Context.— Transgender men and transmasculine persons experience a discordance between the female sex they were assigned at birth and their gender. They may choose to take hormone therapy and/or undergo surgery to masculinize the body. Understanding the common (and less common) histologic changes present in patients taking masculinizing hormones will empower pathologists to better serve this unique patient population. Objective.— To summarize histologic findings in surgical pathology specimens from persons taking masculinizing hormones as a part of gender transition. Data Sources.— A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender men from January 1946 to January 2021. Conclusions.— Publication in this area has markedly increased in the last 2 decades. However, most of the studies identified were descriptive and case reports describing changes seen in specimens removed as a part of masculinizing surgical procedures. Benign histologic findings include stromal hyalinization and epithelial atrophy in the breast, polycystic ovarian syndrome–like changes in the ovary, and transitional cell metaplasia in the cervix. The most commonly reported neoplastic finding was adenocarcinoma of the breast, with rare cases of ovarian, endometrial, cervical, vaginal, pituitary, pancreatic, and cardiovascular neoplasia also reported. Ongoing research in this area is needed to better characterize the histologic findings in persons taking masculinizing hormones to provide a deeper understanding of the effect of these treatments on different tissues and facilitate better patient management.

Immunohistochemistry (IHC) is a testing methodology that is widely used for large number of diagnostic, prognostic, and predictive biomarkers. Although IHC is a qualitative methodology, in addition to threshold-based stratification (positive vs. negative), the increasing levels of expression of some of these biomarkers often lead to more intense staining, which published evidence linked to specific diagnosis, prognosis, and responses to therapy. It is essential that the descriptive thresholds between positive and negative staining, as well as between frequently used graded categories of staining intensity (eg, 1+, 2+, 3+) are standardized and reproducible. Histo-score (H-score) is a frequently used scoring system that utilizes these categories. Our study introduces categorization of the cutoff points between positive and negative results and graded categories of staining intensity for nuclear IHC biomarker assays based on color interaction between hematoxylin and diaminobenzidine (DAB); the Blue-brown Color H-score (BBC-HS). Six cases of diffuse large B-cell lymphoma were stained for a nuclear marker MUM1. The staining was assessed by H-score by 12 readers. Short tutorial and illustrated instructions were provided to readers. The novel scoring system in this study uses the interaction between DAB (DAB, brown stain) and hematoxylin (blue counterstain) to set thresholds between “0” (negative nuclei), “1+” (weakly positive nuclei), “2+” (moderately positive nuclei), and “3+” (strongly positive nuclei). The readers recorded scores for 300 cells. Krippendorff alpha (K-alpha) and intraclass correlation coefficient (ICC) were calculated. We have also assessed if reliability improved when counting the first 100 cells, first 200 cells, and for the total 300 cells using K-alpha and ICC. To assess the performance of each individual reader, the mean H-score and percent positive score (PPS) for each case was calculated, and the bias was calculated between each reader’s score and the mean. K-alpha was 0.86 for H-score and 0.76 for PPS. ICC was 0.96 for H-score and 0.92 for PPS. The biases for H-score ranged from −58 to 41, whereas for PPS it ranged from −27% to 33%. Overall, most readers showed very low bias. Two readers were consistently underscoring and 2 were consistently overscoring compared with the mean. For nuclear IHC biomarker assays, our newly proposed cutoffs provide highly reliable/reproducible results between readers for positive and negative results and graded categories of staining intensity using existing morphologic parameters. BBC-HS is easy to teach and is applicable to both human eye and image analysis. BBC-HS application should facilitate the development of new reliable/reproducible scoring schemes for IHC biomarkers.

Context.— Transgender women experience health disparities in all areas of medicine. Within surgical pathology, knowledge gaps relating to the concepts of transgender care exist. Medical transition for transgender women and transfeminine persons may involve hormone therapy and/or surgery to feminize the body. Understanding the common histologic changes in specimens from feminizing surgeries, as well as other specimens from patients on feminizing hormone therapy, will aid surgical pathologists in providing better care to this unique patient population. Objective.— To summarize histologic findings in surgical pathology specimens from transgender women taking feminizing hormones. Data Sources.— A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender women from 1946 to 2019. Conclusions.— Much of the literature to date describing histologic findings in transgender women comes from the examination of genitourinary specimens removed during feminizing surgeries. Common benign changes associated with feminizing hormone therapy include the development of acini and lobules in the breast, testicular tubular changes, and squamous metaplasia of the prostate and urethra. Neoplastic cases include breast adenocarcinoma and fibroepithelial lesions, testicular germ cell tumors, prostatic adenocarcinoma, anal squamous cell carcinoma, pituitary adenomas, and meningiomas. Additional studies assessing the findings in other organ systems as well as population-based studies assessing rates of neoplasia are needed. However, future research relies on engagement within the surgical pathology community as well as collaboration with clinicians and patients to achieve optimal results.

Objectives The objective of this review is to characterize the literature addressing postprocedural complications in persons undergoing gender-affirming surgeries. Methods A literature search using the OVID MEDLINE and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender persons from 1946 to April 2021. The studies describing postsurgical complications were categorized based on anatomic site, type of complication, study design, publication region, and date. Results Thirty-nine studies describing postsurgical complications in transgender women were identified. The most common sites of postprocedural pathology included the breasts and neovagina, with additional studies including buttocks and thighs, cutaneous sites, and the pulmonary system. Most of the literature comprised case reports, followed by case series and comparative studies. The search did not identify any studies of complications secondary to masculinizing surgeries. Conclusions This body of literature is small but growing. Most studies are case reports. There are significant gaps in the literature. The literature in this area is not yet mature enough to support a meta-analysis.