Cytomorphologic findings of cervical Pap smears from female‐to‐male transgender patients on testosterone therapy

Abstract

BackgroundThe cervical cancer screening recommendation for transgender female‐to‐male (FTM) patients is the same as that for cisgender females. A lack of literature on testosterone‐induced changes in cervical cytology in these patients may result in interpretation errors, especially without a proper clinical history. The aim of this study was to delineate the Papanicolaou (Pap) test findings in this patient population.MethodsA pathology laboratory information system was used to obtain a cohort of FTM transgender patients on testosterone therapy (2009‐2019). A cohort of age‐matched, atrophic, control cisgender female patients (postpartum or menopausal) was selected. A retrospective review of the cytomorphologic findings on cervical Pap smears, pertinent follow‐up, and human papillomavirus (HPV) test results was performed.ResultsFourteen transgender patients (age range, 21‐64 years; mean age, 42.5 years) receiving testosterone therapy with 17 Pap smears were identified. One of the 5 available HPV tests was positive for HPV, and 4 were negative. A Pap smear review revealed the following: negative for intraepithelial lesion (NILM; 82.4%), unsatisfactory (5.9%), atypical squamous cells of undetermined significance (ASCUS; 5.9%), and low‐grade squamous intraepithelial lesion (5.9%). The Pap smears of the atrophic cisgender cohort (102 patients) revealed the following: NILM (92.5%), unsatisfactory (0.9%), ASCUS (5.6%), and high‐grade squamous intraepithelial lesion (0.9%). The difference between the rates of epithelial cell abnormality in the 2 cohorts was not statistically significant. Although atrophy was noted in both groups, cytomorphologic findings of transitional cell metaplasia (TCM; 88.2%) and “small cells” (82.4%) were characteristic of the testosterone‐treated transgender cohort. Histologic correlates of TCM and small cells were noted in hysterectomy specimens from 6 patients.ConclusionsSmall cells and TCM are common cytomorphologic findings in Pap smears of testosterone‐treated transgender (FTM) patients. On the basis of histologic follow‐up, small cells most likely represent atrophic parabasal cells of cervical‐vaginal epithelium.

Histologic Findings in Surgical Pathology Specimens From Individuals Taking Masculinizing Hormone Therapy for the Purpose of Gender Transition

“…67 Six studies describe transitional cell metaplasia in 5 of 6, 13 of 28,17 of 27, 7 of 7, 6 of 6, and 1 of 1 cases, which may be confused for a squamous intraepithelial lesion. 38,52,62,66,68,69 However, immunohistochemical staining for p16 in cervixes with transitional cell metaplasia shows negative staining, which helps to differentiate is from the latter. 38 One study also described collections of small cells at the surface of both atrophic cervical epithelium and epithelium with transitional metaplasia, which was seen on Papinicolau smears as well as histologic sections in 5 of 6 individuals.…”

“…38 One study also described collections of small cells at the surface of both atrophic cervical epithelium and epithelium with transitional metaplasia, which was seen on Papinicolau smears as well as histologic sections in 5 of 6 individuals. 69 Neoplastic Findings in the Cervixes of Persons Taking Masculinizing Hormones.-Six cases of cervical neoplasia in transgender men taking androgens were identified. Adkins et al 67 reported a case of low-grade squamous intraepithelial lesion and a case of high-grade squamous intraepithelial lesion, each of which was associated with human papillomavirus infection and initially identified by Papanicolaou smear and confirmed on a biopsy specimen.…”

Surface prostatic metaplasia, transitional cell metaplasia and superficial clusters of small basophilic cells in the uterine cervix: prevalence in gender‐affirming hysterectomies and comparison with benign hysterectomies from cisgender women

“…Although it is not exclusive to TGD individuals, transitional cell metaplasia of the cervix is well documented as a reaction to exogenous androgen therapy 3–5 . Transitional cell metaplasia is characterized by cells with ovoid grooved nuclei that are vertically oriented in deeper cell layers and stream horizontally in superficial layers 3 .…”

“…Although it is not exclusive to TGD individuals, transitional cell metaplasia of the cervix is well documented as a reaction to exogenous androgen therapy 3–5 . Transitional cell metaplasia is characterized by cells with ovoid grooved nuclei that are vertically oriented in deeper cell layers and stream horizontally in superficial layers 3 . Transitional cell metaplasia may be misdiagnosed as high‐grade squamous intraepithelial lesion (HSIL), and some pathologists consider it to be a manifestation of squamous atrophy 6,7 .…”

Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery

“…Previous reports showed higher percentage of unsatisfactory and abnormal cervical cytologies among transmasculine individuals receiving testosterone than among cisgender women. [23][24][25] Similar to histopathologic evaluation, cytologic changes in atrophic epithelium can mimic HSIL (Figure 2, E) and can represent a diagnostic pitfall without the proper history of testosterone exposure. Presence of glycogenated cells has been reported in cytology specimens with androgenic atrophy; this finding was rarely seen in this study, but could represent a potential mimicker of low-grade squamous intraepithelial neoplasia.…”