Clonal analysis by polymerase chain reaction of B-cell lymphoma with late relapse: A report of five cases

BACKGROUND. Little is known about the clonal heterogeneity of non- Hodgkin's lymphoma between presentation and relapse, although several such reports have been published on acute lymphoblastic leukemia. METHODS. We examined five patients with B-cell lymphoma who relapsed more than 5 years after initial presentation. Formalin fixed, paraffin embedded tissues were analyzed for clonal immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction (PCR) and sequencing of the PCR products. Four specimens retained the original histologic type, but one showed histologic transformation from diffuse large cell lymphoma to follicular small cleaved cell lymphoma. RESULTS. Although the size of the PCR products looked identical on the gel between presentation and relapse in all patients, only three of the four specimens that retained the original type had identical gene rearrangements at both presentation and relapse. One of these four and the fifth specimen showed novel gene rearrangements. CONCLUSIONS. This study suggests that late relapse lymphoma may present as a new clone. Sequencing of the PCR products is important in the evaluation of clonal heterogeneity.