T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL)

by David Li MD
May 1, 2024

T-lymphoblastic leukemia (also known as T-cell acute lymphoblastic leukemia or T-ALL) and T-lymphoblastic lymphoma (T-LBL) are cancers made up of immature T cells called lymphoblasts. These cancer are primarily seen in teens and children but can occur in adults about 25% of the time.

What is the difference between T-lymphoblastic leukemia and T-lymphoblastic lymphoma?

T-ALL and T-LBL are related conditions. Typically, the name T-ALL is used when cancer cells are found primarily in the blood and bone marrow. In contrast, the name T-LBL is used when cancer cells are found primarily in lymph nodes, the thymus, or other areas of the body.

What are the symptoms of T-lymphoblastic leukemia and T-lymphoblastic lymphoma?

The symptoms of T-ALL and T-LBL vary based on the extent of the disease. Patients often have a large tumor in a part of the chest called the mediastinum. Shortness of breath can be caused by fluid buildup in the chest cavity (this is called a pleural effusion) and in the sac that covers the heart (this is called a pericardial effusion). Other symptoms of T-ALL and T-LBL include fatigue, bone pain, easy bruising, and enlarged liver and spleen. For patients with T-ALL, blood tests typically show high levels of white blood cells (WBCs).

What causes T-lymphoblastic leukemia and T-lymphoblastic lymphoma?

The cause of T-ALL and T-LBL is currently unknown, but a variety of genetic changes are known to play a role in the development of the disease. Factors that are associated with an increased risk for developing T-ALL and T-LBL include exposure to chemicals or radiation, inherited genes, and immune deficiency (lowered immune system activity).

Where in the body are T-lymphoblastic leukemia and T-lymphoblastic lymphoma found?

The leukemia form of the disease (T-ALL) is found in the blood and bone marrow, and the lymphoma form of the disease (T-LBL) is found in the chest cavity (mediastinum). For some patients, the disease involves lymph nodes, skin, liver, spleen, central nervous system, and testes.

How is this diagnosis made?

The diagnostic process starts with a thorough medical history and physical exam, followed by a blood draw to examine the cells in the blood. The examination of the cells in the blood includes performing a complete blood count (CBC). Usually, a bone marrow biopsy or lymph node biopsy is needed to make the diagnosis. Additional laboratory tests that look for genetic changes in the tumour cells may also be performed to confirm the diagnosis (see below for more information).

Microscopic features of T-lymphoblastic leukemia and T-lymphoblastic lymphoma

Both T-ALL and T-LBL are made up of immature T cells called T-lymphoblasts. These cells are described as immature because they are not yet fully functional T cells. T lymphoblasts are normally found in the bone marrow, where they change over a period of several days in mature T cells. However, the abnormal T-lymphoblasts in both T-ALL and T-LBL remain in an immature state.

When examined under the microscope, the immature T-lymphoblasts are round purple cells. The cells look purple because the nucleus (the part of the cell that holds the genetic material) is very large compared to the cytoplasm (body) of the cell. Pathologists often describe these cells as having a high N:C ratio.

What other tests may be performed to confirm the diagnosis?

Pathologists often perform a combination of additional tests before diagnosing T-ALL or T-LBL. These tests include flow cytometry, immunohistochemistry (IHC), and molecular or genetic assays.

Flow cytometry

Flow cytometry is a type of laboratory testing that allows pathologists to identify individual cells based on the chemicals (proteins) made by the cells. Since T-lymphoblasts are T cells in origin, they typically express some T cell markers, including CD3, CD7, CD2, CD5, CD1a, CD4, and CD8. Flow cytometry is important because it helps confirm the diagnosis and rule out other conditions that can look like T-ALL and T-LBL.

Maturation is the process by which young cells turn into fully functioning mature cells. T cell maturation normally occurs in a part of the body called the thymus. Depending on the stage of development, different T cell markers can be expressed at different times. Historically, T-ALL has been subclassified into various stages of T cell maturation based on the antigens expressed.

Markers of T cell maturation include:

Early thymocyte: Positive for CD3, CD2, CD5, and CD7
Common thymocyte: Positive for CD1a, CD3, and CD4/CD8 (double positive)
Late thymocyte: Positive for CD4 or CD8

Immunohistochemistry

Immunohistochemistry (IHC) is another test that allows pathologists to identify cells based on the chemicals (proteins) made by the cells. IHC works by placing very thin slices of the tumor on a glass slide. Staining chemicals are then applied to the tumor on the slide. A dye, typically brown, is used in the staining process. If the cells turn brown, it indicates a positive result. In both T-ALL and T-LBL, the tumour cells are typically positive for T cell markers such as CD3, CD7, CD2, CD5, CD1a, CD4, and CD8. The cells may also be positive for markers of immaturity, such as CD34 and TdT. IHC is important because it helps confirm the diagnosis and rule out other conditions that can look like T-ALL and T-LBL.

Molecular tests

Several genetic abnormalities have been identified in both T-ALL and T-LBL. Some of the more common abnormalities include translocations involving chromosomes 14q, 7q, and 7p, deletion of chromosome 9p, and mutations involving the genes NOTCH1 and FBXW7. These abnormalities allow the cancer cells to live longer and divide more often than normal, healthy cells.

Minimal residual disease

Minimal residual disease (MRD) is a term used to describe the small number of cancer cells that remain in the body after cancer treatment. These cells have the potential to cause relapse in patients. MRD testing can help doctors determine how well the treatment worked, the risk of developing recurrent disease (relapse), and if further treatment is needed. MRD is a measure used for T-ALL/T-LBL and other types of immune system cancer.

To test for MRD, doctors use samples from either a blood draw or a bone marrow biopsy. They use very sensitive methods that can find even a single cancer cell in 1 million healthy cells. These methods include flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS).

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL)

Approximately 10% of T-ALL cases are classified as ETP-ALL, denoting a unique immunophenotype (pattern of protein expression) limited to early T cell differentiation. The cells in ETP-ALL express CD7 but lack CD1a and CD8 and are positive for myeloid markers such as CD33, CD34, and CD117. Initially, ETP-ALL was thought to have a poor outcome compared to other types of T-ALL; however, more studies have shown little to no significant difference in outcome with the proper therapy.

Are T-lymphoblastic leukemia and T-lymphoblastic lymphoma given a tumour stage like other types of cancer?

Acute leukemias such as T-ALL are not staged like solid tumors. The prognosis is based on many factors, including age, complete blood count (CBC), genetic abnormalities, treatment response, and minimal residual disease (MRD) status. For example, younger patients do better than older patients. 5-year survival in children is 80-90%, compared to around 50% in adults. A lower white blood cell (WBC) level at diagnosis tends to have a better prognosis. Patients with MRD are more likely to have relapse. The primary treating oncologist has to take all of these factors into consideration.

What other information may be found in a pathology report for T-lymphoblastic leukemia?

In addition to the diagnosis of T-ALL, the bone marrow biopsy report may describe the amount of bone marrow involved by the tumour (this result is usually expressed as a percentage). For example, you may see phrases like “30% blasts” or “90% marrow involvement.” Other information, such as the presence of any normal bone marrow elements, is also included.

What happens next?

Patients diagnosed with T-ALL and T-LBL are typically followed closely by a team of specialists who will perform tests to see how the cancer responds to treatment. These tests include a complete blood count (CBC), which looks at the numbers and types of cells in the blood, and bone biopsies to look for cancer cells inside the bone. Minimal residual disease (MRD) testing, either by flow cytometry or molecular tests, is currently the gold standard for disease monitoring. These are high-sensitivity and high-complexity testing performed by special laboratories. These tests are also typically reviewed and analyzed by pathologists.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us if you have any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.

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