Richter transformation

Richter transformation (also known as Richter syndrome) refers to the development of a more aggressive type of cancer in a person who already has a specific type of blood cancer called chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In most cases, the cancer transforms into a fast-growing type of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (DLBCL). Less commonly, it can transform into other aggressive cancers such as Hodgkin lymphoma.

What types of cancer undergo Richter transformation?

Richter transformation is most commonly seen in people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). These are two forms of the same slow-growing blood cancer. Although rare, other low-grade lymphomas may also undergo a similar transformation, but the term “Richter transformation” is generally used to describe the changes seen in CLL/SLL.

Why is Richter transformation important?

Richter transformation is important because it usually signals a change to a more aggressive cancer that may require a different treatment approach. The transformed cancer tends to grow faster and spread more quickly and may not respond as well to the treatments used for CLL or SLL. Identifying Richter transformation is a key step in ensuring that patients receive the most effective treatment for their condition.

What types of cancer does Richter transformation lead to?

The most common type of cancer caused by Richter transformation is diffuse large B-cell lymphoma (DLBCL), a fast-growing and aggressive form of non-Hodgkin lymphoma. This accounts for the majority of cases. Less commonly, CLL or SLL can transform into Hodgkin lymphoma, another type of lymphoma that behaves differently and requires a unique treatment approach. Rarely, other aggressive types of cancer may arise, but these are less well-studied. The specific type of cancer resulting from this change significantly influences the treatment plan and prognosis.

What causes Richter transformation?

Although the exact cause of Richter transformation is not fully understood, research suggests that changes in the genetic material of cancer cells may play a role. These genetic changes allow the cells to grow and divide more rapidly, becoming more aggressive. In some cases, infections or a weakened immune system may also contribute to the transformation. However, it is important to know that this change can occur even in otherwise healthy people.

How is this diagnosis made?

The diagnosis of Richter transformation usually starts with noticing a sudden change in the behaviour of CLL or SLL. For example, patients may develop new symptoms such as rapidly growing lymph nodes, fever, night sweats, or unexplained weight loss.

To confirm the diagnosis, doctors may perform additional tests, including:

• A biopsy of an enlarged lymph node or another affected area to look at the cancer cells under a microscope.
• Immunohistochemistry or flow cytometry to identify specific markers on the cancer cells that indicate a more aggressive lymphoma.
• Genetic tests to look for changes in the DNA of the cancer cells.
• Imaging tests such as CT scans or PET scans to assess the extent of the disease.

These tests help doctors confirm the diagnosis and plan the most appropriate treatment.

Microscopic features

Under the microscope, cancer cells in Richter transformation appear very different from the slower-growing cells in CLL or SLL. In most cases, the transformed cells are much larger and more aggressive-looking. The nucleus, which holds the genetic material, is often irregularly shaped and takes up much of the cell. These cells often divide more rapidly, so pathologists may see more mitotic figures (dividing cells). The transformed cells may also lose the appearance of small, round lymphocytes typical of CLL/SLL and instead resemble the larger, irregular cells seen in diffuse large B-cell lymphoma (DLBCL).

Pathologists use special tests like immunohistochemistry to identify specific markers that confirm the transformation, helping distinguish it from other types of lymphoma.