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by David Li MD

A bone marrow biopsy is one of the most informative tests in medicine for conditions affecting the blood and immune system. If you have received a bone marrow biopsy report, you may be facing a diagnosis of leukemia, lymphoma, myeloma, anemia, or another blood disorder — or your doctor may still be working out what is wrong. In either case, the report can be difficult to read without guidance. This article explains what a bone marrow biopsy involves, what the laboratory does with the sample, and what the terms and findings in your report mean.


What is bone marrow and what does it do?

Bone marrow is the soft, spongy tissue found inside many of the body’s larger bones, including the hip bones, breastbone, and spine. It is the body’s blood-cell factory. Every day, bone marrow produces billions of new blood cells to replace those that have reached the end of their natural lifespan.

Bone marrow produces three main types of blood cells:

  • Red blood cells. These carry oxygen from the lungs to every tissue in the body. A shortage of red blood cells causes a condition called anemia, which leads to fatigue, shortness of breath, and paleness.
  • White blood cells. These are the cells of the immune system. They fight infections and help the body recognize and destroy abnormal cells. There are several types of white blood cells, including neutrophils, lymphocytes, eosinophils, and basophils, each with a different role.
  • Platelets. These are tiny cell fragments that help the blood clot when a blood vessel is injured. A shortage of platelets can cause easy bruising or bleeding.

All three types of blood cells begin their lives in the bone marrow as immature cells called stem cells. Through a carefully regulated process called hematopoiesis, these stem cells develop into the mature, specialized cells that circulate in the blood. When something goes wrong with this process — whether due to cancer, a genetic change, a nutritional deficiency, or another cause — a bone marrow biopsy can help identify what is happening.


Why is a bone marrow biopsy done?

Your doctor may recommend a bone marrow biopsy for many different reasons. The most common are:

  • To investigate abnormal blood test results. If a complete blood count shows unexplained low or high levels of red blood cells, white blood cells, or platelets, a bone marrow biopsy can help find the cause.
  • To diagnose a blood cancer. Conditions such as leukemia, lymphoma, multiple myeloma, and myelodysplastic syndrome often involve the bone marrow. A biopsy is usually essential to confirm the diagnosis and identify the specific type.
  • To stage a known cancer. Some cancers that begin elsewhere in the body, such as lymphoma, can spread to the bone marrow. A biopsy helps determine how widespread the disease is, which affects treatment planning.
  • To monitor treatment response. A biopsy performed after treatment for a blood cancer can show whether the cancer has responded, whether the marrow is recovering, or whether any residual disease remains.
  • To investigate unexplained symptoms. Persistent fatigue, unexplained fevers, night sweats, unexplained weight loss, or bone pain may prompt a bone marrow biopsy to look for an underlying condition.
  • To evaluate a bone marrow transplant. After a stem cell or bone marrow transplant, a biopsy can confirm whether the donor cells have successfully established themselves in the marrow.

How is a bone marrow biopsy performed?

The biopsy is almost always performed from the posterior iliac crest, which is the curved ridge of the hip bone at the back of the pelvis. This site is preferred because it is easy to access, the bone is large enough to yield an adequate sample, and the area is away from major blood vessels and nerves.

The skin and the bone surface are numbed with a local anesthetic. Most patients feel pressure rather than sharp pain during the procedure, though the experience varies. The procedure typically takes only a few minutes.

Two types of samples are usually collected at the same time during a single visit:

  • Bone marrow aspirate. A thin, hollow needle is inserted into the marrow space and a small amount of liquid marrow is drawn out, like drawing blood. The liquid is spread onto glass slides so that individual cells can be examined in detail. The aspirate is particularly useful for counting cells, assessing their appearance, and performing specialized tests such as flow cytometry and genetic testing.
  • Core biopsy (also called a trephine biopsy). A slightly larger needle is used to remove a small, solid cylinder of bone and marrow tissue, typically one to two centimetres long. This solid core preserves the architecture of the marrow — how cells are organized and distributed within the space — which cannot be assessed on the aspirate alone. The core biopsy is especially important when the marrow is scarred or when cancer cells are not evenly distributed throughout the marrow.

In some situations, such as when the marrow is heavily scarred, a dry tap may occur. This means the aspirate needle fails to draw back liquid marrow. When this happens, the core biopsy becomes the primary source of diagnostic information.


What does the pathology laboratory do with the sample?

Once the samples reach the laboratory, they are processed differently depending on the specimen type.

The aspirate smears are stained with special dyes and examined under the microscope. Additional tests, including flow cytometry and cytogenetic analysis, are usually set up immediately from the fresh liquid marrow.

The core biopsy is fixed in a preservative solution and then treated with a decalcifying agent to soften the bone so it can be cut into very thin slices. These slices are placed on glass slides and stained with several different dyes to highlight different cell types and structures. The whole process for the core biopsy typically takes one to two days longer than the aspirate.

Because bone marrow biopsy reports often require integration of results from multiple tests — microscopy, flow cytometry, genetic studies, and sometimes special stains — it is common for an initial or preliminary report to be issued first, with a final report following once all results are available. Your doctor will explain what has been reported and what is still pending.


What does a bone marrow biopsy report contain?

Bone marrow biopsy reports vary in format by laboratory and clinical situation, but most contain the same core elements. The following sections explain what each part means.

Adequacy of the sample

The pathologist begins by assessing whether the samples received are adequate for diagnosis. For the core biopsy, adequacy usually requires a minimum length of tissue containing evaluable marrow. For the aspirate, there must be enough cells to count and assess. If the sample is inadequate, the report will say so, and a repeat biopsy may be recommended.

Cellularity

Cellularity describes the proportion of the marrow space occupied by blood-forming cells relative to fat cells. Normal bone marrow contains both, and the expected balance changes with age. A rough guide is that normal cellularity approximates 100 minus the patient’s age as a percentage — so a 60-year-old would be expected to have roughly 40% cellularity. However, this is a general guide, and pathologists use their overall experience rather than a strict formula.

  • Normocellular. The proportion of blood-forming cells is appropriate for the patient’s age. This is the expected finding in a healthy marrow.
  • Hypercellular. The marrow contains more blood-forming cells than expected for the patient’s age. This can be seen in leukemia, myeloproliferative neoplasms (such as polycythemia vera or chronic myeloid leukemia), infections, and other conditions that drive increased blood cell production.
  • Hypocellular. The marrow contains fewer blood-forming cells than expected, with more fat than normal. This can be seen in aplastic anemia, after chemotherapy or radiation, in certain infections, and in some chronic illnesses.

Hematopoiesis

Hematopoiesis is the process by which the bone marrow produces blood cells. The pathologist examines whether all three main cell lines — red blood cell precursors, white blood cell precursors, and platelet-producing cells — are present and developing normally. When all three are present and normal, the report may describe this as trilineage hematopoiesis.

  • Erythroid lineage. The cells that develop into red blood cells. The pathologist assesses their number, maturity, and whether they show any abnormalities.
  • Granulocytic (myeloid) lineage. The cells that develop into white blood cells, such as neutrophils, eosinophils, and basophils. These are assessed for their number, maturity, and the ratio of immature to mature forms.
  • Megakaryocytic lineage. The large cells that produce platelets. The pathologist notes whether megakaryocytes are present in normal numbers and whether they appear normal or abnormal in shape.

The report may note that one or more of these lineages is increased, decreased, or shows dysplasia. Dysplasia means the cells look abnormal in size, shape, or organization, which can be a sign of myelodysplastic syndrome or another marrow disorder.

Blast percentage

Blasts are the most immature blood-forming cells in the bone marrow. In a healthy marrow, blasts normally make up less than 5% of all cells. An increased blast percentage is one of the most important findings in a bone marrow report because it can indicate leukemia or progression of a pre-existing blood disorder.

  • Less than 5% blasts. Normal.
  • 5–19% blasts. Elevated but below the diagnostic threshold for most types of acute leukemia. This level may be seen in myelodysplastic syndrome or in conditions that are progressing toward leukemia.
  • 20% blasts or more. This is the threshold used to diagnose most types of acute leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia. However, some specific genetic subtypes of leukemia are diagnosed regardless of the blast count when the defining genetic change is present.

The blast percentage is counted on the aspirate smear, where individual cells can be assessed clearly. The report will state whether blasts are of myeloid or lymphoid type, which determines the specific diagnosis.

Fibrosis (scarring)

Fibrosis means scarring of the bone marrow. When the normal marrow tissue is replaced by fibrous scar tissue, it interferes with the marrow’s ability to produce blood cells. Fibrosis is detected using a special stain called a reticulin stain, which highlights the fibrous framework of the marrow.

Marrow fibrosis is graded on a scale from MF-0 (no fibrosis, normal) to MF-3 (dense, severe fibrosis). The grades are:

  • MF-0. No fibrous network beyond what is normally present. Normal finding.
  • MF-1. A slight increase in fibrous fibers, loosely arranged. This can be a normal variation or an early sign of a marrow disorder.
  • MF-2. A moderate increase in fibrous fibers, with areas where they cross each other. This is seen in more significant marrow disorders, including primary myelofibrosis and other myeloproliferative neoplasms.
  • MF-3. Dense, coarse scarring throughout the marrow. This degree of fibrosis severely impairs blood cell production and is associated with advanced disease.

When fibrosis is severe, it often causes a dry tap on aspiration, meaning no liquid marrow can be withdrawn, and the diagnosis must rely on the core biopsy.

Iron stores

Iron is stored in the bone marrow and is essential for red blood cell production. A special stain called a Prussian blue or iron stain is often used to assess the amount and form of iron in the marrow.

  • Absent or reduced iron stores. This can be a sign of iron-deficiency anemia, the most common cause of anemia worldwide. When iron stores are absent from the marrow, the body cannot make enough hemoglobin, the protein in red blood cells that carries oxygen.
  • Normal iron stores. A normal finding that helps rule out iron deficiency as the cause of anemia.
  • Increased iron stores. Can be seen in anemia of chronic disease, hemolytic anemias, or conditions in which iron is not used properly.
  • Ring sideroblasts. These are red blood cell precursors in which iron granules form an abnormal ring around the nucleus. Their presence is associated with specific types of myelodysplastic syndrome and helps classify the subtype.

Special tests that may be performed on bone marrow samples

Because bone marrow diseases are often complex and require precise classification, several specialized tests are routinely performed alongside the microscopic examination. These tests provide information that cannot be obtained from the biopsy slides alone. Your report may include results from some or all of these.

Flow cytometry and immunophenotyping

Flow cytometry is a laboratory technique that analyzes thousands of individual cells very rapidly. Cells from the aspirate are tagged with fluorescent antibodies that attach to specific proteins on the cell surface or inside the cell. A machine then measures which proteins each cell carries.

This test is used to:

  • Identify whether abnormal cells are of myeloid type (as in acute myeloid leukemia) or lymphoid type (as in acute lymphoblastic leukemia or lymphoma).
  • Detect abnormal patterns of protein expression that indicate cancer.
  • Confirm a diagnosis of conditions such as chronic lymphocytic leukemia, multiple myeloma, or hairy cell leukemia.
  • Detect minimal residual disease — very small amounts of cancer cells that remain after treatment, below the level visible under the microscope.

The results of flow cytometry are described using the names of the proteins detected. These proteins are named with the prefix CD followed by a number (for example, CD3, CD19, CD34, CD138). Each blood cell type has its own characteristic pattern of CD markers, and abnormal cells often show an unusual combination. Your report may list these markers and describe them as positive or negative.

Immunohistochemistry

Immunohistochemistry uses antibodies applied directly to the core biopsy slides to detect specific proteins within the marrow tissue. It is complementary to flow cytometry and is particularly useful when the aspirate has been inadequate or when assessing the distribution and pattern of abnormal cells within the marrow space. Common applications include identifying plasma cells in myeloma, detecting lymphoma involvement, and assessing whether cancer cells carry specific proteins relevant to treatment decisions.

Cytogenetic analysis (karyotype)

Cytogenetics is the study of chromosomes. In a bone marrow biopsy, cells from the aspirate are grown in the laboratory for several days and then examined to count and analyze all 46 chromosomes. This is called a karyotype.

Changes in chromosomes — such as missing chromosomes, extra chromosomes, or pieces of chromosomes that have moved to a different location (translocations) — are extremely important in blood cancers because they often define the specific type of leukemia or lymphoma, predict how the disease will behave, and guide treatment choices. For example, the Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22, defines chronic myeloid leukemia and a specific subtype of acute lymphoblastic leukemia.

Cytogenetic results are usually reported as a karyotype formula using internationally standardized notation. Your report may include a line such as 46,XY [20] (which means 46 chromosomes, a normal male karyotype, seen in 20 cells counted) or a more complex description of an abnormal chromosome pattern.

Fluorescence in situ hybridization (FISH)

FISH is a more targeted genetic test that uses fluorescent probes designed to attach to specific regions of chromosomes. Unlike a full karyotype, which surveys all chromosomes at once, FISH looks for specific, known abnormalities in a large number of cells very quickly. It is particularly useful for detecting abnormalities that are too subtle to see on a standard karyotype, and for confirming specific changes suspected from other results.

Common examples of FISH tests in haematological diseases include testing for BCR::ABL1 fusion in chronic myeloid leukemia, deletion of chromosome 17p in chronic lymphocytic leukemia, and specific translocations in myeloma.

Molecular and genetic testing

Molecular testing looks for specific gene mutations or fusion genes at the DNA or RNA level. Modern techniques such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) can detect very small genetic changes in leukemia or lymphoma cells that are not visible under the microscope or detectable by cytogenetics or FISH.

Molecular testing serves several purposes:

  • Confirming a specific diagnosis when a characteristic mutation is found.
  • Predicting how aggressive a cancer is likely to be and how it will respond to treatment.
  • Identifying mutations that make certain targeted therapies likely to work.
  • Monitoring for minimal residual disease after treatment with extreme sensitivity.

Molecular results are often reported as detected or not detected for specific mutations or fusion genes, along with a variant allele frequency (VAF) — which is the proportion of cells carrying the mutation — expressed as a percentage. A high VAF means most cells carry the mutation. A low VAF after treatment suggests only a small number of residual cancer cells remain.


What does the diagnosis section of the report tell me?

The diagnosis section integrates findings from microscopy, flow cytometry, cytogenetics, and molecular testing to state the final conclusion. Depending on your situation, the diagnosis may be one of several types.

A specific diagnosis

In many cases, the report will state a clear diagnosis, such as acute myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, follicular lymphoma, or myelodysplastic syndrome. The report will typically include information about the specific subtype, which is determined by the combination of microscopic features and special test results. Subtype matters because different subtypes behave differently and respond to different treatments.

Involvement by a known disease

If you already have a diagnosed cancer, the bone marrow biopsy may have been performed to determine whether that cancer has spread to the marrow. In this case, the report may state that the marrow shows involvement by your known cancer — for example, “involvement by follicular lymphoma” or “metastatic carcinoma.” This finding affects staging and treatment planning.

Reactive or benign changes

Sometimes the bone marrow shows abnormalities that are caused by a non-cancerous condition such as infection, inflammation, nutritional deficiency, or the effects of medication. In this case, the report will describe the findings and offer a possible explanation. Reactive changes are important to distinguish from cancer, and additional clinical information or follow-up tests may be needed to clarify the picture.

Inadequate or inconclusive result

Occasionally, the biopsy does not yield enough tissue or cells for a definitive conclusion. The report will say so, and a repeat biopsy is often recommended. This is not necessarily a cause for alarm — bone marrow biopsy is a technically challenging procedure, and repeat sampling frequently yields an adequate result.

Pending results

Because bone marrow reports depend on tests that take different amounts of time to complete, your initial report may include a note that additional results are pending, such as cytogenetics or molecular testing. A final or amended report will be issued once all results are available. It is important to ask your doctor whether your report is final or whether additional results are expected.


What happens after the bone marrow biopsy report is finalized?

Once the complete report is available, your haematologist or oncologist will review all of the findings with you and explain what they mean for your diagnosis and treatment plan. For many blood conditions, the bone marrow biopsy is one piece of a larger assessment that also includes blood tests, imaging, and your symptoms and medical history.

If a cancer has been diagnosed, your doctor will discuss the specific type and subtype, what is known about its typical behavior, and what treatment options are available. For some conditions, treatment begins promptly. For others, such as slow-growing lymphomas or some cases of myelodysplastic syndrome, a period of careful monitoring without immediate treatment may be appropriate.

If a repeat biopsy is needed to monitor your disease or assess your response to treatment, your doctor will explain when and why it is recommended.


Questions to ask your doctor

  • What did my bone marrow biopsy show?
  • Is the report final, or are there additional test results still expected?
  • Was the sample adequate, or do I need a repeat biopsy?
  • What is the specific diagnosis, and what subtype is it?
  • What do the blast percentage, cellularity, and fibrosis findings mean for me?
  • What did the flow cytometry, cytogenetics, or molecular tests show?
  • Has the cancer or disease spread into the bone marrow, or does it originate there?
  • Does my biopsy result affect my treatment options or prognosis?
  • Will I need a repeat bone marrow biopsy during or after treatment?
  • Should I be referred to a haematologist or haematological oncologist if I have not seen one already?

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