ALK-negative anaplastic large cell lymphoma, null type with aberrant expression of PAX5 and CD138: A diagnostic pitfall.

A 72-year-old man was found to have generalized lymphadenopathy, splenomegaly, and elevated serum lactate dehydrogenase. Fine-needle aspiration and core needle biopsy of a cervical lymph node revealed a large lymphoid cell proliferation with features suggestive of anaplastic large cell lymphoma (ALCL). However, immunophenotypically, the neoplastic cells expressed PAX5 and CD138 in addition to CD30, CD45, MUM-1 and were negative for T-cell markers, B-cell markers, CD15, ALK-1, HHV-8, EBER, kappa, lambda, and pancytokeratin. The ambiguous phenotype triggered further workup. Subsequent molecular studies demonstrated T-cell receptor gene rearrangement and lack of immunoglobulin gene rearrangement. Based on these findings, a diagnosis of ALK-negative ALCL, null type with aberrant expression of PAX5 and CD138, was rendered. The patient received palliative care due to his poor condition and died of the disease. This case presents a diagnostic pitfall and highlights the importance of cytological evaluation and complete workup in the diagnosis of unconventional lymphomas.

Mincle Signaling Promotes Con A Hepatitis.

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because 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/EBPß and hypoxia-inducible factor-1α (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 C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κß-related signaling intermediates C/EBPß 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/EBPß and HIF-1α 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.