INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Patients with DLBCL refractory to initial treatment or who experience relapse have low rates of prolonged disease-free survival. Fluorescence in situ hybridization (FISH) revealing rearrangements in the MYC gene along with either the BCL2 or BCL6 genes (double- and triple-hit lymphomas) demonstrate inferior outcomes when treated with standard front-line chemoimmunotherapy. Immunohistochemistry (IHC) testing for MUM1, CD10, BCL6, and MYC also provides important prognostic information and is used in the Hans algorithm to determine the cell of origin. We assessed how frequently these crucial tests were performed on DLBCL patients within the Veterans Health Administration (VHA).
METHODS: We performed a retrospective chart review of 1,605 randomly selected records of patients diagnosed with lymphoma seen within the VHA nationwide between 1/1/2011 and 12/31/2017. We included patients diagnosed with DLBCL. We excluded patients whose workup and treatment were outside of the VHA system, and patients with primary CNS lymphoma. We analyzed pathology reports. The proportion of patients who had IHC and FISH testing for each marker was assessed.
RESULTS: 725 patients were included in the study. Our patients were predominantly male (96.8%), with a median age of 67 years. Out of the patients analyzed, IHC to determine cell of origin was performed in 481 (66.3%). Out of those tested, 316 (65.7%) were of germinal center B-cell (GCB) origin, and 165 (34.3%) were non-GCB origin. FISH testing was performed in only 242 patients (33.4%). Out of the population tested, 25 (10.3%) were double- or triple-hit.
CONCLUSION: Pathological characterization is key to the diagnosis, prognosis, and treatment of DLBCL. It is recommended by the National Comprehensive Cancer Network (NCCN) to obtain IHC testing for MUM1, BCL6, CD10, and MYC, and FISH testing for MYC (with BCL2 and BCL6 if MYC is positive) in all patients with DLBCL. Our study shows that more than one half of patients did not have FISH testing, and that cell of origin was not determined in about one third of patients, indicating a need for improved testing of these protein expressions and gene rearrangements within the VHA.