Clonal heavy chain isotype switching within the proliferation centers of a small lymphocytic lymphoma: Implications regarding the origin of proliferation centers

Abstract

We describe an unusual case of small lymphocytic lymphoma with multiple prominent pseudofollicular proliferation centers in which immunohistochemistry reveals that the small cells are surface IgM kappa positive and the large pseudofollicular cells are surface IgA kappa positive. We further show by genomic DNA analysis that the tumor tissue contains two J H rearrangements, one C mu rearrangement, one C alpha rearrangement, and a single C kappa rearrangement, strongly suggesting that the large cells within the proliferation centers have arisen from the small cells via a clonal heavy chain immunoglobulin isotype switch. Isotype switching in human lymphoma and leukemia appears to be an uncommon event. However, there are reports that strongly support isotype switching in pre-B-cell leukemia, Richter's syndrome, lymphoid blast crisis of chronic myelogenous leukemia, and multiple myeloma. To our knowledge, there have been no previous reports demonstrating isotype switching within the proliferation centers of small lymphocytic lymphoma. We present evidence of in vivo intratumoral isotype switching within the proliferation centers of a small lymphocytic lymphoma documented at the level of immunohistochemistry and DNA rearrangement.