DiGeorge syndrome (DGS) is a congenital immunodeficiency that predisposes to and causes mimics of lymphoproliferative disorders. We report a diagnostically challenging Epstein–Barr virus (EBV)-driven lymphoproliferation in a patient with DiGeorge syndrome. A young adult male presented with fevers, massive lymphadenopathy and a high peripheral blood EBV viraemia. Histology from the excisional lymph node biopsy was consistent with angioimmunoblastic T-cell lymphoma (AITL) with Epstein–Barr encoding region in situ hybridisation positive cells. However, testing by next-generation sequencing revealed no somatic variants (typically seen in up to 95% of AITL diagnoses), 1 and TCRB1-based flow cytometry and TCR clonality analysis merely demonstrated oligoclonality raising the possibility of a non-neoplastic viral T-cell proliferation mimic. Viral load and adenopathy increased despite initial rituximab monotherapy. Both clinical and virological responses were observed following CHOEP chemotherapy, ultimately favouring AITL as the diagnosis. Assays based on T-cell receptor diversity have intrinsic limitations in patients with DGS due to thymic underdevelopment and resultant reduced T-cell diversity. 2 This case specifically demonstrates the limitations of T-cell clonality studies for lymphoma in the context of a thymic defect. It therefore underscores the importance of integrating molecular, immunohistochemical, and virologic data in the diagnostic formulation.
Lane et al. (Sun,) studied this question.