Understanding cytomorphologic changes in Pap tests of transgender men on testosterone therapy

Abstract

Abstract Introduction/Objective Pap test findings in transgender men on testosterone therapy can often lead to misdiagnosis of dysplasia, especially in the setting of a positive HPV test. We reviewed relevant literature to analyze the cytomorphological nuances and applicable correlations to subsequent pathology in Pap tests of transgender men on testosterone therapy. Methods/Case Report We searched peer-reviewed journals on PubMed, synthesizing five articles published from 2018-2022 that specifically address cytomorphological findings on cervical Pap tests and biopsy results in transgender men on testosterone therapy. Results (if a Case Study enter NA) Various cytological changes, such as small parabasal-type cells and transitional cell metaplasia (TCM) can be mistaken for dysplasia in transgender men. In fact, these changes are representative of atrophy due to testosterone, as such findings have been observed in patients undergoing tamoxifen therapy. Small parabasal-type cells are described as clusters or sheets with intermittent nuclear enlargement and hyperchromatic nuclei, whereas TCM comprises flat sheets of cells with oval to spindle-shaped nuclei, powdery chromatin, and prominent nuclear grooves. Relevant clinical history can often help clarify cytologic diagnoses, as Pap tests that show atrophic changes can be misinterpreted as being abnormal. In several cases described in the literature, original diagnoses of atypical squamous cells of undetermined significance (ASCUS) were re-interpreted as atrophic changes after eliciting a history relevant for testosterone therapy. Small parabasal-type cells found on cytology have correlated with sections of the ectocervix that have groups of small hyperchromatic cells attached to the surface of atrophic cervical epithelium or areas of TCM. These cells may be mistaken for endometrial cells, especially in patients over 45 years old. Distinguishing atrophic changes from dysplasia on surgical pathology may modify cytologic diagnoses. Conclusion Transgender men on testosterone therapy often retain their cervix, necessitating ongoing cervical cancer screening. However, Pap test results from these individuals often exhibit atrophic changes through the presence of small parabasal-type cells and TCM. Differentiating between atrophy and dysplasia can pose a diagnostic challenge, especially in the setting of positive HPV testing or inflammation. Continued analyses into these cytomorphological nuances will assist providers in refining their diagnostic approaches and providing personalized care to transgender men.