Recent Advances in Genitourinary Tumors: Updates From the 5th Edition of the World Health Organization Blue Book Series.

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.

-associated metastatic abdominopelvic primitive neuroectodermal tumor with an rearrangement in a 16-yr-old female.

We report a case of a -associated -rearranged malignant primitive neuroectodermal tumor (PNET) arising in a patient with DICER1 tumor predisposition syndrome. A 16-yr-old female with a history of multinodular goiter presented with a widely metastatic abdominal small round blue cell tumor with neuroectodermal differentiation. gene rearrangement was identified in the tumor by fluorescence in situ hybridization (FISH).

Clonal Origin Evaluated by Trunk and Branching Drivers and Prevalence of Mutations in Multiple Lung Tumor Nodules.

Introduction: Differentiation between intrapulmonary metastasis (IPM) and multiple primary lung cancers (MPLC) in patients with synchronous or metachronous lung tumor nodules is critical but challenging.

Objective: We proposed an algorithm to evaluate clonal origin based on trunk (initiating) versus branching drivers and the prevalence of mutations in lung adenocarcinomas.

Methods: Driver mutations were examined using next-generation sequencing in five trunk driver genes (BRAF, EGFR, ERBB2, KRAS, and NRAS) and three branching driver genes (ATK1, PIK3CA, and TP53).

IDH1 and IDH2 mutations in lung adenocarcinomas: Evidences of subclonal evolution.

Background: Selective IDH1 and IDH2 inhibitors have been approved for targeted therapy of acute myeloid leukemia. Clinical trials for solid tumors with IDH1 and IDH2 (IDH1/2) mutations are ongoing. Reports of IDH1/2-mutated non-small cell lung cancers (NSCLCs), however, are limited.

Clinical Validation of Discordant Trunk Driver Mutations in Paired Primary and Metastatic Lung Cancer Specimens.

Objectives: To propose an operating procedure for validation of discordant trunk driver mutations.

Methods: Concordance of trunk drivers was examined by next-generation sequencing in 15 patients with two to three metastatic lung cancers and 32 paired primary and metastatic lung cancers.

Results: Tissue identity was confirmed by genotyping 17 single-nucleotide polymorphisms within the panel.

Clinical Validation of Coexisting Activating Mutations Within EGFR, Mitogen-Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung Cancers.

Context.—: Mutations within the same signature transduction pathway are redundant and, therefore, most are mutually exclusive. Laboratory errors, however, may introduce unexpected coexisting mutations.

PD-L1 expression in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumor is a rare mesenchymal tumor occurring at many anatomic sites, with a predilection for children and young adults. Often indolent, they can be locally aggressive and can metastasize, resulting in significant morbidity and mortality. Therapeutic options are often limited.

Clinical mutational profiling of 1006 lung cancers by next generation sequencing.

Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine , , , , , , and genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity.

The Utility of NKX2.2 and TLE1 Immunohistochemistry in the Differentiation of Ewing Sarcoma and Synovial Sarcoma.

Although molecular testing can definitively distinguish Ewing sarcoma (EWS) from synovial sarcoma (SS) it is frequently desirable to provide a confident preliminary diagnosis before such analysis can be completed. Recently, the nuclear markers NKX2.2 and TLE1 have been shown to have good sensitivity but imperfect specificity, respectively, for EWS and SS.

Clinicopathologic study of calcifying fibrous tumor of the gastrointestinal tract: a case series.

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion known to arise at multiple body sites that may clinically mimic other more aggressive lesions in the gastrointestinal (GI) tract. In this study we describe the clinicopathologic findings of 28 GI tract CFTs. Tumors predominantly arose in middle-aged adults with a slight female predominance.

A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction.

The development of cystic fibrosis transmembrane conductance regulator (CFTR) targeted therapy for cystic fibrosis has generated interest in maximizing membrane residence of mutant forms of CFTR by manipulating interactions with scaffold proteins, such as sodium/hydrogen exchange regulatory factor-1 (NHERF1). In this study, we explored whether COOH-terminal sequences in CFTR beyond the PDZ-binding motif influence its interaction with NHERF1. NHERF1 displayed minimal self-association in blot overlays (NHERF1, K = 1,382 ± 61.

Occupational Asthma Due to Inhalation of Aerosolized Lipophilic Coating Materials.

We present a case of onset of severe asthma in a 59-year-old patient who worked in an aerospace plant. He was noted to have wheezing on exam and obstruction on PFTs. Review of his occupational history revealed exposure to lipophilic industrial compounds.

Heterogeneity of resistance mutations detectable by nextgeneration sequencing in TKI-treated lung adenocarcinoma.

EGFR-mutated lung adenocarcinomas routinely develop resistance to tyrosine kinase inhibitors (TKI). To better characterize the relative frequencies of the resistance mechanisms, we analyzed 48 EGFR-mutated TKI-resistant specimens from 41 patients. Next-generation sequencing of post-treatment specimens detected EGFR p.

Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas.

senX3-independent contribution of regX3 to Mycobacterium tuberculosis virulence.

Background: Mycobacterium tuberculosis (Mtb) must adapt to various stress conditions during host infection. The two-component regulatory system (2CRS) SenX3-RegX3 is required for Mtb virulence. We showed recently that the senX3-regX3 intergenic region contains promoter activity, driving senX3-independent regX3 expression.

Adenocarcinoma arising in an extralobar sequestration: a case report and review of the literature.

Extralobar sequestration is a type of bronchopulmonary foregut malformation defined as an isolated portion of lung tissue with a systemic arterial supply, its own pleural investment, and no bronchial communication. While it may be recognized in utero or in the neonatal period, depending on its location and associated anomalies, it can also go unrecognized until later in life when it may present as a mass. We report the first case of adenocarcinoma arising in an extralobar sequestration.

Pleural Fluid Cytology of the Polymorphous Variant of EBV-Positive Diffuse Large B-Cell Lymphoma: First Report and Distinction from a Reactive Process.

EBV-positive diffuse large B-cell lymphoma of the elderly is a newly described aggressive lymphoma predominantly affecting patients >50 years of age. Patients may present with nodal and/or extranodal involvement. The lung is one of the more common extranodal sites.

Multi-institutional retrospective cohort study of spontaneous pneumothorax.

Spontaneous pneumothorax (SP) affects only a subset of patients in a variety of disorders. This multi-institutional study attempted to identify unique clinicopathologic features of spontaneous pneumothorax (SP) in a large cohort. A total of 111 cases from 109 patients were retrieved from 3 institutions over an 11-year period: 27 women, 82 men.

Potent rifamycin-sparing regimen cures guinea pig tuberculosis as rapidly as the standard regimen.

Strategies involving new drug combinations, as well as new uses of existing drugs, are urgently needed to reduce the time required to cure patients with drug-sensitive or multidrug-resistant (MDR) tuberculosis (TB). We compared the sterilizing activity of the standard first-line antitubercular regimen, rifampin-isoniazid-pyrazinamide (RHZ), with that of the novel regimen PA-824-moxifloxacin-pyrazinamide (PaMZ), which is currently being studied in clinical trials (NCT01498419), in the guinea pig model of chronic TB infection, in which animals develop necrotic granulomas histologically resembling their human counterparts. Guinea pigs were aerosol infected with ~2 log10 bacilli of wild-type Mycobacterium tuberculosis H37Rv, and antibiotic treatment was initiated 6 weeks after infection.

The polyphosphate kinase gene ppk2 is required for Mycobacterium tuberculosis inorganic polyphosphate regulation and virulence.

The Mycobacterium tuberculosis gene Rv3232c/MT3329 (ppk2) encodes a class II polyphosphate kinase, which hydrolyzes inorganic polyphosphate (poly P) to synthesize GTP. We assessed the role of ppk2 in M. tuberculosis poly P regulation, antibiotic tolerance, and virulence.

A unique, histopathologic lesion in a subset of patients with spontaneous pneumothorax.

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.

Vibrio vulnificus septicemia in a patient with the hemochromatosis HFE C282Y mutation.

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.

Autopsy pathology of pediatric posttransplant lymphoproliferative disorder.

Objectives: Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death.

Methods: Postmortem examinations were performed on 7 patients after bone marrow (n = 3) or liver (n = 4) transplant.