A Background on Mantle Cell Lymphoma

Michael L. Wang, MD:Mantle cell lymphoma is a rare subtype of B-cell lymphoma. In America, the lymphoma population includes about 1 million people. In other words, 1 million United States citizens live with lymphoma. Overall, lymphoma has 2 parts: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Non-Hodgkin’s lymphoma has T-cell lymphoma, about 5% to 10%, but the vast majority is B-cell lymphoma, which is about 85% to 90%. Within the B-cell lymphoma, which is the most common type of lymphoma, there are many subtypes. Large cell lymphoma is most common, followed by follicular lymphoma, and then marginal zone lymphoma. Marginal zone lymphoma is just 1 of the many B-cell lymphomas. It is rare, but incidence is about 4000 to 5000 cases every year. So, if a patient lives for, let’s say, the 5 to 10 years, on average 7, you would say that about 5000 times 7—that’s 35,000— people live with mantle cell lymphoma in the United States. It’s not a big number, but it matters for each individual patient. So, mantle cell lymphoma is a rare subtype of B-cell lymphoma that is not yet curable, but much progress has been made in this field. There are specific medicines approved by FDA just for mantle cell lymphoma. This subtype of lymphoma is a little rare, but it is enjoying rapid progress.

Mantle cell lymphoma is driven by cyclin D1. So, with the 11;14 translocation, there’s cyclin D1, which is supposed to drive the pathogenesis of mantle cell lymphoma. And when there’s a translocation of this gene from the 11^thchromosome on to the 14^thchromosome, where there’s a heavy chain promoter—heavy chain is around the most number of proteins. The amount of heavy chain in our body is a lot, so this promoter has a lot of work to do. It drives the B-cell to make a lot of heavy chain antibodies. So, if any protein gene is placed after this promoter, this promoter overdrives the protein expression. In this case, it happens under genetic environmental factors. The cyclin D1 gene is misplaced on the 14^thchromosome, just after the heavy gene promoter. That’s overproduction of cyclin D1, which could drive the pathogenesis of mantle cell lymphoma together with many other factors on the molecular level and the cell pathway level.

With morphologic variants, there’s a controversy, but most variants are nodular, morphologically diffuse, and then pleomorphic and blastoid. So, with the growth rate, nodular is the slowest, and diffuse is a little faster. The slowest we know for lymphoma, we call it indolent mantle cell lymphoma, the nodular. The diffuse is a little faster, pleomorphic is very aggressive, and blastoid is most aggressive. But sometimes, people think the slowest mantle cell lymphoma is mantle zone lymphoma, and this was described by a hematopathologist from the University of Texas MD Anderson Cancer Center. But it’s not overly used. Only certain people who know this literature use mantle zone lymphoma. This mantle zone lymphoma usually never needs treatment for up to around 20 years—mantle cell lymphoma is rare, and mantle zone lymphoma is even rarer. A lot of oncologists or pathologists never get to see this.

Transcript edited for clarity.

March 2013

• A 55-year-old male presents to his physician complaining of fatigue, unexplained weight loss, and neck swelling
• PMH: unremarkable
• Physical exam:
  • Bilateral cervical lymphadenopathy
• Laboratory findings:
  • Leukocytes, 9.0 X 10⁹/L
  • Hb, 9.8 g/dL
  • LDH, 520 U/L
  • Beta2-microglobulin; 6.4 mg/L
  • AST, 167 U/L; ALT 202 U/L
• Excisional biopsy of the right cervical node:
  • Immunophenotyping: IgM+, CD5+, CD10-, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
• CT imaging of the neck, chest, abdomen, pelvis: marked¹⁸F-FDG uptake and enlargement of bilateral cervical lymph nodes (right, 4.6 cm; left, 3.1 cm) and mesenteric lymph node (9.2 cm)
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage III
• The patient was started on induction therapy with R-hyper-CVAD and achieved significant reduction in tumor burden
• Consolidation with autologous stem cell transplant resulted in complete remission

March 2017

• The patient reports having symptoms of fatigue and weight loss
• PET/CT shows diffuse uptake of¹⁸F-FDG in the right lung and mediastinal lymph nodes
• The patient was started on therapy with ibrutinib