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Context.--Mutations within the same signature transduction pathway are redundant and, therefore, most are mutually exclusive. Laboratory errors, however, may introduce unexpected coexisting mutations. Objective.--To validate coexisting mutations within epidermal growth factor receptor (EGFR), mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. Design.--In this retrospective study for quality assessment of next-generation sequencing in a clinical diagnostics setting, coexisting mutations within EGFR, KRAS, NRAS, BRAF, AKT1, and PIK3CA genes were examined in 1208 non-small cell lung cancers. Results.--EGFR mutations did not coexist with BRAF mutations, neither kinase-activated nor kinase-impaired mutations. There was a low but similar incidence (3.3%5.1%) of PIK3CA mutations in BRAF-, EGFR-, and KRAS-mutated lung cancers and a rare incidence of coexisting KRAS and EGFR mutations detected in 1 of 1208 lung cancers (0.08%) or 1 of 226 EGFR-mutated lung cancers (0.4%). Coexisting BRAF p.V600E mutation was observed in 3 of 4 AKT1 p.E17K-mutated lung cancers. Mutational profiling of DNA reisolated from subareas with the same or different histomorphology, using an alternative assay, confirmed that coexisting mutations might present within the same (whole or subclonal) population or different populations and clarified that the so-called coexisting activating KRAS and BRAF mutations originally reported in a specimen were indeed present in separate lung nodules submitted in the same block. Conclusions.--The results supported that EGFR and BRAF mutations are early driver mutations in lung cancers. Guidelines from official organizations to establish standard operating procedures are warranted to validate unexpected coexisting mutations and, if clinically indicated, to determine their presence in the same or different tumor populations. doi: 10.5858/arpa.2017-0495-OA, Several therapeutic agents have been approved by the US Food and Drug Administration in the United States for targeted therapy of metastatic non-small cell lung cancers (NSCLCs). (1) These include [...]

* Context.--Spontaneous pneumothorax can be idiopathic (primary), or it can occur in association with an underlying predisposing condition (secondary). Spontaneous pneumothorax may be a harbinger of an undiagnosed clinical condition, which may be associated with serious systemic abnormalities, making early recognition and diagnosis important. The pulmonary pathology of some of these disorders has not been fully elucidated. Objective.--To review cases of pneumothorax in the hope of identifying pathologic features that might correlate to specific clinical syndromes. Design.--The pathology computer files at 3 hospitals were searched for all cases of spontaneous pneumothorax, primary and secondary, regardless of etiology during a 11year period. Ninety-two cases were retrieved. Each of the cases was evaluated for reactive eosinophilic pleuritis, elastosis, pleural fibrosis, emphysema, intra-alveolar macrophages, cholesterol clefts, vasculopathy, and intraparenchymal or intrapleural cysts. Clinical information regarding asthma and smoking history, site of the pneumothorax, family history, radiographic findings, predisposing conditions, recurrence, age, and sex were extracted from the medical records. Results.--In 11 patients (12% of all the patients with spontaneous pneumothorax), a distinctive pattern of pleural fibrosis with islands of fibroblastic foci within a myxoid stroma was noted at the pleural-parenchymal interface or leading edge. These lesions correlated with a select subset of patients, consisting predominantly of young men. Conclusions.--Our review identified a distinct pattern of pneumothorax-associated fibroblastic lesions in a subset of cases of spontaneous pneumothorax. Whether this is related to the pathogenesis of the pneumothorax remains to be elucidated. (Arch Pathol Lab Med. 2012; 136:1522-1527; doi: 10.5858/arpa.2012-0330-OA), Spontaneous pneumothorax (SP) is a well-recognized pulmonary complication of a wide variety of disorders, ranging from endometriosis to metastatic malignancy. It has been separated into primary and secondary types, where [...]

* Vibrio vulnificus is an extremely invasive gram-negative bacillus found in marine waters that causes overwhelming bacteremia and shock that is associated with high mortality. Impaired iron metabolism has been implicated in the susceptibility to V vulnificus bacterial infections. We report a case of fatal V vulnificus sepsis in a 56-year-old man who died within 1 to 3 days after consuming raw seafood. At autopsy, he was found to have micronodular cirrhosis and iron overload. Postmortem genetic analysis revealed the presence of the hemochromatosis gene (HFE) C282Y mutation. To our knowledge, this is this first documented fatal case of V vulnificus infection in a patient proven to carry the HFE C282Y mutation. Because this patient was heterozygous for the major hereditary hemochromatosis mutation and was not previously diagnosed with clinical iron overload, the spectrum of clinical susceptibilities to V vulnificus infection may include carriers of the C282Y mutation. (Arch Pathol Lab Med. 2001;125:1107-1109), Vibrio vulnificus is a halophilic noncholera Vibrio species that is a common microbe in seawater and may cause gastroenteritis and wound infections.[1] Primary septicemia can occur in patients who have [...]

Context.--: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume, highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice. Objective.--: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology. Data sources.--: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours. Conclusions.--: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice. [ABSTRACT FROM AUTHOR]