PCR analysis of immunoglobulin heavy chain (IgH) and TcR-gamma chain gene rearrangements in the diagnosis of lymphoproliferative disorders: Results of a study of 525 cases

This report summarizes a cumulative 4-year experience in polymerase chain r eaction (PCR) analysis of immunoglobin heavy chain (IgH) and TcR-gamma chai n gene rearrangements In 525 cases of lymphoproliferative disorders. Becaus e the sensitivity of the PCR methodology was found to be tissue dependent, in the study of the presence of clonal cell population In tissues containin g a small number of polyclonal lymphocytes, such as skin and gastrointestin al biopsy specimens, we used the multiple-PCR run approach. In this latter methodology, we repeat the PCR reaction from the same sample at least three times to confirm the reproducibility of the results. In the study of 273 c ases of B- or T-cell lymphomas with characteristic Immunomorphological and clinical features, a clonal IgH or TcR-gamma chain gene rearrangement was d etected in approximately 80% of cases. A clonal rearrangement involving bot h IgH and TcR-gamma chain genes was found in 10% of cases of both B-cell an d T-cell lymphomas. The study of 167 cases of nonneoplastic lymphoid tissue samples showed the presence of clonally rearranged cell populations for Ig H or TcR-gamma genes in 3 and 9% of cases, respectively. We also applied PC R for the study of 85 cases of lymphoproliferations with no definite diagno sis (Le., benign versus malignant) after immunomorphological analysis, In 6 5 cases (76%), the correlation of immunomorphological features with the pre sence (48 cases) or the absence (17 cases) of clonal lymphoid cell populati ons led to a definite diagnosis. In almost all these cases, the final diagn osis was found to be in agreement with the clinical course. In the 20 remai ning cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in detecting bcl-2/J(H) gene rearrangement as an additional c lonal marker in the diagnosis of follicular lymphoma Bcl-2/J(H) rearrangeme nt and/or IgH gene rearrangement was found in approximately 85% (71/85) of follicular lymphoma cases studied, phoid cell populations led to a definite diagnosis. In almost all these cases, the final diagnosis was found to be in agreement with the clinical course. In the 20 remaining cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in dete cting bcl-2/J(H) gene rearrangement as an additional clonal marker in the d iagnosis of follicular lymphoma Bcl-2/J(H) rearrangement and/or IgH gene re arrangement was found in approximately 85% (71/85) of follicular lymphoma c ases studied.