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* Context.--There have been exceedingly few reports of epidermodysplasia verruciformis (EV) or EV-like lesions in the vulva. We describe the first observation of vulvar lesions displaying synchronous EV-like histology and conventional high-grade squamous intraepithelial lesion (HSIL), a finding hitherto unreported in medical literature. Objectives.--To describe this novel vulvar lesion with hybrid features of HSIL and EV, attempt to confirm the hypothesis of coinfection with [alpha] and [beta] human papillomavirus ([alpha]-HPV and [beta]-HPV) genotypes, and describe relevant underlying genetic mutations. Design.--Cases were retrospectively selected from our institutional archive. Detailed review of clinical information, histologic examination, and whole genome sequencing (WGS) were performed. Results.--Five samples from 4 different patients were included. Three of 4 patients had a history of either iatrogenic immune suppression or prior immune deficiency, and all 3 featured classic HSIL and EV changes within the same lesion. One 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 HSIL. By WGS, several uniquely mappable reads pointed toward infection with multiple HPV genotypes, including both [alpha]-HPVs and [beta]-HPVs. Mutations in genes implicated in cell-mediated immunity, such as DOCK8, CArMiL2, MST1, and others, were also found. Conclusions.--We provide the first description of vulvar lesions harboring simultaneous HSIL and EV features in the English-language literature, a phenomenon explained by coinfection with [alpha]-HPV and [beta]-HPV genotypes. The finding of EV-like changes in a vulvar specimen should prompt assessment of the patient's immune status. (Arch Pathol Lab Med. 2024;148:1014-1021; doi: 10.5858/arpa.2023-0193-OA), Human papillomaviruses (HPVs) are nearly ubiquitous among the adult population, with more than 200 recognized genotypes across 5 genera. (1) Infection by [alpha]-HPV subtypes (eg, HPV16 and HPV18) is a [...]

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-fullthickness 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. doi: 10.5858/arpa.2021-0426-OA, Human papillomavirus (HPV) in the postmenopausal age group is complex. Not only is there a more serious risk of disease progression because of decreased clearance of virus (1) and more [...]

Context.--Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. Design.--Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. Results.--Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. Conclusion.--Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium., Endometrioid carcinoma is often preceded by characteristic histopathologic lesions designated as endometrial hyperplasia, (1-4) and currently it is accepted that there is a continuum of changes that evolve to endometrioid [...]

The article presents a case study related to a 54-year-old woman with bilateral pelvic masses. She had undergone a total abdominal hysterectomy for fibroids several years earlier. Exploratory laparotomy and possible staging were planned. Intraoperative consultation was obtained, and a right-sided adnexal mass, and a leftsided adnexal mass were found. Both the tumors had similar gross appearance and microscopic features. Pathologic diagnosis was well-differentiated papillary serous carcinoma arising in serous adenofibroma of borderline malignancy. Such carcinomas are believed to have an indolent clinical course.