An Epithelioid Smooth Muscle Neoplasm Mimicking a Signet Ring Cell Carcinoma in the Ovary.

A 53-yr-old woman who presented with elevated renal indices was discovered to have a 4.5 cm right renal mass and an incidental 9.7 cm left ovarian mass on imaging studies. She underwent a partial nephrectomy and bilateral salpingo-oophorectomy, revealing a chromophobe renal cell carcinoma and an unusual ovarian neoplasm with epithelioid cells displaying prominent signet ring cell-like morphology. Immunohistochemical analysis of the ovarian neoplasm demonstrated that the tumor cells were diffusely immunoreactive for smooth muscle markers and negative for all tested cytokeratins and epithelial membrane antigen. On the basis of these results, the tumor was interpreted as an unusual epithelioid smooth muscle neoplasm with extensive signet ring cell-like features. Along with primary ovarian signet ring stromal tumors and sclerosing stromal tumors, this example adds epithelioid smooth muscle neoplasms with unusual cytologic alterations to the list of uncommon nonepithelial tumors that can simulate metastatic signet ring cell carcinoma (Krukenberg tumor) in the ovary.

Clinicopathologic Features and Genetic Alterations of a Primary Osteosarcoma of the Uterine Corpus.

Primary osteosarcoma (OS) of the uterus is distinctly rare. We report a case of primary uterine OS with pulmonary metastasis in a 74-yr-old woman. Histopathologic features of the uterine tumor were in keeping with a pure chondroblastic OS composed of neoplastic cells with osteoblastic/chondroblastic differentiation and neoplastic bone formation. Despite treatment with Doxorubicin and Olaratumab and later with palliative radiation therapy, the patient died 7 mo after hysterectomy due to multiple distant metastases. A targeted next-generation sequencing assay based on a 637-gene panel was performed to analyze genetic alterations in this highly aggressive tumor, but no somatic mutations that are amenable to targeted therapy were detected. Rather, a 51-nucleotide deletion mutation including partial exon 2 of mediator complex subunit 12 (MED12), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified. Given the MED12 mutation in this uterine OS, we propose possible mechanisms that account for the origin and development of this tumor.

Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.

Polyomavirus Replication and Smoking Are Independent Risk Factors for Bladder Cancer After Renal Transplantation.

BACKGROUND: Solid organ transplant recipients are at increased risk for developing malignancies. Polyomaviruses (PV) have been historically associated with experimental tumor development and recently described in association with renourinary malignancies in transplant patients. The aim of this study was to investigate the relationship between PV replication and smoking, and the development of malignant neoplasms in kidney transplant recipients. METHODS: A retrospective case-control study was conducted for PV replication in all kidney biopsies and urine cytologies performed between 1998 and 2014 from kidney transplant recipients at the University of Maryland Medical Center. Polyomavirus-positive patients (n = 943) were defined as having any of the following: a kidney biopsy with PV associated nephropathy, any urine cytology demonstrating "decoy" cells, and/or significant polyomavirus BK viremia. Polyomavirus-negative matched patients (n = 943) were defined as lacking any evidence of PV replication. The incidence of malignancy (excluding nonmelanoma skin tumors) was determined in these 1886 patients and correlated with demographic data and history of smoking. RESULTS: There was a 7.9% incidence of malignant tumors after a mean posttransplant follow-up of 7.9 ± 5.4 years. Among all cancer subtypes, only bladder carcinoma was significantly associated with PV replication. By multivariate analysis, only PV replication and smoking independently increased the risk of bladder cancer, relative risk, 11.7 (P = 0.0013) and 5.6 (P = 0.0053), respectively. CONCLUSIONS: The findings in the current study indicate that kidney transplant recipients with PV replication and smoking are at particular risk to develop bladder carcinomas and support the need for long-term cancer surveillance in these patients.