An adult man, from Southern Africa, presented to a public health centre with symptoms of progressive fatigue. Peripheral blood morphology showed marked basophilia and 21
Psoriasis is an independent risk factor for classic Hodgkin lymphoma (cHL). Guselkumab has a favorable malignancy safety profile in clinical trials. To report the first documented Epstein-Barr virus (EBV)-positive cHL arising in a biologic-naive patient with psoriatic arthritis during guselkumab therapy for chronic plaque psoriasis, and to describe its tumor microenvironment. Excisional biopsy with immunohistochemistry, EBER in situ hybridization, and targeted sequencing, plus spatial single-cell proteomics (9-plex sequential immunofluorescence) of the diagnostic lymph node. A man in his early 40s developed night sweats, syncope, and bulky right cervical lymphadenopathy 7 months after starting guselkumab. Biopsy showed mixed-cellularity EBV-positive cHL (latency IIa: EBER+, LMP1+, EBNA-2−). HRS cells were weak PAX5+, CD20 negative, CD15+, strong CD30+, OCT2 negative/weak, BOB1 negative/weak, and strong CD200+. The microenvironment contained CTLA4+ immunosuppressive T cells (10.15
We report a case of a patient with large, unilateral inguinal lymphadenopathy. Excisional biopsy demonstrated expansion of the lymph node sinuses by a population of large histiocytoid cells with abundant granular eosinophilic cytoplasm and large, eccentric nuclei with prominent central nucleoli. The findings were morphologically suspicious for Rosai–Dorfman disease; however, emperipolesis was conspicuously absent. Immunohistochemical work-up demonstrated that the infiltrate consisted of metastatic melanoma with histiocytoid morphology and admixed reactive sinus histiocytes.
VEXAS syndrome is a somatic autoinflammatory disorder caused by UBA1 mutations in hematopoietic progenitor cells, typically affecting older men and characterized by systemic inflammation and hematologic abnormalities. Early-onset cases are extremely rare. We report a 25-year-old male patient presenting with recurrent fever, weight loss, arthralgia, and inflammation mimicking orbital cellulitis. Imaging demonstrated orbital soft tissue inflammation. Laboratory investigations revealed macrocytic anemia, leukopenia, thrombocytopenia, and elevated inflammatory markers; FDG-PET/CT showed splenomegaly and hypermetabolic lymphadenopathy. Bone marrow examination revealed hypercellularity, multilineage morphological abnormalities, and vacuolated blasts. Following exclusion of infectious and classical autoinflammatory diseases, the somatic UBA1 c.121A > G (p.Met41Val) mutation confirmed VEXAS syndrome. The patient initially responded to corticosteroids but subsequently developed refractory disease and progressive pancytopenia despite tocilizumab therapy. He underwent allogeneic hematopoietic stem cell transplantation from a 10/10 HLA-matched sibling donor using a myeloablative conditioning regimen. At 3 months post-transplantation, 99
Large B-cell lymphoma with IRF4 rearrangement (IRF4-R LBCL) is a rare entity recognised in the current WHO-HAEM5 classification and the International Consensus Classification (ICC). This study aimed to evaluate the clinicopathologic and fluorescence in situ hybridisation (FISH) findings of IRF4-R LBCL across a broad age spectrum. Seven cases diagnosed with IRF4-R LBCL at the Department of Pathology, Hacettepe University Faculty of Medicine, were retrospectively reviewed. Clinical, morphological, immunohistochemical, and FISH findings were evaluated. Patients’ ages ranged from 13 to 77 years; three were aged 40 years or older. Cases under 40 years of age were localised to the head and neck region and gastrointestinal tract, and all remained in remission. In contrast, cases aged 40 years or older demonstrated more heterogeneous anatomical distribution and clinical behaviour, with one disease-related death during follow-up. Immunohistochemical analysis showed CD20 and MUM1/IRF4 positivity in all cases, whilst CD10, BCL6, and BCL2 expression was variable. IRF4 rearrangement was identified in all cases. MYC and BCL2 rearrangements were absent in all cases, whereas BCL6 rearrangement was detected in one adult patient and could not be assessed in one case. Consistent with the literature, IRF4-R LBCL in children and young adults generally shows a favourable clinical course and characteristic clinicopathologic features. In adult patients, however, greater clinicopathologic and cytogenetic heterogeneity, including occasional additional abnormalities such as BCL6 rearrangement, may be observed. Accurate identification of IRF4 rearrangement is critical for differential diagnosis and may also have implications for clinical management, particularly when interpreted in conjunction with patient age and clinicopathologic features.
