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, immunophenotyping 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 controversial cases. SETTING Single institution, tertiary care centre. PATIENTS All 273 patients whose lymphoid tissue samples were sent for molecular analysis by Southern blotting over a 4-year period. INTERVENTIONS Patient reports were retrieved from the laboratory data system. 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 of Hodgkin's disease, 80 of benign lymphoid hyperplasia, 16 of atypical lymphoid hyperplasia and other diagnoses. Of the 130 NHL cases diagnosed by morphologic study, 22 (17%) did not show gene rearrangement. Of the 80 morphologically benign samples, 4 (5%) showed gene rearrangement, and malignant disease developed later in those patients. Five (31%) of the 16 cases of atypical lymphoid hyperplasia showed gene rearrangement. Six of the remaining 11 cases had no detectable gene rearrangement, but hematologic malignant disease developed. No gene rearrangement was detected in Hodgkin's disease samples. One carcinoma showed gene rearrangement. Of the NHL group, 86% of the B cells and 50% of the T cells showed gene rearrangement. Seven samples showed 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 sensitivity (83%) to the development of a lymphoproliferative disorder.