We all know that non-Hodgkin lymphoma is not just one lymphoma, said Eric D. Hsi, MD, Chair of the Department of Laboratory Medicine, Professor of Pathology at Lerner College of Medicine, and member of Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, at the NCCN 2020 Virtual Congress: Hematologic Malignancies. The WHO classification includes 42 main entries for B-cell malignancies and 27 for mature T-cell and NK-cell neoplasms alone.1
“I spend a lot of my time staring down the barrel of a microscope, wondering what the diagnosis is,” said Dr. Hsi. “We've come a long way from several decades ago when all we had was routine [hematoxylin & eosin] sections, and we're now able to apply different technologies to examine cell proteins on cell surfaces or within cells by flow cytometry, where we label cells with fluorescent antibodies. We can do this now with 10 to 12 antibodies at the same time, analyzing thousands of cells within a few seconds, and coming up with a characteristic phenotype of a lymphoma cell.”
According to Dr. Hsi, remembering the central dogma of molecular biology can help cut through the confusion in classifying lymphoma subtypes: techniques to detect DNA, RNA, and protein should be applied to help characterize lymphoid malignancies and to answer specific diagnostic, prognostic, and therapeutic questions. DNA makes up the building blocks of genetic information and can undergo replication. DNA is then transcribed to RNA, which is then translated into protein. “The ancillary studies that we perform will look at one or multiple of these types of molecules: DNA, RNA and protein. We use these to characterize lymphoid malignancies, make a diagnosis, prognosticate, and sometimes make therapeutic decisions,” he said. “It can be confusing, but if we remember the central dogma of molecular biology, we can take stock of what we're looking at and make sense of it.”
Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Lyon, France: IARC Press; 2017.
Horwitz SM, Ansell S, Ai WZ, et al. NCCN Clinical Practice Guidelines in Oncology: Primary Cutaneous Lymphomas. Version 1.2021. Accessed October 20, 2020. Available at: NCCN.org
Petrich AM, Gandhi M, Jovanovic B, et al. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood 2014;124:2354–2361.
Morschhauser F, Tilly H, Chaidos A, et al. Phase 2 multicenter study of tazemetostat, an EZH2 inhibitor, in patients with relapsed or refractory follicular lymphoma [abstract]. Blood 2019;134(Suppl 1):Abstract 123.