Cervicovaginal cytology, HPV testing and vaginal flora in transmasculine persons receiving testosterone
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
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.
Evidence for Continuity of the Interstitium Through the Gynecologic Tract [Meeting Abstract]
Evidence for Continuity of the Interstitium Through the Gynecologic Tract [Meeting Abstract]
Live tumor imaging shows macrophageÂ induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination
Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. Here, we employ high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the hallmark of disseminating tumor cells. CSCs are enriched near macrophages, particularly near macrophage-containing intravasation sites called Tumor Microenvironment of Metastasis (TMEM) doorways. Substantial enrichment of CSCs occurs on association with TMEM doorways, contributing to the finding that CSCs represent >60% of circulating tumor cells. Mechanistically, stemness is induced in non-stem cancer cells upon their direct contact with macrophages via Notch-Jagged signaling. In breast cancers from patients, the density of TMEM doorways correlates with the proportion of cancer cells expressing stem cell markers, indicating that in human breast cancer TMEM doorways are not only cancer cell intravasation portals but also CSC programming sites.
Cytologic Findings in Cervicovaginal Smears from Transmasculine Individuals Receiving Testosterone [Meeting Abstract]
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]
Pathologic findings after gender-affirming surgery: Evaluation of cervical pap smears and gynecological tissue from transmasculine individuals [Meeting Abstract]
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
Lessons Learned From an Anatomic Pathology Department in a Large Academic Medical Center at the Epicenter of COVID-19
Many state-wide, city-wide, and hospital-wide changes have been implemented due to the ongoing COVID-19 crisis. We describe lessons learned in an anatomic pathology division at a tertiary care center during the peak of the COVID-19 pandemic in the hopes that knowledge of our experiences can benefit other pathology departments as they encounter this pandemic. Five categories that are critical in strategic planning for the COVID-19 pandemic are discussed: workload, departmental policy revisions, impact on faculty, workforce staffing, and impact on educational programs, including residency and fellowship training. Although the volume of COVID-19 testing had grown placing increased demands on the clinical pathology laboratory, the volume of anatomic pathology cases had declined during the COVID-19 peak. Lessons learned were widespread including changes in the anatomic pathology workflow due to declining surgical and cytologic case volumes and increases in autopsy requests. Modifications were required in gross room policies, levels of personal protective equipment, and workforce. Travel and meeting policies were impacted. Adaptations to residency and fellowship programs were vast and included innovations in didactic and interactive education. We must learn from our experiences thus far in order to move forward, and we hope that our experiences in an anatomic pathology department in the epicenter of the COVID-19 pandemic can help other pathology departments across the country.
Effects of Image Quantity and Image Source Variation on Machine Learning Histology Differential Diagnosis Models
Aims/UNASSIGNED:Histology, the microscopic study of normal tissues, is a crucial element of most medical curricula. Learning tools focused on histology are very important to learners who seek diagnostic competency within this important diagnostic arena. Recent developments in machine learning (ML) suggest that certain ML tools may be able to benefit this histology learning platform. Here, we aim to explore how one such tool based on a convolutional neural network, can be used to build a generalizable multi-classification model capable of classifying microscopic images of human tissue samples with the ultimate goal of providing a differential diagnosis (a list of look-alikes) for each entity. Methods/UNASSIGNED:We obtained three institutional training datasets and one generalizability test dataset, each containing images of histologic tissues in 38 categories. Models were trained on data from single institutions, low quantity combinations of multiple institutions, and high quantity combinations of multiple institutions. Models were tested against withheld validation data, external institutional data, and generalizability test images obtained from Google image search. Performance was measured with macro and micro accuracy, sensitivity, specificity, and f1-score. Results/UNASSIGNED:In this study, we were able to show that such a model's generalizability is dependent on both the training data source variety and the total number of training images used. Models which were trained on 760 images from only a single institution performed well on withheld internal data but poorly on external data (lower generalizability). Increasing data source diversity improved generalizability, even when decreasing data quantity: models trained on 684 images, but from three sources improved generalization accuracy between 4.05% and 18.59%. Maintaining this diversity and increasing the quantity of training images to 2280 further improved generalization accuracy between 16.51% and 32.79%. Conclusions/UNASSIGNED:This pilot study highlights the significance of data diversity within such studies. As expected, optimal models are those that incorporate both diversity and quantity into their platforms.s.
Lepidic-Like Pattern of Metastasis in Solitary Pulmonary Nodules: A Systematic Review with Radiologic-Pathologic Correlation of a Deceptive Phenomenon [Meeting Abstract]