Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.
Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.
Plasmablastic lymphoma (PBL) is a rare but aggressive subtype of diffuse large B-cell lymphoma (DLBCL). The diagnosis of PBL is challenging as its features overlap with lymphoma and myeloma. The most common presentation involves the oral cavity/jaw in human immunodeficiency virus (HIV)–positive patients. It has also been reported in the gastrointestinal (GI) tract, lymph nodes, and soft tissues. Usually, if PBL involves the GI tract, it presents as a gut tumor mass. In this report, we present an HIV-positive patient with PBL presenting with multiple peritoneal nodules. To our knowledge, this is the first case of PBL presenting as multiple peritoneal and retroperitoneal nodules in an HIV-positive patient. This case emphasizes the rare presentation of a rare malignancy, difficulties in establishing a diagnosis, and the importance of proper and timely management.
Breast carcinosarcoma is an aggressive subtype of cancer that accounts
for less than a percent of all breast malignancies. Carcinosarcoma is
difficult to diagnose and treat. In the following, we present a case of
breast carcinosarcoma with the treatment method.
An extremely rare form of breast cancer, breast carcinosarcoma accounts for less than a percent of all breast malignancies and is highly aggressive. Composed of both cancerous epithelial and mesenchymal cell types, breast carcinosarcoma is associated with a poor prognosis compared to more common breast cancers, and typically lack the receptors typical of other breast carcinomas, which minimize potential targets for treatment. In this case report, we discuss a 56‐year‐old patient affected by carcinosarcoma of the breast at a T2N1 stage, and the decision‐making process that factored into her treatment plan.
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