Urothelial papillomas and low-grade urothelial carcinomas have shown a high incidence of fibroblast growth factor receptor 3 (FGFR3) mutations and are associated with a favorable prognosis. The association of FGFR3 mutations with inverted papillomas is less known. We analyzed 20 cases of inverted papilloma in the urinary tract. Mutations of FGFR3 (exons 7, 10, and 15) and TP53 genes were evaluated by DNA sequencing in these cases. Point mutations of the FGFR3 gene were identified in 45% (9 of 20) of inverted papillomas with four cases exhibiting mutations at multiple exons. Seven cases had exon 7 mutations containing R248C, S249T, L259L, P260P, and V266M. Two cases had exon 10 and 15 mutations including A366D, H412H, E627D, D641N, and H643D; five cases had N653H. The most frequent mutation was identified at R248C. None of the inverted papillomas exhibited mutations in TP53. During a mean follow-up of 78 months, none had recurrence or developed urothelial carcinoma. These findings support the concept that low-grade and low-stage urothelial neoplasms arise in a background of molecular changes that are distinctly different from the molecular changes of high-grade and high-stage urothelial cancers. Modern Pathology ( Keywords: urinary bladder; urinary tract; inverted papilloma; fibroblast growth factor receptor 3; tumorigenesis; TP mutationsThe fibroblast growth factor receptor 3 (FGFR3) is a member of a family of tyrosine kinase receptors and is composed of an extracellular ligand-binding domain, a transmembrane region, and a cytoplasmic domain with tyrosine kinase activity. Ligand binding causes receptor dimerization and subsequent activation of intracellular tyrosines. Activating mutations of FGFR3 gene lead to constitutive activation of the receptor subsequently inducing the downstream molecular pathogenesis. Activating point mutations of FGFR3 have been associated with autosomal dominant dwarfism and severe achondroplasia. An oncogenic role for FGFR3 in human cancer has emerged recently and FGFR3 mutations were reported to be associated with multiple myeloma, urothelial, and cervical cancers.Urothelial carcinomas harboring FGRFR3 mutations, in general, tend to be of low histological grade and of low pathological stage, and consequently are associated with a more favorable clinical outcome.
Castleman disease is a rare hematologic disorder, closely linked to the HHV-8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS-1 defect, a 15-month-old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T-cell and CD20+ B-cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV-8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well-functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV-8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.
Food loss and waste is a significant issue in the global food system. The agricultural practice of gleaning-recovery and distribution of unharvested produce directly from farms or the recovery of unsold produce from farmers markets-is seen as a multifunctional intervention, with the potential to address food loss, food insecurity, and the reliance of food pantries on processed food. While research has identified food donation and food recovery programs such as gleaning as potential solutions to issues of food loss and food insecurity, more research is needed to examine the actual communicative organizing practices associated with food recovery and gleaning efforts. With the aim of better conceptualizing the role that gleaning organizations might play in improving community food security and alleviating food loss, this study examines how gleaning programs develop and maintain relationships in emergency food systems. Based on 12 semistructured interviews with Vermont gleaning professionals, we aim (1) to describe the relationship between gleaning coordinators and farmers, with a focus on effective communication strategies for initiating and maintaining the relationship; and (2) to determine if participation in gleaning can add value to a farm enterprise. Results demonstrate the importance of farmers' sense of community responsibility and gleaners' individualized communication with farmers and knowledge of farming practices to the development and maintenance of gleaning relationships.
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