Neuroepithelial tumor with EWSR1-BEND2 fusion: Case report and review of literature

A 26-year-old female initially presented at an outside institution with migraines and blurry vision four years ago. Imaging revealed a 4.5 cm frontal lobe mass. Pathology of the mass was consistent with a poorly differentiated epithelial neoplasm with focal neuroendocrine features. She underwent extensive but unsuccessful workup in search of a possible primary lesion. The patient declined radiation to the tumor bed at that time. Three years later, her symptoms advanced to bilateral blindness. Imaging of her brain showed progression of the disease with multifocal enhancing masses. Reexcision in our institution showed a cellular and circumscribed neoplasm composed of small to medium cells in nests and interconnected follicular/cribriform structures with luminal eosinophilic material. The tumor cells showed strong and diffuse immunoreactivity for epithelial markers (EMA, Cam5.2) and patchy immunoreactivity to CD56 while being negative for all neural and glial markers including synaptophysin and GFAP. The MIB-1 proliferation index was 3%. FISH for isochromosome 12p was negative. NGS analysis revealed an in frame fusion of exon 7 of Ewing sarcoma breakpoint region 1 gene (EWSR1) on chromosome 22 with exon 2 of BEN domain containing 2 (BEND2) on chromosome X as a result of t(X; 22) (p22; q12). This novel fusion has been identified in subsets of astroblastomas in spinal cord, brain stem and cerebrum. This tumor, while circumscribed, did not show astroblastoma like rosettes or hyalinization. There was no immunohistochemical evidence of glial or neuronal differentiation. The prominent epithelial differentiation led to an exhaustive but unsuccessful search for a primary. Our case adds to the spectrum of morphological and immunohistochemical findings seen in this emerging group of tumors

The need for rapid cytogenetics in the era of vyxeos therapy for acute myeloid leukemia with myelodysplasia related changes (AML-MRC)

Background: AML-MRC criteria includes i) history of Myelodysplastic syndrome (MDS) or Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN) or ii) MDS- related cytogenetic abnormality or iii) Multilineage dysplasia (\u3e50 % dysplasia in at least 2 lineages). Recently, the drug Vyxeos was approved for the treatment of adults with newly diagnosed therapy related AML or AML-MRC and confers a significantly better survival than standard therapy. We aimed to identify the proportion of cases diagnosed as AML-MRC solely based on MDS associated cytogenetic abnormality (i.e. not meeting the morphologic criteria and/or not having history of MDS or MDS/MPN). Design: A cohort of 64 AML-MRC cases were re-examined morphologically to assess for and exactly quantify the degree of dysplasia. We examined bone marrow aspirate smears, touch preps, bone marrow biopsy and clot sections to assess for dysplasia. We categorized dysplasia into three categories; less than 10%, 10-50% and \u3e50%. The other categories were normal/no dysplasia and not enough nonblast cells to accurately assess for dysplasia. Results: Out of 64 cases of AML- MRC, 53 had complex cytogenetics (83%), 5 had del (5q) or t (5q) (8%), 4 cases had -7 or del (7q) (6%) and 2 had other MDS associated abnormalities (3%). Only 30% of cases had more than 50% dysplasia in two or more lineages. 70% of cases required either a relevant clinical history (MDS or MDS/MPN) or MDS associated cytogenetic abnormalities for AML-MRC diagnosis. More than 50% dysplasia in two lineages was seen in 34% of cases with complex cytogenetics, 20% of del (5q)/ t(5q) cases and 0% of -7/ del (7q) cases. Most frequently reported dysplastic cell line was myeloid (45%) followed by megakaryocytic (38%) followed by erythroid (16%). 22% of cases had cytogenetic abnormalities other than those tested on a routine MDS or AML FISH panel. Conclusions: 63% of our cases needed an MDS associated cytogenetic abnormality to render a diagnosis of AML-MRC. 22% of cases had cytogenetic abnormalities which would have been missed on a routine MDS or AML FISH panel. In the absence of an AML-MRC diagnosis, patients are put on the standard 7+3 chemotherapy regimen and cannot be generally switched to Vyxeos at a later time. Considering the routine turnaround time of 7-21 days for conventional chromosomal analysis, it is imperative to have a preliminary cytogenetic result (generally 5 cell based) or a rapid chromosomal microarray analysis within 2-3 days of AML diagnosis to enable Vyxeos therapy

Lack of alloimmunization to the D antigen in D-negative orthotopic liver transplant recipients receiving D-positive red blood cells perioperatively

BACKGROUND AND OBJECTIVES: D-negative patients undergoing orthotopic liver transplantation (OLT) might require a large number of red blood cell (RBC) units, which can impact the inventory of D-negative blood. The blood bank might need to supply these patients with D-positive RBCs because of inventory constraints. This study evaluates the prevalence of anti-D formation in D-negative OLT patients who received D-positive RBCs perioperatively, as this will assist in successful patient blood management. MATERIALS AND METHODS: This was a retrospective study performed at a single academic medical centre. Electronic medical records for all 1052 consecutive patients who underwent OLT from January 2007 through December 2017 were reviewed. D-negative patients who were transfused perioperatively with D-positive RBCs and had antibody screening at least 30 days after transfusion were included. RESULTS: Of a total of 155 D-negative patients, 23 (14.8%) received D-positive RBCs perioperatively. Seventeen patients were included in the study. The median age was 54 years (range 36-67 years); 13 (76.5%) were male. The median number of D-positive RBC units transfused perioperatively was 7 (range 1-66 units). There was no evidence of D alloimmunization in any patient after a median serologic follow-up of 49.5 months (range 31 days to 127.7 months). The average number of antibody screening post OLT was 7.29. CONCLUSION: Our study showed that transfusion of D-positive RBCs in D-negative OLT recipients is a safe and acceptable practice in the setting of immunosuppression. This practice allows the conservation of D-negative RBC inventory