Approaches for the diagnosis and treatment of VEXAS syndrome: the importance of clinical suspicion and the use of methotrexate.

Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is caused by mutations in the UBA1 gene in myeloid precursors, leading to systemic inflammatory manifestations. We present the case of a 75-year-old man presenting with fever, panniculitis, and macrocytic anemia testing repeatedly negative for UBA1 mutations in peripheral blood samples, but ultimately found positive on bone marrow mononuclear cell DNA. The man has been successfully treated with prednisone and methotrexate.

Intrasinusoidal bone marrow involvement in mantle cell lymphoma: a case series with review of the main differential diagnoses.

Intrasinusoidal bone marrow involvement is an infrequent histological pattern observed in a limited number of B and T cell lymphomas. Mantle cell lymphoma is a biologically and prognostically heterogeneous B cell lymphoma that frequently involves the bone marrow, with interstitial, nodular-paratrabecular, or diffuse patterns. Intrasinusoidal bone marrow involvement has been described only anecdotally in this lymphoma. Here, we describe the clinical, histopathological, and molecular features of four patients diagnosed with advanced-stage mantle cell lymphoma, showing intrasinusoidal bone marrow involvement, and other peculiar immunophenotypical features. As similar cases may represent a relevant issue in bone marrow diagnostic histopathology, we also reviewed the literature to discuss differential diagnoses of B and T cell lymphomas with intrasinusoidal bone marrow involvement.

Whole-exome sequencing is feasible on a fresh-frozen skin sample of intravascular large B cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions.