West Nile virus (WNV) causes disease in approximately 20% of infected humans. We previously reported that homozygosity for CCR5Delta32, a nonfunctional variant of chemokine receptor CCR5, is markedly increased among symptomatic WNV-seropositive patients from Arizona and Colorado. To confirm this, we analyzed cohorts from California and Illinois. An increase in CCR5-deficient subjects was found in both (for California, odds ratio [OR], 4.2 [95% confidence interval {CI}, 1.5-11.9] [P= .004]; for Illinois, OR, 3.1 [95% CI, 0.9-11.2] [P= .06]). A meta-analysis of all 4 cohorts showed an OR of 4.2 (95% CI, 2.1-8.3 [P= .0001]). Thus, CCR5 deficiency is a strong and consistent risk factor for symptomatic WNV infection in the United States.

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In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.

Idelalisib is a highly specific small-molecule phosphoinositide-3-kinase δ inhibitor that was recently approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. The known side effects of idelalisib include severe diarrhea and colitis. Here we report the histologic findings in idelalisib-associated enterocolitis in 11 patients with chronic lymphocytic leukemia or follicular lymphoma receiving idelalisib over a 5-year period (2011 to 2015) at our institution. All 11 patients were receiving idelalisib and underwent colonoscopy for the evaluation of diarrhea. None of the patients had previously received a stem cell transplant. Histologically, the colon biopsies in all 11 cases showed some degree of apoptosis within crypts, with 5 cases showing moderate to severe apoptosis involving the majority of the crypts with loss of goblet cells. No viral inclusions were seen in any case and immunohistochemical stains for cytomegalovirus performed in 9/11 cases were negative. All cases showed at least focal acute cryptitis, and 8 of these cases showed mild architectural distortion. Increased inflammation within the lamina propria was seen in 7 cases, and increased intraepithelial lymphocytes within crypts was seen in 8 cases; the lymphocytes were mostly T cells with a predominance of CD8 T cells, with the majority expressing the α/β T-cell receptor. Diagnoses of graft-versus-host disease, autoimmune enteropathy, infectious enterocolitis, and although thought to be less likely, inflammatory bowel disease were considered in each case. The presence of numerous intraepithelial lymphocytes in addition to severe villous blunting and apoptosis in the small intestinal biopsies from a subset of these patients additionally raised the possibility of autoimmune enteropathy, common variable immunodeficiency, or less likely, celiac disease. Awareness of the histologic features of idelalisib-associated enterocolitis is important to distinguish it from potential mimics, particularly graft-versus-host disease, autoimmune enteropathy, and cytomegalovirus/infectious enterocolitis.

Primary cutaneous signet‐ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next‐generation sequencing. The patient is an 85‐year‐old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet‐ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next‐generation sequencing revealed a CDH1 mutation, which is known to confer signet‐ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.

Background & Aims Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have demonstrated similar efficacy in removal of neoplastic esophageal lesions. However, significant controversy exists over the preferred resection technique. Our primary aim was to compare the pathologic specimens produced via EMR and ESD and secondarily gauge their effect on clinical decision making and patient outcomes. Methods Using a retrospective cohort study design, all esophageal Barrett's‐associated neoplastic lesions resected by a single provider from 2012 to 2017 were reviewed. The pathology was re‐reviewed by two blinded authors for diagnosis, margins, and adverse outcomes and recurrence rates were also collected. Results Thirty‐one EMR and 20 ESD cases were identified. Baseline demographics and lesion characteristics were similar. ESD produced more R0 resections and more en bloc resections compared to EMR. EMR produced more equivocal lateral (13/31, 41.9% vs 1/20, 5.0%) and vertical margins (13/31, 41.9% vs. 0/20, 0%, both P < 0.05). This led to an inability to reach a definitive diagnosis in 13/31 EMR vs 0/20 ESD pathology specimens (P = 0.003). Of the 13 EMR specimens with equivocal pathology, 11 were noted to have ‘at least intramucosal adenocarcinoma’. Four of the 11 patients chose to undergo elective esophagectomy with final surgical pathology demonstrating ≤T1a disease in 2, and ≥T1b disease in two. Conclusion Compared to ESD, EMR was associated with greater pathologic uncertainty in Barrett's‐associated neoplasia.

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Immunoglobulin A (IgA) vasculitis or Henoch-Schönlein purpura (HSP) typically occurs in the pediatric population, although rare cases also occur in adults. Gastrointestinal (GI) involvement is common. The "classic" histologic finding in IgA vasculitis (HSP) is leukocytoclastic vasculitis (LCV); other histologic features in biopsies of IgA vasculitis (HSP) have only been rarely described. The pathology archival files at our institution were searched for GI biopsies from patients with IgA vasculitis (HSP). Slides were retrieved and histologic and clinical features were reviewed. We identified 16 patients with IgA vasculitis (HSP) with a GI biopsy series, including both adult and pediatric patients. The most common histologic abnormality was lamina propria hemorrhage (all cases) with many cases also showing lamina propria fibrin deposition with red cell sludging and nuclear debris (7 cases). Twelve of the 16 duodenal biopsies had acute duodenitis; 3 of which were severe and erosive. Several also had an eosinophilic infiltrate. Seven of the 9 jejunal and/or ileal biopsies had acute jejunitis or ileitis. An acute colitis or proctitis was observed in 9/12 colorectal biopsies. Four biopsies contained LCV; in each of these cases, the involved vessels were small capillaries within the lamina propria. Only 1 biopsy contained deeper submucosal vessels, but they were uninvolved. Sites involved by LCV included the colorectum (2 cases), colorectum and terminal ileum, terminal ileum only, duodenum, and jejunum (1 case each). All patients presented with abdominal pain; 13/16 developed a rash, 1 following the index biopsy. Other presenting symptoms included diarrhea and/or hematochezia (8 cases), nausea/vomiting (5 cases), and intussusception (1 case). Four patients had concurrent skin biopsies showing LCV; only 1 of these patients had LCV on GI biopsy. Indications for biopsy included nonspecific presenting symptoms, absence of rash at presentation, and/or failure to respond adequately to steroid therapy. Biopsies are commonly performed in patients with or without suspected IgA vasculitis (HSP) to rule out infection, inflammatory bowel disease, and less commonly, vasculitis. In general, vasculitis is not commonly observed in GI biopsies of patients with IgA vasculitis (HSP), and the spectrum of findings includes neutrophilic infiltrate within the small bowel and colon, with the duodenum most commonly affected. While the clinical and histologic findings may mimic early inflammatory bowel disease, the presence of predominant small bowel involvement, especially erosive duodenitis, should raise suspicion for IgA vasculitis (HSP). Biopsies should be obtained before steroid therapy is initiated, if possible.