosis.jpg File:Neutrophilic urticarial dermatosis.jpg Dermatitis herpetiformis Subepidermal vesicles and blisters associated with accumulation of neutrophils at the papillary tips. Sometimes presence of eosinophils, giving an appearance similar to bullous pemphigoid. The histopathology is unspecific in approximately 35%–40% of the cases, and direct immunofluorescence is needed, showing deposition of IgA in the papillary dermis in a granular or fibrillar pattern. File:Micrograph of dermatitis herpetiformis.jpg File:Dermatitis herpetiformis.jpg Early linear IgA bullous dermatosis Subepidermal blister formation. File:Micrograph of linear IgA bullous dermatosis.jpg File:Linear IgA bullous dermatosis.jpg Early febrile neutrophilic dermatosis (Sweet's syndrome) Neutrophilic and lymphohistiocytic infiltrate and edema. File:Sweet's syndrome pathology.jpg File:Sweet's syndrome Crohn's disease.gif Connective tissue disorders Usually associated with epidermal changes. (Systemic lupus erythematosis pictured) File:Histopathology of systemic lupus erythematosus.jpg File:Butterfly rash of lupus erythematosus.jpg Cutaneous small-vessel vasculitis Neutrophils with nuclear dust (dashed arrows in image), with high affinity for postcapillary venules. Features of vascular injury: fibrinoid necrosis (asterisks) and erytrocyt extravasation (solid arrows) File:Micrograph of cutaneous small-vessel vasculitis.jpg File:Cutaneous small-vessel vasculitis.jpg Acute inflammation (not otherwise specified) Neutrophilic infiltrate not conforming to any of the above mentioned conditions. File:Histopathology of dermal edema.jpg Dermal edema in a case of cellulitis. No visible pathology 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 Main page Main page of Patholines References Image sources Benign non-inflammatory skin conditions Author: Mikael Häggström These are aberrations that do not display signs of suspected malignant excisions or dermatitis. These may present as skin cysts. Fixation Generally 10% neutral buffered formalin.   See also: General notes on fixation Gross processing Gross pathology processing of skin lesions with benign appearance, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with well-defined lesion.png File:Tissue selection from skin excision 4-8 mm with well-defined lesion.png File:Tissue selection from skin excision 9-15 mm with well-defined lesion.png 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: Epidermis Ulceration: On the outer ear, consider chondrodermatitis nodularis chronica helicis (pictured): With the ulceration surrounded by acanthosis and parakeratosis. Ulceration: On the outer ear, consider chondrodermatitis nodularis chronica helicis (pictured): With the ulceration surrounded by acanthosis and parakeratosis. Perinuclear vacuolization, most likely insignificant as an isolated finding. In case of dermatitis, consider Vacuolar interface dermatitis Perinuclear vacuolization, most likely insignificant as an isolated finding. In case of dermatitis, consider Vacuolar interface dermatitis Hyperkeratosis, a thickening of stratum corneum Hyperkeratosis, a thickening of stratum corneum Dermis Elastosis is the buildup of elastin in tissues (actinic or "solar" elastosis pictured). Elastosis is the buildup of elastin in tissues (actinic or "solar" elastosis pictured). Sebaceous hyperplasia: Increased volume of multiple, mature sebaceous lobules attached central dilated ducts in the upper dermis.[2] Sebaceous hyperplasia: Increased volume of multiple, mature sebaceous lobules attached central dilated ducts in the upper dermis. Edematous granulation tissue, low magnification Edematous granulation tissue, low magnification Edematous granulation tissue, high magnification, with connective tissue, inflammatory cells and blood vessels. Edematous granulation tissue, high magnification, with connective tissue, inflammatory cells and blood vessels. Desmoplasia of the skin, an increase of fibrous or connective tissue Desmoplasia of the skin, an increase of fibrous or connective tissue Keloid: Wide bands of collagen with large, brightly eosinophilic, glassy fibers, parallel to fibroblasts and myofibroblasts. Keloid: Wide bands of collagen with large, brightly eosinophilic, glassy fibers, parallel to fibroblasts and myofibroblasts. Hypertrophic scar: Replacement of the papillary and reticular dermis by scar tissue with prominent vertically oriented blood vessels.[3] Hypertrophic scar: Replacement of the papillary and reticular dermis by scar tissue with prominent vertically oriented blood vessels. Fatty tissue Lipomatous tumors cause expansion of fatty tissue. Lipomatous tumors cause expansion of fatty tissue. Notes Main page Main page of Patholines References Image sources Keloid Author: Mikael Häggström Gross processing Gross pathology processing of skin lesions with benign appearance, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with well-defined lesion.png File:Tissue selection from skin excision 4-8 mm with well-defined lesion.png File:Tissue selection from skin excision 9-15 mm with well-defined lesion.png 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.jpg A keloid is characterized by wide bands of collagen with large, brightly eosinophilic, glassy fibers, parallel to fibroblasts and myofibroblasts. Keloid versus hypertrophic scar - Typical findings Keloid Hypertrophic scar File:Histopathology of a keloid.jpg File:Histopathology of a hypertrophic scar, medium magnification.jpg Flattening of the overlying epidermis No Yes Scarring of the papillary dermis No Yes Collagen Thick hyalinized bundles Whorl-like or nodular arrangements Vertically oriented blood vessels Yes No Prominent disarray of fibrous fascicles/nodules Yes No 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 Main page Main page of Patholines References Image sources Hypertrophic scar Author: Mikael Häggström Gross processing Gross pathology processing of skin lesions with benign appearance, by lesion size: <4 mm 4 - 8 mm 9 - 15 mm File:Tissue selection from skin excision less than 4 mm with well-defined lesion.png File:Tissue selection from skin excision 4-8 mm with well-defined lesion.png File:Tissue selection from skin excision 9-15 mm with well-defined lesion.png 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 hypertrophic scar, medium magnification.jpg A hypertrophic scar is characterized by replacement of the papillary and reticular dermis by scar tissue with prominent vertically oriented blood vessels. Keloid versus hypertrophic scar - Typical findings Keloid Hypertrophic scar File:Histopathology of a keloid.jpg File:Histopathology of a hypertrophic scar, medium magnification.jpg Flattening of the overlying epidermis No Yes Scarring of the papillary dermis No Yes Collagen Thick hyalinized bundles Whorl-like or nodular arrangements Vertically oriented blood vessels Yes No Prominent disarray of fibrous fascicles/nodules Yes No 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 Main page Main page of Patholines References Image sources