B-lymphoblastic lymphoma (B-LBL) is a rare and aggressive type of non-Hodgkin lymphoma. It originates from immature B cells, a type of lymphocyte (a white blood cell) that normally helps the body fight infections. B-LBL is closely related to B-cell acute lymphoblastic leukemia (B-ALL), with the main difference being where the disease primarily manifests. In B-LBL, the cancer cells mainly form tumours in lymph nodes or other tissues outside the bone marrow, whereas in B-ALL, the cancer cells are predominantly found in the blood and bone marrow.
B-LBL most commonly affects children and young adults, though it can occur at any age. The disease progresses quickly and requires prompt treatment, typically involving intensive chemotherapy.
What are the symptoms of B-lymphoblastic lymphoma?
The symptoms of B-LBL may vary depending on the location of the lymphoma and the stage of the disease.
Common symptoms include:
Swollen lymph nodes: Painless enlargement of lymph nodes, especially in the neck, armpits, or groin, is a common sign.
Mediastinal mass: A mass in the chest, known as a mediastinal mass, can cause symptoms like cough, shortness of breath, or chest pain. This is more common in B-LBL than in other types of lymphoma.
B symptoms: These include unexplained fever, night sweats, and significant weight loss.
Fatigue: A general feeling of tiredness or weakness, which can occur as the disease progresses.
Bone pain: Some patients may experience pain in bones or joints.
Compression symptoms: If the tumour compresses nearby structures, it can cause symptoms related to the affected area, such as difficulty swallowing or abdominal pain.
What causes B-lymphoblastic lymphoma?
The exact cause of B-LBL is not fully understood, but it is believed to involve a combination of genetic and environmental factors:
Genetic mutations: B-LBL arises from genetic mutations in immature B cells. These mutations cause the cells to grow uncontrollably and avoid normal cell death, leading to the formation of tumours.
Environmental factors: Although no specific environmental causes have been conclusively identified, factors such as exposure to certain chemicals or radiation may increase the risk of developing B-LBL.
Inherited predisposition: A family history of lymphoid malignancies may slightly increase the risk of developing B-LBL, suggesting a possible genetic predisposition.
Down syndrome: Children with Down syndrome are at an increased risk of developing B-LBL. Down syndrome is associated with a higher likelihood of developing certain types of leukemia and lymphoma, including B-LBL, due to genetic factors linked to the extra copy of chromosome 21.
How is the diagnosis of B-lymphoblastic lymphoma made?
The diagnosis of B-LBL is made through clinical evaluation, imaging studies, and laboratory tests, including biopsy and molecular analysis.
Here’s how the diagnosis is typically established:
Clinical evaluation: The first step in diagnosing B-LBL involves a thorough clinical assessment by a doctor. This includes taking a detailed medical history, discussing symptoms, and performing a physical examination, mainly checking for swollen lymph nodes, an enlarged spleen, or other masses.
Imaging studies: Imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans are often used to identify the location and extent of the disease. These scans help visualize enlarged lymph nodes, mediastinal masses, or other areas of involvement.
Biopsy: A biopsy is crucial for diagnosing B-LBL. A tissue sample, usually from an enlarged lymph node or tumor mass, is removed and examined under a microscope by a pathologist. The biopsy confirms the presence of lymphoblasts, the immature B cells characteristic of B-LBL. The biopsy sample is also subjected to additional tests, such as immunohistochemistry and flow cytometry, to determine the specific type of lymphoma.
Bone marrow aspiration and biopsy: While B-LBL primarily affects tissues outside the bone marrow, a bone marrow aspiration and biopsy may be performed to check for the presence of lymphoma cells in the bone marrow. This is important for staging the disease and determining the extent of its spread.
Complete blood count (CBC): A CBC is often performed to assess the overall health of the blood cells. In B-LBL, the results may show anemia (low red blood cells), thrombocytopenia (low platelets), or abnormal white blood cell counts.
What are the microscopic features of B-lymphoblastic lymphoma?
When B-LBL is examined under a microscope, the following features are typically observed:
Lymphoblasts: The lymphoma is composed of lymphoblasts, which are immature B cells. These cells are medium to large in size and have a high nuclear-to-cytoplasmic ratio, meaning the nucleus occupies most of the cell’s volume.
Nucleus: The nucleus of the lymphoblasts is often irregular in shape and contains finely dispersed chromatin with one or more prominent nucleoli.
Cytoplasm: The cytoplasm is scant and usually appears basophilic (stains blue) under standard staining techniques.
Diffuse growth pattern: The tumour cells typically have a diffuse growth pattern, infiltrating the lymph nodes or other tissues without forming distinct structures like follicles.
Mitoses: A high number of mitotic figures (cells in the process of dividing) may be observed, indicating rapid cell proliferation.
Necrosis: Due to the disease’s aggressive nature, areas of necrosis (dead cells) may be present, particularly in larger tumours.
This image shows B-lymphoblastic lymphoma in a lymph node.
What additional tests may be performed to confirm the diagnosis and what will these tests show?
To confirm the diagnosis of B-LBL and to gather more information about the disease, several additional tests are commonly performed:
Immunohistochemistry (IHC): This test uses antibodies to detect specific proteins on the surface of the lymphoma cells. In B-LBL, the cells typically express B cell markers such as CD19, CD20 (though often weak or absent), CD22, CD79a, and TdT (terminal deoxynucleotidyl transferase), which is a marker of immaturity.
Flow cytometry: This test analyzes the expression of various surface proteins on the lymphoma cells in a liquid sample (such as blood or bone marrow). It confirms the B cell origin of the lymphoblasts and helps differentiate B-LBL from other types of lymphoma or leukemia.
Cytogenetic analysis: This test examines the chromosomes of the lymphoma cells for specific abnormalities, such as translocations or other genetic mutations. The presence of certain genetic changes, like the Philadelphia chromosome, can influence treatment decisions.
Polymerase chain reaction (PCR): This test can detect specific genetic mutations or rearrangements in the DNA of lymphoma cells, providing additional confirmation of the diagnosis and helping to identify any targetable genetic abnormalities.
These tests are crucial for confirming the diagnosis of B-LBL, determining the specific characteristics of the disease, and guiding the treatment choice. Each test provides different information that, when combined, gives a comprehensive understanding of the disease.
Genetic tests
The World Health Organization (WHO) divides 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 based on new basic science research and clinical trial results. The prognosis differs for each subtype and is managed differently depending on the subtype. For example, B-LBL with ETV6::RUNX1 fusion and high hyperdiploidy is associated with a favorable prognosis, and B-LBL with KMT2A rearrangement, BCR::ABL1 fusion, and BCR::ABL1-like features is associated with an unfavorable prognosis. B-LBL 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-LBL. Pathologists look for MRD by performing sensitive tests to 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 lymphoma given a tumour stage like other types of cancer?
Lymphomas such as B-LBL are not staged like other 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-LBL. 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-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 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.