Faculty Bibliography

To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) ≥1% and combined positive score (CPS) ≥1 were considered positive for PD-L1. CD8+ TILs were counted in each core, and CD8+ TIL density (CD8TILD) was calculated. Cases were classified as CD8Neg (<1.4/mm2 CD8TILD), CD8Pos (≥1.4/mm2 CD8TILD) and CD8HIGH (≥14/mm2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1Pos/CD8Pos, (2) PD-L1Neg/CD8Neg, (3) PD-L1Pos/CD8Neg, and (4) PD-L1Neg/CD8Pos. PD-L1 expression by TPS and CPS was detected in 19.8% and 39.6% cases, respectively. Kaplan-Meier curves with log-rank analysis showed that higher density of CD8+ TILs were associated with longer overall survival (OS) (P=0.05 for CD8Pos and P=0.014 for CD8HIGH), and CD8HIGH status was associated with longer OS irrespective of tumor stage (P=0.045, hazard ratio: 0.11, 95% confidence interval: 0.014-0.951). Thirty-three percent of patients belonged to TIME group 1. PD-L1 expression and TIME groups were not associated with OS or progression-free survival. We found that high density of CD8+ TILs is an independent indicator of better OS. In 33% cases PD-L1 expression is associated with increased CD8+ TILs ("acquired immune evasion" pattern of PD-L1 expression), hence they may benefit from anti PD-1/PD-L1 therapy. PD-L1 expression alone and TIME groups do not affect survival in gynecologic carcinosarcoma.

BACKGROUND:Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone. METHODS:This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes. RESULTS:The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL. CONCLUSION/CONCLUSIONS:Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.

CONTEXT.—/UNASSIGNED:Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs. OBJECTIVE.—/UNASSIGNED:To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens. DESIGN.—/UNASSIGNED:This is an institutional review board-approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists. RESULTS.—/UNASSIGNED:Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18-56) and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy. CONCLUSIONS.—/UNASSIGNED:A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population.

Introduction: Testosterone therapy is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies demonstrated that testosterone can induce morphologic changes in the genital tract. Here, we aim to evaluate cervicovaginal cytology specimens from transmasculine individuals receiving testosterone.
Material(s) and Method(s): This is a retrospective study that included 33 transmasculine individuals receiving testosterone with available cervicovaginal cytology reports or slides for review from 2013 to 2021.
Result(s): The median age was 28 years (range: 19-56) and median time of testosterone use was 2.6 years (range: 0.3-25). Thirty-five cervicovaginal cytology reports were included with the following results: 25 negative for intraepithelial lesion or malignancy (71%), 3 atypical squamous cells of undetermined significance (ASCUS) (9%), 2 high-grade squamous intraepithelial lesion (HSIL) (6%), and 5 unsatisfactory (14%). Endocervical component was present in 74% of cases (36/35). Among 19 available HPV tests, 5 were positive for high-risk HPV (2 negative, 1 ASCUS and 2 HSIL), and 14 were negative (11 negative, 1 ASCUS and 2 unsatisfactory). No evidence of other cervicovaginal infection was detected. After reviewing slides of 18 cases, additional findings not included in pathology reports were noted. Atrophy (Figure 1A), a known mimicker of HSIL, was present in 94% (17/18), including those with ASCUS (Figure 2A) and HSIL (Figure 2B). Glycogenated cells (Figure 1B), which can be mistaken for koilocytes, were seen in 22% (4/18). Lactobacilli were substantially decreased in 94% (17/18) (Figure 3A, 3B).
Conclusion(s): Our study cohort demonstrated a high percentage of abnormal cervicovaginal smears in transmasculine persons receiving testosterone. Changes following testosterone administration can represent diagnostic pitfalls of squamous lesions. Testosterone seems to induce changes in the vaginal flora. [Formula presented] [Formula presented] [Formula presented]
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Background: Gender affirming surgery is part of a multidisciplinary approach in the gender transition process, allowing patients to align their physical anatomy to their internal sense of identity. Our study evaluates the cytology and histopathology of transmasculine gynecological specimens. A deeper examination of the pathologic findings may strengthen care for transmasculine individuals and increase our understanding of the influence of hormonal therapy in specific organs.
Design(s): This is an IRB-approved retrospective study that included all transmasculine individuals undergoing a gender-affirming gynecological surgery from January 2015 to June 2020. All surgical pathology and cytology slides were reviewed. Clinical data were retrieved from electronic health records.
Result(s): Forty patients were identified with a median age of 26.5 years (range 17-56) and a median body mass index of 25.38 kg/m2 (range 18.9 - 43.4). The majority of patients were white (52%), were receiving androgen therapy for at least 6 months (95%) and had a previous bilateral mastectomy (92%). The histologic samples comprised of 40 uteri, 40 bilateral fallopian tubes and 36 bilateral ovaries. The overall findings are summarized in table 1. The majority of the endometria were inactive (75%) with significant stromal fibrosis (80%). Some patients showed evidence of cycling endometrium with proliferative (17.5%) and secretory (7.5%) patterns. The most common findings in the ovaries were the presence of multiple bilateral cystic follicles (50%), stromal hyperplasia (14%) and of corpora lutea (14%). The most common findings in the cervix was transitional metaplasia (42.5%). Of the 8 available cervical cytology specimens, 2 were unsatisfactory, 4 were negative for intraepithelial lesion or malignancy and 2 had atypical squamous cells of undetermined significance (ASC-US).
Conclusion(s): Despite prolonged use of androgens, endometria in transmasculine individuals may show cycling activity with proliferative and secretory patterns. The presence of multiple bilateral cystic ovarian follicles provides evidence that androgens can result in abnormal follicular development, similar to polycystic ovary syndrome. The chronic use of androgens in young individuals seems to induce transitional metaplasia in the cervix, which can impact cervical cytology results including increase the percentage of unsatisfactory samples and ASC-US and has the potential to mimic high-grade squamous dysplasia

Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.

Fine needle aspiration cytology (FNAC) of mediastinal masses allows for rapid on-site evaluation and the triaging of material for ancillary studies. However, surgical pathology is often considered to be the gold standard for diagnosis. This study examines the sensitivity and specificity of FNAC compared to a concurrent or subsequent surgical pathology specimen in 77 mediastinal lesions. The overall sensitivity for mediastinal mass FNAC was 78% and the overall specificity was 98%. For individual categories the sensitivity and specificity of FNAC was respectively as follows: inflammatory/infectious (33%, 99%), metastatic carcinoma (93%, 100%), lymphoma (84%, 97%), cysts (25%, 100%), soft tissue tumors (100%, 100%), paraganglioma (50%, 100%), germ cell tumor (100%, 99%), thymoma (87%, 94%), thymic carcinoma (60%, 100%), benign thymus (0%, 100%), and indeterminate (100%, 90%). For different locations within the mediastinum the sensitivity and specificity of FNAC was respectively as follows: anterosuperior mediastinum (80%, 98%), posterior mediastinum (33%, 95%), middle mediastinum (100%, 100%), and mediastinum, NOS (79%, 99%). Thus, mediastinal FNAC is fairly sensitive, very specific, and is a valuable technique in the diagnosis of mediastinal masses.