Starting pathology (Female Reproductive system)

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).