Primary/Congenital Immunodeficiency: 2015 SH/EAHP Workshop Report-Part 5.

Objectives: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review primary immunodeficiency and related lymphoproliferations.

Methods: Primary immunodeficiencies were divided into immune dysregulation, DNA repair defects, low immunoglobulins, and combined immunodeficiencies.

Results: Autoimmune lymphoproliferative syndrome (ALPS) is a prototypical immune dysregulation-type immunodeficiency, with defects in T-cell signaling or apoptosis, expansion of T-cell subsets, and predisposition to hemophagocytic lymphohistiocytosis. DNA repair defects directly predispose to malignancy. Low immunoglobulin immunodeficiencies such as common variable immunodeficiency (CVID) have underlying T-cell repertoire abnormalities predisposing to autoimmunity and B-cell lymphoproliferations. The full spectrum of B-cell lymphoproliferative disorders occurs in primary immunodeficiency.

Conclusions: Lymphoproliferations in primary immunodeficiency mirror those in other immunodeficiency settings, with monomorphic B- and sometimes T lymphoproliferative disorders enriched in DNA repair defects. Distinctive T-cell subset expansions in ALPS, CVID, and related entities can mimic lymphoma, and recognition of double-negative T-cell or cytotoxic T-cell expansions is key to avoid overdiagnosis.