Cervicovaginal cytology, HPV testing and vaginal flora in transmasculine persons receiving testosterone
Lin, Lawrence Hsu; Zhou, Fang; Elishaev, Esther; Khader, Samer; Hernandez, Andrea; Marcus, Alan; Adler, Esther
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 28â€‰years and median time of testosterone use was 3â€‰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.
Histologic Findings in Gynecologic Tissue From Transmasculine Individuals Undergoing Gender-Affirming Surgery
Lin, Lawrence Hsu; Hernandez, Andrea; Marcus, Alan; Deng, Fang-Ming; Adler, Esther
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.
Cytologic Findings in Cervicovaginal Smears from Transmasculine Individuals Receiving Testosterone [Meeting Abstract]
Lin, L; Hernandez, A; Marcus, A; Adler, E
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]
COVID-19 Infection and Placental Histopathology in Women Delivering at Term
Patberg, Elizabeth T; Adams, Tracy; Rekawek, Patricia; Vahanian, Sevan A; Akerman, Meredith; Hernandez, Andrea; Rapkiewicz, Amy V; Ragolia, Louis; Sicuranza, Genevieve; Chavez, Martin R; Vintzileos, Anthony M; Khullar, Poonam
BACKGROUND:- There is a paucity of data describing the effects of COVID-19, especially in asymptomatic patients, on placental pathology. Although the pathophysiology of COVID-19 is not completely understood, there is emerging evidence that it causes a severe systemic inflammatory response and results in a hypercoagulable state with widespread microthrombi. We hypothesized that it is plausible that a similar disease process may occur in the fetal-maternal unit. OBJECTIVE:- The aim of this study was to determine whether COVID-19 in term patients admitted to Labor and Delivery, including women without COVID-19 symptomatology, is associated with increased placental injury compared to a cohort of COVID-19 negative controls. STUDY DESIGN/METHODS:- This was a retrospective cohort study performed at NYU Winthrop Hospital between 3/31/2020 and 6/17/2020. During the study period all women admitted to Labor and Delivery were routinely tested for SARS-CoV-2 regardless of symptomatology. The placental histopathological findings of COVID-19 patients (n=77) who delivered a singleton gestation at term were compared to a control group of term patients without COVID-19 (n=56). Controls were excluded if they had obstetric or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy or thrombophilia. Multivariable logistic regression models were performed for variables that were significant in univariable analyses. A subgroup analysis was also performed comparing asymptomatic COVID-19 cases to negative controls. RESULTS:- In univariable analyses, COVID-19 cases were more likely to have evidence of fetal vascular malperfusion, i.e. presence of avascular villi and/or mural fibrin deposition (32.5% (25/77) vs. 3.6% (2/56), p<0.0001) and villitis of unknown etiology (20.8% (16/77) vs. 7.1% (4/56), p=0.030). These findings persisted in a subgroup analysis of asymptomatic COVID-19 cases compared to COVID-19 negative controls. In a multivariable model adjusting for maternal age, race/ethnicity, mode of delivery, preeclampsia, fetal growth restriction and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the COVID-19 group (OR= 12.63, 95% CI [2.40, 66.40]). While the frequency of villitis of unknown etiology was more than double in COVID-19 cases compared to controls, this did not reach statistical significance in a similar multivariable model (OR=2.11, 95% CI [0.50, 8.97]). All neonates of mothers with COVID-19 tested negative for SARS-CoV-2 by PCR. CONCLUSIONS:- Despite the fact that all neonates born to mothers with COVID-19 were negative for SARS-CoV-2 by PCR, we found that COVID-19 in term patients admitted to Labor and Delivery is associated with increased rates of placental histopathologic abnormalities, particularly fetal vascular malperfusion and villitis of unknown etiology. These findings appear to occur even among asymptomatic term patients.
Pathologic findings after gender-affirming surgery: Evaluation of cervical pap smears and gynecological tissue from transmasculine individuals [Meeting Abstract]
Lin, L; Hernandez, A; Marcus, A; Adler, E
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
Scoring of Programmed Death-Ligand 1 Immunohistochemistry on Cytology Cell Block Specimens in Non-Small Cell Lung Carcinoma
Hernandez, Andrea; Brandler, Tamar C; Chen, Fei; Zhou, Fang; Xia, Yuhe; Zhong, Judy; Moreira, Andre L; Simms, Anthony; Sun, Wei; Wei, Xiao Jun; Simsir, Aylin
OBJECTIVES/OBJECTIVE:Recent investigations have shown strong correlations between cytology and surgical non-small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement. METHODS:PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (<1%), low positive (1%-49%), and high positive (â‰¥50%) and interrater agreement were assessed. RESULTS:Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with Îº = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (Îº = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (Îº = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters. CONCLUSIONS:There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.
Reporting of Benign Endometrial Cells in Papanicolaou Tests
Hernandez, Andrea; Schatz-Siemers, Nina; Zhou, Fang; Brandler, Tamar C; Negron, Raquel; Modi, Lopa; Elgert, Paul A; Simsir, Aylin
OBJECTIVES/OBJECTIVE:The 2014 Bethesda System (TBS 2014) guidelines for reporting cervical cytology revised the age for reporting benign endometrial cells (BECs) from 40 years or older to age 45 years or older. We evaluated this change and further investigated if extending the reporting age to 50 years or older may be acceptable. METHODS:We reviewed cases with BECs reported on Papanicolaou tests in women age 40 years or older and 45 years or older before and after implementation of TBS 2014. Follow-up endometrial biopsy/curettage results were categorized as benign, endometrial hyperplasia with or without atypia, or malignant. Hyperplasia and malignant follow-up were considered clinically significant. Clinical data were documented. Results were compared for women age 40 to 44, 45 to 49, and 50 years or older. RESULTS:Follow-up in 15 (100%) women age 40 to 44 years was benign. In women age 45 to 49 years, 61 (96.8%) had benign follow-up, one (1.6%) had atypical hyperplasia, and one (1.6%) had malignant follow-up. In women age 50 years or older, 57 (86.5%) had benign follow-up, four (6%) had malignant follow-up, and seven (7.5%) had atypical or nonatypical hyperplasia. There was a significant difference in follow-up between the age groups of 40 to 49 and 50 or older (P = .023). CONCLUSIONS:We conclude that the TBS 2014 revision was justified. Our data suggest that age 50 years or older rather than age 45 years or older may be an acceptable cutoff for reporting BECs.
Pathologic Evaluation of Breast Tissue From Transmasculine Individuals Undergoing Gender-Affirming Chest Masculinization
Hernandez, Andrea; Schwartz, Christopher J; Warfield, Dana; Thomas, Kristen M; Bluebond-Langner, Rachel; Ozerdem, Ugur; Darvishian, Farbod
CONTEXT.â€”/UNASSIGNED:Bilateral mastectomy for chest masculinization is one of the gender-affirming procedures for transmasculine individuals. OBJECTIVE.â€”/UNASSIGNED:To optimize gross handling protocols and assess histopathologic findings in transmasculine breast tissue specimens. DESIGN.â€”/UNASSIGNED:We identified all gender-affirming mastectomies from 2015 to 2018. We sequentially identified reduction mammoplasty (RM) cases for macromastia from the same period as control. Significant findings were defined as atypical ductal or lobular hyperplasia (ADH, ALH), ductal or lobular carcinoma in situ (DCIS, LCIS), or invasive carcinoma. RESULTS.â€”/UNASSIGNED:Significant findings were present in 6 of 211 gender-affirming mastectomies (2.8%) as follows: ADH (n = 5) and LCIS together with ALH (n = 1). By comparison, 19 of 273 RM specimens (7%) yielded significant findings as follows: ALH (n = 11), ADH (n = 4), LCIS (n = 2), DCIS (n = 1), and invasive lobular carcinoma (n = 1). In the gender-affirming group, 142 transmen underwent androgen therapy before surgery, of whom 2 had significant pathologic findings. Thirty and 41 individuals had a family history of breast cancer in the gender-affirming and RM group, of whom 1 and 3 individuals had significant pathologic findings, respectively. CONCLUSIONS.â€”/UNASSIGNED:Our study demonstrates that we handle transmasculine mastectomy specimens by examining 2.8 times more slides on average than for RMs, with a 2.5 times lower rate of significant pathologic findings. Prior family history of breast cancer or the use of androgen therapy before surgery in gender-affirming individuals did not increase the risk of identifying significant breast lesions. We recommend submitting 4 tissue blocks per mastectomy for individuals undergoing gender-affirming breast surgery.
Hurthle cell lesions on thyroid fine needle aspiration cytology: Molecular and histologic correlation
Schatz-Siemers, Nina; Brandler, Tamar C; Oweity, Thaira; Sun, Wei; Hernandez, Andrea; Levine, Pascale
BACKGROUND:Hurthle cell lesions often pose diagnostic challenges, despite their common occurrence on thyroid fine-needle aspiration cytology (FNAC). The associated molecular alterations are also not well understood. Therefore, our study aimed to delineate the molecular profile of HÃ¼rthle cell lesions classified as Bethesda Categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNAC and to correlate this molecular profile with surgical resection findings. METHODS:This study consisted of 188 HÃ¼rthle cell lesions with indeterminate cytology and ThyroSeqÂ® v2/v3 molecular testing results. Surgical follow-up was available for 33 cases. RESULTS:The majority of indeterminate HÃ¼rthle cell lesions had negative ThyroSeqÂ® results (61%) and were benign on available surgical follow-up. The most prevalent mutations involved the RAS gene (21%), which were associated with benign lesions, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and malignancy. The remaining mutations involved less than 18% of the cases, including PAX8/PPARG (3.7%), TSHR (3.7%), EIF1AX (2.7%), MET (2.1%), PTEN (1.6%), clonal copy number alteration (1.6%), TERT (1.1%), and 0.5% each of GNAS, PIK3CA, and TP53 mutations. On follow-up, 45% were benign, 24% were NIFTP, and 30% were malignant. The malignant cases had different molecular alterations. CONCLUSION/CONCLUSIONS:No single molecular alteration defines cytologically indeterminate HÃ¼rthle cell lesions; the majority of cases have low-risk or no molecular alterations and are benign on follow-up. These findings suggest that molecular testing may be useful, but is not definitive, in determining which cases may be managed conservatively; additional studies are needed to fully determine the negative predictive value in ruling out malignancy.
Mesonephric Remnants With Epididymis-Like Virilization in a Postmenopausal Woman
Hernandez, Andrea; Marcus, Alan