Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published March 3, 2021


What are the two molecular subtypes of diffuse large B-cell lymphoma?

Large B-cell lymphomas, with an estimated 150,000 new cases annually worldwide, represent almost 30% of all cases of non-Hodgkin’s lymphoma. Despite the advanced stage at presentation in the majority of patients, more than 60% can be cured with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The updated World Health Organization classification has refined the categorization of large B-cell lymphomas, which are a heterogeneous collection of clinicopathological entities of which diffuse large B-cell lymphoma, not otherwise specified (henceforth referred to simply as DLBCL), is the most common. Read the NEJM Review Article here.

Clinical Pearls

Q: What are some of the epidemiologic features of DLBCL?

A: The median age at diagnosis of DLBCL is the mid-60s; 30% of patients are older than 75 years of age. Although the majority of patients present without a history of lymphoma, DLBCL can arise as a transformation from an underlying known or occult low-grade B-cell lymphoma. Although DLBCL is not considered a heritable disease, genomewide association studies have identified multiple genetic susceptibility loci, implicating pathways involved with immune function.

Q: How is tissue best obtained for diagnosis of DLBCL?

A: Diagnosis of large B-cell lymphomas relies on a detailed examination of tumor tissue, best achieved with an excisional biopsy specimen. In addition to morphologic characteristics, an accurate lymphoma classification requires specialized tests, including immunohistochemistry, flow cytometry, fluorescence in situ hybridization, and molecular testing. Biopsy specimens obtained by fine-needle aspiration are inadequate for pathological assessment. Although specimens from core biopsy are routinely used, they are often insufficient for a complete evaluation, and core biopsy should be performed only if excisional biopsy is not feasible.

Morning Report Questions

Q: What are the two molecular subtypes of DLBCL?

A: Gene expression profiling has delineated two distinct molecular subtypes of DLBCL, the germinal center B-cell–like (GCB) subtype and the activated B-cell–like (ABC) subtype; 10 to 15% of cases are unclassifiable. These subtypes are believed to arise from different stages of lymphoid differentiation (cell of origin), relying on separate oncogenic mechanisms, with the ABC subtype having an inferior outcome (3-year progression-free survival, approximately 40 to 50%, vs. 75% with the GCB subtype). This phenotypic distinction is relevant because targeted agents may be preferentially active in one subtype. Although gene expression profiling is rarely performed in clinical practice, platforms suitable for routine care may soon be available. 

Q: How common is primary refractory disease in patients treated with R-CHOP?

A: Approximately 10 to 15% of patients treated with R-CHOP have primary refractory disease (i.e., an incomplete response or a relapse within 6 months after treatment), and an additional 20 to 25% will have a relapse after an initial response, typically within the first 2 years. Outcomes remain poor for patients in whom frontline treatment fails, particularly patients with refractory disease, for whom the median overall survival is approximately 6 months. Patients with late relapses (>2 years after treatment) have somewhat better outcomes, although relapse with indolent lymphoma can occur, underscoring the need for repeat biopsy. Two CAR T-cell products have received regulatory approval for patients with relapsed or refractory aggressive B-cell lymphoma who have received at least two lines of systemic therapy, and randomized studies are evaluating the possibility of replacing autologous stem-cell transplantation with CAR T-cell therapy.

Browse more Clinical Pearls & Morning Reports »