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Background Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children. Methods We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition. Results Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-[lambda], two showed IgG3-[kappa], and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course. Conclusions Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID., Author(s): Paul Miller [sup.1] , Andrew Y. Xiao [sup.1] [sup.2] , Vanderlene L. Kung [sup.3] , Richard K. Sibley [sup.1] , John P. Higgins [sup.1] , Neeraja Kambham [sup.1] , [...]

* Context.--Accurate HER2 testing in breast cancer is crucial for appropriate precision therapy. HER2 testing is most commonly accomplished by a combination of immunohistochemistry and in situ hybridization techniques, as gene amplification is closely tied to protein overexpression. During the last 5+ years, brightfield dual in situ hybridization (DISH) has replaced fluorescence methods (fluorescence in situ hybridization [FISH]) in some laboratories. Objective.--To analyze routine HER2 DISH performance in the field. Design.--We reviewed our experience with HER2 DISH performed at outside laboratories and referred for patient care. Results.--Of 273 identified retrospective DISH results, 55 had repeated FISH testing at our institution; 7 (13%) were discordant. Additional cases had technical flaws hampering appropriate scoring. In 23 cases (42%), HER2 DISH was performed without immunohistochemistry. Slide review of a prospective cohort of 42 consecutive DISH cases revealed 14 (33%) with technical or interpretative limitations potentially jeopardizing results. Commonly identified problems include lack of or weak signals in most tumor cells, and silver precipitate or red signals outside of nuclei, resulting in false-negative or false-positive interpretations, respectively. Further, 44% (24 of 55) of DISH reports lacked complete data, specifically average HER2 signals/cell. Conclusions.--While HER2 DISH can be an efficient and effective alternative to FISH, we illustrate pitfalls and reinforce that careful attention to slide quality and technical parameters are critically important. HER2 DISH cotesting with immunohistochemistry could help minimize false-negative or false-positive HER2 results. doi: 10.5858/arpa.2019-0510-OA, The human epidermal growth factor receptor 2 (HER2) is encoded by the ERBB2 gene on chromosome 17. (1) Sentinel studies in the 1980s demonstrated that overexpression of this tyrosine kinase [...]