Immunoglobulin Gene Rearrangement in Abnormal Lymph Node Hyperplasia

Abstract

The histologic designation "abnormal lymphoid hyperplasia" is applied to lymph nodes demonstrating varying degrees of architectural effacement and/or cytologic atypia. Although some of these cases may be suggestive of non-Hodgkin's lymphoma, a definitive diagnosis is not possible despite careful morphologic and immunophenotypic studies. Because the demonstration of immunoglobulin and T-cell receptor gene rearrangements by Southern blot analysis provides a sensitive marker of lineage and clonality in lymphoid malignant conditions, the frequency with which such gene rearrangements could be identified in abnormal hyperplasia and their significance were studied. DNA samples from lymph node biopsy samples of 11 patients with abnormal lymphoid hyperplasia were analyzed for rearrangements of immunoglobulin and T-cell receptor genes by Southern blot hybridization. Six of these patients had monoclonal B-cell populations identified by immunoglobulin gene rearrangements; all were found subsequently to have non-Hodgkin's lymphoma by repeated biopsy from 8 days to 46 months later. Two patients with negative Southern blot studies also developed lymphoma, one a T-cell non-Hodgkin's lymphoma and one a cutaneous B-cell non-Hodgkin's lymphoma. Three patients without detectable gene rearrangements showed no evidence of malignant lymphoma at 36-, 45-, and 60-month follow-up evaluations. Southern blot analysis thus identified monoclonal B-cell lymphoid populations in a subset of patients with abnormal lymphoid hyperplasia; the presence of clonal immunoglobulin gene rearrangement predicted progression to overt non-Hodgkin's lymphoma.

Endemic Burkitt Lymphoma

“…BL has been reported to arise from follicular lymphoma as well as reactive lymph node hyperplasia [73][74][75] . Progression from reactive lymphoid hyperplasia (follicular hyperplasia) to high grade lymphoma has been reported and infections like EBV may lead to development of lymphoma in benign lymphadenopathy [76][77][78] . In patients with lymphoid malignancies, the transformation from an indolent to a histologic pattern with a more aggressive course is well known 79 .…”

Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders

“…When important proto‐oncogenes such as c‐myc , p53 , or the Bcl‐2 , Bax‐ , Bad superfamily exert their action [ 15–18], oligoclonal lymphocytes present in the autoimmune tissue infiltrate may acquire apoptotic, cell cycle‐related abnormalities in such a way that the inflammatory infiltrate in time turns into a low‐grade malignant lymphoma [ 19–21]. The initially polyclonal cell infiltrates, resembling what were earlier called pseudolymphomas, can be difficult to distinguish from a monoclonal, low‐grade malignant lymphoma, especially in case of maltomas and paltomas [ 22–25]. Therefore, molecular markers become useful tools in distinguishing between monoclonal and polyclonal proliferating lymphocytes.…”