Bone Mar row Patholog y

1 t r a P

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

Bone Marrow Pathology

Bone marrow basics Red cell diseases White cell diseases Other diseases

Bone Marrow Pathology

Bone marrow basics
Hematopoiesis Bone marrow structure Obtaining bone marrow Interpreting bone marrow

Red cell diseases White cell diseases Other diseases

Bone Marrow Facts

Largest organ in body 4.5% of body weight 3375 grams in 75 kilogram person Adults have about 1.7 liters 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 Atlas of Sternal Bone Marrow Abbott Laboratories, 1946

Bone Marrow Structure

Periosteum
Outer fibrous layer, inner osteogenic layer

Periosteum

Cortical bone Subcortical hypocellular region

Bone
Cortex - Lamellar bone Trabeculae - Cancellous bone, define medullary region Endosteal cells - Inner cortex and trabeculae, osteoblasts and osteoclasts

Bony trabeculae

Connective tissue
Intertrabecular regions of medulla Reticular cells, fat cells, fibroblasts, macrophages, nerve fibers and meshwork of blood vessels Hematopoietic tissue

Hematopoietic tissue
Lie in cords or wedges between sinusoids Normally confined to interstitium Mature hematopoietic cells pass transcellularly through sinusoids

Functional Structure of Bone Marrow

Major components
Capillary-venous sinus Blood-forming spaces

Capillary-venous sinus
Endothelial cells Basement membrane Adventitial (stromal) cells

Blood cells are formed outside vessels, delivered through sinusoidal barrier into vascular sinuses

Bone Marrow Microenvironment

Hematopoietic island Osteoclast Erythroid island Macrophage (Nursing Cell) with Erythroid Precursors

Bony trareculae

Mast cell

Venous sinusoid

Adipocytes

Megakaryocyte releasing platelets Stromal cells

Stromal cells

Fibroblasts Endothelial cells Macrophages Adipose cells Lymphocytes Smooth muscle cells

Bone Marrow Microenvironment

Extracellular matrix

Collagen Fibronectin Laminin Proteoglycans Thrombospondin Vibronectin Adhesion molecules

Regulatory factors

Growth factors Inhibitory proteins

Bone marrow spicule

Trail

Bone Marrow Biopsy

Erythroblasts
Proerythroblast ~20 mm Largest erythroid precursor Fine, uniform chromatin with one or more nucleoli Agranular basophilic cytoplasm Basophilic erythroblast 10-18 mm BN I - Intensely staining, slightly coarse nuclear chromatin, deeply basophilic cytoplasm BN II - Condensed, spoke-like nuclear chromatin Polychromatophilic normoblast 10 - 15 mm Relatively coarse, intensely staining chromatin Active hemoglobin formation Polychromatophilic cytoplasm

Erythroblasts
Orthochromatic erythroblast 10-15 mm Incapable of cell division Small, dense pyknotic nucleus, pinkish cytoplasm Extrusion of nucleus produces reticulocyte Reticulocyte 10-15 mm Released into peripheral blood Contain mitochondria, ribosomes, Golgi body remnants Hemoglobin synthesis continues (20-30%) Erythrocyte 6-8 mm Biconcave shape Incapable of hemoglobin synthesis Life span of 120 days

Granulocytic Cells
Myeloblast 12-20 mm Moderately basophilic cytoplasm, few granules Diffuse chomatin, several nucleoli Capable of cell division Promyelocyte 15-25 mm Basophilic cytoplasm, reddish-purple granules Slightly indented nucleus, nucleolus, Golgi zone Capable of cell division Myelocyte 10-20 mm Slightly basophilic cytoplasm, no nucleolus Specific neutrophilic, eosinophilic, or basophilic granules Partial chromatin condensation, no nucleoli Two generations, early forms capable of cell division

Granulocytic Cells
Metamyelocyte 10-12 mm Specific neutrophilic, eosinophilic, or basophlic granules Indented or U-shaped nucleus Incapable of cell division Bands 15-25 mm Basophilic cytoplasm, reddish-purple granules Slightly indented nucleus, nucleolus, Golgi zone Capable of cell division Mature neutrophils 10-20 mm Slightly basophilic cytoplasm, no nucleolus Specific neutrophilic, eosinophilic, or basophilic granules Partial chromatin condensation, no nucleoli Two generations, early forms capable of cell division

Other Marrow Cells

Mast cells 5-25 mm, elliptical or elongated Central nucleus, round or oval, nonlobated Numerous dark purple cytoplasmic granules Usually perivascular or near endosteum Osteoblasts 20-50 mm, mesenchymal origin Responsible for bone deposition, usually in children Eccentric nucleus, small nucleous, basophilic cytoplasm Appear in rows along bony spicules Osteoclasts 30-100 mm, multinucleated giant cells Separate, uniform nuclei, slightly oval, single nucleolus Voluminous cytoplasm, azurophilic granules Lie in hollows known as Howships lacunae

Other Marrow Cells

Adipose cell Aspirate - Oval nucleus within empty cytoplasm Biopsy - Usually clustered, adjacent to trabeculae Important part of bone marrow microenvronment Increases with age Lymphocyte Small, high nuclear/cytoplasmic ratio, scant cytoplasm Some chromatin condensation Numerous in infants, 10% of adult nucleated cells CD8-positive T cells in adults, hematogones in children Plasma cell 15-20 mm, eccentric nucleus, basophilic cytoplasm Prominent paranuclear Golgi zone Coarsely-clumped chromatin, clock-face in biopsy Close proximity to capillaries in biopsy