Abstract. X-linked Alport syndrome (XLAS) is a progressive disorder of basement membranes caused by mutations in the COL4A5 gene, encoding the ␣5 chain of type IV collagen. A mouse model of this disorder was generated by targeting a human nonsense mutation, G5X, to the mouse Col4a5 gene. As predicted for a nonsense mutation, hemizygous mutant male mice are null and heterozygous carrier female mice are mosaic for ␣5(IV) chain expression. Mutant male mice and carrier female mice are viable through reproductive age and fertile. Mutant male mice died spontaneously at 6 to 34 wk of age, and carrier female mice died at 8 to 45 wk of age, manifesting proteinuria, azotemia, and progressive and manifold histologic abnormalities of the kidney glomerulus and tubulointerstitium. Ultrastructural abnormalities of the glomerular basement membrane, including lamellation and splitting, were characteristic of human XLAS. The mouse model described here recapitulates essential clinical and pathologic findings of human XLAS. With ␣5(IV) expression reflecting X-inactivation patterns, it will be especially useful in studying determinants of disease variability in the carrier state.

Background Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. Methods and findings A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. Conclusions The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a proven modality for the diagnosis of primary pancreatic neoplasms. We describe our experience in diagnosing nonprimary pancreatic tumors by EUS-FNA. Cytology files were searched for all EUS-FNA of the pancreas for the period 2000-2002. All cases diagnosed as neoplasms were selected and those diagnosed as nonprimary pancreatic tumors were reviewed and analyzed. One hundred ninety-one of 468 cases were diagnosed as neoplasms. Eleven of these cases were diagnosed as nonprimary pancreatic tumors (2.4% of all diagnoses and 5.7% of all neoplasms). The diagnoses were supported by clinical history (n = 7), cytological findings (n = 11), cell block histology (n = 11), cell block immunohistochemistry (n = 6), and flow cytometry (n = 1). EUS-FNA is a safe and minimally invasive method for the diagnosis of nonprimary pancreatic neoplasms. Evaluation of clinical history, cytomorphology, and ancillary techniques, especially those applied to cell block material, are essential for accurate diagnoses.

Carcinosarcomas are malignant neoplasms with biphasic carcinomatous and sarcomatous or sarcoma-like components. In general, the sarcomatous component is accepted to be the result of divergent mesenchymal differentiation of the epithelial component. Although well characterized in some anatomic locations (e.g. uterus, upper aerodigestive tract and lung), carcinosarcomas of the skin are rare. Reported epithelial components include squamous, adnexal, neuroendocrine and basaloid. Including this case, only 47 cases of primary cutaneous basal cell carcinosarcoma have been reported in the literature to date. We performed an extensive immunophenotypic evaluation in our case, which confirmed the previously reported coexpression of p53 in both components, and revealed a hitherto unreported coexpression of p16 and p63. Additionally, this report reviews the clinical, pathologic, immunophenotypic characteristics and outcomes of the basal cell carcinosarcomas reported in the literature, in order to emphasize the overall uniform characteristics and clinical behavior of this neoplasm.