Immune dysregulation with lymphoproliferation progressing to a rare T-cell non-hodgkin lymphoma

Background: Primary immunodeficiencies and immune dysregulatory disorders have an increased susceptibility to develop lymphomas. As in the general population, the vast majority being B cell lymphomas whereas T cell lymphomas (TCL) are extremely rare and carry a poor prognosis. Most cases of TCL were observed in patients with predominantly antibody deficiency or combined immunodeficiencies with associated or syndromic features. Methods/Results: The patient presented in 2017 with recurrent skin abscesses and severe transient neutropenia. In addition, he developed diffuse lymphadenopathies and splenomegaly with reduced serum immunoglobulin levels (IgG and IgM) and peripheral blood analysis showed an atypical monoclonal CD4+CD7-lymphocytosis. Lymph node biopsy showed atypical paracortical hypertrophy, suggestive of a reactive hyperplasia in the context of an underlying immunodeficiency. Two years later, the patient presented with B symptoms, generalized adenopathy and splenic infarction. Histologic examination of the spleen showed nodular white-pulp hyperplasia with periarteriolar T-zone hyperplasia and granulomas, as was observed in a cohort of CVID patients. A repeat lymph node biopsy revealed progression of the clonal lymphoid hyperplasia to a peripheral PTCL-NOS (peripheral T cell non-Hodgkin lymphoma, not otherwise specified). Conclusions: Immunodeficiency-associated lymphoid hyperplasia is challenging. Isolated evidence of clonality in biopsy material can precede the diagnosis of lymphoma. Currently, further investigations are ongoing in this patient, to define a genetic cause for the underlying immunodeficiency by analysis for germline-encoded mutations in patient’s fibroblasts and somatic mutational analysis of the tumor sample.