We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P = .022) and displayed inferior outcome compared with wild-type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy (P =022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P = .003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma with systemic manifestations, including fever, lymphadenopathy, rash, and rarely arthritis. We report the case of a patient who presented with symmetric inflammatory polyarthritis and skin nodules resembling rheumatoid arthritis (RA). The patient responded initially to low-dose prednisolone, but 12 months later, he developed typical features of AITL. The characteristics of AITL-associated arthritis from 16 additional cases from the English literature are also reviewed. AITL-associated arthritis is an uncommon manifestation of angioimmunoblastic lymphoma that can mimic RA, especially when the typical systemic features of lymphoma are absent. This type of arthritis should be included in the differential diagnosis of patients presenting with an inflammatory polyarthritis.A ngioimmunoblastic T-cell lymphoma (AITL) is a nonHodgkin lymphoma (NHL) that was first described independently by Frizzera and Lukes in 1975. Initially, it was termed immunoblastic lymphadenopathy or angioimmunoblastic lymphadenopathy with dysproteinemia. In 1988, it was included in the Kiel Updated Classification for Lymphomas and it is currently classified as a peripheral T-cell non-Hodgkin lymphoma-nodal type in the World Health Organization classification of lymphomas. Currently, it accounts for 2% of all cases of NHLs. 1 Patients with AITL uncommonly develop an inflammatory arthritis with clinical features suggestive of rheumatoid arthritis (RA). 2 In the majority of cases, arthritis appears together or soon after the onset of lymphoma. Arthritis preceding the diagnosis of AITL for more than 6 months is extremely uncommon, having been reported only once in the literature. 3 We present the case of a male patient with symmetric inflammatory polyarthritis and skin nodules that preceded the onset of AITL by 12 months. We also review 16 additional well-described cases of AITL-associated arthritis from the English literature. 2-14 CASE REPORTA 50-year-old man presented to our department with a 1-month history of lymphadenopathy, fever, and rash. Twelve months before his admission, he had developed symmetric polyarthritis that involved the metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrist, elbow, and ankle joints. Small, hard subcutaneous nodules less than 0.5 cm in size were also noted in the extensory surfaces of his elbows bilaterally. A full laboratory workup at that time, including antinuclear antibodies (ANA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), was unremarkable. His medical history was significant only for Hashimoto thyroiditis.Six months before his admission, the patient reported a generalized erythematous nonpruritic skin rash. A skin biopsy revealed nonspecific perivascular inflammation of the dermis extending to the dermal-epidermal junction. The patient's rash and arthritis responded dramatically to lowdose prednisolone (10 mg/d orally). A month before his admission, while his prednisolon...

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The case of a woman with insulin-dependent diabetes mellitus, autoimmune thyroiditis, atrophic gastritis, pernicious anemia, and immunologic thrombocytopenic purpura consisting of autoimmune polyglandular syndrome type 3 associated with a history of gonadal failure is reported. Hepatitis C viral infection added xerophthalmia, lymphocytic sialadenitis, and exacerbation of idiopathic thrombocytopenic purpura. This unique disease constellation was complicated with splenic marginal zone lymphoma and gastric carcinoids. A lung infection, initially treated on an outpatient basis, proved fatal to the patient.

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