Aims As gender‐affirming surgery is becoming more common, it is important for pathologists to recognize potential benign findings to avoid misinterpretation. Cervical transitional cell metaplasia and superficial clusters of small basophilic cells have been described in the context of gender‐affirming testosterone therapy; these findings may be misdiagnosed as high‐grade squamous intraepithelial lesions or endometrial cells on Pap smears. Prostatic metaplasia has been reported in the surface squamous epithelium of the vagina and the uterine cervix in individuals undergoing gender‐affirming androgen therapy; this finding is often associated with NKX3.1‐positive basal keratinocytes. The aim of this study was to assess the morphological and immunohistochemical features of the uterine cervix in gender‐affirming hysterectomies in comparison with benign hysterectomies from cisgender women. Methods and results We assessed the morphological and immunohistochemical features of the uterine cervix in 49 gender‐affirming hysterectomies as compared with 57 hysterectomies from cisgender patients to establish the relative prevalences of surface prostatic metaplasia, NKX3.1‐positive basal keratinocytes, transitional cell metaplasia, and small basophilic cells in the cervical squamous epithelium. The cervical tissue from the gender‐affirming therapy cohort showed significantly higher prevalences of NKX3.1‐positive basal keratinocytes (86% versus 1.8%), transitional cell metaplasia (80% versus 3.5%), superficial clusters of small basophilic cells (67% versus 7%), and surface prostatic metaplasia (43% versus 3.5%). Conclusion NKX3.1‐positive basal keratinocytes, transitional cell metaplasia, small basophilic cells and surface prostatic metaplasia are all more prevalent in the cervices of individuals receiving gender‐affirming testosterone therapy; awareness of this fact allows pathologists to avoid the overdiagnosis of dysplasia or the recommendation of unnecessary follow‐up procedures.

Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) is challenging, in part due to the sometimes subtle nature of its atypia. Many dVIN lesions demonstrate aberrant p53 staining; however, staining patterns overlap between dVIN and benign/reactive entities. We evaluate a p53/CK17 dual stain in an initial cohort of dVIN (n=30), benign vulvar skin (n=5), lichen sclerosus (LS, n=10), lichen simplex chronicus (LSC, n=10), and pseudoepitheliomatous hyperplasia (PEH, n=10). In the initial cohort, aberrant p53 staining was seen only in dVIN (50%, 15/30). Equivocal p53 staining patterns were seen in dVIN (37%, 11/30), LS (50%, 5/10), LSC (40%, 4/10), and PEH (40%, 4/10). All 30 dVIN cases were positive for CK17 (strong partial-thickness or full-thickness staining), but positive CK17 staining was also seen in LS (70%, 7/10), LSC (50%, 5/10), and PEH (100%, 10/10). In the initial cohort, the combination of aberrant p53 and positive CK17 was seen only for dVIN (50%, 15/30). Forty cases of LS with known follow-up (20 with progression to dVIN, 20 without) were stained to assess prognostic value. Three LS cases showed aberrant p53 staining with CK17 positivity; all progressed to dVIN. Equivocal p53 staining and CK17 positivity were seen in cases with and without progression. The p53/CK17 dual stain is more diagnostically useful than either stain alone. Negative/focal staining for CK17 argues against a diagnosis of dVIN, while aberrant p53 staining with CK17 positivity strongly supports the diagnosis.