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Context.— Human papillomavirus (HPV) in the postmenopausal age group is complex, with infected patients in this age group at increased risk of progressing to invasive disease and showing decreased clearance of the virus. Additionally, atrophic changes of the cervix can make histologic distinction of high-grade squamous intraepithelial lesions (HSILs) difficult. Objective.— To determine morphologic and ancillary testing characteristics of atrophy and HSIL in postmenopausal patients. Design.— Files of patients at least 65 years of age were examined, with 81 patients (109 cases [53 benign, 56 HSIL]) included in the study. Results of morphology, immunostaining (p16 and Ki-67), and HPV RNA in situ hybridization (ISH) were noted on all cases with available material. Results.— Atrophy was present in 96 of 109 cases (88%) overall. Coarse nuclear chromatin was noted in none of the benign cases, in 19 of 30 HSIL biopsies (63%), and in 24 of 26 HSIL excisions (92%). All benign cases were negative for p16 and ISH. In the HSIL cases, 45 of 53 (89%) were positive for p16, and of cases with sufficient tissue for ISH, 44 of 45 (98%) were positive. Of the ISH/p16 discordant cases (n = 7), most were p16 negative/ISH positive (6 of 7; 86%), whereas 1 of 7 (14%) was p16 positive and ISH negative. A majority of HSIL cases showed near–full-thickness elevation of Ki-67 (45 of 54; 83%), whereas mitotic figures were less elevated. Conclusions.— In postmenopausal patients with HSIL, mitotic activity is not reliably elevated, but Ki-67 is consistently high. ISH is a more direct method of HPV detection and should be considered in cases where morphology and immunolabeling show discordance.

To determine the frequency of the HPV associated endocervical adenocarcinomas diagnosed at a tertiary referral laboratory in Kenya over a one-year period and classify them by histologic subtypes according to the proposed criteria by IECC.This was a collaborative cross-sectional descriptive study. Formalin-fixed parrafin embedded tissue blocks of 29 confirmed cases of endocervical adenocarcinoma diagnosed at AKUHN between July 2017 and July 2018 were analyzed for presence of 14 hrHPV subtypes including types 16 and 18 using GenomeMETM's GeneNavTm HPV One qPCR kit. Variables analyzed included age, histologic subtype and presence or absence of hrHPV.Twenty-nine cases were analyzed (median age=48years, range 23-70 years), of which 27(93.1%) were positive for hrHPV, with type 16 alone positive in 11(40.7%) cases and present alone or in combination with others including type 18 in 21(72.4%) cases. All hrHPV positive cases had either type 16 or 18. Twenty cases (69.0%) were classified as usual type adenocarcinoma, all positive for hrHPV. Other HPV associated adenocarcinomas identified were mucinous, signet ring cell type (4), villoglandular (2) and mucinous, NOS (1). There were only two cases of non-HPV associated adenocarcinoma.In this series, we show that the proportion of HPV associated endocervical adenocarcinoma in Kenya is high and is particularly driven by types 16 and 18. Policy makers, hospitals and laboratories in East Africa should make an effort to avail the various techniques of detecting hrHPV critical in screening and diagnosis of endocervical adenocarcinoma.

Variables predicting outcome of high-grade squamous intraepithelial lesion (HSIL) in pregnancy are unknown. The HSIL is usually managed conservatively during pregnancy. We aim to assess morphological features of HSIL diagnosed during pregnancy and identify variables predicting HSIL outcome in pregnant and non-pregnant women.ThinPrep pap smears with HSIL in pregnant (2014-2019) and non-pregnant females (2017-2019) were identified. The pathology material from follow-up cervical samples was reviewed by two participating pathologists (TP and KS). Regression was defined as benign or residual low-grade squamous intraepithelial lesion. Histological findings were recorded and compared between pregnant and non-pregnant cohort.The HSIL regression rate was higher in colposcopic samples (16% vs. 0%;The higher rate of benign findings during HSIL follow up in pregnancy is likely related to duration and stromal inflammation. HSIL regression is frequently noted following CIN2 diagnosis in non-pregnant setting. HSIL histology is similar in postpartum and non-pregnant females.

There have been exceedingly few reports of epidermodysplasia verruciformis (EV) or EV-like lesions in the vulva. We describe the first case series featuring vulvar lesions displaying synchronous EV-like histologic changes and conventional high-grade intraepithelial lesion (VIN 3), a finding hitherto unreported in medical literature. We hypothesized that this could be caused by coinfection with α-HPV and β-HPV genotypes. Cases were retrospectively selected from our institutional archive. Detailed review of clinical information, histologic examination and whole genome sequencing (WGS) were performed in 5 samples from 4 different patients. Three of four patients had a history of either iatrogenic immune suppression or prior immune deficiency, and all featured classic VIN 3 and EV changes within the same lesion. The fourth patient had no history of immune disorders, presented with EV-like changes and multinucleated atypia of the vulva, and was the sole patient without conventional high-grade intraepithelial lesion. By WGS, several uniquely mappable reads pointed towards infection with multiple HPV genotypes including both α-HPVs and β-HPVs. Mutations in genes implicated in cell-mediated immunity, such as DOCK8, CARMIL2, MST1 and others, were also found. Our findings provide novel insight into EV and HPV pathogenesis, vulvar precancerous lesions and expand the clinicopathological spectrum of genetic alterations linked to unconventional immune deficiencies.

Stratified mucin-producing intraepithelial lesion (SMILE) is a histologic subtype of HPV-associated endocervical adenocarcinoma in situ. We have observed benign endocervical changes resembling SMILE. We aim to characterize this pattern and explore its potential association with dysplasia. We retrospectively retrieved all 296 consecutive cases accessioned as endocervical biopsies. Some included multiple specimens, totaling 483 biopsies and 219 endocervical curettages (ECC), n = 702. We included cases showing endocervical epithelial stratification often with pencillate (triangular-shaped) nuclei. We rejected cases in which layering represented tangential sectioning, metaplasia, microglandular hyperplasia, gastric type epithelial changes, and dysplasia. We found benign stratified intraepithelial mucinous proliferation in 51 patients, either with a multilayered (n = 27) or a two-layered appearance (n = 24). Overall, multilayered proliferation occurred in 6 % (29/483) of biopsies and in 0.9 % of ECCs (2/219). Two-layering was identified in 4 % of all biopsies (20/482) and was not seen in ECCs. Histologic findings included stratification, intracytoplasmic mucin, paler cytoplasm, low nuclear-to-cytoplasmic ratio, often pencillate nuclei, rare mitoses, and no apoptotic bodies. P16 immunohistochemistry (n = 12) was negative, suggesting absence of underlying high-risk HPV infection. HSIL was concomitant in 29.6 % (8/27) of patients with multilayered proliferation. Concurrent SMILE was not observed. We also reviewed 13 SMILE cases. Concurrent multilayered benign proliferation was identified in 54 % (7/13) of cases. We describe benign stratified intraepithelial mucinous proliferation of the cervix, which morphologically may overlap with SMILE. Its presence in most SMILE cases suggests a potential relationship. The multilayered form represents a diagnostic pitfall when mitotically active. Because of the often-coexistent HSIL, we propose that its presence should prompt scrutiny to rule out any associated dysplasia.

The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was

The lobular carcinoma in situ (LCIS) subtypes include classic (CLCIS), pleomorphic (PLCIS), and florid LCIS (FLCIS). The CLCIS is considered a breast cancer risk factor, but clinical significance and natural history of other LCIS subtypes are unclear. The outcome data on PLCIS and FLCIS is limited. The aim of current study is to compare excision and follow-up findings of CLCIS and nonclassic LCIS (NCLCIS). The breast needle biopsies (NBs) with LCIS during 01/2007-12/2017 were identified. The imaging, clinical findings, and outcome were compared between CLCIS and NCLCIS. A total of 36 NBs from 32 patients with NCLCIS (14 PLCIS & 22 FLCIS) and 73 NBs from 68 patients with CLCIS were identified. The NCLCIS patients were older (57 vs 52 years; P = .02) and presented more often with calcifications (78% vs 44%; P = .01). Seven (19%) PLCIS were initially diagnosed as ductal carcinoma in situ (DCIS). The microscopic invasion was frequent with NCLCIS (25%). No invasion was identified in NBs with CLCIS. A separate concurrent NBs with a carcinoma (29% vs 6%; P = .018) or ductal atypia (12% vs 3%; P = .1) was more frequent with CLCIS. The upgrade rate (invasion or DCIS) was higher with NCLCIS (25% vs 4%). Four NCLCIS developed ipsilateral recurrences: 2 NCLCIS, 1 IDC, and 1 ILC (50; 10-96 months). No breast event was reported in 24 pure CLCIS (60; 8-144 months). Invasive carcinoma with NCLCIS, unlike CLCIS, is always lobular type. Recurrences following NCLCIS are ipsilateral lobular tumors. NCLCIS subtypes are nonobligate precursors to invasive lobular carcinoma.

Saccharomyces cerevisiae-like 1 (SEC14L1) is a member of the SEC14 family and is involved in liposoluble vitamin transfer, and in a large cohort of breast cancer cases, was one of the most significant genes associated with lymphovascular invasion (LVI), and had a significant relationship with human epidermal growth factor receptor 2 status, survival, and histologic grade. In this study, 111 separate gynecologic tumors were studied for SEC14L1 protein expression, including: uterine adenosarcoma, ovarian clear cell carcinoma, endometrial stromal sarcoma, endometrioid carcinoma of the uterus, high-grade serous carcinoma, ovarian endometrioid carcinoma, uterine leiomyosarcoma, low-grade serous carcinoma, uterine carcinosarcoma, and uterine serous carcinoma (USC). Overall, LVI was noted in 31/111 (28%) cases, highest in uterine carcinosarcoma (5/11; 45%), high-grade serous carcinoma (9/21; 43%), and ovarian clear cell carcinoma (4/10; 40%). SEC14L1 was positive in 25/111 (23%) cases; the highest percentage and only statistically significant finding by tumor type was USC at 9/12 (75%) cases positive. No relation between LVI or survival and SEC14L1 expression was noted. The relation between USC, a tumor known to show human epidermal growth factor receptor 2 overexpression and SEC14L1 is a novel finding, the significance of which warrants further study.

Agricultural land and resources reduced annually because of climate change thus it is necessary to further increase the productivity of the major staple food rice to sustain food security worldwide. However, rice productivity enhancement is one of the key challenges in abiotic stress-prone environments. The integration of cutting-edge breeding approaches and research management methods in the current varietal improvement pipelines can make a step-change towards varietal improvement for the abiotic stress-prone environments. Proper implementation of breeder’s equations in the crop improvement pipeline can deliver a higher rate of genetic gain. Single Seed Descent based Rapid Generation Advance (RGA) technique in field and greenhouse is the most promising innovations and low-cost, high-throughput marker-assisted selection approaches are applied for rapid and efficient selection for abiotic stress-tolerances. Also improving efficiency, intensity, and accuracy of selection and reducing breeding cycle time through holistic rice breeding that can play an important role in developing climate-smart abiotic stress-tolerant rice for target environments. This information can use as the future direction for rice breeders and other researchers.

PAX8 is a specific marker for kidney, ovarian, and thyroid tissue. Antibody-dependent cross-reactivity for PAX8 has been reported in mesothelial, pancreatic, and B-cell proliferations. We recently described antibody clone-dependent aberrant PAX8 expression in breast cancer. In this study we systematically analyze PAX8 expression in breast cancer on whole tissue sections, using MRQ50 and BC12 PAX8 monoclonal antibodies. Immunohistochemistry was performed on formalin-fixed paraffin-embedded whole tissue sections from 85 invasive mammary carcinomas. Immunostaining was evaluated at ×10 objective; extent (intervals of 10%, 0% to 100%) and intensity (weak, moderate, and strong) of nuclear staining was evaluated in the tumor, benign breast tissue, and lymphocytes. With MRQ50 variable PAX8 nuclear positivity was identified in tumor cells in 35/85 (41%) cases. Of 35 PAX8 cases, 23 (66%) showed only weak expression in 1% to 10% cells, 8 (23%) were weakly (5/8) or moderately (3/8) PAX8 in 11% to 50% cells, and 4 (11%) showed weak PAX8 positivity in >50% tumor cells. All 3 (3.5%) cases that showed moderate nuclear PAX8 staining with MRQ50 were histologic grade 3. No PAX8 expression was noted in benign lobules/ducts with either antibody. Breast carcinomas can show nuclear immunostaining with MRQ50 PAX8 antibody with up to 3.5% cases showing moderately intense expression. The BC12 PAX8 antibody does not cross-react with breast carcinoma and lymphocytes. During workup of metastatic carcinoma, weak to moderate PAX8 nuclear expression with MRQ50 clone should be interpreted with caution.

Objectives To measure the correlation of molecular biomarkers between biopsy and final pathology specimens in uterine serous cancer (USC) and to establish the overall prevalence of specific biomarkers among subjects with USC. Methods Twenty eight patients with a diagnosis of USC and sufficient biopsy and hysterectomy specimens were identified. IHC was used to measure the biomarker status of EGFR, phospho-AKT, ER, PR, Her2/neu, and PTEN in FFPE tissue. The presence or absence of individual biomarkers was then compared between a given subject's diagnostic biopsy specimen and final hysterectomy specimen. Results In the cohort identified, average age was 72 and average BMI was 29. 75% of patients had full lymphadenectomy performed. The average time from biopsy to surgery was 33 days (range 9–91 days). The distribution of disease was 61% stage I (n = 17), 14% stage II (n = 4), 22% stage III (n = 6) and 4% stage IV (n = 1). Biopsy and hysterectomy specimens agreed 67% of the time for phospho-AKT, 80% for ER, 73% for PR, 83% for EGFR, 100% for Her2/neu and 95% for PTEN loss. Conclusions The measurement of specific biomarkers correlated well between subjects' biopsy and hysterectomy specimens in women with USC as measured by a pathologist using routine clinical techniques. Preoperative diagnostic biopsy may be a useful tool for guiding neoadjuvant targeted therapy in USC., Highlights • Molecular biomarkers can be measured in endometrial biopsy specimens using routine clinical techniques. • There was 100% correlation between biopsy and hysterectomy specimen staining for Her2/neu. • Standardization of staining for molecular markers in endometrial cancers has potential to expand treatment options.

Adenomatoid tumor is a benign neoplasm of mesothelial origin. Adenomatoid tumor in female genital tract shows typical morphologic features with bland nuclei. Deciduoid morphology has not been reported in adenomatoid tumor. Tumors with deciduoid cells and atypical nuclear features may pose a diagnostic challenge and raise the suspicion of malignancy. We present a case of fallopian tube adenomatoid tumor with deciduoid morphology and atypical nuclear features in a 39-year-old woman with prolonged progestin therapy. We hypothesize that the unusual morphological changes in adenomatoid tumor, like deciduoid morphology and nuclear atypia, may be secondary to hormone effects.

Highlights • Bilateral ovarian low-grade serous carcinoma presenting with extensive osseous metaplasia. • Both lesions arising directly from ovarian cystadenofibromas, skipping the “borderline phase”. • No micropapillary serous borderline component was identified. • This case may represent a “skipped step” in low-grade serous carcinogenesis.

Nonneoplastic lesions of the endometrium encompass a broad spectrum of epithelial alternations ranging from metaplasia, hormonal related changes, inflammatory processes, reparative conditions, endometrial polyps, and gestational alterations. Many of these conditions can mimic various malignant or premalignancy lesions of the endometrium, particularly when present in a small biopsy or curettage specimen. Endometrial hyperplasia and atypical hyperplasia are preneoplastic conditions that precede the most common endometrioid adenocarcinoma. Serous and clear cell carcinomas are high-grade carcinomas by definition and account for about 10–15% of endometrial malignancy. Other histological types are rare, including high neuroendocrine carcinomas, undifferentiated carcinomas, dedifferentiated carcinoma, and mixed carcinomas. Molecular classification of endometrial cancers may provide added diagnostic and prognostic information.

Although overwhelming majority of uterine cervical carcinomas are high-risk human papilloma virus (hrHPV)-associated tumors, growing body of literature suggests the existence of a significant percentage of non-HPV cervical adenocarcinomas. This has led to the recent proposal of categorizing cervical adenocarcinomas into hrHPV-associated and hrHPV-nonassociated tumors. Rare examples of non-HPV-associated squamous cell carcinoma are also available in the literature, although that is not the norm. In addition, one should always remember the possibility of metastatic tumors, gestational trophoblastic tumors, and the great mimicker malignant melanoma while evaluating cervical biopsies/resections. Some benign lesions of the cervix can also create diagnostic challenges for practicing pathologists as these are not too frequently encountered in daily practice. This chapter attempts to address some of the questions and scenarios that a practicing pathologist may face in their daily practice.

During breast cancer staging, histological evaluation of axillary sentinel lymph nodes (SLN) is usually straightforward. However, the exact characterization of a small epithelial deposit in an SLN can be challenging, especially during the frozen section examination. We report the first case of endosalpingiosis involving bilateral axillary lymph nodes. We review published literature on axillary endosalpingiosis and discuss the differential diagnosis of small epithelial deposits in an axillary SLN. Pathologists should consider benign epithelial rests and displaced epithelium as differential diagnoses for the microscopic epithelial nodal deposit, especially during the frozen section examination.

Highlights • Unique overexpression of Her2/neu in uterine serous carcinoma. • Testing hysterectomy specimen may be better. • Metastatic tumor or tissue with tumor emboli testing is better. • Intratumoral heterogeneity of Her2/neu overexpression is more pronounced compared to breast tumors. • Fixation time and cold ischemia time should be recorded as in breast carcinomas., The human epidermal growth factor receptor 2 (Her2) is tested in many human cancers, including breast, bladder, pancreatic, ovarian and stomach. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) have issued Clinical Practice Guidelines for reporting Her2 results for breast carcinomas (Wolf et al., 2018). For the last 1–2 years Her2/neu is tested in endometrial serous carcinoma, especially in recurrent tumors or non-responsive tumors as an option for additional treatment. College of American Pathologists (CAP) offers a template for prognostic marker reporting results for specimens with endometrial carcinomas (Fitzgibbons et al., 2019). Her2/neu testing by immunohistochemistry (IHC) mandates rigorous fixation time control, e.g., fixation time should fall within 6–72 h (Recommendations for Her2 Testing in Breast Cancer, 2013). For that reason, in breast cancers, Her2/neu testing is done on initial core biopsy specimens. The test is however, repeated on excision specimen in high grade tumors where Her2/neu expression was initially negative on core biopsies. For endometrial serous carcinoma no guidelines have been set or proposed as of yet. The Gynecologic Oncologists request this test because of proven benefit of adding Trastuzumab (Fader et al., 2018) and that is why it is important to documenting the findings in this report in the literature so that an informed request can be made by the treating oncologist when multiple tissue samples from the same patient are available for testing. Similarly pathologists also can decide which would be the best sample to test when no instruction is received. We report here three separate scenarios of uterine serous carcinomas in which the Her2/neu expressions were unique enough to justify documentation and therefore have implications for determining which specimen is ideal for the Her2 overexpression testing and likely to have highest possibility in identifying the Her2/neu overexpressed clone in the tumor which would expand the therapeutic options for the patients.

Certain tumors are more difficult to recognize when they present in an unusual location. Within the urinary tract, primary melanomas, carcinoid tumors, or epithelioid angiosarcoma could present diagnostic challenges due to their infrequent occurrence. This article emphasizes the clinical and histopathologic features of these entities and their differential diagnoses including the immunophenotype and their prognoses.

Highlights • Mullerian carcinosarcoma can occur in extragenital sites. • Malignant transformation of endometriosis is common in the rectosigmoid area. • MLH1 hypermethylation has been implicated in endometriosis-associated carcinomas. • Adequate sampling is essential in determining the etiology of colonic tumors.

Background The incidence of abnormal cervical smears in the United Arab Emirates (UAE) is 3.6%. Data regarding specific high-risk HPV (hrHPV) genotypes are insufficient. Identification of hrHPV subtypes is essential to allow formulating effective vaccination strategies. Methods A total of 75 archival cervical cone biopsies with HSIL or higher lesions (2012–2016) were retrieved from a tertiary hospital, including HSIL (n = 70), adenocarcinoma in-situ (n = 1) and squamous cell carcinoma (n = 4). Five tissue sections (10-μ-thick each) were cut and DNA extracted using the QIAamp DNA FFPE Tissue Kit. GenomeMeTM’s GeneNavTM HPV One qPCR Kit was used for specific detection of HPV 16 and 18; and non-16/18 samples were typed by GenomeMeTM’s GeneNavTM HPV Genotyping qPCR Kit. Results Median age was 34 years (range 19–58) with 70% UAE Nationals. hrHPV detected were 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, 66 & 68. hrHPV testing was negative in 12% of cases. Most common types were HPV 16 (49%), HPV 31 (20%) and HPV 18 (6.6%). hrHPV 16 and/or 18 represented 56% and rare subtypes 32%. Co-infection was present in 16%. Eight cases had two-viral subtype infections and 4 cases had 3 subtype infections. Multi-viral HPV infection was limited to hrHPV 16, 18, 31 & 33 subtypes. Conclusions Infection by non HPV 16/18 is fairly common. A higher than expected incidence of rare subtype (20% hrHPV31) and multi-viral hrHPV (16%) were detected. This finding stresses the importance of this pilot study as currently only quadravalent vaccine is offered to control the HPV infection in the UAE population.

Focal micropapillary features in invasive urothelial carcinoma is sometimes difficult to distinguish from retraction artifact morphologically. Cell polarity reversal has been demonstrated in micropapillary tumors by epithelial membrane antigen (EMA) immunostaining. We have previously described the use of E-cadherin as a cell polarity marker in ovarian micropapillary serous borderline tumors. The aim of this study was to evaluate the utility of immunohistochemistry for EMA and E-cadherin in differentiating micropapillary urothelial carcinoma from retraction artifact. We identified 29 invasive urothelial carcinomas with micropapillary features and 30 invasive urothelial carcinomas without reported micropapillary features but with areas of retraction artifact. Cell polarity reversal was considered present if E-cadherin showed membranous apical cup-like staining or if EMA demonstrated a well-defined basal staining towards the stroma. Twenty-seven of 29 cases (93%) of urothelial carcinoma with micropapillary features demonstrated EMA or E-cadherin staining patterns consistent with cell polarity reversal. Staining consistent with micropapillary architecture was identified with both markers in 20 of these 27 cases (74%). Six cases showed reversal of polarity by E-cadherin alone, whereas 1 case showed polarity reversal by EMA alone. Retraction artifacts showed circumferential staining by E-cadherin and lacked well-defined basal staining by EMA. Three cases originally classified as with retraction artifact showed reversal of cell polarity by both EMA and E-cadherin and were reclassified as micropapillary. Our data show that pathologists can reliably make this distinction in most cases. However, in some cases with ambiguous features, EMA and E-cadherin immunostaining may aid in resolving this diagnostic dilemma.

Objective: The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aids in classification of atypical cells in cervical cytology. There is limited literature regarding reproducibility and interobserver variability in the application of the 2014 AGC criteria. Our aim is to assess the interobserver variability of AGC with a focus on how diagnostic categories link with guideline-driven management. Study Design: Three observers re-reviewed 51 previously diagnosed AGC Papanicolaou tests. The diagnoses were categorized as follows: (1) according to guideline-specified management, and (2) as glandular vs. squamous lesions. The κ statistic was used to evaluate interobserver agreement. Results: The interobserver variability per guideline management by weighted 2-observer κ ranged from 0.009 to 0.530, with half of the interobserver pairings meeting the threshold for at least fair-moderate agreement. For categorization as glandular, squamous, or both, unweighted κ yielded at best fair interobserver agreement (κ = 0.250) in 1 pairing, with low κ scores in the remainder of reviewer pairs (range 0.015–0.152). Conclusions: There is significant interobserver variability in the diagnosis of AGC. The AGC cases when divided by clinical management had fair-moderate interobserver agreement, suggesting that diagnostic variability likely has a real effect on patient care. This diagnostic uncertainty should be understood by cytologists and clinicians.

A 63-year-old Caucasian woman underwent total hysterectomy with bilateral salpingo-oophorectomy due to abnormal uterine bleeding. Gross examination of the hysterectomy specimen revealed a large polypoid mass filling the endometrial cavity. Histological examination revealed a tumor with two unique morphologic patterns with no overlap or transition from one pattern to the other. The low-grade component consisted of FIGO grade 1 endometrioid adenocarcinoma with unusual “balloon-cell” change, while the high grade component was an undifferentiated carcinoma with neuroendocrine features. Both components exhibited MLH1 and MSH6 loss by immunohistochemistry. To our knowledge, the current case is only the 5th documented case of dedifferentiated endometrioid carcinoma with neuroendocrine features. Keywords: Endometrium, Dedifferentiated carcinoma, Neuroendocrine features, Balloon-cell change, Microsatellite instability

Highlights • Localized amyloidosis is only identified in Usual-type HPV-associated VINs. • Subtypes of hrHPV in both localized amyloidosis and non-amyloid cases are similar. • VINs with localized amyloidosis appear to have a better prognosis. • Amyloid deposits persisted even after regression of VINs. • Localized amyloid deposits in VINs may be a manifestation of body’s defense mechanism., Localized cutaneous amyloidosis was reported recently in association with vulvar squamous intraepithelial neoplasia (VIN). High-risk human papillomavirus (hrHPV) type 16 is the most commonly reported subtype found in usual-type VIN. However, it is unknown whether any hrHPV subtype(s) is/are prevalent in simultaneous squamous intraepithelial lesions and localized amyloidosis in the same individual - the subject matter of this report. To observe the potential clinical significance, study cases were followed and compared to usual-type VINs without amyloid deposition. Of 45 patients of usual-type VINs associated with amyloidosis, 33 had detectable hrHPV, and 12 were negative. HPV 16 alone or in combination with HPV 31 accounted for 72%, HPV 51 alone accounted for 2% of the cases, and 26% were negative for hrHPV. Lack of demonstrable hrHPV in a significant proportion of cases (26%) raises the possibility of a novel or presently undetected hrHPV subtype. Five of the total 22 (23%) patients with amyloid had either Squamous cell carcinoma or high-grade VIN on follow-up. In contrast, 14 of 18 (78%) patients exhibiting lesions without amyloid had disease on follow-up. These findings may indicate that amyloid deposition may represent a feature of regression or a potential favorable prognostic indicator.

Gastric-type adenocarcinomas of the uterine cervix have been described within the literature in detail; however, the description of gastric-type endometrial adenocarcinomas is a recent development, with only two cases originating from Japan in the world literature to date. According to these prior reports, the recognition of this pattern of differentiation is critical, as it is often associated with deep myoinvasion, positive regional lymph nodes, and poor outcome despite appropriate adjuvant treatment. We present two cases of endometrial adenocarcinoma with gastric-type differentiation in patients from the United States with superficial myoinvasion and positive patient outcomes. Gastric-type differentiation in endometrial adenocarcinomas is rare and likely underrecognized. Continued reporting of these cases is necessary to further understand the natural history and clinical implications of this entity.

Mesonephric ducts regress in genotypic females, leaving behind few remnants. These vestigial structures are often recognized in the mesosalpinx and paracervical regions. We report here 3 cases of female-to-male transgenders who underwent hysterectomy following testosterone treatment. Both female and male genital structures were identified on histologic examination. Although the morphologic appearances of the specimens were unremarkable, histologically 1 case revealed a well-formed fallopian tube as well as an epididymis and 2 cases showed prostate glands to be present in the cervical squamous epithelium.

Routine histopathologic examination of hemorrhoidectomy specimens is controversial having been described as not useful and expensive with few of these common cases demonstrating incidental lesions. However, unexpected premalignant and malignant lesions have been detected on excised hemorrhoids. The high-risk human papillomavirus (HR-HPV) types associated with these incidentally identified high-grade lesions are presently unknown. We aimed to identify cases of incidental high-grade anal intraepithelial neoplasia (HG-AIN) and anal squamous cell carcinoma incidentally discovered on hemorrhoidectomy specimens, genotype HR-HPVs from these lesions, and assess p53 and p16 expression by immunohistochemistry to identify risk factors for their development. With institutional approval, cases with associated demographics from 1995 to 2015 were reviewed to identify and confirm incidental HG-AIN or squamous cell carcinoma in hemorrhoidectomy specimens. Genotyping for HR-HPV types and immunohistochemical staining for p53 and p16 was performed. Statistical analysis comparing HPV genotypes, p53 and p16 staining, and potential risk factors by the Fisher exact test was performed. In the largest series of incidental high-grade lesions on hemorrhoidectomy, HPV 16 was the most common HR-HPV detected though multiple-type infections were common including some HPV 16/18-negative cases. By genotyping, HPV 39 was significantly associated with IV-drug abuse history (P=0.0015) and HIV-positive status (P=0.037), whereas HPV 58 detection correlated with chemotherapy-induced immunosuppression (P=0.029). There was frequent overlap between p53 staining and HPV positivity, particularly when HPV 31 was detected. We also identified several mimickers of HG-AIN that may present diagnostic challenges in these specimens. Our data support continued routine examination of hemorrhoidectomy specimens and suggest that adjunctive studies such as immunohistochemistry for challenging cases may be useful.