Differences in single gene expression patterns and signaling pathways between Black and White patients in high grade endometrioid endometrial cancer independent of BMI.

Objective: Endometrial cancer (EC) incidence and mortality are increasing with striking racial disparities. Race and obesity are known risk factors for EC, however, their relationship and impact on tumor biology in higher grade endometrioid EC are unclear. The objective of this pilot study was to identify gene- and pathway-level changes in tumors from Black patients compared to White, both in general and in the context of dichotomized BMI. Methods: A single institution retrospective convenience sample was obtained for grade 2 or 3 endometrioid EC, equally distributed amongst Black and White patients. Tumor samples were analyzed with the Tempus Laboratories xT NGS-based genome profiling test. DESeq2 was applied to identify differentially expressed genes, and then subjected to ingenuity pathway analysis (IPA). Continuous variables were analyzed using unpaired t-tests, and categorical using Chi-squared and Fisher exact tests. Results: 39 representative cases were identified and analyzed from 2006 to 2021. Baseline clinicopathologic characteristics were similar. 157 genes were differentially expressed in tumors from Black patients compared to White regardless of BMI. IPA identified 81 significantly different pathways between Black and White patients with a BMI < 40 kg/m2, and 117 with a BMI ≥ 40 kg/m2. Of these, eleven pathways were consistently and significantly activated or deactivated regardless of BMI. Conclusion: Differences in gene expression and pathway activation in EC exist between race and BMI, which highlights the need for further research to better understand the implications of these differences on endometrioid EC progression, outcomes, and treatment in this historically underserved patient population.

Does the Vaginal Microbiome Operate Differently by Race to Influence Risk of Precervical Cancer?

Background: The vaginal microbiome (VMB) plays an important role in the persistence of human papillomavirus (HPV) infection and differs by race and among women with cervical intraepithelial neoplasia (CIN). Materials and Methods: We explored these relationships using 16S rRNA VMB taxonomic profiles of 3050 predominantly Black women. VMB profiles were assigned to three subgroups based on taxonomic markers indicative of vaginal wellness: optimal (Lactobacillus crispatus, L. gasseri, and L. jensenii), moderate (L. iners), and suboptimal (Gardnerella vaginalis, Atopobium vaginae, Ca. Lachnocurva vaginae, and others). Multivariable Firth logistic regression models were adjusted for age, smoking, VMB, HPV, and pregnancy status. Results: VMB prevalence by subgroup was 18%, 30%, and 51% for the optimal, moderate, and suboptimal groups, respectively. In fully adjusted models, the risk of CIN grade 3 (CIN3) among non-Latina (nL) Blacks was twice that of nL Whites (odds ratio [OR] = 2.0, 95% confidence interval [CI]: 1.1, 3.9, p = 0.02). The VMB modified this association (p = 0.04) such that the risk of CIN3 was significantly higher for nL Blacks than for nL Whites only among women with optimal VMBs (OR = 7.8, 95% CI: 1.7, 74.5, p = 0.007). Within racial groups, the risk of CIN3 was only elevated among nL White women with suboptimal VMBs (OR = 6.0, 95% CI: 1.3, 56.9, p = 0.02) compared with their racial counterparts with optimal VMBs. Conclusions: Our findings suggest that race is a modifier of the VMB in HPV carcinogenesis. An optimal VMB does not appear to be protective for nL Black women compared with nL White women.

Emergomyces pasteurianus in Man Returning to the United States from Liberia and Review of the Literature.

A 65-year-old man with HIV sought treatment for fever, weight loss, and productive cough after returning to the United States from Liberia. Fungal cultures grew Emergomyces pasteurianus, and the patient's health improved after beginning voriconazole. We describe the clinical case and review the literature, treatment, and susceptibilities for E. pasteurianus.

Cutaneous endosalpingiosis arising from C-section scar: A case report with review of literature.

Endosalpingiosis is a pathologic phenomenon in which non-neoplastic fallopian tube epithelium implants in ectopic locations. It is an uncommon and poorly understood condition, with most cases occurring within the abdominopelvic cavity. Cutaneous presentations of endosalpingiosis are even more rare, with only six cases described in international literature to-date. This report describes an additional case of cutaneous endosalpingiosis. The lesion arose within the scar tissue of a Pfannenstiel incision from 4 years prior in a 24-year old, previously healthy African American female. Punch biopsy of the lesion revealed a cystic mass lined by PAX8+ ciliated columnar cells and a surrounding fibrotic stroma with focal CD10-positivity, consistent with a histopathologic diagnosis of endosalpingiosis. In addition, this report provides a comprehensive review of the other documented cases of cutaneous endosalpingiosis, as well as the proposed pathogenesis, histopathologic and clinical features, and potential treatment avenues for this unique clinical entity.

Usefulness of Cyclin D1/Podoplanin Dual Immunohistochemical Stain to Differentiate Malignant Mesothelioma From Reactive Mesothelial Proliferations.

OBJECTIVES: To examine the potential of cyclin D1/podoplanin dual immunohistochemical stain to differentiate malignant mesothelioma from reactive mesothelial proliferations. METHODS: Cyclin D1/podoplanin dual immunohistochemistry was performed on 34 surgical cases of reactive mesothelial proliferations, malignant mesothelioma, and nonmesothelioma malignancies. RESULTS: All 15 reactive mesothelial proliferations demonstrated less than 50% cyclin D1 staining with variable to diffuse podoplanin staining. In 6 (60%) of 10 cases of epithelioid malignant mesothelioma, the dual stain supported the diagnosis. Less than 50% cyclin D1 staining was noted in the remaining four cases, including small biopsy specimens or cases with focal papillary architecture. The five cases of sarcomatoid/desmoplastic/biphasic mesothelioma showed more than 50% cyclin D1 staining with focal to absent podoplanin staining. Well-differentiated papillary mesothelioma appears to demonstrate less than 25% cyclin D1 staining. CONCLUSIONS: The cyclin D1/podoplanin dual stain is reliable and may be used to aid in differentiation of benign mesothelial proliferations from malignant tumors. In addition, histologic features and other ancillary testing may support the classification of cases with an inconclusive cyclin D1/podoplanin staining.

Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report.

This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3+) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.

Fine needle aspiration and core needle biopsy of the spleen: A case series illustrating current practices and challenges.

INTRODUCTION: Splenic fine needle aspiration (FNA) and core needle biopsies (CNB) are rare specimen types, potentially avoided due to clinical concern for hemorrhagic complications. The safety and utility of splenic FNA, the role of rapid onsite evaluation (ROSE), as well as the diagnostic utility of CNB versus FNA have not been recently reviewed. MATERIALS AND METHODS: A 10-year retrospective review was performed of percutaneous image-guided FNA and CNB of the spleen. Clinical indications, outcomes, ROSE findings, and final diagnoses were reviewed and correlated. RESULTS: Forty-four specimens from 39 patients were identified. The commonest indication for biopsy was a radiographic mass found during assessment for patient complaint (45%, 20/44), evaluation for malignancy (primary or metastatic) (39%, 17/44), and incidentally (16%, 7/44). Malignant diagnoses were rendered in 10 cases, 80% hematolymphoid and 20% nonhematolymphoid. Thirty-one cases were nonneoplastic and identified as infectious/inflammatory processes 39%, cysts 10%, vascular lesions 13%, benign splenic elements 22%, accessory or atrophic spleen 10%, and extramedullary hematopoiesis 6%. The nondiagnostic rate was 7%. Cases with subsequent splenectomy showed 100% specificity and 86% sensitivity. The concordance of ROSE and final interpretation was 90% within the neoplastic category. Finally, the significant complication rate was 6.8% with no bias to occurrence following FNA or CNB. CONCLUSIONS: This series affirms the safety and efficacy of splenic FNA and CNB by complication rates comparable to prior studies and high rate of concordance. The diagnostic accuracy may be further improved by ROSE, and CNB in cases reliant on staining and tissue architecture.

Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples.

Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this disease has not been well-characterized. B-Myb is associated with cell proliferation through formation of the MMB (Myb and MuvB core) protein complex required for transcription of mitotic genes. High B-Myb expression disrupts the formation of another transcriptional cell cycle regulatory complex involving the MuvB core, DREAM (DP, RB-like, E2F, and MuvB), in human cell lines. DREAM coordinates cell cycle dependent gene expression by repressing over 800 cell cycle genes in G0/G1. Here, we take a bioinformatics approach to further evaluate the effect of B-Myb expression on DREAM target genes in HGSOC and validate our cellular model with clinical specimens. We show that MYBL2 is highly expressed in HGSOC and correlates with expression of DREAM and MMB target genes in both The Cancer Genome Atlas (TCGA) as well as independent analyses of HGSOC primary tumors (N = 52). High B-Myb expression was also associated with poor overall survival in the TCGA cohort and analysis by a DREAM target gene expression signature yielded a negative impact on survival. Together, our data support the conclusion that high expression of MYBL2 is associated with deregulation of DREAM/MMB-mediated cell cycle gene expression programs in HGSOC and may serve as a prognostic factor independent of its cell cycle role. This provides rationale for further, larger scale studies aimed to determine the clinical predictive value of the B-Myb gene expression signature for treatment response as well as patient outcomes.

Vulvar Hibernoma: An Unusual Lipomatous Tumor in an Adolescent.

BACKGROUND: Lipomatous tumors of the vulva are exceedingly rare, particularly in adolescents. We describe the work-up and management of an adolescent girl who presented with a large, well-vascularized vulvar mass. CASE: A 14-year-old girl presented with a large vulvar mass of unclear etiology. Magnetic resonance imaging of this mass revealed an ill-defined, well-vascularized mass with fat signal characteristics suggestive of a lipomatous tumor that was concerning for malignancy. We performed complete resection of the mass, and histologic evaluation revealed a vulvar hibernoma. There have been no signs of recurrence 1 year later. SUMMARY AND CONCLUSION: Although rare, a hibernoma of the vulvar region may present in adolescence and may be concerning for malignancy on imaging. Complete resection of these tumors is recommended for definitive diagnosis and treatment.

Criteria for Risk Stratification of Vulvar and Vaginal Smooth Muscle Tumors: An Evaluation of 71 Cases Comparing Proposed Classification Systems.

Accurate risk stratification of smooth muscle tumors (SMTs) is essential for appropriate patient management. Yet, the rarity of SMTs of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar SMTs and 1 for vaginal SMTs have been proposed, it is our experience that many pathologists tend to apply criteria for uterine SMTs when evaluating vulvovaginal tumors. We retrospectively reviewed a large cohort of vulvovaginal SMTs with clinical follow-up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow-up was available for 63 patients (89%), and ranged from 1 to 234 months (median: 64 mo). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying tumors as nonsarcoma according to patient outcome. We recommend that uterine SMT criteria and nomenclature be adopted for evaluation and classification of vulvovaginal SMTs.

Cytopathologic features of clear cell papillary renal cell carcinoma: A recently described variant to be considered in the differential diagnosis of clear cell renal epithelial neoplasms.

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a distinctive variant of renal cell carcinoma that has been formally adopted by the new Word Health Organization classification. An emerging consensus has documented its particularly indolent course and emphasized its separation from conventional clear cell renal cell carcinoma (CCRCC) for treatment planning. CCPRCC features in cytologic preparations have not been studied. METHODS: This study retrospectively identified a series of CCPRCCs that had cytology samples before the histopathologic diagnosis and reviewed corresponding cytologic materials, including aspirate smears, cell block materials, touch preparations, and core biopsy samples. The identified clinicopathologic and cytologic features were tabulated. RESULTS: Five cases of CCPRCC with cytopathologic materials were identified from 4 women and 1 man aged 34 to 70 years (2 with end-stage renal disease), and the sampled lesions were 1.8 to 11.0 cm. The original cytopathologic diagnostic considerations ranged from atypical cyst-lining cells to angiomyolipoma to CCRCC and CCPRCC. The aspirate and touch preparation samples showed scant cellularity with scattered sheets and clusters of small, bland epithelial cells (much smaller than admixed renal tubular cells) with optically clear cytoplasm (lacking conspicuous cytoplasmic vacuolization) and small, grade 1 nuclei. The cell block materials and the core biopsy samples showed cyst walls with prominent myomatous stroma lined by low-grade epithelium with optically clear cytoplasm, inverse nuclear polarization, and a characteristic cytokeratin 7-positive/carbonic anhydrase IX-positive phenotype. Three cases were treated with resection, 1 case was treated with ablation, and 1 case was under surveillance. CONCLUSIONS: CCPRCC demonstrates recognizable cytomorphologic features and merits consideration in the cytologic differential diagnosis for kidney lesions. With increasing experience, more conservative management may be contemplated. Cancer Cytopathol 2016;124:565-72. © 2016 American Cancer Society.

Histopathology of Bipolar Radiofrequency Ablation in the Human Atrium.

BACKGROUND: The Cox maze IV operation has become the preferred surgical treatment for atrial fibrillation, as it is associated with less morbidity and complexity than the Cox maze III procedure, yet is still highly effective. Numerous studies have been conducted in animals to examine the histopathology of this operation on the heart but studies on human hearts that have undergone the Cox maze IV operation have not been performed. METHODS: We report the histopathologic findings in 3 patients from whom tissue was available for histologic study. In 2 patients it was obtained at autopsy within a month after undergoing a Cox maze IV operation, and in the remaining patient, atrial tissue was obtained immediately after ablation. RESULTS: The lesions were clearly visible on the atria at day 6 and day 18. Microscopic examination showed that the hearts were in different stages of healing. We also found that, compared with animal models, human myocardium had significant preexisting underlying damage with myocyte hypertrophy and fibrosis. Although most of the ablative lesions were transmural, not all spanned from the epicardium to the endocardium. The chronic changes present in these hearts may have prevented transmurality by impeding energy delivery from fully penetrating the tissue. CONCLUSIONS: The atrial myocardial substrate studied in experimental conditions is markedly different from the human hearts that frequently express histopathologic changes secondary to the underlying disease process. That may prevent creating true transmural lesions and impact final efficacy of the procedure.