Bone Marrow

Background

Examination of the bone marrow is one of the basic diagnostic examinations that a pathologist performs. Pathologists are often called upon to perform the procedure. In most cases, both a biopsy and an aspirate of the marrow is obtained. Aspirate samples are smeared on slides and usually stained with a Wright-Giemsa stain. Any remainder aspirate is allowed to clot and submitted for permanent paraffin sections. The biopsy is decalcified to soften the bone and then embedded in paraffin. Several elements are routinely analyzed in this examination.

OUTLINE

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Commonly Used Terms

Internet Links

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

ANOREXIA NERVOSA

Bone marrow changes in anorexia nervosa are correlated with the amount of weight loss and not with other clinical findings.

Abella E, Feliu E, Granada I, Milla F, Oriol A, Ribera JM, Sanchez-Planell L, Berga LI, Reverter JC, Rozman C.

Hematology Department, University Hospital Germans Trias i Pujol, Autonomous University of Barcelona, Badalona, Spain.

Am J Clin Pathol 2002 Oct;118(4):582-8 Abstract quote
The clinical history and biochemical and hematologic variables for 44 consecutive patients diagnosed with anorexia nervosa were recorded.

Bone marrow aspirates and biopsy specimens were analyzed by standard morphologic procedures, and bone marrow adipocytes were studied morphometrically. The bone marrow of the 44 patients was classified as normal (5 cases [11%]), hypoplastic or aplastic (17 [39%]), with partial or focal gelatinous degeneration (13 [30%]), or with complete gelatinous degeneration of the bone marrow (GDBM; 9 [20%]). These patterns correlated with amount of weight loss (P = .005) but not other clinical findings. WBC counts were lower in patients with GDBM (P = .0189), but this and other peripheral blood variables did not always reflect the severity of bone marrow damage.

Hypoplastic or aplastic bone marrow showed an increase in bone marrow fat fraction due to an increase in adipocyte diameters, while in GDBM, fat fraction and adipocyte diameters decreased. Morphologic changes in bone marrow and stereologic alterations in bone marrow adipocytes may be observed in anorexia nervosa.

The extent of damage is related to the amount of weight loss, not to other factors. Peripheral blood cell counts may not reflect the extent of damage. In some patients, this process may be reversible with reestablishment of adequate nutritional intake.

METASTATIC DISEASE

Comparison of relative value of bone marrow aspirates and bone marrow trephine biopsies in the diagnosis of solid tumor metastasis and Hodgkin lymphoma: institutional experience and literature review.

Moid F, DePalma L.

Department of Pathology, George Washington University Hospital, Washington, DC 20037, USA.

Arch Pathol Lab Med. 2005 Apr;129(4):497-501. Abstract quote

CONTEXT: Bone marrow aspirates as well as bone marrow trephine biopsies are frequently performed to assess whether there is marrow involvement by a malignancy. Numerous reports differ in the relative value of these 2 procedures and fail to provide concise guidelines that can help choose the appropriate technique in this clinical situation.

OBJECTIVE: To compare the relative value of aspirates and trephine biopsies in the diagnosis of solid tumor metastasis and Hodgkin lymphoma. In addition, we correlate our findings with those of the literature to provide a concise practice guideline.

DESIGN: Sixty-six cases showing bone marrow involvement by solid tumor and Hodgkin lymphoma in bone marrow aspirates, bone marrow trephine biopsies, or both were included in the study. The diagnosis and findings made on aspirates were compared with those made on trephine biopsies in each case.

RESULTS: In those cases where both aspirate and trephine biopsy were available for evaluation, there was a 22% positive correlation in the findings on aspirates and trephine biopsies. The correlation between aspirates and trephine biopsies was highest in cases of small cell carcinoma of the lung (3/11, or 36.3%) followed by breast carcinoma (7/20, or 35%), prostate carcinoma (1/9, or 11.1%), and Hodgkin lymphoma (1/20, or 5%). Two of 5 cases from the miscellaneous category demonstrated simultaneous involvement of aspirate and trephine biopsy by a gastric carcinoma as well as an adrenal gland carcinoma.

CONCLUSIONS: Bone marrow aspirate and bone marrow trephine biopsy should both be performed in patients with proven or suspected malignancies where staging may affect management. However, bone marrow aspirate has only a minimal role, if any, in detecting bone marrow involvement by Hodgkin lymphoma. In cases of breast carcinoma, small cell carcinoma of lung, and prostate carcinoma, aspirate evaluation may confirm trephine biopsy results or, more rarely, provide the sole confirmation of the malignancy.

HISTOPATHOLOGY CHARACTERIZATION

BONE MARROW ELEMENT ANALYZED EXPECTED FINDINGS

Fat:Cell Ratio Varies by age of the patient
1st decade 10:90
Adult Varies from 30:70 to 70:30

Myeloid:Erythroid Ratio Varies from 2.5:1 to 4:1

Myeloid Series See Table below

Erythroid Series 15-37% of nucleated cells

Megakaryocytes 0.5-2% of nucleated cells

Lymphocytes and Lymphreticular Lesions 8-24% of nucleated cells
T:B cells 3:1

Plasma Cells 3-6% of nucleated cells
Absent at birth
Normal immunogobulin ratio of kappa:lambda 4:1

Metastatic Disease May require special stains for confirmation

Reticulin and Collagen Proliferation Reticulin is reported as normal or increased, it usually preceedes collagen deposition

Granulomatous Changes
Nonspecific lipid granulomas are the most common type of granulomas and are not associated with infection

Other caseating and noncaseating granulomas require evaluation with special stains or cultures

Stainable Iron Stores
Prussian blue stain highlights iron on biopsy and clot sections
Usually graded on a scale of 0-4 with 2-3 being adequate and 4-increased

Myeloid Precursors and Other Hematopoeitic Cells with Normal Range in Bone Marrow

Cell Type Range %

Myeloblasts 0-2

Promyelocytes 2-5

Myelocytes (neutrophilic) 9-16

Metamyelocytes 7-23

Band forms 8-15

Neutrophils 4-10

Myelocytes (eosinophilic) 0-2

Band
0-2

Mature
0-3

Monocytes/macrophages 0-3

Basophils 0-1

Mast cells 0-2

Plasma cells 3-6

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

CD34

CD34/QBEND10 immunostaining in the bone marrow trephine biopsy: a study of CD34-positive mononuclear cells and megakaryocytes.

Torlakovic G, Langholm R, Torlakovic E.

Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway.
Arch Pathol Lab Med 2002 Jul;126(7):823-8 Abstract quote
CONTEXT: The immunohistochemical detection of CD34 protein using QBEND10 antibody in bone marrow trephine biopsies was shown recently to be a precise method for quantitation of blasts and a possibly useful approach in diagnosis and classification of myelodysplastic syndrome.

OBJECTIVES: To evaluate CD34+ cells in bone marrow biopsies with various diagnoses and to assess how counts obtained using this method correlate with blast counts obtained by traditional morphologic evaluation of bone marrow smears. DESIGN: Bone marrow trephine biopsies from 108 adult patients were evaluated by immunohistochemistry using anti-CD34 antibody (QBEND10). CD34+ mononuclear cells were counted and compared with the blast counts in the bone marrow aspirate smears or imprints. CD34+ mononuclear cell clusters and CD34+ megakaryocytes were also recorded. The type of positivity (membranous vs cytoplasmic) and the percentage of CD34+ megakaryocytes were evaluated because the presence of CD34+ megakaryocytes was recently suggested to be present in myelodysplastic syndrome, but not in myeloproliferative disease or nonneoplastic bone marrow.

RESULTS: Six of 24 biopsies with partial involvement by non-Hodgkin lymphoma and 5 of 60 biopsies with reactive changes had 5% to 10% CD34+ mononuclear cells and were associated with lymphocytosis and increased hematogones. The CD34+ mononuclear cell clusters were found only in myelodysplastic syndrome and myeloproliferative disease. The CD34+ megakaryocytes were present in all diagnostic groups.

CONCLUSION: The number of CD34+ mononuclear cells was often slightly higher than the number of myeloid blasts in the bone marrow smears, probably due to increased hematogones. The presence and the number of CD34+ megakaryocytes do not appear to have diagnostic value, but this finding should be further investigated in relation to clinical parameters.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
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Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated April 7, 2005

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Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Commonly Used Terms
Internet Links

HISTOPATHOLOGY	CHARACTERIZATION
BONE MARROW ELEMENT ANALYZED	EXPECTED FINDINGS
Fat:Cell Ratio	Varies by age of the patient 1st decade 10:90 Adult Varies from 30:70 to 70:30
Myeloid:Erythroid Ratio	Varies from 2.5:1 to 4:1
Myeloid Series	See Table below
Erythroid Series	15-37% of nucleated cells
Megakaryocytes	0.5-2% of nucleated cells
Lymphocytes and Lymphreticular Lesions	8-24% of nucleated cells T:B cells 3:1
Plasma Cells	3-6% of nucleated cells Absent at birth Normal immunogobulin ratio of kappa:lambda 4:1
Metastatic Disease	May require special stains for confirmation
Reticulin and Collagen Proliferation	Reticulin is reported as normal or increased, it usually preceedes collagen deposition
Granulomatous Changes	Nonspecific lipid granulomas are the most common type of granulomas and are not associated with infection Other caseating and noncaseating granulomas require evaluation with special stains or cultures
Stainable Iron Stores	Prussian blue stain highlights iron on biopsy and clot sections Usually graded on a scale of 0-4 with 2-3 being adequate and 4-increased

Cell Type	Range %
Myeloblasts	0-2
Promyelocytes	2-5
Myelocytes (neutrophilic)	9-16
Metamyelocytes	7-23
Band forms	8-15
Neutrophils	4-10
Myelocytes (eosinophilic)	0-2
Band	0-2
Mature	0-3
Monocytes/macrophages	0-3
Basophils	0-1
Mast cells	0-2
Plasma cells	3-6

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
CD34
CD34/QBEND10 immunostaining in the bone marrow trephine biopsy: a study of CD34-positive mononuclear cells and megakaryocytes. Torlakovic G, Langholm R, Torlakovic E. Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway.	Arch Pathol Lab Med 2002 Jul;126(7):823-8 Abstract quote CONTEXT: The immunohistochemical detection of CD34 protein using QBEND10 antibody in bone marrow trephine biopsies was shown recently to be a precise method for quantitation of blasts and a possibly useful approach in diagnosis and classification of myelodysplastic syndrome. OBJECTIVES: To evaluate CD34+ cells in bone marrow biopsies with various diagnoses and to assess how counts obtained using this method correlate with blast counts obtained by traditional morphologic evaluation of bone marrow smears. DESIGN: Bone marrow trephine biopsies from 108 adult patients were evaluated by immunohistochemistry using anti-CD34 antibody (QBEND10). CD34+ mononuclear cells were counted and compared with the blast counts in the bone marrow aspirate smears or imprints. CD34+ mononuclear cell clusters and CD34+ megakaryocytes were also recorded. The type of positivity (membranous vs cytoplasmic) and the percentage of CD34+ megakaryocytes were evaluated because the presence of CD34+ megakaryocytes was recently suggested to be present in myelodysplastic syndrome, but not in myeloproliferative disease or nonneoplastic bone marrow. RESULTS: Six of 24 biopsies with partial involvement by non-Hodgkin lymphoma and 5 of 60 biopsies with reactive changes had 5% to 10% CD34+ mononuclear cells and were associated with lymphocytosis and increased hematogones. The CD34+ mononuclear cell clusters were found only in myelodysplastic syndrome and myeloproliferative disease. The CD34+ megakaryocytes were present in all diagnostic groups. CONCLUSION: The number of CD34+ mononuclear cells was often slightly higher than the number of myeloid blasts in the bone marrow smears, probably due to increased hematogones. The presence and the number of CD34+ megakaryocytes do not appear to have diagnostic value, but this finding should be further investigated in relation to clinical parameters.