Mantle Cell Lymphoma

What It Is, Causes, Signs and Symptoms, Diagnosis, and More

Author: Emily Miao, PharmD

Editor: Alyssa Haag, MD

Editor: Ian Mannarino, MD, MBA

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator: Abbey Richard, MSc

Modified: Jan 06, 2025

What is mantle cell lymphoma?

Mantle cell lymphoma is a specific subtype of lymphoma (i.e., hematologic malignancy of white blood cells) that originates from a part of the lymph node called the mantle zone of germinal follicles. The mantle zone is the outer ring of B-cells, a type of white blood cell responsible for fighting infection and producing antibodies, which surround the center of a lymphatic nodule/follicle. Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma and accounts for approximately 5 to 6% of all non-Hodgkin lymphoma cases in the United States. It occurs when B-cells abnormally and rapidly proliferate and expand within the mantle zone of a lymph node.

Lymphomas are often categorized into two subtypes which present differently, yield different prognoses, and help guide treatment selection: Hodgkin lymphoma (i.e., localized lymph node involvement, associated with Epstein-Barr virus, and has a good prognosis) and non-Hodgkin lymphoma (i.e., extranodal lymph node involvement, associated with HIV and autoimmune diseases, and typically a poorer prognosis).

An infographic detailing the background, causes, signs and symptoms, diagnosis, and treatment of mantel cell lymphoma.

What causes mantle cell lymphoma?

Nearly all causes of mantle cell lymphoma are caused by a translocation (i.e., genomic abnormality where a part of one chromosome breaks off and re-attaches itself to a separate chromosome) of chromosomes 11 and 14. The cyclin D1 gene, which plays a regulatory role in the cell cycle, transitioning cells from the growth to synthesis phase, and the immunoglobulin heavy chain (IGH) gene, which plays a crucial role in B-cell or immunoglobulin production, are located on chromosomes 11 and 14, respectively. In mantle cell lymphoma, the translocation of chromosomes 11 and 14, also denoted by t(11;14), occurs, in which a part of chromosome 11, containing the cyclin D1 gene, breaks off and becomes fused with the IGH gene on chromosome 14. This results in the overexpression of the cyclin D1 gene and subsequently, the overproduction of the cyclin D1 protein. Additionally, since it is fused with the IGH gene, there is an overproduction of abnormal B-cells or lymphoma cells.

Risk factors for mantle cell lymphoma include increased age, as it is commonly diagnosed at 60 to 70 years of age; being assigned male at birth; and a weakened immune system (e.g., prior history of cancer, HIV/AIDs, or chronic immunosuppression).

What are the signs and symptoms of mantle cell lymphoma?

People with mantle cell lymphoma present with a variety of constitutional symptoms also known as “B” symptoms such as fever, chills, night sweats, and unintentional weight loss. Other signs and symptoms of mantle cell lymphoma may include swollen lymph nodes, easy bruising, bleeding gums, swollen tonsils, liver and spleen enlargement (i.e., hepatosplenomegaly), epigastric pain, nausea, and vomiting.

How is mantle cell lymphoma diagnosed?

Diagnosis of mantle cell lymphoma begins with a thorough review of symptoms and medical history. A comprehensive physical examination of the body can identify any areas of lymphadenopathy (i.e., enlarged lymph nodes), hepatosplenomegaly, and adenoid involvement (i.e., swollen tonsils). Routine laboratory blood tests such as complete blood count with differential, serum chemistries (e.g., comprehensive metabolic panel, uric acid), and infectious disease screening (e.g., hepatitis B and HIV) may be ordered. Some individuals with mantle cell lymphoma may also have higher levels of certain proteins in the blood such as lactate dehydrogenase (LDH) and beta-2 microglobulin. These proteins serve as biomarkers in determining how aggressive the individual’s mantle cell lymphoma is and may guide treatment decisions. Imaging studies such as a computed tomography scan (CT scan) are often performed for a comprehensive evaluation of the neck, chest, abdomen, and pelvis, and to identify any enlarged lymph nodes that may have not been apparent on physical examination. After imaging, a tissue biopsy of the lymph node is taken to characterize the histology and morphology. Mantle cell lymphoma histology findings typically reveal small to intermediate-sized B-cells with irregular nuclei scattered across the mantle zones of lymph nodes. Immunohistochemistry (IHC) tests are also used to identify certain proteins that are positive in mantle cell lymphoma (e.g., cyclin D1 and B-cell specific antigens like CD19, CD20, CD22, CD79a) for confirmation.

In select individuals, further testing may be warranted. For example, if gastrointestinal symptoms (e.g., nausea, vomiting, epigastric pain) are present, an upper endoscopy and colonoscopy may be performed to exclude the possibility of the spread of cancer cells into the gastrointestinal tract. In individuals with cytopenias (i.e., abnormally low white blood cell counts), a bone marrow biopsy may be obtained for further evaluation to rule out primary hematologic malignancy (e.g., leukemias). Finally, if neurologic symptoms (e.g., seizures, altered mental status) are present, brain imaging with either a CT scan or MRI can be considered to exclude metastasis to the brain.

How is mantle cell lymphoma treated?

Treatment for mantle cell lymphoma depends on various factors including the extent and severity of the disease, and the individual’s functional status. Individuals with asymptomatic and slowly progressive mantle cell lymphoma, known as indolent disease, may opt for close surveillance and defer treatment to avoid treatment-related side effects. Individuals with symptomatic or active disease usually start treatment with a combination of chemotherapy agents (e.g., rituximab and bendamustine; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, known as “R-CHOP”).

Treatment is typically separated into an induction phase, which is the initial chemotherapy regimen to destroy as many cancer cells as possible, and a maintenance phase, which is the additional chemotherapy given following the induction phase, to further eliminate residual cancer cells for a sustained response. A stem cell transplant (i.e., healthy stem cells are transplanted into the bone marrow or blood) may also be used in the maintenance phase and is preferred if an individual achieves a complete response (i.e., no residual disease) to the initial induction chemotherapy. For individuals with refractory or resistant disease, other treatment options may include targeted therapy (e.g., pirtobrutinib) and participation in clinical trials, which are ongoing research studies designed to test novel therapies.

What are the most important facts to know about mantle cell lymphoma?

Mantle cell lymphoma is a specific type of lymphoma caused by a translocation of chromosomes 11 and 14, which results in the overproduction of abnormal B-cells, or lymphoma cells. People with mantle cell lymphoma present with a variety of constitutional symptoms also known as “B” symptoms such as fever, chills, night sweats, and unintentional weight loss. Other signs and symptoms of mantle cell lymphoma may include swollen lymph nodes, hepatosplenomegaly, and epigastric pain. Diagnosis of mantle cell lymphoma begins with a thorough review of symptoms and medical history. Ultimately, a tissue biopsy is required for a histologic diagnosis, which typically reveals small to intermediate-sized B-cells with irregular nuclei scattered across the mantle zones of lymph nodes. Treatment for mantle cell lymphoma depends on various factors including the extent and severity of the disease, and the individual’s functional performance status. Treatment options include combination chemotherapy, targeted therapy, stem cell transplant, and participation in active, ongoing clinical trials.

References

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Zelenetz AD, Gordon LI, Chang JE, et al. NCCN Guidelines® insights: B-cell lymphomas, version 5.2021. J Natl Compr Canc Netw. 2021;19(11):1218-1230. doi:10.6004/jnccn.2021.0054