Introduction to mantle cell lymphoma

Mantle Cell Lymphoma (MCL) is a relatively rare subtype of non-Hodgkin's lymphoma, comprising 3-10% of NHL cases, that affects B cells. It is characterised by overexpression of the Cyclin D1 gene due to the translocation (11,14).¹ Cyclin D1 serves a critical function in cell growth, and overexpression of this protein causes aberrant cell growth.² The yearly MCL incidence ranges from 0.5 to 1 case per 100,000 people. Compared to females, men are more likely to develop MCL and patients between the ages of 65 and 74 are diagnosed with the majority of instances.³

The clinical presentation of MCL is usually heterogeneous. It can range from slow-growing to aggressive. About 90% of patients with MCL experience swelling of lymph nodes. In addition, fever, sweating at night, fatigue, weight loss, distension of the abdomen from hepatosplenomegaly, and, less frequently, discomfort from extra-nodal involvement in the lungs, central nervous system, and gastrointestinal tract are among the prevalent clinical symptoms. The tumour invasion of bones, which is a complication of the MCL, leads to a decreased number of blood cells, particularly neutrophils, RBCs and platelets. The worsening of MCL also causes leukocytosis, pulmonary, GI tract and CNS complications.⁴

The severity of mantle cell lymphoma

MCL is a high-grade neoplasm because of its rapid spread and potential to progress into an advanced stage of cancer. MCL can be controlled and put into remission by treatment. Many patients achieve an adequate overall response rate (ORR) ranging from 60% to 97% for upfront treatment. However, the patients who benefit from treatment may tend to have disease relapse.⁵

Until conventional treatment is no longer able to bring the disease into remission, the cycle of remission and relapse turns more swiftly with time. Mantle cell lymphoma remission times have greatly extended with more recent targeted therapies.⁶

Staging of mantle cell lymphoma

The staging of MCL is based on the number of organs affected by the lymphoma. There are usually four stages of lymphoma: stages 1 - 4. Stages 1 and 2 are the early stages, while 3 and 4 are advanced disease states. MCL is usually diagnosed in advanced stages because patients do not exhibit significant symptoms in the early stage.

Early stage (Stages 1 and 2)

In the first stage, one lymph node, a cluster of nearby lymph nodes, or an additional lymphatic site is affected. However, the second stage includes two or more lymph nodes on one side of the diaphragm or Stage I or 2 with nearby non-lymph node involvement.¹
Individuals diagnosed with MCL in its early stages could benefit from less intensive treatment or a minimum strategy using shortened courses of chemotherapy and radiation therapy to optimise disease control while minimising adverse effects. Patients with early-stage MCL differ from those with advanced-stage MCL in certain ways, most notably in having an extended overall survival rate independent of the type of treatment.⁷

Advanced Stage (Stages 3 and 4)

In the third stage, the lymphoma affects the lymph nodes on both sides of the diaphragm. However, stage 4 is the most severe and involves the bone marrow or other organs such as the lungs, brain, and liver.¹ Depending on the clinical characteristics, some patients with stage 2 bulky lymphoma may also be classified as advanced illness.⁸

Even after the chemotherapy treatment is completed, stage 4 MCL may relapse or refractory. It is frequently difficult to treat. Moreover, it may become resistant to chemotherapy, which holds back remission. The initial course of treatment typically involves chemoimmunotherapy, a potent combination of chemotherapy drugs and immunotherapy aimed at inhibiting the abnormal growth of cancer cells. Treating advanced-stage disease has been undergoing research.⁹

Diagnosis of mantle cell lymphoma

Physical examinations are performed to find any palpable masses in the lymph nodes in certain regions, such as the tonsils, neck, back of the throat, behind the nose, underarms, and groin. Additional areas are examined to look for abnormal fluid accumulation or swelling linked to lymphatic system disorders and to check for the enlargement of any particular internal organs, such as the liver or spleen.¹⁰

The mantle cell lymphoma (MCL) diagnosis involves conducting a biopsy and laboratory tests. A biopsy is a procedure that involves removing a piece of tissue or cells from the body for laboratory testing. To diagnose nodal mantle cell lymphoma, lymph node excision or adequate core biopsy is required. In cases of non-nodal presentation, the diagnosis can be obtained through tissue biopsy or peripheral blood tests.¹¹

For the diagnosis of follicular lymphoma, standard tests include Complete Blood Count (CBC) with differential, Lactate Dehydrogenase (LDH) and beta-2 microglobulin, bone marrow biopsy, and imaging such as CT or FDG-PET/CT. The tests examine particular proteins in the blood as they serve as indirect indicators of the disease's severity and how quickly it is advancing. The presence of lactate dehydrogenase (LDH) in the blood is indicative of cell damage, and elevated LDH levels may suggest the presence of cancer or other health issues. In the context of cancer, high LDH levels can be an indication of extended cancer. Additionally, beta-2 microglobulin emitted into the blood by B cells can show increased levels due to fast-growing cancer or other health concerns.¹²

MCL can be distinguished from other small B-cell lymphomas by immunophenotyping. A gene study is conducted to determine the severity and prognosis of MCL. CT scanning is essential for the initial staging and assessing the patient's reaction to treatment. PET scans can also be used to monitor the disease's progression and evaluate the effectiveness of therapy. A radioactive substance at a low dose is injected during this process. Cancer cells absorb this radioactive substance. After the body is scanned from different perspectives, an image illustrates the locations within the body where the radioactive chemical has accumulated.¹³

Mantle cell lymphoma international prognostic index

A method used to evaluate risk in patients with MCL is the Mantle Cell Lymphoma International Prognostic Index (MIPI). It focuses on four important factors: age, performance status, LDH levels, and elevated white blood cell count. MIPI does not precisely predict all MCL patients' outcomes. Additional factors such as TP53 mutations, cytogenetics, and KI 67 can be considered to improve the accuracy of risk estimations.¹

Summary

Mantle Cell Lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma, making up 3-10% of cases. It's characterised by the overexpression of the Cyclin D1 gene due to a genetic translocation, which causes abnormal cell growth. The incidence rate is about 0.5 to 1 case per 100,000 people annually, mainly affecting men aged 65-74. MCL shows symptoms like swollen lymph nodes, fever, night sweats, weight loss, and fatigue. In advanced cases, it can lead to complications like leukocytosis and involvement of the lungs, GI tract, and CNS.

MCL is a fast-progressing type of cancer that often needs immediate treatment to achieve remission and commonly results in relapse. However, remission times have improved with newer targeted therapies. MCL is staged from 1 to 4 depending on the degree of organ involvement, with most cases being diagnosed at advanced stages due to minimal early symptoms. Less intense treatments may suit early-stage MCL, whereas advanced stages often necessitate more aggressive chemoimmunotherapy.

Diagnosis includes physical examinations, biopsies, and lab tests such as CBC, LDH, and beta-2 microglobulin. Imaging techniques like CT and PET scans are crucial for determining the disease's stage and assessing the treatment's effectiveness. Immunophenotyping and genetic studies further help to refine the diagnosis and prognosis.

The Mantle Cell Lymphoma International Prognostic Index (MIPI) evaluates risk based on age, performance status, LDH levels, and white blood cell count. Still, it may not accurately predict outcomes for all patients. Factors like TP53 mutations, cytogenetics, and KI 67 levels can improve risk estimation and help plan therapy.