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Kidney complications can occur due to infective endocarditis, one of which is glomerulonephritis. Most often, an immune complex or complement‐mediated glomerulonephritis is seen on kidney biopsy. In a minor subset of cases, pauci‐immune glomerulonephritis may be present. Most often, such patients will demonstrate the presence of antineutrophil cytoplasmic antibodies (ANCA) on serologic testing. A growing number of cases of ANCA‐associated glomerulonephritis due to Bartonella endocarditis have been reported. This type of endocarditis can present diagnostic difficulties given that these patients are often culture negative. Herein, we report a challenging case of ANCA‐negative pauci‐immune glomerulonephritis showing florid crescents on biopsy that was associated with Bartonella endocarditis. [ABSTRACT FROM AUTHOR]

Histopathology interpretation remains an essential, foundational method for disease diagnosis in medical practice. (1) Standard histopathology assessment is initiated through interpretation of hematoxylin and eosin--stained glass microscope slides prepared from [...], * Context.--The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. Objective.--To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. Design.--The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. Results.--The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, -0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. Conclusions.--WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology.

Next-generation sequencing technologies have revolutionized our understanding of the genomic landscapes of human cancers (1,2), but we have only a poor appreciation of the genetic determinants of metastasis, the leading [...], Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis. Shared mutations between primary carcinomas and their matched metastases have the distinct A-to-T signature of the initiating carcinogen dimethylbenzanthracene, but non-shared mutations are primarily G-to-T, a signature associated with oxidative stress. The existence of carcinomas that either did or did not metastasize in the same host animal suggests that there are tumor-intrinsic factors that influence metastatic seeding. We also demonstrate the importance of germline polymorphisms in determining allele-specific mutations, and we identify somatic genetic alterations that are specifically related to initiation of carcinogenesis by Hras or Kras mutations. Mouse tumors that mimic the genetic heterogeneity of human cancers can aid our understanding of the clonal evolution of metastasis and provide a realistic model for the testing of novel therapies.

Sequencing studies of human cancers have identified a number of mutation 'signatures', suggesting that tumours carry an imprint of the environmental agents to which patients were exposed (2-4). At present, [...], Next-generation sequencing of human tumours has refined our understanding of the mutational processes operative in cancer initiation and progression, yet major questions remain regarding the factors that induce driver mutations and the processes that shape mutation selection during tumorigenesis. Here we performed whole-exome sequencing on adenomas from three mouse models of non-small-cell lung cancer, which were induced either by exposure to carcinogens (methyl-nitrosourea (MNU) and urethane) or by genetic activation of Kras ([Kras.sup.LA2]). Although the MNU-induced tumours carried exactly the same initiating mutation in Kras as seen in the [Kras.sup.LA2] model (G12D), MNU tumours had an average of 192 non-synonymous, somatic single-nucleotide variants, compared with only six in tumours from the [Kras.sup.LA2] model. By contrast, the [Kras.sup.LA2] tumours exhibited a significantly higher level of aneuploidy and copy number alterations compared with the carcinogen-induced tumours, suggesting that carcinogen-induced and genetically engineered models lead to tumour development through different routes. The wild-type allele of Kras has been shown to act as a tumour suppressor in mouse models of non-small-cell lung cancer. We demonstrate that urethane-induced tumours from wild-type mice carry mostly (94%) Kras Q61R mutations, whereas those from Kras heterozygous animals carry mostly (92%) Kras Q61L mutations, indicating a major role for germline Kras status in mutation selection during initiation. The exomewide mutation spectra in carcinogen-induced tumours overwhelmingly display signatures of the initiating carcinogen, while adenocarcinomas acquire additional C > T mutations at CpG sites. These data provide a basis for understanding results from human tumour genome sequencing, which has identified two broad categories of tumours based on the relative frequency of single-nucleotide variations and copy number alterations (1), and underline the importance of carcinogen models for understanding the complex mutation spectra seen in human cancers.

Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus‐8 (HHV‐8) infection. KS is most often seen in individuals with acquired immunodeficiency syndrome but can occur in patients who are on immunosuppressive therapy. While the skin and oral mucosa are the typical sites for KS, lesions of the tonsil are quite rare with only a few reported cases. Here, we present a case of tonsillar KS occurring in a renal transplant patient. He presented with dysphagia, odynophagia, and weight loss. Oral examination revealed tonsillar hypertrophy with purple discoloration. Imaging revealed diffuse enlargement of Waldeyer's ring with enlarged right cervical lymph nodes, worrisome for post‐transplant lymphoproliferative disorder. Microscopic examination of the tonsillectomy specimen showed a vascular proliferation positive for HHV‐8, consistent with KS. The patient was subsequently treated with immunosuppression reduction and the addition of sirolimus, which resulted in complete resolution of oropharyngeal and cervical lesions. [ABSTRACT FROM AUTHOR]

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk. [ABSTRACT FROM AUTHOR]

Immunotactoid deposits are defined by their ultrastructural appearance and are characterized by microtubular or cylindrical structures typically measuring greater than 30 nm in diameter. Although a rare entity, immunotactoid deposition most often manifests as immunotactoid glomerulopathy and is associated with underlying lymphoplasmacytic disorders. Corneal immunotactoid deposition known as immunotactoid keratopathy has also been reported in patients with paraproteinemia. Here, we describe the first reported case of immunotactoid deposition in the stomach. The deposits were composed solely of kappa immunoglobulin light chains without significant lambda light chain or immunoglobulin heavy chain components. The patient displayed no renal signs or symptoms, and additional thorough clinical examination failed to detect any evidence of a paraproteinemia or plasma cell dyscrasia. Thus, the gastric immunotactoid deposits in this case appear to be an isolated finding of light chain deposition, of which the significance and etiology are unclear. [ABSTRACT FROM AUTHOR]