MISDIAGNOSIS OF NON-HODGKIN'S LYMPHOMA IN COMMON VARIABLE IMMUNODEFICIENCY
- Tukisa D. Smith, United States of America
Abstract
Background and Aims
Lymphoid hyperplasia and splenomegaly are found in 20% of patients with common variable immunodeficiency (CVID). The incidence of lymphoma, the most common malignancy, is increased (3-8%). Distinguishing between benign and malignant lymphoid proliferation presents challenges. We present 5 patients with known CVID in which non-Hodgkin’s lymphoma (NHL) was diagnosed; 4 cases underwent chemotherapy.
Methods
Original pathology reports, slides and tissue blocks were submitted to the NIH/National Cancer Institute Hematopathology Section for expert pathology review. Immunohistochemical studies (CD20, CD3, CD79a, IgD, kappa, lambda, Ki-67, BCL2, BCL6 and MUM1; CyclinD1, CD5 in selected cases), in situ hybridization for Epstein-Barr virus and gene rearrangement analysis were performed.
Results
Five CVID patients (3 males and 2 females; age at diagnosis: 25-46 years) were diagnosed with NHL (4 with marginal zone lymphomas, 1 with diffuse B-cell lymphoma; age at cancer diagnosis: 27-63 years) often based on evidence of clonality (Table 1). None were EBV positive. Chemotherapy was given to 4 patients and suggested for the fifth, who declined and sought a second opinion. However, on expert review, histologic morphology, cell markers and molecular characteristics were not consistent with lymphoma but benign lymphoproliferation characteristic of CVID.
Conclusions
There is a risk of lymphoma in CVID due to immune defects and dysregulation; however, B-cell proliferation and clonality may be mistaken for lymphoma. Expert hematopathology review including histology, thorough immunophenotyping, molecular and genetic studies are required in such cases to prevent unnecessary and potentially deleterious therapy.