by David Li MD
October 31, 2025
B-lymphoblastic lymphoma (B-LBL) is a rare and aggressive form of non-Hodgkin lymphoma that starts from immature B cells, a type of white blood cell that helps the body fight infections.
It is closely related to B-cell acute lymphoblastic leukemia (B-ALL). The two conditions are part of the same disease spectrum and differ mainly in where the cancer cells are found:
In B-LBL, cancer cells grow mainly as tumours in lymph nodes or tissues outside the bone marrow.
In B-ALL, the same type of cells multiply within the bone marrow and often spill into the blood.
B-LBL can affect people of any age but is most common in children and young adults. It tends to grow quickly and requires prompt, intensive treatment, usually with chemotherapy.
The symptoms of B-LBL depend on where the tumour develops and how far the disease has spread.
Common symptoms include:
Swollen lymph nodes in the neck, armpits, or groin that are usually painless.
Chest mass (mediastinal mass): A large tumour in the chest may cause cough, shortness of breath, or chest pain.
“B symptoms”: Unexplained fever, night sweats, and weight loss.
Fatigue or weakness from low red blood cell counts (anemia).
Bone or joint pain.
Compression symptoms: Tumours pressing on nearby organs can cause swallowing difficulty or abdominal pain.
Because the disease can appear in many different places, symptoms vary widely from one person to another.
The exact cause is not known, but B-LBL begins when genetic mutations occur in immature B cells, allowing them to grow uncontrollably and resist normal cell death.
Possible contributing factors include:
Random genetic changes that occur during cell division.
Environmental exposures, such as radiation or certain chemicals (though no specific trigger has been confirmed).
Inherited predisposition: Rarely, people with a family history of lymphoid cancers have a slightly higher risk.
Down syndrome: Children with Down syndrome are at increased risk of developing B-LBL and related leukemias due to extra copies of genes on chromosome 21 that affect blood cell development.
The diagnosis of B-LBL is made through several steps that combine clinical evaluation, imaging, blood testing, and microscopic and molecular studies of tumour tissue.
A doctor begins with a thorough history and physical exam, looking for swollen lymph nodes, enlarged spleen or liver, or masses in other parts of the body. They will also ask about fever, weight loss, and night sweats (“B symptoms”).
Imaging helps determine where the disease is located and how far it has spread.
CT (computed tomography) scans and MRI (magnetic resonance imaging) show tumours in the chest, abdomen, or other organs.
PET (positron emission tomography) scans detect areas of active disease and help guide biopsy.
These scans provide a “map” of the disease before treatment begins.
A complete blood count (CBC) measures the numbers of red blood cells, white blood cells, and platelets.
Some patients have anemia (low red blood cells) or thrombocytopenia (low platelets).
The white blood cell count may be normal or abnormal depending on whether the bone marrow is affected.
Other blood tests evaluate kidney and liver function before treatment and may include lactate dehydrogenase (LDH), which can be elevated when cancer cells grow rapidly.
A biopsy is required to confirm the diagnosis. A small piece of tissue is taken from an enlarged lymph node or tumour mass and sent to a pathologist, a doctor who examines tissues under the microscope.
A bone marrow biopsy may also be done to check for cancer cells inside the marrow. This helps distinguish B-LBL (tumour outside the bone marrow) from B-ALL (cancer mainly in the bone marrow).
Under the microscope, B-LBL is made up of lymphoblasts—immature B cells that are medium to large in size with very little cytoplasm (cell body) and large nuclei that take up most of the cell. The nuclei have finely scattered chromatin and one or more prominent nucleoli (round areas inside the nucleus).
The cells grow in a diffuse pattern, meaning they spread throughout the tissue rather than forming nodules or follicles. Many cells are actively dividing (high mitotic activity), and areas of necrosis (dead cells) may be seen in larger tumours.
These features confirm that the tumour is made up of immature lymphoid cells.
Immunohistochemistry uses special antibodies to detect proteins on or inside the tumour cells. This test confirms that the cells are immature B cells and not another type of lymphoma or leukemia.
In B-LBL, the cells usually express:
B-cell markers: CD19, CD22, CD79a
Immaturity markers: TdT (terminal deoxynucleotidyl transferase) and CD34
Variable expression of CD20 (may be weak or absent)
IHC helps confirm the diagnosis and distinguish B-LBL from other aggressive lymphomas or leukemias.
Flow cytometry is a laboratory test that studies cells in a liquid sample—usually from the biopsy, blood, or bone marrow. It uses fluorescent antibodies to measure the presence and strength of specific proteins on the surface of each cell.
In B-LBL, flow cytometry confirms that the cells are B cells with markers of immaturity, such as TdT. It also provides information about how uniform the cells are—when all cells look the same, it confirms that the population is clonal, meaning they all came from one original abnormal cell.
Flow cytometry is an essential test for confirming the diagnosis and distinguishing B-LBL from other lymphoid cancers.
PCR is a highly sensitive test that can detect small genetic changes or rearrangements in DNA that identify the tumour as coming from B cells. PCR can also detect gene fusions (when two genes join abnormally) or chromosomal rearrangements characteristic of specific subtypes of B-LBL.
PCR results help confirm the diagnosis and may identify targetable genetic changes that influence treatment decisions.
Next-generation sequencing (NGS) is a modern molecular test that reads the DNA of the tumour in great detail. It can detect multiple mutations, chromosomal translocations, or copy-number changes at once.
Pathologists use NGS to identify specific subtypes of B-LBL, as defined by the World Health Organization (WHO). For example, some subtypes show fusions like BCR::ABL1 or ETV6::RUNX1, while others have too many or too few chromosomes (called hyperdiploidy or hypodiploidy). These genetic differences help doctors choose the best treatment and predict prognosis.
B-LBL and B-ALL are classified by the genetic and molecular changes found in the tumour cells. Some examples include:
B-LBL with high hyperdiploidy: Tumour cells have extra copies of certain chromosomes; generally associated with a good prognosis.
B-LBL with BCR::ABL1 fusion (“Philadelphia chromosome”): Associated with a more aggressive course; targeted drugs such as tyrosine kinase inhibitors may be used.
B-LBL with KMT2A rearrangement or iAMP21: Often requires more intensive treatment due to a higher risk of relapse.
Your pathology report will describe any genetic alterations detected and may list the WHO subtype based on those findings.
After treatment, pathologists and oncologists monitor minimal residual disease (MRD)—the tiny number of cancer cells that may remain after therapy. MRD testing uses flow cytometry, PCR, or NGS to detect one cancer cell among a million normal cells.
MRD testing is the most sensitive way to measure treatment response and predict relapse risk. Patients with no detectable MRD after therapy have a better prognosis.
Unlike most solid tumours, lymphomas are not staged in the same way because they can involve multiple areas of the body simultaneously. Prognosis depends on factors such as:
Patient age (outcomes are best in children).
Blood counts and bone marrow involvement.
Genetic abnormalities in the cancer cells.
Response to treatment and MRD status.
Children with B-LBL generally have an excellent prognosis, with complete remission rates over 95%. Adults have lower remission rates (60–85%), and outcomes vary depending on genetics and response to therapy.
After diagnosis, patients are managed by a team of specialists including hematologists, oncologists, and pathologists.
Treatment typically involves combination chemotherapy, and in some cases, targeted therapy or stem cell transplantation. During and after treatment, patients are monitored with:
Complete blood counts (CBCs) to check bone marrow recovery.
Bone marrow biopsies to evaluate remission.
MRD testing using flow cytometry, PCR, or NGS to ensure no remaining disease.
Your pathology report forms the foundation of your treatment plan by confirming the diagnosis, describing the genetic subtype, and identifying features that may affect prognosis.
What tests were done to confirm my diagnosis?
What genetic findings were identified in my report, and what do they mean?
Is my disease considered more aggressive or standard risk?
What treatment plan do you recommend?
How will my response to treatment be monitored (for example, MRD testing)?
What is my long-term outlook?