High grade B cell lymphoma with MYC and BCL2 rearrangements

by Jason Wasserman MD PhD FRCPC and Phil Berardi MD PhD FRCPC
February 26, 2024

High grade B cell lymphoma with MYC and BCL2 rearrangements is a type of cancer that starts in white blood cells called B cells. These cells are part of the immune system and help protect your body from infections and diseases. “High grade” means that this type of cancer is likely to grow and spread quickly requiring prompt and aggressive treatment. The term “with MYC and BCL2 rearrangements” refers to changes in the genes MYC and BCL2. These genetic changes can cause the cells to grow uncontrollably, leading to lymphoma. Another name for this type of cancer is diffuse large B cell lymphoma (DLBCL) with MYC and BCL2 rearrangements.

What are common symptoms of high grade B cell lymphoma with MYC and BCL2 rearrangements?

The symptoms of high grade 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 feeling very tired. These symptoms occur because the cancerous B cells can accumulate in lymph nodes and other parts of the body, affecting how your body functions.

What causes high grade B cell lymphoma with MYC and BCL2 rearrangements?

The exact cause of high grade 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 high grade B cell lymphoma with MYC and BCL2 rearrangements, both genes have moved from their normal 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 is the prognosis for a person diagnosed with high grade B cell lymphoma with MYC and BCL2 rearrangements?

The prognosis, or outlook, for patients with high grade B cell lymphoma with MYC and BCL2 rearrangements can vary widely. Factors that impact prognosis include the stage of the cancer, the patient’s overall health, and how well the cancer responds to treatment. While this type of lymphoma can be aggressive and challenging to treat, advances in therapy have improved outcomes for many patients.

Microscopic features of this tumour

Under the microscope, the cells in high grade B cell lymphoma with MYC and BCL2 rearrangements are larger than normal B cells. The cancer cells also show greater variability in shape and size compared to normal B cells. Mitotic figures (dividing cells) and apoptotic cells (dying cells) are commonly seen throughout the tumour. Some tumours are made up of cells that resemble immature immune cells called blasts. Pathologists often describe these cells as blastoid.

What other tests may be performed to confirm the diagnosis?

Immunohistochemistry (IHC)

Immunohistochemistry (IHC) is a test used to see specific markers (typically proteins) inside cells. The results are often reported as positive (the cells are making the marker) or negative (the cells are not making the marker). The cancer cells in high grade B cell lymphoma with MYC and BCL2 rearrangements are frequently positive for markers expressed by normal B cells including CD19, CD20, CD79a, and PAX-5. The cancer cells are also typically positive for BCL2, BCL6, and CD10. The cancer cells are usually negative for CD34 and TdT.

Fluorescence in situ hybridization (FISH)

Fluorescence in situ hybridization (FISH) is a test that allows pathologists to see genetic changes inside cells. Pathologists use a variety of names including translocations, fusions, or rearrangements to describe these changes but they all mean essentially the same thing. These changes involve a piece of genetic material or DNA moving from its normal location on a chromosome to another part of the chromosome or an entirely different chromosome. As a result, a new gene is formed which alters the behavior of the cell.

As its name suggests, high grade B cell lymphoma with MYC and BCL2 rearrangements contains two genetic rearrangements involving MYC and BCL2. Some tumours will also harbor a rearrangement involving the BCL6 gene, however, this rearrangement is not required to make the diagnosis.

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