HIGH-GRADE TRANSFORMATION OF CHRONIC LYMPHOCYTIC-LEUKEMIA AND LOW-GRADE NON-HODGKINS-LYMPHOMA - GENOTYPIC CONFIRMATION OF CLONAL IDENTITY

The abrupt appearance of a high-grade tumor in patients with low-grade malignant lymphoma usually is associated with an accelerated clinical disease course. The high-grade lymphoma may take a variety of histolo gic forms and often, but not always, represents evolution of the origi nal low-grade disease, as shown by immunophenotypic or immunogenotypic studies. The authors describe the transformation of a variety of low- grade B-cell neoplasms to high-grade tumors in four patients. The init ial diagnoses included chronic lymphocytic leukemia and mantle cell ly mphoma in one patient each and low-grade follicular lymphoma in two pa tients. The high-grade tumors were classified as lymphoblastic lymphom a in one patient and small noncleaved cell lymphoma in two patients. T he high-grade component manifests primarily in the peripheral blood as circulating blast-like cells consistent with large-cell lymphoma in t he remaining patient. In each case, immunophenotypic studies showed id entical monoclonal surface immunoglobulin expression on the low- and h igh-grade tumors. Immunoglobulin heavy chain gene and kappa light chai n gene studies showed identical clonally rearranged bands in paired sa mples from three of the four patients, a finding indicative of clonal identity. Unexpectedly, dissimilar immunoglobulin light and heavy chai n gene rearrangements were detected in the paired samples from one pat ient with previously diagnosed follicular lymphoma, making the relatio nship of the two tumors from this patient uncertain; however, addition al Southern blot analysis of the bcl-2 gene showed identical rearrange ments in both lesions. Furthermore, polymerase chain reaction across t he t(14;18) major breakpoint region in both tumors amplified nucleotid e fragments of identical size, confirming the clonal identity of the l ow- and high-grade lymphomas despite the divergent immunoglobulin gene studies. These studies show that low-grade malignant lymphomas of sma ll lymphocytic, mantle cell, or follicular small cleaved cell types ma y assume high-grade morphologic characteristics, that this change is t he result of transformation of the preexisting low-grade malignant neo plasm, and that this progression, like typical Richter's syndrome, is associated with a dramatically accelerated clinical course. In additio n, these studies confirm previous reports that disparate immunoglobuli n light and heavy chain gene rearrangements are not necessarily an ind icator of different cellular origins, and additional genotypic studies occasionally may be required to show the clonal identity of the cell populations involved in these morphologic transformations.