B-lymphoblastic leukemia (B-ALL)

by David Li MD
September 3, 2024


B-lymphoblastic leukemia, also known as B-cell acute lymphoblastic leukemia (B-ALL), is a type of cancer that affects the blood and bone marrow. It is a form of acute lymphoblastic leukemia (ALL) characterized by the rapid production of immature white blood cells called lymphoblasts. In B-ALL, these lymphoblasts are derived from B cells, a type of lymphocyte (a white blood cell) that normally helps the body fight infections.

What are the symptoms of B-lymphoblastic leukemia?

In B-ALL, the bone marrow produces large numbers of these immature B cell lymphoblasts. These cells do not function properly and accumulate in the blood and bone marrow, crowding out healthy cells. This can lead to a variety of symptoms, including anemia (due to a lack of red blood cells), increased risk of infections (due to a lack of normal white blood cells), and easy bruising or bleeding (due to a lack of platelets). Other symptoms include fatigue, fever, bone or joint pain, swollen lymph nodes, weight loss, and night sweats.

What causes B-lymphoblastic leukemia?

The exact cause of B-ALL is unknown; however, there is an increased risk in children with Down syndrome and other constitutional genetic disorders. Also, there may be an association with ionizing radiation. Mutations in specific genes (GATA3, ARID5B, IKZF1, CEBPE, and CDKN2A/B) appear to increase the risk of developing this type of cancer.

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

B-ALL and B-lymphoblastic lymphoma (B-LBL) are very similar types of cancer made up of essentially the same cancer cells. However, to be called B-ALL, cancer cells must be found in the bone marrow. In contrast, the diagnosis of B-LBL means that cancer cells were found outside of the bone marrow or blood, with frequent sites of involvement being the central nervous system, spleen, liver, testes, skin, soft tissue, bone, and lymph nodes.

How is this diagnosis made?

B-ALL is diagnosed through blood tests, bone marrow biopsy, and sometimes imaging studies. A key part of the diagnosis involves identifying the immature B-cell lymphoblasts in the blood or bone marrow. Additional tests, such as flow immunophenotyping, can help confirm that the leukemia cells are of B cell origin.

What does B-lymphoblastic leukemia look like under the microscope?

B-lymphoblastic leukemia (B-ALL) is diagnosed by examining the blood and bone marrow under a microscope. The key microscopic features of B-ALL include:

Presence of lymphoblasts:

  • Lymphoblasts: Lymphoblasts are the hallmark cells of B-ALL. These are immature precursor B cells that are larger than normal lymphocytes and appear abnormal.
  • Size and Shape: Lymphoblasts are generally larger than mature lymphocytes, with a high nuclear-to-cytoplasmic ratio, meaning the nucleus (the cell’s control center) takes up most of the cell’s space.
  • Chromatin: The chromatin (the genetic material in the nucleus) is usually fine and evenly dispersed. The nucleus may contain one or more prominent nucleoli (small, round structures within the nucleus that are typically visible).
  • Cytoplasm: The cytoplasm (the material surrounding the nucleus) is usually scant and may appear pale or slightly basophilic (blue-staining).

High lymphoblast count:

  • Bone Marrow: The bone marrow is usually hypercellular (packed with cells), with lymphoblasts replacing normal hematopoietic cells (cells that produce blood cells). Normal blood cell production is reduced, leading to a decrease in red blood cells, normal white blood cells, and platelets.
  • Peripheral Blood: In many cases, lymphoblasts can also be seen in the peripheral blood smear. A high blast count in the blood is a key diagnostic feature.

Lack of maturation:

  • Unlike in chronic leukemias, where cells may show some degree of maturation, the cells in B-ALL are mostly immature. This means very few mature B cells will be seen in the bone marrow or blood.
This image shows lymphoblasts in the blood.
This image shows lymphoblasts in the blood.

What other tests may be performed to confirm the diagnosis?

Pathologists often perform a combination of additional tests before diagnosing B-ALL. These tests include flow cytometry, immunohistochemistry (IHC), and molecular or genetic tests such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR).

Flow cytometry and immunohistochemistry (IHC)

Flow cytometry and immunohistochemistry (IHC) are two tests that identify abnormal lymphoblasts in the peripheral blood or bone marrow. An essential characteristic of B-ALL is the expression of B cell markers (proteins normally made by B cells). B cell lymphoblasts are almost always positive for the B cell markers CD19, cytoplasmic CD22, and cytoplasmic CD79a. They may also be positive for markers expressed by other immune cells, including CD10, PAX5, TdT, and CD20. Rarely can they be abnormally positive for markers normally expressed in myeloid cells, such as CD13 and CD33.

The tumour cells in B-ALL showing expression of CD19 by immunohistochemistry.
The tumour cells in B-ALL showing expression of CD19 by immunohistochemistry.
The tumour cells in B-ALL show expression of TdT by immunohistochemistry.
The tumour cells in B-ALL show expression of TdT by immunohistochemistry.

Genetic tests

The World Health Organization (WHO) divides B-ALL into subtypes based on the genetic and molecular abnormalities identified in the cancer cells. For this reason, pathologists perform tests such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR) to identify known genetic and molecular changes.

According to the 5th edition of the WHO Classification on Hematolymphoid Tumours, the subtypes of B-ALL/LBL are:
  • B-lymphoblastic leukemia/lymphoma, not otherwise specified
  • B-lymphoblastic leukemia/lymphoma with high hyperdiploidy
  • B-lymphoblastic leukemia/lymphoma with hypodiploidy
  • B-lymphoblastic leukemia/lymphoma with iAMP21
  • B-lymphoblastic leukemia/lymphoma with BCR::ABL1 fusion
  • B-lymphoblastic leukemia/lymphoma with BCR::ABL1-like features
  • B-lymphoblastic leukemia/lymphoma with KMT2A rearrangement
  • B-lymphoblastic leukemia/lymphoma with ETV6::RUNX1 fusion
  • B-lymphoblastic leukemia/lymphoma with ETV6::RUNX1-like features
  • B-lymphoblastic leukemia/lymphoma with TCF3::PBX1 fusion
  • B-lymphoblastic leukemia/lymphoma with IGH::IL3 fusion
  • B-lymphoblastic leukemia/lymphoma with TCF3::HLF fusion
  • B-lymphoblastic leukemia/lymphoma with other defined genetic abnormalities

This classification may change based on new basic science research and clinical trial results. The prognosis is different for each subtype and is managed differently depending on the subtype. For example, B-ALL with ETV6::RUNX1 fusion and high hyperdiploidy is associated with a favorable prognosis, and B-ALL with KMT2A rearrangement, BCR::ABL1 fusion, and BCR::ABL1-like features is associated with an unfavorable prognosis. B-ALL with iAMP21 requires more intensive therapy because it is associated with a high risk of relapse with standard therapy.

Minimal residual disease (MRD)

Minimal residual disease (MRD) is a term used to describe the small number of cancer cells that remain in the body after cancer treatment. This is especially important in the management and follow-up of patients with B-ALL/LBL. Pathologists look for MRD by performing very sensitive tests that can find even a single cancer cell in 1 million healthy cells. These tests include flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS).

Is B-lymphoblastic leukemia given a tumour stage like other types of cancer?

Acute leukemias such as B-ALL are not staged like solid tumours. The prognosis is based on many factors, including patient age, complete blood count (CBC) results, genetic abnormalities identified in the cancer cells, treatment response, and minimal residual disease (MRD) status. The overall prognosis is good in children with a complete remission rate of > 95%. The prognosis is less favorable in adults with a 60-85% complete remission rate.  Age and white blood cell count are important prognostic features for B-ALL. In general, patients older than 10 and younger than 1 have less favorable outcomes. Central nervous system or testicular involvement at diagnosis is also associated with a worse prognosis.

What happens next?

Patients diagnosed with B-ALL 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 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. Pathologists typically review and analyze these tests.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us with 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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