Adult T cell leukemia/lymphoma

by Jason Wasserman MD PhD FRCPC
November 26, 2024

Adult T cell leukemia/lymphoma (ATLL) is a rare cancer that affects T cells, a type of white blood cell that plays a key role in the immune system. When cancer primarily affects the blood and bone marrow, it is called leukemia, and when it forms a mass in the lymph nodes or other tissues outside the blood, it is called lymphoma. Some cases of ATLL involve both the blood and lymphatic tissues, reflecting the wide range of ways this disease can develop.

This disease occurs in adults infected with the human T-cell lymphotropic virus type 1 (HTLV-1). It can develop in different body parts, including the blood, lymph nodes, skin, and organs. Based on how the disease behaves and the organs involved, ATLL is classified into four types: acute, lymphomatous, chronic, and smoldering.

What are the symptoms of adult T cell leukemia/lymphoma?

The symptoms of ATLL depend on the type and stage of the disease. Common symptoms include:

• Swollen lymph nodes.
• Fatigue.
• Fever and night sweats.
• Unexplained weight loss.
• Skin rashes, lesions, or lumps.
• Bone pain.
• Abdominal discomfort due to an enlarged spleen or liver.
• High calcium levels in the blood can cause nausea, vomiting, and confusion.

What causes adult T cell leukemia/lymphoma?

ATLL is caused by infection with the HTLV-1 virus. However, only a small percentage of people infected with HTLV-1 (about 3–5%) develop ATLL. This cancer is more common in regions where HTLV-1 infection is widespread, such as parts of Japan, the Caribbean, South America, and Africa.

Certain factors increase the risk of developing ATLL, including:

• Being male.
• Older age.
• Having a high number of HTLV-1-infected cells in the blood.
• Having the infection for more than 20 years.
• Getting the infection at a young age, such as during infancy or childhood.

In people with HTLV-1, the virus can cause long-term infection in T cells. Most of these infected cells stay dormant and do not cause problems. However, certain infected cells undergo changes and grow uncontrollably in some cases, eventually becoming cancerous. Additional genetic or environmental changes are usually needed for the disease to develop fully.

How is this diagnosis made?

ATLL is diagnosed through a combination of tests. A biopsy of the affected tissue, such as a lymph node or skin lesion, is examined under a microscope. Additional tests, including blood tests, imaging scans, immunohistochemistry, and flow cytometry, help confirm the diagnosis and classify the type of ATLL.

Microscopic features

When pathologists examine ATLL under the microscope, the appearance of the cancer cells can vary depending on where the lymphoma is found in the body:

• Lymph nodes: The lymph nodes often show cancer cells that have replaced the normal structure. Sometimes, the cancer cells are found in large spaces within the lymph nodes (sinuses), giving a pattern similar to leukemia.
• Skin: In cases involving the skin, the cancer cells can form clusters in the top layer of the skin, creating small collections called microabscesses. Clusters of cancer cells in deeper layers of the skin and fat may also be seen.
• Cells: The cancer cells come in different shapes and sizes. They may have irregular, lobed nuclei (the central part of the cell that holds genetic material). The cells may be smaller and less abnormal in early stages or less aggressive types. In more aggressive types, the cells tend to be larger and more irregular in appearance.

In some cases, larger immune cells infected with Epstein-Barr virus (EBV) may also be seen alongside the ATLL cells, reflecting a weakened immune system.

Immunohistochemistry and flow cytometry

Immunohistochemistry and flow cytometry are special tests that analyze the cancer cells to determine their characteristics.

• Immunohistochemistry: This test stains the cancer cells with dyes that attach to specific proteins. ATLL cells typically express some common T cell markers, such as CD2, CD3, and CD5, but often lack CD7. Most cases are positive for CD4 (a helper T cell marker) and negative for CD8 (a cytotoxic T cell marker), but variations exist. A protein called CD25 is commonly found on ATLL cells. Larger cells may show variable positivity for CD30, a marker also seen in some other cancers. Another protein, CCR4, is frequently expressed and may guide treatment options.
• Flow cytometry: This test evaluates individual cells by measuring the proteins they express. It can detect changes that help classify the disease and predict its behavior. For example, aggressive forms of ATLL often show reduced levels of CD7 and increased levels of CCR4 and CADM1. These findings help doctors understand how advanced the disease is and guide treatment decisions.

Prognosis

The prognosis for ATLL depends on the type of disease (acute, lymphomatous, chronic, or smoldering) and how early it is diagnosed.

• Early-stage or less aggressive forms of ATLL may have better outcomes with appropriate treatment.
• Aggressive forms of ATLL often require more intensive therapies, and newer treatments, including drugs targeting specific markers like CCR4 or immunotherapies, are being developed.

Factors such as older age, high calcium levels in the blood, and a high number of cancerous cells in the blood may indicate a worse prognosis. Regular monitoring and early treatment are essential to improving outcomes.