EWSR1-WT1 gene fusions in neoplasms other than desmoplastic small round cell tumor: a report of three unusual tumors involving the female genital tract and review of the literature.

Desmoplastic small round cell tumor (DSRCT) is a high-grade round cell sarcoma that typically arises in the abdominopelvic cavity of young males, co-expresses keratins and desmin, and carries a pathognomonic EWSR1-WT1 gene fusion. The EWSR1-WT1 gene fusion is generally considered specific for DSRCT, although there are two reports of this fusion in tumors otherwise lacking features of DSRCT. We report three female genital tract tumors with EWSR1-WT1 fusions but showing morphologic and immunohistochemical features incompatible with DSRCT. The tumors occurred in the uterine cervix, uterine corpus/ovaries, and vagina, respectively, of 46, 30, and 20-year-old women. Two tumors consisted of a sheet-like to fascicular proliferation of relatively uniform spindled to occasionally more epithelioid cells arrayed about thick-walled, hyalinized, and capillary-sized vessels, with distinctive areas of pseudovascular change, and absence of desmoplastic stroma. The third tumor resembled a monomorphic spindle cell sarcoma with necrosis. All had diffuse desmin and variable but more limited keratin expression, two of three expressed smooth muscle actin, and all were negative for h-caldesmon, CD10, estrogen receptor, myogenin, N-terminus WT-1, and S100 protein. One patient received neoadjuvant chemotherapy and radiation therapy followed by resection and is disease-free 42 months after diagnosis. Another patient was managed by resection only and is disease-free 9 months after initial diagnosis. The remaining patient recently underwent resection of multifocal pelvic disease. Comprehensive differential gene expression analysis on two tumors compared to two classic DSRCTs with known EWSR1-WT1 fusions resulted in 1726 genes that were differentially expressed (log2 fold change >2 or < -2) and statistically significant (FDR < 5%). In combination with previous reports, our findings suggest pleiotropy of the EWSR1-WT1 fusion is possible and not limited to DSRCT. Subsets of non-DSRCT EWSR1-WT1 positive tumors may represent discrete entities, but further study is necessary.

Fatal postpartum spontaneous liver rupture: case report and literature review.

Maternal hepatic rupture is a rare complication of pregnancy that can be fatal to both mother and child. This phenomenon is most often associated with preeclampsia/eclampsia and/or HELLP syndrome, which is defined by a collection of clinical features including hemolysis (H), elevated liver enzymes (EL), and a low platelet count (LP). These disease processes are typically identified and treated during pregnancy, often in the last trimester. The described case is unusual in that the decedent had no known history of preeclampsia/eclampsia or HELLP syndrome during this pregnancy, and she died suddenly several days postpartum of liver rupture with massive intraperitoneal hemorrhage following a routine cesarean section delivery and an uneventful hospital course. Similar cases are infrequent in the literature, which is reviewed in this report.

Detection of the JAK2V617F mutation by asymmetric PCR and melt curve analysis.

The chronic myeloproliferative disorders (CMPDs) are a heterogeneous group of clonal hematopoietic diseases characterized by production of increased numbers of mature leukocytes, erythrocytes, and/or platelets. Clinically these disorders are often insidious in onset, produce nonspecific thrombotic or hemorrhagic complications, and can be easily confused with a variety of benign, reactive conditions. Thus, confirming a CMPD can be difficult as it is often a diagnosis of exclusion. The recently identified JAK2(V617F) mutation is frequently present in the classic CMPDs polycythemia vera, essential thrombocythemia, and chronic idiopathic myelofibrosis. JAK2(V617F) determination has proven to be a useful diagnostic tool in patients with some clinical features suggestive for a CMPD, and may have benefit as a way to monitor known disease. There are several published molecular assays for the JAK2(V617F) target, of variable sensitivity and technical complexity, many of which are not easily replicated in a typical clinical laboratory. We present a robust, sensitive PCR/melt curve assay for the JAK2(V617F) mutation which uses the widely available Roche LightCycler platform, and is thus applicable to many clinical molecular laboratories.