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Objectives: Differentiated vulvar intraepithelial neoplasia (dVIN) is implicated as a precursor to HPV-negative squamous cell carcinoma of the vulva (SCCV). It has a variable clinical course that has not yet been fully characterized. Data on the clinical and histopathologic features of dVIN, risk of recurrence and progression to SCCV is limited. Our objective was to describe the natural history of dVIN and evaluate predictors of recurrence and disease progression to carcinoma in a cohort of women with histologically confirmed disease. Methods: Under an IRB-approved protocol, we retrospectively identified 27 patients with biopsy-proven dVIN from 2011 to 2020. Cases were independently reviewed by 2 gynecologic pathologists. Demographics, histopathologic features including immunohistochemical (IHC) staining for p16, p53, ER/PR and GATA 3 and clinical course were abstracted. Patients were followed with semi-annual exams and biopsies at the discretion of their gynecologic provider. Results: Median age of the cohort was 70 years (range 43-91). Median follow-up time was 4 months (range 1-21). All women were Caucasian. The majority of women had concurrent lichen sclerosus (LS) adjacent to dVIN (81%). No specific primary treatment (topical versus surgical excision) was superior in preventing recurrence or progression to SCCV. 67% of women had recurrent dVIN at a median of 8 months from the initial diagnosis. 10 women had SCCV during the study period: 4 (15%) at primary diagnosis adjacent to dVIN, and 6 (22%) progressed to SCCV. Median time to progression was 34 months (range 1-120). P53 mutation (including p53 overexpression or p53 null) was associated with progression to SCCV (p Download : Download high-res image (134KB) Download : Download full-size image Conclusions: dVIN has a potentially agressive clinical course with a high risk of recurrence and progression to SCCV, despite treatment. Coexisting LS can challenge accurate histologic interpretation mandating a thorough evaluation to exclude coexisting SCCV. Close surveillance with a low threshold for biopsies in women with dVIN is warranted given that 22% progressed to cancer. In this cohort of patients, there were no clear clinical predictors of recurrence or progression to cancer based upon traditional risk factors for lower gentical tract dysplasia. GATA 3 IHC staining may be a useful marker to identify and triage patients with the highest risk of recurrence or progression to SCCV to more intense surveillance.

Low-grade endometrial stromal sarcoma (LGESS) is a rare malignant uterine tumor with the potential to metastasize years after the primary resection. There is a broad differential diagnosis for endometrial stromal sarcomas (ESS), including both benign and malignant entities. Herein, we present the case of a 64-year-old female with metastatic LGESS to the lung, diagnosed by cytology, 24 years after her initial presentation. This report discusses the cytomorphologic and histopathologic characteristics, and ancillary studies including immunohistochemical stains and recent advances in molecular diagnostics of ESS. Accurate diagnosis of spindle cell lesions in the lung can be challenging. As such, this case highlights the instrumental role of ancillary testing and molecular diagnostics to achieve a more definitive diagnosis.

Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. When it metastasizes, it usually spreads to bone and/or lymph nodes. A handful of cases have described prostatic metastases to the lung; however, this is usually in the setting of existing bone lesions [1]. Here we describe a unique case in which a patient was found to have both metastatic prostate cancer to the lung and a primary lung cancer in the absence of any other evidence of extra-prostatic disease.

Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome.

Intracardiac abscess resulting in complete heart block is an infrequent complication of infective endocarditis. Most presentations of endocarditis are limited to valvular and perivalvular structures, with varying degrees of heart block occurring in the minority of cases. We report a case of endocarditis manifesting as chest pain associated with ST segment elevation and complete heart block. The patient expired unexpectedly within a few hours of presentation. Postmortem examination revealed an atrial septal abscess, purulent pericardial collection, and fibrinous pericarditis. Spread of the abscess into the atrial septum was postulated to be the cause of the complete heart block. In endocarditis, the ominous development of heart block and a poor response to antibiotic therapy imply significant extension of the infection. Management therefore requires prompt ventricular pacing with consideration for valve replacement and possible pericardial drainage.

A 50-year-old man with impaired fasting glucose and Sweet syndrome presented for an annual physical examination. Remarkably, his hemoglobin A1c (HbA1c) concentrations had decreased from 5.7%, 17 months prior, to 4.0%, despite continued impaired fasting glucose concentrations. While there were no additional HbA1c measurements in the intervening 17 months, a gradual decrease in total hemoglobin concentration over the prior 9 months was noted (Figure …