Diagnosis of lymphoproliferative disorders: experience of a single institution in the long-term follow-up of discordant cases

Objective: To evaluate the usefulness of morphologic diagnosis, immunopheno typing and immunoglobulin (Ig) and T-cell receptor (TcR) gene rearrangement studies in the diagnosis of lymphoproliferative disorder. Design: A retrospective cohort study with clinical follow-up of controversi al cases. Setting: Single institution, tertiary care centre. Patients: All 273 patients whose lymphoid tissue samples were sent for mole cular analysis by Southern blotting over a 4-year period. Interventions: Patient reports were retrieved from the laboratory data syst em. Repeat assessment and clinical follow-up was done for discordant cases. Outcome measures: Correlation between morphologic features and the results of immunophenotype and gene rearrangement studies of the samples. Value of the different tests in discordant cases. Results: The 273 samples included 130 of non-Hodgkin's lymphoma (NHL), 23 o f Hodgkin's disease, 80 of benign lymphoid hyperplasia, 16 of atypical lymp hoid hyperplasia and other diagnoses. Of the 130 NHL cases diagnosed by mor phologic study, 22 (17%) did not show gene rearrangement. Of the 80 morphol ogically benign samples, 4 (5%) showed gene rearrangement, and malignant di sease developed later in those patients. Five (31%) of the 16 cases of atyp ical lymphoid hyperplasia showed gene rearrangement. Six of the remaining 1 1 cases had no detectable gene rearrangement, but hematologic malignant dis ease developed. No gene rearrangement was detected in Hodgkin's disease sam ples. One carcinoma showed gene rearrangement. Of the NHL group, 86% of the B cells and 50% of the T cells showed gene arrangement. Seven samples show ed both Ig and TcR gene rearrangement. Conclusions: Gene rearrangement analyses correlate highly with conventional morphologic diagnosis and phenotyping. The detection of gene rearrangement in lymphoid tissue has a high specificity (99%) and a reasonable sensitivi ty (83%) to the development of a lymphoproliferative disorder.