Bone Marrow Aspiration and Biopsy

Definition
Purpose
Description
Diagnosis/Preparation
Aftercare
Risks
Normal results

Definition

Bone marrow aspiration, also called bone marrow sampling, is the removal by suction of the soft, spongy semisolid tissue (marrow) that fills the inside of the body’s long and flat bones. Bone marrow biopsy, or needle core biopsy, is the removal of a small piece (about 0.75 x 0.06 in, 2 x 0.16 cm) of intact bone marrow. The bone marrow is where blood cells are made.

Purpose

Examination of the bone marrow may be the next step that follows an irregular clinical finding, such as an abnormal complete blood count (CBC), and/or an abnormal peripheral blood smear. It may also be performed following an abnormal bone image, such as the finding of a lesion on x rays.

A biopsy of bone marrow shows the intact tissue, so that the structure of the fat cells, lymphocytes, plasma cells, fibrous connective tissue cells, and other cells—and their relationships to each other—can be seen. A bone marrow biopsy is used for all the following:

• diagnose and manage any form of leukemia or other myeloproliferative condition such as multiple myeloma
• rule out or confirm bone marrow infiltration by malignancies such as Hodgkin’s disease, non-Hodgkin’s lymphoma, and metastatic carcinoma
• monitor the effects of chemotherapy and the response or lack of response to treatment of blood disease
• evaluate the success of bone marrow transplantation
• diagnose certain genetic diseases (e.g., lipid storage disease)
• investigate pancytopenia (a decrease of all blood cells in peripheral blood), neutropenia (decreased phagocytic white blood cells), or thrombocytopenia (decreased platelets)
• diagnose an infection of unknown origin
• investigate rare anemias for which a cause cannot be found or which does not respond to treatment as anticipated
• obtain intact bone marrow for laboratory analysis
• diagnose some types of cancer, or anemia and other blood disorders
• identify the source of an unexplained fever (e.g., granulomatous lesions)
• diagnose fibrosis of bone marrow and myeloma when bone marrow aspiration has failed to provide an appropriate specimen

The combination of aspiration and biopsy procedures are commonly used to ensure the availability of the best possible bone marrow specimen. The aspirate is collected at the same time as the bone core biopsy by attaching a syringe to the bone marrow needle and withdrawing the sample before the cutting blades are inserted and the bone core is removed. The aspirate is the sample of choice for studying and classifying the nucleated blood cells of the bone marrow (e.g., determining the ratio of immature white blood cells to red blood cells, which is the M:E ratio). The biopsy is the only sample that shows the blood-forming cells in relation to the structural and connective tissue elements (i.e., the microarchitecture) of the bone marrow. It provides the best sample for evaluating the cellularity of the bone marrow (the percentage of blood-forming tissue versus fat).

Description

Bone marrow aspiration and biopsy are performed by a pathologist, hematologist, or oncologist with special training in this procedure. The procedure may be performed on an outpatient basis. In adults, the specimen is usually taken from the posterior superior iliac crest (top rear part of the hip). The sternum (breastbone) may be used for aspiration, but is less desirable because it carries the risk of cardiac puncture. Other sites that are rarely used are the anterior superior iliac crest or a spinal column bone. When the patient is a child, the biopsy site is generally the anterior tibia, the larger of the two bones in the lower leg. A vertebra may also be used.

The skin covering the biopsy site is cleansed with an antiseptic, and the patient may be given a mild sedative. A local anesthetic such as lidocaine is administered first under the skin with a fine needle and then around the bone at the intended puncture site with a somewhat larger-gauge needle. When the area is numb, a small incision is made in the skin and the biopsy needle is inserted. Pressure is applied to force

KEY TERMS

Antibodies— Proteins that are produced normally by specialized white blood cells after stimulation by a foreign substance (antigen) and that act specifically against the antigen in an immune response.

Aspiration— A procedure to withdraw fluid and cells from the body.

Connective tissue— Cells such as fibroblasts, and material such as collagen and reticulin, that unite one part of the body with another.

Fibrosis— A condition characterized by the presence of scar tissue, or reticulin and collagen proliferation in tissues to the extent that it replaces normal tissues.

Hematologist— A specialist who treats diseases and disorders of the blood and blood-forming organs.

Hematoma— Blood that collects under the skin, forms a blood clot, and causes swelling.

Hemorrhage— Heavy bleeding.

Immune system— Mechanism that protects the body from foreign substances, foreign cells, and pathogens. The thymus, spleen, lymph nodes, white blood cells, including the B cells and T cells, and antibodies are involved in the immune response, which aims to destroy these foreign bodies.

Lymphocytes— Type of white blood cells that are part of the immune system. The lymphocytes are composed of three main cell lines: B lymphocytes, T lymphocytes, and natural killer (NK) cells.

Myeloma (multiple myeloma)— A tumor of plasma cells that originates in bone marrow and usually spreads to more than one bone.

Needle biopsy— The procedure of using a large hollow needle to obtain a sample of intact tissue.

Pathologist— A medical doctor that specializes in identifying diseases by studying cells and tissues under a microscope.

Plasma cells— Cells in the blood and bone marrow that are formed from B lymphocytes, and that produce antibodies.

White blood cells (leukocytes)— Cells of the blood that are responsible for fighting infection.

the needle through the outer bone, and a decrease in resistance signals entry into the marrow cavity. The needle most often used for bone marrow biopsy is a Jamshidi trephine needle or a Westerman-Jensen trephine needle. A syringe is placed on the top of the needle and 1–2 ml of the bone marrow is aspirated into the syringe. In some instances, the marrow cannot be aspirated because it is fibrosed, or packed with neo-plastic cells. The syringe is removed and the medical technologist uses this sample to prepare several smears containing small pieces of bone (spicules). Another syringe is fitted onto the needle hub and another sample of 3 ml is removed and transferred to a tube containing EDTA for analysis by flow cytometry, cytogenetic testing, or other special laboratory procedures. Following aspiration, the cutting blades are inserted into the hollow of the needle until they protrude into the marrow. The needle is then forced over the tips of the cutting blades and the needle is rotated as it is withdrawn from the bone. This process captures the core sample inside the needle. A wire probe is inserted at the cutting end, and the bone marrow sample is pushed through the hub of the needle onto sterile gauze. The specimen is used to make several preparations on glass slides or cover glasses and is transferred to a fixative solution.

In the laboratory, the aspirate slides are stained with Wright stain or Wright-Giemsa stain. The biopsy material is sectioned onto glass slides and stained with hematoxylin-eosin, Giemsa, and Prussian blue stains. Prussian blue stain is used to evaluate the amount of bone marrow iron, and the other stains are used to contrast cell structures under the microscope. In addition, special stains may be used that aid in the classification of malignant white blood cells.

Diagnosis/Preparation

The physician should be informed of any medication the patient is using and of any heart surgery that the patient may have undergone.

Adults require no special preparation for this test. As for infants and children, they need physical and psychological preparation, depending on their age, previous medical experiences, and level of trust.

Infant preparation

Before the test, parents should know that their child will most probably cry, and that restraints might be used. To provide comfort and to help their child through this procedure, parents are commonly asked to be present during the procedure. Crying is a normal infant response to an unfamiliar environment, strangers, restraints, and separation from the parent. Infants cry more for these reasons than because they hurt. An infant will be restrained by hand or with devices because they have not yet developed the physical control, coordination, and ability to follow commands as adults have. The restraints used thus aim to ensure the infant’s safety.

Toddler preparation

Parents should prepare a toddler for bone marrow aspiration directly before the procedure, because toddlers have a very short attention span. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on the body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going home.

Preschooler preparation

Parents should prepare a preschooler for bone marrow aspiration directly before the procedure, so that the child does not worry about it for days in advance. Parents should ensure that the child understands that the procedure is not a punishment. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on the body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel and be honest about any pain that may be felt.
• Allow the child to practice different positions or movements that will be required for the procedure.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going for a treat on the way home.
• Practice deep breathing and other relaxation exercises. Practice also to have the child hold your hand and tell him or her to squeeze it when he or she feels pain during the procedure.

School-age child preparation

Explanations should be limited to 20 minutes, and repeated if required. The older the child, the earlier a parent can start preparation. Guidelines for parents include the ones provided for preschoolers, as well as the following:

• Suggest ways for maintaining control during the procedure; for example, counting, deep breathing, and relaxation (thinking pleasant thoughts).
• Include the child in the decision-making process; for example, the time of day or the body site where the procedure will be performed. These of course depend on the scheduling constraints of the physician and the type of procedure being performed.
• Encourage the child to participate in the procedure; for example, by holding an instrument, if allowed by the attending hospital staff.
• Encourage the child to hold your hand or the hand of a nurse. Physical contact does help reduce pain and anxiety.

Adolescent preparation

An adolescent is best prepared by being provided with detailed information and reasons for the procedure. Adolescents should be encouraged to make as many decisions as possible. An adolescent may or may not wish a parent to be present during the procedure, and such wishes should be respected, since privacy is important during adolescence. Other guidelines include the following:

• Explain the procedure in correct medical terminology, and provide the reason for it.
• As clearly as possible, describe the equipment that will be involved in concrete terms.
• Discuss potential risks honestly and openly.

Aftercare

After the needle is removed, the biopsy site is covered with a clean, dry pressure bandage. The patient must remain lying down and is observed for bleeding for one hour. The patient’s pulse, breathing, blood pressure, and temperature are monitored until they return to normal. The biopsy site should be kept covered and dry for several hours.

The patient should be able to leave the clinic and resume most normal activities immediately. Patients who have received a sedative often feel sleepy for the rest of the day; so driving, cooking, and other activities that require clear thinking and quick reactions should be avoided. Walking or prescribed pain medications

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

A physician requests or orders the procedure. The aspirate and biopsy are most often performed in a hospital or clinic by a hematologist or pathologist that has been trained in the procedure. The analysis of the bone marrow is done by a pathologist, and a written report is added to the patient’s medical record. A histologic technician performs special stains for bone marrow. Clinical laboratory scientists/medical technologists perform smear reviews and analysis of bone marrow cells by flow cytometry. Cytogenetic technologists may perform chromosomal analysis of bone marrow white blood cells.

usually ease any discomfort felt at the biopsy site, and ice can be used to reduce swelling.

A doctor should be notified if the patient:

• feels severe pain for more than 24 hours after the procedure.
• experiences persistent bleeding or notices more than a few drops of blood on the wound dressing.
• has a temperature above 101°F (38.3°C).
• has inflammation and pus at the biopsy site and other signs of infection.

Risks

A small amount of bleeding and moderate discomfort often occur at the biopsy site. Rarely, reactions to anesthetic agents, infection, and hematoma (blood clot) or hemorrhage (excessive bleeding) may also develop. In rare instances, the heart or a major blood vessel is pierced when marrow is extracted from the sternum during bone marrow biopsy. This can lead to severe hemorrhage.

Normal results

Healthy adult bone marrow contains yellow fat cells, connective tissue, and red marrow that produces blood. Bone marrow is evaluated for cellularity, mega-karyocyte production, M:E ratio, differential (classification of blood-forming cells), iron content, lymphoid, bone, and connective tissue cells, and bone and blood vessel abnormalities. The bone marrow of a healthy infant is primarily red (75–100% cellularity), but the distribution of blood-forming cells is very different

QUESTIONS TO ASK THE DOCTOR

• What are the possible risks involved in this procedure?
• How many times will the procedure be required?
• How do I prepare for the procedure?
• Must I do anything special after the procedure?
• How long does it take to know the results?
• How many bone marrow aspirations/biopsies do you perform each year?

than adult marrow. Consequently, age-related normal values must be used.

Microscopic examination of bone marrow can reveal leukemia, granulomas, myelofibrosis, myeloma, lymphoma, or metastatic cancers, bone marrow infection, and bone disease. Bone marrow evaluation is usually not needed to diagnose anemia, but may be useful in cases that cannot be classified by other means.

Resources

BOOKS

Abeloff, M. D., et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004.

Khatri, V. P., and J. A. Asensio. Operative Surgery Manual. 1st ed. Philadelphia: Saunders, 2003.

Townsend, C. M., et al. Sabiston Textbook of Surgery. 17th ed. Philadelphia: Saunders, 2004.

PERIODICALS

Azar, D., C. Donaldson, and L. Dalla-Pozza. “Questioning the Need for Routine Bone Marrow Aspiration and Lumbar Puncture in Patients with Retinoblastoma.” Clinical and Experimental Ophthalmology 31 (February 2003): 57–60.

Jubelirer, S. J., and R. Harpold. “The Role of the Bone Marrow Examination in the Diagnosis of Immune Thrombocytopenic Purpura: Case Series and Literature Review.” Clinical and Applied Thrombosis/Homeostasis 8 (January 2002): 73–76.

ORGANIZATIONS

The Leukemia & Lymphoma Society. 1311 Mamaroneck Avenue, White Plains, NY 10605. (914) 949-5213. http://www.leukemia.org (accessed March 7, 2008).

National Cancer Institute Cancer Information Service. 31 Center Drive, Bethesda, MD 20892-2580. (800) 422-6237. http://www.nci.nih.gov (accessed March 7, 2008).

National Marrow Donor Program. Suite 500, 3001 Broadway Street NE, Minneapolis, MN 55413-1753. (800) 627-7692. http://www.marrow.org (accessed March 7, 2008).

OTHER

“Diagnostic Tests: Bone Marrow Biopsy.” Harvard Family Health Guide. [cited April 2003]. http://www.health.harvard.edu/fhg/diagnostics/marrow/marrow.shtml (accessed March 7, 2008).

Mark A. Best

Monique Laberge, Ph.D.

Rosalyn Carson-DeWitt, MD

Bone marrow aspiration and biopsy

Definition

Bone marrow aspiration, also called bone marrow sampling, is the removal by suction of the soft, spongy semisolid tissue (marrow) that fills the inside of the long and flat bones. Bone marrow biopsy, or needle core biopsy, is the removal of a small piece (about 0.75 X 0.06 in, or 2 X 0.16 cm) of intact bone marrow. The bone marrow is where blood cells are made.

Purpose

Examination of the bone marrow may be the next step that follows an abnormal clinical finding, such as an abnormal complete blood count (CBC), and/or an abnormal peripheral blood smear. It may also be performed following an abnormal bone image such as the finding of a lesion on x rays.

A biopsy of bone marrow shows the intact tissue, so that the structure of the fat cells, lymphocytes, plasma cells, fibrous connective tissue cells, and other cells, and their relationships to each other, can be seen. A bone marrow biopsy is used to:

• diagnose and manage any form of leukemia or other myeloproliferative condition such as multiple myeloma
• rule out or confirm bone marrow infiltration by malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and metastatic carcinoma
• monitor the effects of chemotherapy and the response or lack of response to treatment of blood disease
• evaluate the success of bone marrow transplantation
• diagnose certain genetic diseases (e.g., lipid storage disease)
• investigate pancytopenia (a decrease of all blood cells in peripheral blood), neutropenia (decreased phagocytic white blood cells), or thrombocytopenia (decreased platelets)
• diagnose an infection of unknown origin
• investigate rare anemias for which a cause cannot be found or which does not respond to treatment as anticipated
• obtain intact bone marrow for laboratory analysis
• diagnose some types of cancer or anemia and other blood disorders
• identify the source of an unexplained fever (e.g., granulomatous lesions)
• diagnose fibrosis of bone marrow and myeloma when bone marrow aspiration has failed to provide an appropriate specimen

The combination of aspiration and biopsy procedures are commonly used to ensure the availability of the best possible bone marrow specimen. The aspirate is collected at the same time as the bone core biopsy by attaching a syringe to the bone marrow needle and withdrawing the sample before the cutting blades are inserted and the bone core is removed. The aspirate is the sample of choice for studying and classifying the nucleated blood cells of the bone marrow (e.g., determining the ratio of immature white blood cells to red blood cells (M:E ratio). The biopsy is the only sample that shows the blood forming cells in relation to the structural and connective tissue elements (i.e., the microarchitecture) of the bone marrow. It provides the best sample for evaluating the cellularity of the bone marrow (the percentage of blood-forming tissue versus fat).

Description

Bone marrow aspiration and biopsy are performed by a pathologist, hematologist, or oncologist with special training in this procedure. The procedure may be performed on an outpatient basis. In adults, the specimen is usually taken from the posterior superior iliac crest (hip). The sternum (breastbone) may be used for aspiration, but is less desirable because it carries the risk of cardiac puncture. Other sites that are rarely used are the anterior superior iliac crest or a spinal column bone. When the patient is a child, the biopsy site is generally the anterior tibia, the larger of the two bones in the lower leg. A vertebra may also be used.

The skin covering the biopsy site is cleansed with an antiseptic, and the patient may be given a mild sedative. The patient is positioned, and a local anesthetic such as lidocaine is administered first under the skin with a fine needle and then around the bone at the intended puncture site with a somewhat larger gauge needle. When the area is numb, a small incision is made in the skin and the biopsy needle is inserted. Pressure is applied to force the needle through the outer bone, and a decrease in resistance signals entry into the marrow cavity. The needle most often used for bone marrow biopsy is a Jamshidi trephine needle or a Westerman-Jensen trephine needle. A syringe is placed on the top of the needle and 1–2 ml of the bone marrow is aspirated into the syringe. In some instances, the marrow cannot be aspirated because it is fibrosed or packed with neoplastic cells. The syringe is removed and the medical technologist uses this sample to prepare several smears containing small pieces of bone (spicules). Another syringe is fitted onto the needle hub and another sample of 3 ml is removed and transferred to a tube containing EDTA for analysis by flow cytometry, cytogenetic testing, or other special laboratory procedures. Following aspiration, the cutting blades are inserted into the hollow of the needle until they protrude into the marrow. The needle is then forced over the tips of the cutting blades and the needle is rotated as it is withdrawn from the bone. This process captures the core sample inside the needle. A wire probe is inserted at the cutting end and the bone marrow sample is pushed through the hub of the needle onto sterile gauze. The specimen is used to make several preparations on glass slides or coverglasses and is transferred to a fixative solution.

In the laboratory, the aspirate slides are stained with Wright stain or Wright-Giemsa stain. The biopsy material is sectioned onto glass slides and stained with hematoxylin-eosin, Giemsa, and Prussian blue stains. Prussian blue stain is used to evaluate the amount of bone marrow iron, and the other stains are used to contrast cell structures under the microscope. In addition, special stains may be used that aid in the classification of malignant white blood cells.

Diagnosis/Preparation

The physician should be informed of any medication the patient is using and any heart surgery that the patient may have undergone.

Adults require no special preparation for this test. As for infants and children, they need physical and psychological preparation depending on the child's age, previous medical experiences, and level of trust.

Infant preparation

Before the test, parents should know that their child will most probably cry, and that restraints may be used. To provide comfort, and help their child through this procedure, parents are commonly asked to be present during the procedure. Crying is a normal infant response to an unfamiliar environment, strangers, restraints, and separation from the parent. Infants cry more for these reasons than because they hurt. An infant will be restrained by hand or with devices because they have not yet developed the physical control, coordination, and ability to follow commands as adults have. The restraints used thus aim to ensure the infant's safety.

Toddler preparation

Parents should prepare a toddler for bone marrow aspiration directly before the procedure, because toddlers have a very short attention span. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on his body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going home.

Preschooler preparation

Parents should prepare a preschooler for bone marrow aspiration directly before the procedure, so that the child does not worry about it for days in advance. Explanations should be limited to 10 or 15 minutes, because preschoolers also have a limited attention span. Parents should also ensure that the child understands that the procedure is not a punishment. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on his or her body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel and be honest about any pain that may be felt.
• Allow the child to practice different positions or movements that will be required for the procedure.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going for a treat on the way home.
• Practice deep breathing and other relaxing exercises. Practice also to have the child hold your hand and tell him or her to squeeze it when he or she feels pain during the procedure.

School-age child preparation

Explanations should be limited to 20 minutes, and repeated if required. School-age children have a good concept of time, allowing for preparation in advance of the procedure. The older the child, the earlier a parent can start preparation. Guidelines for parents include the ones provided for preschoolers as well as the following:

• Suggest ways for maintaining control during the procedure. For example, counting, deep breathing, and relaxation (thinking of pleasant thoughts).
• Include the child in the decision-making process, for example, the time of day or the body site where the procedure will be performed. These of course depend on the scheduling constraints of your physician and the type of procedure being performed, but where possible, involve the child in the decisions.
• Encourage the child to participate in the procedure, for example by holding an instrument, if allowed by the attending hospital staff.
• Encourage the child to hold your hand or the hand of a nurse. Physical contact does help reduce pain and anxiety.

Adolescent preparation

An adolescent is best prepared by being provided with detailed information and reasons for the procedure. Adolescents should be encouraged to make as many decisions as possible. An adolescent may or may not wish a parent to be present during the procedure, and such wishes should be respected, since privacy is important during adolescence. Other guidelines include the following:

• Explain the procedure in correct medical terminology, and provide the reason for it. Ask the physician about the specific reason if you are not sure.
• To the best of your ability, describe the equipment that will be involved in concrete terms.
• Discuss potential risks because adolescents are usually quite concerned about any effects on appearance, mental function, and sexuality. These concerns should be addressed honestly and openly.

Aftercare

After the needle is removed, the biopsy site is covered with a clean, dry pressure bandage. The patient must remain lying down and is observed for bleeding for one hour. The patient's pulse, breathing, blood pressure, and temperature are monitored until they return to normal. The biopsy site should be kept covered and dry for several hours.

The patient should be able to leave the clinic and resume most normal activities immediately. Patients who have received a sedative often feel sleepy for the rest of the day; so driving, cooking, and other activities that require clear thinking and quick reactions should be avoided. Walking or prescribed pain medications usually ease any discomfort felt at the biopsy site, and ice can be used to reduce swelling.

A doctor should be notified if the patient:

• feels severe pain for more than 24 hours after the procedure
• experiences persistent bleeding or notices more than a few drops of blood on the wound dressing
• has a temperature above 101°F (38.3°C)
• inflammation and pus at the biopsy site and other signs of infection

Risks

A small amount of bleeding and moderate discomfort often occur at the biopsy site. Rarely, reactions to anesthetic agents, infection, and hematoma (blood clot) or hemorrhage (excessive bleeding) may also develop. In rare instances, the heart or a major blood vessel is pierced when marrow is extracted from the sternum during bone marrow biopsy. This can lead to severe hemorrhage.

Normal results

Healthy adult bone marrow contains yellow fat cells, connective tissue, and red marrow that produces blood. Bone marrow is evaluated for cellularity, megakaryocyte production, M:E ratio, differential (classification of blood forming cells), iron content, lymphoid, bone, and connective tissue cells, and bone and blood vessel abnormalities. The bone marrow of a healthy infant is primarily red (75–100% cellularity), but the distribution of blood forming cells is very different than adult marrow. Consequently, age-related normal values must be used.

Microscopic examination of bone marrow can reveal leukemia, granulomas, myelofibrosis, myeloma, lymphoma, or metastatic cancers, bone marrow infection, and bone disease. Bone marrow evaluation is usually not needed to diagnose anemia, but may be useful in cases that cannot be classified by other means.

Resources

books

Montiel, Milka M. "Bone Marrow." In Clinical Hematology and Fundamentals of Homeostasis. 3rd ed., edited by Denise M. Harmening. Philadelphia: F. A. Davis Company, 1997.

Ryan, Daniel H. "Examination of the Marrow." In Williams Hematology. 6th ed., edited by Ernest Beutler, et al. New York, NY: McGraw-Hill, 2001.

periodicals

Azar, D., C. Donaldson, and L. Dalla-Pozza. "Questioning the Need for Routine Bone Marrow Aspiration and Lumbar Puncture in Patients with Retinoblastoma." Clinical and Experimental Ophthalmology 31 (February 2003): 57–60.

Coop, J. "Bone Marrow Aspiration and Biopsy—2." Nursing Times 97 (August 2–8 2001): 45–46.

Coop, J. "Bone Marrow Aspiration and Biopsy—3." Nursing Times 97 (August 9–15, 2001): 43–44.

Cotelingam, James D. "Bone Marrow Interpretation: The Science and the Art." Pathology Case Reviews (September/October 2000): 239–251.

Goldenberg, A. S., and J. J. Tiesinga. "Clinical Experience with a New Specimen Capturing Bone Marrow Biopsy Needle." American Journal of Hematology 68 (November 2001): 189–193.

Jubelirer, S. J., and R. Harpold. "The Role of the Bone Marrow Examination in the diagnosis of Immune Thrombocytopenic Purpura: Case Series and Literature Review." Clinical and Applied Thrombosis/Homeostasis 8 (January 2002): 73–76.

organizations

The Leukemia & Lymphoma Society. 1311 Mamaroneck Avenue, White Plains, NY 10605. (914) 949-5213. <http://www.leukemia.org>.

National Cancer Institute Cancer Information Service. 31 Center Drive, Bethesda, MD 20892-2580. (800) 422-6237. <http://www.nci.nih.gov>.

National Marrow Donor Program. Suite 500, 3001 Broadway Street NE, Minneapolis, MN 55413-1753. (800) 627-7692. <http://www.marrow.org>.

other

"Bone Marrow Biopsy." Discoveryhealth.com. June 2001 [cited April 2003]. <http://www.health.discovery.com/diseasesandcond/encyclopedia/1087.html>.

CanCareSA Bone Marrow Biopsy. July 1998 [cited April 2003]. <http://www.health.sa.gov.au/cancare/TREATS/TESTS/bmbiop.htm>.

"Diagnostic Tests: Bone Marrow Biopsy." Harvard Family Health Guide. [cited April 2003]. <http://www.health.harvard.edu/fhg/diagnostics/marrow/marrow.shtml>.

Mark A. Best Monique Laberge, PhD

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

A physician requests or orders the procedure. The aspirate and biopsy are most often performed in a hospital or clinic by a hematologist or pathologist that has been trained in the procedure. The analysis of the bone marrow is done by a pathologist, and a written report is added to the patients medical record. A histologic technician performs special stains for bone marrow. Clinical laboratory scientists/medical technologists perform smear reviews and analysis of bone marrow cells by flow cytometry. Cytogenetic technologists may perform chromosomal analysis of bone marrow white blood cells.

QUESTIONS TO ASK THE DOCTOR

• What are the possible risks involved in this procedure?
• How many times will the procedure be required?
• How do I prepare for the procedure?
• Must I do anything special after the procedure?
• How long does it take to know the results?
• How many bone marrow aspirations/biopsies do you perform each year?

Bone marrow aspiration and biopsy

Definition

Bone marrow aspiration , also called bone marrow sampling, is the removal by suction of the soft, spongy semisolid tissue (marrow) that fills the inside of the body's long and flat bones. Bone marrow biopsy, or needle core biopsy, is the removal of a small piece (about 0.75 × 0.06 in, 2 × 0.16 cm) of intact bone marrow. The bone marrow is where blood cells are made.

Purpose

Examination of the bone marrow may be the next step that follows an irregular clinical finding, such as an abnormal complete blood count (CBC), and/or an abnormal peripheral blood smear. It may also be performed following an abnormal bone image, such as the finding of a lesion on x rays.

A biopsy of bone marrow shows the intact tissue, so that the structure of the fat cells, lymphocytes, plasma cells, fibrous connective tissue cells, and other cells—and their relationships to each other—can be seen. A bone marrow biopsy is used for all the following:

• diagnose and manage any form of leukemia or other myeloproliferative condition such as multiple myeloma
• rule out or confirm bone marrow infiltration by malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and metastatic carcinoma
• monitor the effects of chemotherapy and the response or lack of response to treatment of blood disease
• evaluate the success of bone marrow transplantation
• diagnose certain genetic diseases (e.g., lipid storage disease)
• investigate pancytopenia (a decrease of all blood cells in peripheral blood), neutropenia (decreased phagocytic white blood cells), or thrombocytopenia (decreased platelets)
• diagnose an infection of unknown origin
• investigate rare anemias for which a cause cannot be found or which does not respond to treatment as anticipated
• obtain intact bone marrow for laboratory analysis
• diagnose some types of cancer, or anemia and other blood disorders
• identify the source of an unexplained fever (e.g., granulomatous lesions)
• diagnose fibrosis of bone marrow and myeloma when bone marrow aspiration has failed to provide an appropriate specimen

The combination of aspiration and biopsy procedures are commonly used to ensure the availability of the best possible bone marrow specimen. The aspirate is collected at the same time as the bone core biopsy by attaching a syringe to the bone marrow needle and withdrawing the sample before the cutting blades are inserted and the bone core is removed. The aspirate is the sample of choice for studying and classifying the nucleated blood cells of the bone marrow (e.g., determining the ratio of immature white blood cells to red blood cells, which is the M:E ratio). The biopsy is the only sample that shows the blood-forming cells in relation to the structural and connective tissue elements (i.e., the microarchitecture) of the bone marrow. It provides the best sample for evaluating the cellularity of the bone marrow (the percentage of blood-forming tissue versus fat).

Description

Bone marrow aspiration and biopsy are performed by a pathologist, hematologist , or oncologist with special training in this procedure. The procedure may be performed on an outpatient basis. In adults, the specimen is usually taken from the posterior superior iliac crest (top rear part of the hip). The sternum (breastbone) may be used for aspiration, but is less desirable because it carries the risk of cardiac puncture. Other sites that are rarely used are the anterior superior iliac crest or a spinal column bone.

KEY TERMS

Antibodies —Proteins that are produced normally by specialized white blood cells after stimulation by a foreign substance (antigen) and that act specifically against the antigen in an immune response.

Aspiration —A procedure to withdraw fluid and cells from the body.

Connective tissue —Cells such as fibroblasts, and material such as collagen and reticulin, that unite one part of the body with another.

Fibrosis —A condition characterized by the presence of scar tissue, or reticulin and collagen proliferation in tissues to the extent that it replaces normal tissues.

Hematologist —A specialist who treats diseases and disorders of the blood and blood-forming organs.

Hematoma —Blood that collects under the skin, forms a blood clot, and causes swelling.

Hemorrhage —Heavy bleeding.

Immune system —Mechanism that protects the body from foreign substances, foreign cells, and pathogens. The thymus, spleen, lymph nodes, white blood cells, including the B cells and T cells, and antibodies are involved in the immune response, which aims to destroy these foreign bodies.

Lymphocytes —Type of white blood cells that are part of the immune system. The lymphocytes are composed of three main cell lines: B lymphocytes, T lymphocytes, and natural killer (NK) cells.

Myeloma (multiple myeloma) —A tumor of plasma cells that originates in bone marrow and usually spreads to more than one bone.

Needle biopsy —The procedure of using a large hollow needle to obtain a sample of intact tissue.

Pathologist —A medical doctor that specializes in identifying diseases by studying cells and tissues under a microscope.

Plasma cells —Cells in the blood and bone marrow that are formed from B lymphocytes, and that produce antibodies.

White blood cells (leukocytes) —Cells of the blood that are responsible for fighting infection.

The skin covering the biopsy site is cleansed with an antiseptic, and the patient may be given a mild sedative. Alocal anesthetic such as lidocaine is administered first under the skin with a fine needle and then around the bone at the intended puncture site with a somewhat larger-gauge needle. When the area is numb, a small incision is made in the skin and the biopsy needle is inserted. Pressure is applied to force the needle through the outer bone, and a decrease in resistance signals entry into the marrow cavity. The needle most often used for bone marrow biopsy is a Jamshidi trephine needle or a Westerman-Jensen trephine needle. A syringe is placed on the top of the needle and 1–2 ml of the bone marrow is aspirated into the syringe. In some instances, the marrow cannot be aspirated because it is fibrosed, or packed with neoplastic cells. The syringe is removed and the medical technologist uses this sample to prepare several smears containing small pieces of bone (spicules). Another syringe is fitted onto the needle hub and another sample of 3 ml is removed and transferred to a tube containing EDTA for analysis by flow cytometry, cytogenetic testing, or other special laboratory procedures. Following aspiration, the cutting blades are inserted into the hollow of the needle until they protrude into the marrow. The needle is then forced over the tips of the cutting blades and the needle is rotated as it is withdrawn from the bone. This process captures the core sample inside the needle. A wire probe is inserted at the cutting end, and the bone marrow sample is pushed through the hub of the needle onto sterile gauze. The specimen is used to make several preparations on glass slides or cover glasses and is transferred to a fixative solution.

In the laboratory, the aspirate slides are stained with Wright stain or Wright-Giemsa stain. The biopsy material is sectioned onto glass slides and stained with hematoxylin-eosin, Giemsa, and Prussian blue stains. Prussian blue stain is used to evaluate the amount of bone marrow iron, and the other stains are used to contrast cell structures under the microscope. In addition, special stains may be used that aid in the classification of malignant white blood cells.

Diagnosis/Preparation

The physician should be informed of any medication the patient is using and of any heart surgery that the patient may have undergone.

Adults require no special preparation for this test. As for infants and children, they need physical and psychological preparation, depending on their age, previous medical experiences, and level of trust.

Infant preparation

Before the test, parents should know that their child will most probably cry, and that restraints might be used. To provide comfort and to help their child through this procedure, parents are commonly asked to be present during the procedure. Crying is a normal infant response to an unfamiliar environment, strangers, restraints, and separation from the parent. Infants cry more for these reasons than because they hurt. An infant will be restrained by hand or with devices because they have not yet developed the physical control, coordination, and ability to follow commands as adults have. The restraints used thus aim to ensure the infant's safety.

Toddler preparation

Parents should prepare a toddler for bone marrow aspiration directly before the procedure, because toddlers have a very short attention span. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on the body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going home.

Preschooler preparation

Parents should prepare a preschooler for bone marrow aspiration directly before the procedure, so that the child does not worry about it for days in advance. Parents should ensure that the child understands that the procedure is not a punishment. Some general guidelines for parents include the following:

• Explain the procedure in a simple language, using concrete terms and avoiding abstract terminology.
• Make sure that the child understands where on the body the procedure will be performed and that it will be limited to that area.
• Allow the child to yell, cry, or express anything, especially pain, verbally.
• Describe how the test will feel and be honest about any pain that may be felt.
• Allow the child to practice different positions or movements that will be required for the procedure.
• Stress the benefits of the procedure and anything that the child may find enjoyable afterwards, such as feeling better or going for a treat on the way home.
• Practice deep breathing and other relaxation exercises. Practice also to have the child hold your hand and tell him or her to squeeze it when he or she feels pain during the procedure.

School-age child preparation

Explanations should be limited to 20 minutes, and repeated if required. The older the child, the earlier a parent can start preparation. Guidelines for parents include the ones provided for preschoolers, as well as the following:

• Suggest ways for maintaining control during the procedure; for example, counting, deep breathing, and relaxation (thinking pleasant thoughts).
• Include the child in the decision-making process; for example, the time of day or the body site where the procedure will be performed. These of course depend on the scheduling constraints of the physician and the type of procedure being performed.
• Encourage the child to participate in the procedure; for example, by holding an instrument, if allowed by the attending hospital staff.
• Encourage the child to hold your hand or the hand of a nurse. Physical contact does help reduce pain and anxiety.

Adolescent preparation

An adolescent is best prepared by being provided with detailed information and reasons for the procedure. Adolescents should be encouraged to make as many decisions as possible. An adolescent may or may not wish a parent to be present during the procedure, and such wishes should be respected, since privacy is important during adolescence. Other guidelines include the following:

• Explain the procedure in correct medical terminology, and provide the reason for it.
• As clearly as possible, describe the equipment that will be involved in concrete terms.
• Discuss potential risks honestly and openly.

Aftercare

After the needle is removed, the biopsy site is covered with a clean, dry pressure bandage. The patient must remain lying down and is observed for bleeding for one hour. The patient's pulse, breathing, blood pressure , and temperature are monitored until they return to normal. The biopsy site should be kept covered and dry for several hours.

QUESTIONS TO ASK THE DOCTOR

• What are the possible risks involved in this procedure?
• How many times will the procedure be required?
• How do I prepare for the procedure?
• Must I do anything special after the procedure?
• How long does it take to know the results?
• How many bone marrow aspirations/biopsies do you perform each year?

The patient should be able to leave the clinic and resume most normal activities immediately. Patients who have received a sedative often feel sleepy for the rest of the day; so driving, cooking, and other activities that require clear thinking and quick reactions should be avoided. Walking or prescribed pain medications usually ease any discomfort felt at the biopsy site, and ice can be used to reduce swelling.

A doctor should be notified if the patient:

• feels severe pain for more than 24 hours after the procedure.
• experiences persistent bleeding or notices more than a few drops of blood on the wound dressing.
• has a temperature above 101°F (38.3°C).
• has inflammation and pus at the biopsy site and other signs of infection.

Risks

A small amount of bleeding and moderate discomfort often occur at the biopsy site. Rarely, reactions to anesthetic agents, infection, and hematoma (blood clot) or hemorrhage (excessive bleeding) may also develop. In rare instances, the heart or a major blood vessel is pierced when marrow is extracted from the sternum during bone marrow biopsy. This can lead to severe hemorrhage.

Results

Healthy adult bone marrow contains yellow fat cells, connective tissue, and red marrow that produces blood. Bone marrow is evaluated for cellularity, megakaryocyte production, M:E ratio, differential (classification of blood-forming cells), iron content, lymphoid, bone, and connective tissue cells, and bone and blood vessel abnormalities. The bone marrow of a healthy infant is primarily red (75–100% cellularity), but the distribution of blood-forming cells is very different than adult marrow. Consequently, age-related normal values must be used.

Microscopic examination of bone marrow can reveal leukemia, granulomas, myelofibrosis, myeloma, lymphoma, or metastatic cancers, bone marrow infection, and bone disease. Bone marrow evaluation is usually not needed to diagnose anemia , but may be useful in cases that cannot be classified by other means.

Resources

BOOKS

Abeloff, M. D., et al. Clinical Oncology. 3rd ed. Philadelphia: Elsevier, 2004.

Khatri, V. P., and J. A. Asensio. Operative Surgery Manual. 1st ed. Philadelphia: Saunders, 2003.

Townsend, C. M., et al. Sabiston Textbook of Surgery. 17th ed. Philadelphia: Saunders, 2004.

PERIODICALS

Azar, D., C. Donaldson, and L. Dalla-Pozza. “Questioning the Need for Routine Bone Marrow Aspiration and Lumbar Puncture in Patients with Retinoblastoma.”Clinical and Experimental Ophthalmology 31 (February 2003): 57–60.

Jubelirer, S. J., and R. Harpold. “The Role of the Bone Marrow Examination in the Diagnosis of Immune Thrombocytopenic Purpura: Case Series and Literature Review.” Clinical and Applied Thrombosis/Homeostasis 8 (January 2002): 73–76.

ORGANIZATIONS

The Leukemia & Lymphoma Society. 1311 Mamaroneck Avenue, White Plains, NY 10605. (914) 949-5213. http://www.leukemia.org (accessed March 7, 2008).

National Cancer Institute Cancer Information Service. 31 Center Drive, Bethesda, MD 20892-2580. (800) 422-6237. http://www.nci.nih.gov (accessed March 7, 2008).

National Marrow Donor Program. Suite 500, 3001 Broadway Street NE, Minneapolis, MN 55413-1753. (800) 627-7692. http://www.marrow.org (accessed March 7, 2008).

OTHER

http://www.health.sa.gov.au.

“Diagnostic Tests: Bone Marrow Biopsy.” Harvard Family Health Guide. [cited April 2003]. http://www.health.harvard.edu/fhg/diagnostics/marrow/marrow.shtml (accessed March 7, 2008).

Mark A. Best

Monique Laberge Ph.D.

Rosalyn Carson-DeWitt MD

Bone Marrow Aspiration and Biopsy

Definition

Bone marrow aspiration, which is also called bone marrow sampling, is the removal by suction of the soft, spongy semisolid tissue (marrow) that fills the inside of the long and flat bones. Bone marrow biopsy, or needle core biopsy, is the removal of a small piece (about 0.75 by 0.06 inch, or 2 by 0.16 cm) of intact bone marrow. The bone marrow is where blood cells are made.

Purpose

Examination of the bone marrow may be the next step that follows an abnormal clinical finding, abnormal complete blood count (CBC), and/or an abnormal peripheral blood smear. It may be performed following an abnormal bone image such as the finding of a mass lesion on x ray.

A biopsy of bone marrow shows the intact tissue, so that the fat cells, lymphocytes, plasma cells, fibrous connective tissue cells, and other cells can be seen in their overall structure, and in their relationships to each other. Bone marrow biopsy is used to:

• Aid in the diagnosis and management of any form of leukemia or other myeloproliferative condition such as multiple myeloma.

• Rule out or identify bone marrow infiltration of other malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and metastatic carcinoma.
• Monitor the effects of chemotherapy and the response or lack of response to treatment of blood disease.
• Evaluate the success of bone marrow transplantation.
• Diagnose certain genetic diseases (e.g., lipid storage disease).
• Investigate pancytopenia (a decrease of all blood cells in peripheral blood), neutropenia (decreased phagocytic white blood cells), or thrombocytopenia (decreased platelets).
• Diagnose an infection of unknown origin.
• Investigate rare anemias for which a cause cannot be found or which does not respond to treatment as anticipated.
• Obtain intact bone marrow for laboratory analysis.

• Diagnose some types of cancer or anemia and other blood disorders.
• Identify the source of an unexplained fever (e.g. granulomatous lesions).
• Diagnose fibrosis of bone marrow and myeloma when bone marrow aspiration has failed to provide an appropriate specimen.

The combination of aspiration and biopsy procedures are commonly used together to ensure the availability of the best possible bone marrow specimen. The aspirate is collected at the same time as the bone core biopsy by attaching a syringe to the bone marrow needle and withdrawing the sample before the cutting blades are inserted and the bone core is removed. The aspirate is the sample of choice for studying and classifying the nucleated blood cells of the bone marrow (e.g., determining the ratio of immature white blood cells to red blood cells, the M:E ratio). The biopsy is the only sample that shows the blood forming cells in relation to the structural and connective tissue elements (i.e., the microarchitecture) of the bone marrow. It is the best sample to evaluate the cellularity of the bone marrow (the percentage of blood forming tissue versus fat).

Precautions

The bone marrow procedure is performed with strict attention to aseptic technique and universal precautions for the prevention of transmission of blood-borne pathogens. Fixation fluids, slides, and tubes with proper anticoagulant should be at the bedside so that the specimen can be preserved immediately and slides prepared that are of suitable quality. Obesity can affect the ease with which a bone marrow biopsy can be done, and the results can be affected if the patient has had radiation therapy at the biopsy site.

Description

Bone marrow aspiration and biopsy are performed by a pathologist, hematologist, or oncologist with special training in this procedure. The procedure may be performed on an outpatient basis. In adults, the specimen is usually taken from the posterior superior iliac crest (hip). The sternum may be used for aspiration, but is less desirable because it carries the risk of cardiac puncture. Other sites that are rarely used are the anterior superior iliac crest or a spinous process of a vertebra, a spinal column bone. When the patient is a child, the biopsy site is generally the anterior tibia, the larger of the two bones in the lower leg. A vertebra may also be used.

The skin covering the biopsy site is cleansed with an antiseptic, and the patient may be given a mild sedative. The patient is positioned, and a local anesthetic such as lidocaine is administered first under the skin with a fin needle and then around the bone at the intended puncture site with a somewhat larger gauge needle. After the area is numb a small incision is made in the skin and the biopsy needle is inserted. Pressure is applied to force the needle through the outer bone and a decrease in resistance signals entry into the marrow cavity. The needle most often used for bone marrow biopsy is a Jamshidi trephine needle or a Westerman-Jensen trephine needle. A syringe is placed on the hup of the needle and 1-2 mL of the bone marrow is aspirated into the syringe. In some instances, the marrow cannot be aspirated because it is fibrosed or packed with neoplastic cells. The syringe is removed and the medical technologist uses this sample to prepare several smears containing small bone spicules. Another syringe is fitted onto the needle hub and another sample of 3 mL is removed and transferred to a tube containing EDTA for analysis by flow cytometry, cytogenetic testing or other special laboratory procedure. Following aspiration, the cutting blades are inserted into the hollow of the needle until they protrude into the marrow. The needle is then forced over the tips of the cutting blades and the needle is rotated as it is withdrawn from the bone. This process captures the core sample inside the needle. A wire probe is inserted at the cutting end and the bone marrow sample is pushed through the hub of the needle onto sterile gauze. The specimen is used to make several touch preparations on glass slides or coverglasses and is transferred to a fixative solution.

In the laboratory the aspirate slides are stained with Wright stain or Wright-Giemsa stain. The biopsy material is sectioned onto glass slides and stained with hematoxylin-eosin, Giemsa, and Prussian blue stains. Prussian blue stain is used to evaluate the amount of bone marrow iron and the other stains are used to evaluate cell morphology. In addition, special stains may be used that aid in the classification of malignant white blood cells.

Preparation

The physician should be told of any medication the patient is using and any heart surgery that the patient has undergone.

Aftercare

After the needle is removed, the biopsy site will be covered with a clean, dry pressure bandage. The patient must remain lying down and is observed for bleeding for one hour. The patient's pulse, breathing, blood pressure, and temperature are monitored until they return to normal. The biopsy site should be kept covered and dry for several hours.

The patient should be able to leave the clinic and resume most normal activities immediately. Patients who have received a sedative often feel sleepy for the rest of the day; so driving, cooking, and other activities that require clear thinking and quick reactions should be avoided. Walking or prescribed pain medications usually ease any discomfort felt at the biopsy site, and ice can be used to reduce swelling.

A doctor should be notified if the patient:

• Feels severe pain more than 24 hours after the procedure.
• Experiences persistent bleeding or notices more than a few drops of blood on the wound dressing.
• Has a temperature above 101°F (38.3°C). Inflammation and pus at the biopsy site and other signs of infection should also be reported to a doctor without delay.

Complications

A small amount of bleeding and moderate discomfort often occur at the biopsy site. Rarely, reactions to anesthetic agents, infection, and hematoma (blood clot) or hemorrhage (excessive bleeding) may also develop. In rare instances, the heart or a major blood vessel is pierced when marrow is extracted from the sternum during bone marrow biopsy. This can lead to severe hemorrhage.

Results

Healthy adult bone marrow contains yellow fat cells, connective tissue, and red marrow that produces blood. Bone marrow is evaluated for cellularity, megakaryocyte production, M:E ratio, differential (classification of blood forming cells), iron content, lymphoid, bone, and connective tissue cells, and bone and blood vessel abnormalities. The bone marrow of a healthy infant is primarily red (75-100% cellularity), but the distribution of blood forming cells is very different than adult marrow. Consequently, age related normal values must be used.

Microscopic examination of bone marrow can reveal leukemia, granulomas, myelofibrosis, myeloma, lymphoma, or metastatic cancers, bone marrow infection, and bone disease. Bone marrow evaluation is usually not needed to diagnose anemia, but may be useful in cases that cannot be classified by other means.

KEY TERMS

Aspiration— A procedure to withdraw fluid and cells from the body.

Connective tissue— Cells such as fibroblasts, and material such as collagen and reticulin, that unites one part of the body with another.

Fibrosis— A condition characterized by the presence of scar tissue, or reticulin and collagen proliferation in tissues to the extent that it replaces normal tissues.

Hematologist— A specialist who treats diseases and disorders of the blood and blood-forming organs.

Hematoma— Blood that collects under the skin, forms a blood clot, and causes swelling.

Hemorrhage— Heavy bleeding.

Lymphocytes— Certain white blood cells that have an immune function. The lymphocytes are composed of three main cell lines; B lymphocytes, T lymphocytes, and natural killer (NK) cells.

Myeloma (multiple myeloma)— A tumor of plasma cells that originates in bone marrow and usually spreads to more than one bone.

Needle biopsy— The procedure of using a large hollow needle to obtain a sample of intact tissue.

Pathologist— A medical doctor that specializes in the study of diseases and laboratory tests.

Plasma cells— Cells in the blood and bone marrow that are formed from B lymphocytes, and that produce antibodies.

White blood cells (leukocytes)— Cells of the blood that are composed of neutrophils, monocytes, lymphocytes, eosinophils, and basophils.

Health care team roles

A physician requests or orders the procedure. The aspirate and biopsy are most often performed by a hematologist or pathologist that has been trained in the procedure. The analysis of the bone marrow is done by a pathologist, and a written report is added to the patients medical record. A histologic technician performs special stains for bone marrow. Clinical laboratory scientists/medical technologists perform smear reviews and analysis of bone marrow cells by flow cytometry. Cytogenetic technologists may perform chromosomal analysis of bone marrow white blood cells.

Resources

BOOKS

Montiel, Milka M. "Bone Marrow." In Clinical Hematology and Fundamentals of Hemostasis, 3rd ed., edited by Harmening, Denise M., Philadelphia, PA: F. A. Davis Company, 1997.

Ryan, Daniel H. "Examination of the Marrow." In Williams Hematology, 6th ed., edited by Ernest Beutler, et al. New York, NY: McGraw-Hill, 2001.

PERIODICALS

Cotelingam, James D. "Bone Marrow Interpretation: The Science and the Art." Pathology Case Reviews (September/October, 2000): 239-251.

ORGANIZATIONS

The Leukemia & Lymphoma Society. 1311 Mamaroneck Avenue, White Plains, NY 10605. (914) 949-5213. 〈http://www.leukemia.org/〉.

National Cancer Institute Cancer Information Service. 31 Center Drive, Bethesda, MD 20892-2580. (800) 422-6237. 〈http://www.nci.nih.gov/〉.

National Marrow Donor Program. Suite 500, 3001 Broadway Street NE, Minneapolis, MN 55413-1753. (800) 627-7692. 〈http://www.marrow.org/〉.

OTHER

CanCareSA Bone Marrow Biopsy. 〈http://www.health.sa.gov.au/cancare/TREATS/TESTS/bmbiop.htm〉.

Bone Marrow Aspiration and Biopsy

Definition

Bone marrow aspiration, also called bone marrow sampling, is the removal by suction of fluid from the soft, spongy material that lines the inside of most bones. Bone marrow biopsy, or needle biopsy, is the removal of a small piece of bone marrow.

Purpose

Bone marrow aspiration is used to:

• pinpoint the cause of abnormal blood test results
• confirm a diagnosis or check the status of severe anemia (abnormally low numbers of red blood cells in the bloodstream) of unknown cause, or other irregularities in the way blood cells are produced or become mature.
• evaluate abnormalities in the blood's ability to store iron.
• diagnose infection

Bone marrow biopsy is used to:

• obtain intact bone marrow for laboratory analysis
• diagnose and stage some types of cancer or anemia and other blood disorders
• identify the source of an unexplained fever
• diagnose fibrosis of bone marrow or myeloma (a tumor composed of cells normally found in the bone marrow) when bone marrow aspiration has failed to provide an appropriate specimen

Bone marrow aspiration and bone marrow biopsy are also used to gauge the effectiveness of chemotherapy and other medical treatments. These procedures are often used together to ensure the availability of the best possible bone marrow specimen.

KEY TERMS

Aspiration— A procedure to withdraw fluid from the body.

Connective tissue— Material that links one part of the body with another.

Fibrosis— A condition characterized by the presence of scar tissue or fiber-containing tissues that replace normal tissues.

Hematologist— A medical specialist who treats diseases and disorders of the blood and blood-forming organs.

Hematoma— Blood that collects under the skin and causes swelling.

Hemorrhage— Heavy bleeding.

Myeloma— A tumor that originates in bone marrow and usually spreads to more than one bone.

Nurse practitioner— A registered nurse who is qualified to perform some specialized duties.

Precautions

Allergies or previous adverse reactions to medications should be discussed with the doctor. Any current medications, including herbal or nutritional supplements, should be evaluated for the potential to interfere with proper coagulation (clot formation). These would include coumadin, aspirin, and other agents used as blood thinners. Caution should be used when the herbs gingko, ginger, garlic, br ginseng have been utilized as supplements, due to a risk of bleeding.

Pregnancy, lactation (production and secretion of milk), and preexisting platelet or bleeding disorders should be evaluated before either procedure is undertaken.

Description

Bone marrow aspiration and biopsy should be performed by a physician or nurse clinician. Each procedure takes about 20 to 30 minutes and is usually performed on an outpatient basis, but can be done in a hospital if necessary.

The skin covering the biopsy site is cleansed with an antiseptic, and the patient may be given a mild sedative. A local anesthetic is administered. The hematologist or nurse clinician performing the procedure will not begin until the anesthetic has numbed the area from which the specimen is to be extracted. In both adults and children, aspiration and biopsy are most commonly performed on the rear bone of the hip (posterior iliac crest). In adults, sampling from the sternum (breastbone) is sometimes done. The latter location is technically easier, but is somewhat more painful for the patient and presents the risk of heart injury. On rare occasions, a long bone of the leg (tibia) may be used as a sample site for an infant.

In a bone marrow aspiration, a special needle is inserted beneath the skin and rotated until it penetrates the cortex, or outer covering of the bone. At least half a teaspoon of marrow is withdrawn from the bone by a syringe attached to the needle. The patient may experience discomfort when the needle is inserted or when the marrow is aspirated. If more marrow is needed, the needle is repositioned slightly, a new syringe is attached, and a second sample is taken. The samples are transferred from the syringes to slides and vials, then sent to a laboratory for analysis.

Bone marrow biopsy may be performed immediately before or after bone marrow aspiration. The procedure utilizes a special large-bore needle that is used to drill out a core of marrow. In bone marrow biopsy, the needle is inserted, rotated from side to side, withdrawn, and reinserted at a different angle. This procedure is repeated if needed until a small core, about 0.4 inches (1 cm) long, is separated from the bone marrow. The needle is again removed, and a piece of fine wire threaded through its tip transfers the specimen onto sterile gauze. The patient may feel discomfort or pressure when the needle is inserted and experience a brief, pulling sensation when the marrow is withdrawn. Unlike aspiration specimens, which are smeared, these samples contain structurally intact bone marrow. Microscopic examination can show what material its cells contain and how they are alike or different from one another. The bone may either be embedded intact in paraffin (a type of wax), or be decalcified (a process which takes place overnight) for a different type of staining and examination. Each type of preparation has certain advantages.

Preparation

A current history and physical are obtained from the patient, along with proper consent. The patient is generally placed in a prone position (lying face down) for preparation, and local anesthetic, with or without sedation, is administered.

Aftercare

After the needle is removed, the biopsy site will be covered with a clean, dry bandage. Pressure is applied to control bleeding. The patient's pulse, breathing, blood pressure, and temperature are monitored until they return to normal, and the patient may be instructed to remain in a supine position (lying face up) for half an hour before getting dressed.

The patient should be able to leave the clinic and resume normal activities immediately. Patients who have received a sedative often feel sleepy for the rest of the day; driving, cooking, and other activities that require clear thinking and quick reactions should therefore be avoided.

The biopsy site should be kept covered and dry for several hours. Walking or taking prescribed pain medications usually ease any discomfort felt at the biopsy site, and ice can be used to reduce swelling.

A doctor should be notified if the patient:

• feels severe pain more than 24 hours after the procedure.
• experiences persistent bleeding or notices more than a few drops of blood on the wound dressing.
• has a temperature above 101 °F (38.3 °C). Inflammation and pus at the biopsy site and other signs of infection should also be reported to a doctor without delay.

Risks

Bleeding and discomfort often occur at the biopsy site. Infection and hematoma may also develop. In rare instances, the heart or a major blood vessel is pierced when marrow is extracted from the sternum during bone marrow biopsy. This can lead to severe hemorrhage.

Normal results

Healthy adult bone marrow contains yellow fat cells, connective tissue, and red marrow that produces blood. The bone marrow of a healthy infant is primarily red due to active production of red cells necessary for growth.

Abnormal results

Culture of bone marrow aspirate may yield information about an infectious agent. Microscopic examination of bone marrow can reveal granulomas, myelofibrosis, lymphomas, leukemias, or other cancers. Analyzing specimens can help doctors diagnose iron deficiency, vitamin B12 deficiency, and folate deficiency, as well as anemia.

Obesity can affect the ease with which a bone marrow biopsy can be done, and the results of either procedure can be affected if the patient has had radiation therapy at the biopsy site.