Aims: Metanephric adenomas (MAs) are conventionally regarded as rare renal tumours with indolent behaviour; limited case reports have described MAs with aggressive features. Conventional MAs harbour hotspot BRAF V600E mutations. A BRAF V600E senescence pathway, mediated by cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16, has been proposed to confer MA benignity. Aside from BRAF, the molecular landscape in both conventional MAs and those with aggressive features has not been fully characterised. The aim of this study was to molecularly profile a series of MAs to investigate the correlation between genomic findings and clinical outcome. Methods and results: We retrospectively examined the histomorphology and patient outcomes of 11 conventional MAs and one MA with aggressive features. Each was subjected to capture-based next-generation DNA sequencing of 479 cancer-related genes and immunohistochemical profiling. All tumours were positive for WT1 immunostaining and BRAF V600E mutation. One conventional MA contained an additional somatic BRCA2 pathogenic mutation. The MA with aggressive features had a biphasic appearance: one component was epithelial, with areas morphologically consistent with conventional MA; the second component was sarcomatous, with areas of solid and angiosarcomatous growth. Differential profiling of the two populations revealed identical BRAF, EIF1AX and TERT promoter hotspot mutations in the epithelial and sarcomatous components. Deep deletion of CDKN2A and MYC amplification were identified only in the sarcomatous component. Conclusions: Although the vast majority of MAs show indolent behaviour, rare pathogenic alterations can occur in conventional MAs in addition to BRAF. Molecular profiling of a case with aggressive clinical and pathological features shows genetic evidence for malignant evolution in MAs.
Though medicolegal death investigation (MDI) systems are generally associated with criminal justice, they serve an integral role in the realm of public health and safety. Medicolegal death investigation offices collect information, including medical records, from a variety of outside sources. For data to travel efficiently, transmission should be fully integrated between the MDI office and external organizations. This is often not the case. Delays in the transmission of medical records in particular lead to subsequent delays in autopsy report completion and death certification or to resource waste in cases where a timely record would have let the pathologist know an autopsy was not required. Almost no peer-reviewed literature currently exists regarding the problem of record acquisition by MDI systems. To develop a better understanding of how electronic medical records have impacted MDI systems, we conducted a mixed methods survey through the National Association of Medical Examiners (NAME) e-mail listserv. We inquired about the medical records acquisition processes at MDI systems around the nation to gauge opinions about the use of electronic health data and the integration of MDI data in public health. Concurrently, we piloted a quality improvement project at the Alameda County Sheriff-Coroner's Office (ACSCO) in Oakland, California, in which we worked with various hospitals to get ACSCO employees direct access to decedents' electronic health records. With data from the survey and pilot project, we were able to document the barriers encountered when attempting to reform medical record acquisition and to suggest systemic changes to reduce delays and wasted resources.
Background: Renal involvement in systemic lupus erythematosus (SLE) is a key predictor of morbidity and mortality. Immunofluorescence (IF) staining of glomeruli is typically positive for IgG, IgA, IgM, C3, and C1q – the “full house” (FH) pattern. However, a subset of patients with membranous lupus nephritis (MLN) have a “non-full house” (NFH) IF pattern more typical of idiopathic membranous nephropathy (IMN). Methods: From a multi-institutional cohort of 113 MLN cases, we identified 29 NFH MLN biopsies. NFH MLN was defined by IF criteria: ≥1+ glomerular capillary loop IgG staining; and <1+ IgA, IgM, and C1q. FH MLN was defined as ≥1+ staining for all five antibodies. “Intermediate” (Int) cases did not meet criteria for FH or NFH. We compared the pathological and clinical characteristics and outcomes among patients with FH, NFH, and Int IF patterns on kidney biopsy. Results: NFH MLN represents a subset of MLN biopsies (13.4%). Compared to FH MLN patients, NFH MLN patients were older at SLE diagnosis (29 vs. 22.5 years), had a longer time to initial kidney biopsy (8 vs. 3.16 years), and had fewer SLE manifestations (2.5 vs. 3.36 involved systems). NFH MLN biopsies showed lower C3 IF intensity (1.16+ vs. 2.38+). Int biopsies had findings intermediate between those of NFH and FH groups. Conclusions: NFH IF pattern defines a small subset of MLN biopsies and appears to be associated with milder clinical manifestations and slower disease progression. Less robust C3 deposition in NFH MLN may suggest a pathophysiology distinct from that of FH MLN.
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