Diffuse large B cell lymphoma with MYC and BCL2 rearrangements

by Jason Wasserman MD PhD FRCPC and Phil Berardi MD PhD FRCPC
October 10, 2024


Diffuse large B cell lymphoma (DLBCL) with MYC and BCL2 rearrangements is a type of cancer affecting B cells, a white blood cell that helps protect the body from infections. In this condition, the cancer cells grow and spread quickly. The term “diffuse” refers to how the cancer cells spread out and replace normal tissue. In this type of cancer, there are genetic changes (rearrangements) in two important genes, MYC and BCL2, which make the cells grow out of control. Another name for this type of cancer is high grade B cell lymphoma (DLBCL) with MYC and BCL2 rearrangements.

What are the symptoms of diffuse large B cell lymphoma with MYC and BCL2 rearrangements?

The symptoms of diffuse large  B cell lymphoma with MYC and BCL2 rearrangements can vary but often include swollen lymph nodes (which might feel like lumps under your skin), fever, night sweats, unintentional weight loss, and tiredness. These symptoms occur because the cancerous B cells can accumulate in lymph nodes and other body parts, affecting how your body functions.

What causes diffuse large B cell lymphoma with MYC and BCL2 rearrangements?

The exact cause of diffuse large B cell lymphoma with MYC and BCL2 rearrangements is not fully understood. However, it’s known that the rearrangements of the MYC and BCL2 genes play a crucial role. These genetic changes are not inherited from your parents but occur during your lifetime. Factors that might contribute to these changes include certain infections, exposure to specific chemicals, or a weakened immune system, but often, the cause is unknown.

What are MYC and BCL2 rearrangements, and how do they contribute to this disease?

MYC and BCL2 are genes that control cell growth and survival. In diffuse large B cell lymphoma with MYC and BCL2 rearrangements, both genes have moved from their regular positions in the DNA. This causes the cells to grow rapidly and resist dying when they should, making the cancer more aggressive and more challenging to treat.

What are the microscopic features of diffuse large B cell lymphoma with MYC and BCL2 rearrangements?

Under the microscope, diffuse large B cell lymphoma with MYC and BCL2 rearrangements shows a “diffuse” pattern, meaning the cancer cells replace the normal tissue evenly. The most common appearance is similar to the more common diffuse large B cell lymphoma NOS, where the cells are large and divide quickly. Necrosis (dying tumour cells) and macrophages (immune cells) cleaning up the debris may give the tumour a “starry sky” appearance.

In some cases, the cancer cells look more like a type of lymphoma called Burkitt lymphoma, with medium to large cells dividing rapidly. Other cases may show smaller, rounder cells that resemble immature B cells (lymphoblasts), known as the “blastoid variant.”

What additional tests are used to make this diagnosis?

Immunohistochemistry

Immunohistochemistry (IHC) is a lab test that looks for specific proteins on the surface of the cancer cells. In diffuse large B cell lymphoma with MYC and BCL2 rearrangements, the cells usually show markers also found in normal B cells, including CD19, CD20, CD79a, and PAX5. Other common markers found in this type of lymphoma include:

  • CD10: Present in 88-98% of cases
  • BCL6: Present in 75-89% of cases
  • MYC: Present in 78-86% of cases
  • BCL2: Present in 90-95% of cases

Most tumors in this group are called “dual expressors” because they express both MYC and BCL2 proteins. A test called Ki-67 shows how fast the cells are dividing, and in most cases, it is very high (50-100%). However, a lower Ki-67 result does not rule out this diagnosis.

Fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) is a test that looks for specific gene changes. This test can confirm the gene rearrangements in diffuse large B cell lymphoma with MYC and BCL2 rearrangements. This helps doctors make the correct diagnosis and guide treatment decisions.

What is the prognosis for a person diagnosed with diffuse large B cell lymphoma with MYC and BCL2 rearrangements?

Diffuse large B cell lymphoma with MYC and BCL2 rearrangements is an aggressive type of cancer, meaning it can grow and spread quickly. Treatment usually involves chemotherapy, and sometimes a stem cell transplant is needed. The outlook depends on factors such as the person’s overall health, age, and how well the cancer responds to treatment. Some patients can go into remission, where the cancer is no longer detectable, but it can be more challenging to treat than other types of lymphoma.

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