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

by David Li MD
May 1, 2024

B-lymphoblastic leukemia, also known as B-cell acute lymphoblastic leukemia (B-ALL), and B-lymphoblastic lymphoma (B-LBL), are related cancers made up of immature B cells called lymphoblasts. It is primarily a disease of children (75% of cases occur in children < 6 years old) with an estimated annual incidence of 1-5 cases per 100,000 population.

What are the symptoms of B-lymphoblastic leukemia/lymphoma?

Most patients with B-ALL/B-LBL present with consequences of bone marrow failure, including thrombocytopenia (low platelet count), anemia (low red blood cell count), and neutropenia (low neutrophil count). Symptoms such as bone pain, fatigue, easy bruising, fever, night sweats, and weight loss are often present. Patients may also have enlarged lymph nodes, spleen, and/or liver. Occasionally there may be symptoms related to central nervous system involvement.

What causes B-lymphoblastic leukemia/lymphoma?

The exact cause of B-ALL/B-LBL 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 certain genes appear to be associated with increased risk (GATA3, ARID5B, IKZF1, CEBPE, and CDKN2A/B).

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

B-ALL and B-LBL are very similar types of cancer made up of essentially the same types of cancer cells. However, to be called B-ALL, cancer cells must be found in the bone marrow, however, cancer cells are also usually found in the blood. 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?

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 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.

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

In lymph nodes, tumour cells are small to medium in size with a high nuclear-to-cytoplasmic ratio (the nucleus is large relative to the body of the cell), fine chromatin, and minimal cytoplasm. The nucleus may be oval or convoluted.

B ALL lymph node
B-LBL. Tumour cells in a lymph node.

In the peripheral blood and bone marrow, tumour cells vary in size from small cells with condensed chromatin and scant cytoplasm to larger cells with open chromatin and moderate cytoplasm.

B ALL blood
B-ALL. Tumour cells in the blood (purple cells).

What other tests may be performed to confirm the diagnosis?

Pathologists often perform a combination of additional tests before diagnosing B-ALL or B-LBL. 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 used to identify abnormal lymphoblasts in the peripheral blood, bone marrow, or lymph node. An essential characteristic of B-ALL or B-LBL 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 types of 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/B-LBL 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 over time based on new basic science research and clinical trial results. The prognosis is different for each subtype and is, therefore, 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).

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

Acute leukemias such as B-ALL/B-LBL 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. In general, the overall prognosis is good in children with a complete remission rate of > 95%. The prognosis is less favorable in adults with a complete remission rate of 60-85%.  Age and white blood cell count appear to be important prognostic features for B-ALL/B-LBL. In general, patients who are 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 and B-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

This article was written by doctors 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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