Mantle cell lymphoma

Mantle cell lymphoma

Other Names: Lymphoma, mantle cell

Mantle cell lymphoma (MCL) belongs to a group of diseases known as non-Hodgkin’s lymphomas (NHL). NHL's are cancers that affect the the lymphatic system (part of the immune system). In MCL, there are cancerous B-cells (a type of immune system cell). The cancerous B-cells are within a region of the lymph node known as the mantle zone. Although MCLs are slow-growing cancers, the cancer is usually widespread by the time it is diagnosed. In these situations, treatment must be intensive since MCL can become life threatening within a short period of time. MCL accounts for 6% of all NHL's and is mostly found in males during their early 60s.

Lymph node with mantle cell lymphoma (low power view, H&E)

Cause Most lymphomas are not inherited, but rather are acquired when the DNA within select body cells has been damaged (somatic DNA damage).

Risk factors

Some risk factors for non-Hodgkin lymphomas (NHL) include age (older), gender (male), race (white), and having a condition which weakens the immune system, such as autoimmune conditions, certain genetic disorders, being on immune suppressing medications, HIV/AIDS, HTLV-1, Ebstein-Barr virus, and helicobacter pylori infection.

Pathogenesis

A defining characteristic of MCL is mutation and overexpression of cyclin D1, a cell cycle gene, that contributes to the abnormal proliferation of the malignant cells. MCL cells may also be resistant to drug-induced apoptosis, making them harder to cure with chemotherapy or radiation. Cells affected by MCL proliferate in a nodular or diffuse pattern with two main cytologic variants, typical or blastic. Typical cases are small to intermediate-sized cells with irregular nuclei. Blastic (aka blastoid) variants have intermediate to large-sized cells with finely dispersed chromatin, and are more aggressive in nature. The tumor cells accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually rendering the system dysfunctional. MCL may also replace normal cells in the bone marrow, which impairs normal blood cell production.

Symptoms

Signs and symptoms of mantle cell lymphoma (MCL) may include swelling of the lymph nodes, fever, night sweats, weight loss, and fatigue. Some people have no to few signs of MCL leading to delayed diagnosis and treatment. Of note, people with MCL may be at an increased risk for gastrointestinal issues, such as obstruction, intussusception, and multiple intestinal polyps, as well as a very high white blood cell count. 80%-99% of people have these symptoms

• B-cell lymphoma
• Lymphadenopathy(Swollen lymph nodes)

30%-79% of people have these symptoms

• Abnormality of bone marrow cell morphology
• Anorexia
• Fatigue(Tired)
• Fever
• Splenomegaly(Increased spleen size)
• Weight loss

5%-29% of people have these symptoms

• Abnormality of the gastrointestinal tract

Diagnosis

The following tests and procedures may be used to diagnose mantle cell lymphoma:[5]

Micrograph of terminal ileum with mantle cell lymphoma (bottom of image). H&E stain.

Micrograph of terminal ileum with mantle cell lymphoma (bottom of image - brown colour). Cyclin D1 immunostain.

• Physical exam and medical history
• Flow cytometry
• Bone marrow aspiration or biopsy
• Lymph node biopsy (surgical removal of all or part of a lymph node)

If cancer is found, the following tests may be done to study the cancer cells:

• Immunohistochemistry
• Cytogenetic analysis
• FISH
• Immunophenotyping:The immunophenotype profile consists of CD5+ (in about 80%), CD10-/+, and it is usually CD5+ and CD10-. CD20+, CD23-/+ (though plus in rare cases). Generally, cyclin D1 is expressed but it may not be required. Cyclin D1 negative mantle cell lymphoma can be diagnosed by detecting SOX11 marker. The workup for Mantle cell lymphoma is similar to the workup for many indolent lymphomas and certain aggressive lymphomas.

Mantle cell lymphoma is a systemic disease with frequent involvement of the bone marrow and gastrointestinal tract (generally showing polyposis in the lining). There is also a not-uncommon leukemic phase, marked by presence in the blood. For this reason, both the peripheral blood and bone marrow are evaluated for the presence of malignant cells. Chest, abdominal, and pelvic CT scans are routinely performed.

Since mantle cell lymphoma may present a lymphomatous polyposis coli and colon involvement is common, colonoscopy is now considered a routine part of the evaluation. Upper endoscopy and neck CT scan may be helpful in selected cases. In some patients with the blastic variant, lumbar puncture is done to evaluate the spinal fluid for involvement.

CT scan - Computerized tomography scan yields images of part or whole body. Gives a large number of slices on X-ray image.

PET scan - Generally of the whole body, shows a three-dimensional image of where previously injected radioactive glucose is metabolized at a rapid rate. Faster-than-average metabolism indicates that cancer is likely present. Metabolism of radioactive glucose may give a false positive, particularly if the patient has exercised before the test.

PET scans are much more effective when the information from them is integrated with that from a CT scan to show more precisely where the cancer activity is located and to more accurately measure the size of tumors.

Treatment

Treatment of Mantle cell lymphoma (MCL) most often involves a combination of chemotherapy and immunotherapy. Additionally, hematopoietic stem cell transplantation may be considered in some cases. Surgery is usually not helpful. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Acalabrutinib (Brand name: Calquence) Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
• Lenolidomide (Brand name: Revlimid)Treatment of mantle cell lymphoma whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.
• Bortezomib (Brand name: Velcade®)Treatment of multiple myeloma patients who have received at least one prior therapy. Treatment of patients with mantle cell lymphoma.

Epidemiology

6% of non-Hodgkin lymphoma cases are mantle cell lymphoma. The ratio of males to females affected is about 4:1.

NIH genetic and rare disease info

• NIH info on Mantle cell lymphoma

Mantle cell lymphoma is a rare disease.

Mantle cell lymphoma Resources
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