Primary cutaneous follicle center cell lymphomas and large B cell lymphomas of the leg descend from germinal center cells. A single cell polymerase chain reaction analysis

Abstract

Primary cutaneous B cell lymphomas are defined as non-Hodgkin lymphomas that occur in the skin without extracutaneous involvement for 6 mo after diagnosis. They are characterized by a less aggressive course and better prognosis than their nodal counterparts. According to the European Organization for Research and Treatment of Cancer classification, the major subentities of primary cutaneous B cell lymphoma are follicle center cell lymphomas, immunocytomas, and large B cell lymphomas of the leg, which differ considerably regarding their clinical behavior, the former two being indolent, the latter being of intermediate malignancy. In this study, we applied a single cell polymerase chain reaction approach to analyze immunoglobulin V(H)/V(L) genes in 532 individual B lymphocytes from histologic sections of four follicle center cell lymphomas localized on the head and trunk, and four large B cell lymphomas on the leg. We found: (i) in six of eight patients a clonal heavy chain, and in seven of eight patients a clonal light chain rearrangement, all being potentially productive; (ii) no bias in VH gene usage, in four of seven light chain rearrangements the V kappa germline gene IGVK3-20*1 was used; (iii) no biallelic rearrangements; (iv) all V(H)/V(L) genes are extensively mutated (mutation rate 5.4-16.3%); (v) intraclonal diversity in six of eight cases (three of each group); and (vi) low replacement vs silent mutation ratios in framework regions indicating preservation of antigen-receptor structure, as in normal B cells selected for antibody expression. Our data indicate a germinal center cell origin of primary cutaneous follicle center cell lymphomas and large B cell lymphomas independent of those belonging to one of these subentities.