Mantle cell lymphoma

by Rosemarie Tremblay-LeMay MD MSc FRCPC
March 2, 2022

What is mantle cell lymphoma?

Mantle cell lymphoma is a type of cancer that comes from immune cells called B-lymphocytes. In most cases, the cancer cells have a genetic change called a translocation involving the gene CCND1.

Where in the body is mantle cell lymphoma found?

The most common sites involved by mantle cell lymphoma are lymph nodes, followed by the spleen and the bone marrow. Cancer cells are often also found in the blood. Other sites, such as the gastrointestinal tract, can be affected.

How do pathologists make the diagnosis of mantle cell lymphoma?

The diagnosis of Mantle cell lymphoma is usually made after a small piece of tissue is removed in a procedure called a biopsy. The tissue sample is usually removed from an enlarged lymph node although other parts of the body may also be involved. The tissue sample is then sent to your pathologist who examines it under the microscope.

What other tests are performed for mantle cell lymphoma?

Immunohistochemistry

Your pathologist will perform a test called immunohistochemistry to better characterize the tumour and to exclude other diseases that can look similar to mantle cell lymphoma under the microscope.

Immunohistochemistry is a test that uses antibodies to highlight different types of proteins produced by cells. When the cells produce a protein, pathologists describe the result as positive or reactive. When the cells do not produce the protein, the result is described as negative or non-reactive.

The cancer cells in mantle cell lymphoma come from B-lymphocytes and they produce proteins normally made by B-lymphocytes such as CD20, PAX5 or CD79a. They also produce BCL2 and CD5. The cancer cells produce cyclin D1 in >95% of cases and it is a good marker for mantle cell lymphoma, as only a few other types of lymphoma are positive for cyclin D1.

Another common protein is SOX11, which will also be positive in the few cyclin D1-negative cases. Other proteins commonly tested in the diagnosis of lymphomas, such as CD10, Bcl6, or LEF1, are usually negative.

Pathologists can also use immunohistochemistry to determine the proliferation index. The proliferation index is a measure of how fast the cancer cells are dividing to create new cancer cells. A marker called Ki-67 (also called MIB1) will be positive in cells that are in the process of dividing to produce more cells. In general, a tumour that has a high proliferation index grows faster and behaves more aggressively.

Molecular tests

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce a piece of the machine called a protein.

Sometimes, a piece of DNA falls off one chromosome and becomes attached to a different chromosome. This is called translocation and it can result in the cell making a new and abnormal protein. If the new protein allows the cell to live longer than other cells or spread to other parts of the body, the cell can become a cancer (a malignant tumour).

Mantle cell lymphoma is characterized by a translocation in the gene CCND1, which encodes the protein cyclin D1 (see Immunohistochemistry above). Pathologists usually test for these molecular changes by performing fluorescence in situ hybridization (FISH) on a piece of the tissue from the tumour. This type of testing can be done on the biopsy specimen or when your tumour has been surgically removed. These tests are used to confirm the diagnosis of mantle cell lymphoma, which is especially useful if the results of the immunohistochemistry performed were not typical.

What does blastoid variant of mantle cell lymphoma mean?

Mantle cell lymphoma is typically made up of mature (fully developed) B-lymphocytes. Mantle cell lymphoma is described as blastoid variant if the tumour cells look more like immature (less developed) B-lymphocytes. The blastoid variant is important because it is associated with more aggressive behaviour than classic (non-variant) mantle cell lymphoma.

What does pleomorphic variant of mantle cell lymphoma mean?

Mantle cell lymphoma is typically made up of small to medium-sized tumour cells that look very similar to each other. Mantle cell lymphoma is described as pleomorphic variant if the tumour cells vary greatly in shape or size. Some very large tumour cells are also usually seen. The pleomorphic variant is important because it is associated with more aggressive behaviour than classic (non-variant) mantle cell lymphoma.