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R.S.Riley,M.D.,Ph.D.

BoneMarrowPathology

Part1

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Bone marrow basicsRed cell diseases

White cell diseases

Other diseases

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Bone marrow basics

HematopoiesisBone marrow structure

Obtaining bone marrow

Interpreting bone marrow

Red cell diseasesWhite cell diseases

Other diseases

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Largest organ in body

4.5% of body weight

3375 grams in 75kilogram person

Adults have about 1.7liters of bone marrow

Daily production rates

50-100 x 109 PMNs

150-200 x 109 RBCs

150-200 x 109 platelets

Reich, C.

A Clinical Atlasof Sternal Bone Marrow

Abbott Laboratories, 1946

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Periosteum

Outer fibrous layer, inner osteogenic layer

Bone

Cortex - Lamellar bone

Trabeculae - Cancellous bone, define

medullary region

Endosteal cells - Inner cortex and

trabeculae, osteoblasts and osteoclasts

Connective tissue

Intertrabecular regions of medulla

Reticular cells, fat cells, fibroblasts,

macrophages, nerve fibers and meshwork

of blood vessels

Hematopoietic tissue

Lie in cords or wedges between sinusoids

Normally confined to interstitium

Mature hematopoietic cells pass

transcellularly through sinusoids

Periosteum

Subcorticalhypocellular

region

Cortical bone

Bonytrabeculae

Hematopoietictissue

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Major components

Capillary-venous sinus

Blood-forming spaces

Capillary-venous sinus

Endothelial cells

Basement membrane

Adventitial (stromal) cells

Blood cells are formedoutside vessels, deliveredthrough sinusoidal barrierinto vascular sinuses

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Macrophage (Nursing Cell)

with Erythroid Precursors

Osteoclast

Hematopoietic island

Erythroid

island

Venous

sinusoidAdipocytes

Megakaryocyte releasing

platelets

Stromal cells

Bony trareculae

Mast cell

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Stromalcells

Extracellularmatrix

Regulatoryfactors

Fibroblasts

Endothelial cells

Macrophages

Adipose cells

Lymphocytes

Smooth muscle cells

Collagen

Fibronectin

Laminin

Proteoglycans

Thrombospondin

Vibronectin

Adhesion molecules

Growth factors

Inhibitory proteins

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Bone marrow spicule

Trail

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Bone Marrow Biopsy

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Proerythroblast

Basophilic erythroblast

Polychromatophilic normoblast

~20 mm

Largest erythroid precursorFine, uniform chromatin with one or more nucleoliAgranular basophilic cytoplasm

10-18 mm

BN I - Intensely staining, slightly coarse nuclearchromatin, deeply basophilic cytoplasmBN II - Condensed, spoke-like nuclear chromatin

10 - 15 mm

Relatively coarse, intensely staining chromatinActive hemoglobin formationPolychromatophilic cytoplasm

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Orthochromatic erythroblast

Reticulocyte

Erythrocyte

10-15 mm

Incapable of cell divisionSmall, dense pyknotic nucleus, pinkish cytoplasmExtrusion of nucleus produces reticulocyte

10-15 mm

Released into peripheral bloodContain mitochondria, ribosomes, Golgi body remnantsHemoglobin synthesis continues (20-30%)

6-8 mm

Biconcave shapeIncapable of hemoglobin synthesisLife span of 120 days

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Myeloblast

Promyelocyte

Myelocyte

12-20 mm

Moderately basophilic cytoplasm, few granulesDiffuse chomatin, several nucleoliCapable of cell division

15-25 mm

Basophilic cytoplasm, reddish-purple granulesSlightly indented nucleus, nucleolus, Golgi zoneCapable of cell division

10-20 mm

Slightly basophilic cytoplasm, no nucleolusSpecific neutrophilic, eosinophilic, or basophilic granulesPartial chromatin condensation, no nucleoli

Two generations, early forms capable of cell division

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Metamyelocyte

Bands

Mature neutrophils

10-12 mm

Specific neutrophilic, eosinophilic, or basophlic granulesIndented or U-shaped nucleusIncapable of cell division

15-25 mm

Basophilic cytoplasm, reddish-purple granulesSlightly indented nucleus, nucleolus, Golgi zoneCapable of cell division

10-20 mm

Slightly basophilic cytoplasm, no nucleolusSpecific neutrophilic, eosinophilic, or basophilic granulesPartial chromatin condensation, no nucleoliTwo generations, early forms capable of cell division

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Mast cells

Osteoblasts

Osteoclasts

5-25 mm, elliptical or elongated

Central nucleus, round or oval, nonlobatedNumerous dark purple cytoplasmic granulesUsually perivascular or near endosteum

20-50 mm, mesenchymal origin

Responsible for bone deposition, usually in childrenEccentric nucleus, small nucleous, basophilic cytoplasmAppear in rows along bony spicules

30-100 mm, multinucleated giant cells

Separate, uniform nuclei, slightly oval, single nucleolusVoluminous cytoplasm, azurophilic granulesLie in hollows known as Howships lacunae

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Adipose cell

Lymphocyte

Plasma cell

Aspirate - Oval nucleus within empty cytoplasmBiopsy - Usually clustered, adjacent to trabeculaeImportant part of bone marrow microenvronmentIncreases with age

Small, high nuclear/cytoplasmic ratio, scant cytoplasmSome chromatin condensationNumerous in infants, 10% of adult nucleated cellsCD8-positive T cells in adults, hematogones in children

15-20 mm, eccentric nucleus, basophilic cytoplasm

Prominent paranuclear Golgi zoneCoarsely-clumped chromatin, clock-face in biopsyClose proximity to capillaries in biopsy