Bone

Last revised 12 May 2008

Last major update June 2005

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See also Bone marrow-nonneoplastic, Joints, Mandible/maxilla

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Table of contents for Bone

Primary references, normal anatomy, normal histology, bone growth, biopsy

Developmental abnormalities: achondrogenesis, achondroplastic dwarfism, fibrodysplasia ossificans progressiva, malformations, scoliosis, syndromes, thanatophoric dwarfism

Osteomyelitis: general, amebic, bacterial, chronic multifocal, echinococcus, fungal, syphilitic, tuberculous, xanthogranulomatous

Non-neoplastic or metabolic disease: aseptic bone necrosis, black bone, black cartilage, cartilaginous rest, fracture, giant cystic arachnoid granulations, glomus coccygeum, hyperostosis cranii ex vacuo, hyperparathyroidism, hypophosphatasia, infarct, metal toxicity, mucopolysaccharidoses, necrosis, osteogenesis imperfecta, osteopathia striata, osteopetrosis, osteopoikilosis, osteoporosis, Paget’s disease, radiation necrosis, renal osteodystrophy, rickets / osteomalacia, SAPHO syndrome

Fibrous/fibroosseous tumors of bone: cortical irregularities of femur, fibrous dysplasia, fracture callus, liposclerosing myxofibrous tumor, metaphyseal fibrous defect, myositis ossificans, ossifying fibroma, osteofibrous dysplasia, post-traumatic

Bone forming tumors (not osteosarcoma): general, adamantinoma, metastatic calcification, ossifying fibromyxoid tumor, osteoblastoma, osteoid osteoma, osteoma

Osteosarcoma: general, chemotherapy effect, anaplastic, epithelioid, fibrohistiocytic, high grade surface, low grade central, osteoblastoma-like, Paget’s disease associated, parosteal, periosteal, small cell, telangiectatic, well differentiated intramedullary

Cartilage forming tumors (not chondrosarcoma): bizarre parosteal osteochondromatous proliferations, chondroblastoma, chondroma, chondromyxoid fibroma, mesenchymoma, osteochondroma

Chondrosarcoma: general, conventional, clear cell, dedifferentiated, mesenchymal, myxoid, secondary

Hematologic neoplasms: general, lymphoma-general, acute leukemia, anaplastic large cell lymphoma, Burkitt’s lymphoma, diffuse large B cell lymphoma, Hodgkin’s lymphoma, lymphoblastic lymphoma, mastocytosis, myeloma, plasmacytoma

Vascular tumors: angiosarcoma, epithelioid hemangioendothelioma, glomus tumor, hemangioma, hemangioendothelioma, hemangiopericytoma, lymphangioma

Other tumors of bone: amyloid, aneurysmal bone cyst, benign fibrous histiocytoma, benign notochordal cell tumors, brown tumor of hyperparathyroidism, chest wall hamartoma, chordoma, cyst of degenerative joint disease, desmoplastic fibroma, desmoplastic small cell tumor, ecchordosis physaliphora, epidermoid inclusion cyst, Erdheim-Chester, Ewing’s/PNET, fibrosarcoma, ganglion cyst of bone, giant cell granuloma, giant cell tumor, implant related sarcoma, infantile myofibromatosis, inflammatory myofibroblastic tumor, Langerhans cell histiocytosis, leiomyosarcoma, lipoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, massive osteolysis, meloreostosis, metastases to bone, myofibrosarcoma, myxoma, neurofibroma, osteitis fibrosa cystica, osteochondromyxoma, phosphaturic mesenchymal tumor, post-radiation sarcoma, rhabdomyosarcoma, schwannoma, sinus histiocytosis with massive lymphadenopathy, solitary bone cyst, solitary fibrous tumor, subungual exostosis, subungual keratoacanthoma, xanthoma

Miscellaneous: staging, features to report, grossing

 

Primary references

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AJCC Cancer Staging Manual (6th Ed)

American Journal of Surgical Pathology (AJSP), March 1977 to June 2005

Archives of Pathology and Laboratory Medicine (Archives), January 1976 to May 2005

Human Pathology (Hum Path), March 1970 to April 2005

Modern Pathology (Mod Path), Jan 1988 to May 2005

Rosai, J:  Ackerman’s Surgical Pathology (9th Ed); C. V. Mosby, 2004

Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004  

Unni, K. K. - Dahlin’s Bone Tumors (5th Ed); Lippincott Raven, 1996

Websites: www.BoneTumor.org

UMDNJ (New Jersey, USA)-case studies 1-20

University of Pittsburgh cases 1-431

Journal search terms: bone, cartilage

 

Please refer to these primary references for more detailed discussions and photographs

 

Normal anatomy

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The 206 bones in the body can be classified by shape (long bones-femur; flat bones-pelvis or short tubular bones-hands/feet). They can also be classified as axial (vertebrae and girdles) or appendicular, or based on their embryological origin (endochondral-formed via an intermediate cartilage model, or intramembranous-formed directly from mesenchyme without an intermediate cartilage model)

Parts of a long bones: diaphysis (shaft), physis (growth plate), epiphysis (ends of bone, partially covered by articular cartilage), metaphysis (junction of diaphysis and epiphysis, most common site of primary bone tumors)

Cross section: periosteum, cortex (composed of cortical bone or compact bone), medullary space (composed of cancellous or spongy bone)

Blood supply: diaphysis: a nutrient artery enters medullary canal at center of diaphysis, divides and supplies entire diaphysis; also contributions from vessels within the Volkmann / Haversian system;

epiphyses: supplied by medullary arteries; sometimes from the epiphysis along additional vessels that traverse the joint

metaphysis: supplied by vessels within the medulla that loop back

Vascular channels: 2 types in compact bone, either haversian (longitudinal) canals or transverse/oblique (Volkmann’s canals)

  Drawings: haversian canals

Bone composition: 35% organic (cells, proteins), 65% calcium hydroxyapatite (contains 99% of body's calcium, 85% of phosphorus, 65% of sodium, also magnesium)

Hydroxyapatite crystal is formed via phase transition; 12 day lag between matrix deposition and mineralization

Collagen resists tension, hydroxyapatite and proteoglycans in cartilage resist compression

Thicker cortex in middle of long bones resists bending; cancellous bone at ends of long bones resists compression

Drawings of bones:

general anatomy #1; #2

skeleton with major bones labeled

femur: femoral head; anterior surface; posterior surface; distal femur; upper femur longitudinal midsection

finger: developing finger (image)

feet: phalanges and metatarsals

humerus: anterior view; posterior view; longitudinal section of humerus head

patella: anterior surface; posterior surface

pelvis: male; female

radius and ulna: anterior surface; posterior surface

skull: portions labeled

tibia: proximal; tibia and fibula-anterior surface; posterior surface

 

Normal histology

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Bone: mineralized osteoid; either lamellar bone or woven bone (see below)

Micro images: cortical bone #1; #2; #3 (various); cancellous (spongy) bone; cancellous bone-various; bone and cartilage-various

Drawings: cortical bone #1; #2

Virtual slides: normal rib

 

Cement line: junction between original resorbed surface and new bone; sharp and basophilic with routine staining; also called reversal front activate osteoclastic surface

 

Lamellar bone: layered bone with concentric parallel lamellae; gradually replaces woven bone; normal type of bone found in adult skeleton; stronger than woven bone

Micro images: cross section #1; #2; #3; polarized light

 

Osteoblasts: arise from marrow mesenchymal cells; when active, are plump and present on bone surface; eventually are encased within the collagen they produce and get flattened (see osteocytes below); have a perinuclear halo resembling plasma cells in cytologic preparations due to prominent Golgi zone; synthesize and transport collagenous matrix, initiate and regulate mineralization, control removal of bone via osteoclasts, express Vitamin D receptors; activity is promoted by physical activity (Wolf’s law); express parathormone receptors (mediates the activation of osteoclasts)

Osteoblasts control osteoclast activity via parathyroid hormone (parathormone), PHRP (Parathyroid hormone related protein), IL-1, TNF alpha; digestion of bone by osteoclasts releases cytokines and growth factors for osteoblasts

Express parathormone receptors (mediate the activation of osteoclasts)

Micro images: osteoblasts and osteoclasts; osteoblasts

Positive stains: alkaline phosphatase, estrogen receptors, parathyroid hormone

EM: resemble fibroblasts due to well developed rough endoplasmic reticulum and Golgi

 

Osteoclasts: cause bone resorption due primarily to remodeling and not calcium homeostasis; derived from monocyte fusion; multinucleated (2-12 nuclei) giant cells, associated with bone surface; use their ruffled borders (with villous extensions) to bind to matrix adhesion proteins, produce resorption pits/bays (shallow concavities) called Howship’s lacunae; plasma membrane forms a seal with bone; osteoclast acidifies extracellular area, which solubilizes the mineral and releases enzymes which dissolve the matrix; contains tartrate-resistant acid phosphatase

Micro images: osteoclasts #1; #2; #3

EM: numerous mitochondria, rare lysosomes; ruffled edge in area of cell membrane is associated with bone resorption

EM images: osteoclast

 

Osteocytes: the mature form of osteoblasts after they are surrounded by matrix; most numerous cell in bone; communicate with each other via osteocytic cell processes with gap junctions that travel through canaliculi (bone tunnels); may maintain serum calcium and phosphorus levels; can translate mechanical forces into biologic activity

Drawings: osteocytes

Micro images: osteocyte #1; #2; #3

EM images: cell process extending from an osteocyte through a canaliculus in the bone matrix

 

Osteoid: non mineralized bone always present at the formative surface of bone, but usually a very thin layer; resembles hyalinized collagen; composed of type I collagen (90%), acid mucopolysaccharides, noncollagen proteins including bone morphogenetic protein (may initiate bone formation), adhesion proteins (fibronectin, osteopontin, thrombospondin), calcium binding proteins (osteonectin, bone sialoprotein), mineralization proteins (osteocalcin), enzymes (collagenase, alkaline phosphatase); increased if increased bone formation (fracture callus, Paget’s disease, hyperparathyroidism), if inadequate mineralization or if toxic / inhibitory structures present in bone (aluminum, iron, fluoride)

EM images: osteoblast adjacent to new bone osteoid

 

Osteon: dense compact cylindrical unit underlying cortical bone; formed in childhood by ingrowth of periosteal vessels that follow a cutting cone of osteoclasts through the cortex; tunnel is haversian canal, is filled in partially with osteoblast created bone matrix

Micro images: haversian systems #1; #2; #3

 

Osteoprogenitor cells: mesenchymal stem cells near bony surfaces, can produce osteoblasts

 

Periosteum: outer fibrous layer and inner cellular (cambium) layer of osteoprogenitor cells (fibroblasts and osteoclasts); contains nerve fibers, Sharpey’s fibers/perforating collagenous fibers that penetrate outer layer of bone; may become detached from bone due to benign or malignant processes, causing new bone formation between elevated periosteum and bone and producing radiologic changes

Drawings: perforating fibers

Micro images: perforating fibers

 

Tetracycline: binds to actively mineralizing surfaces and fluoresces in ultraviolet light

Micro images: double tetracycline labeling of bone; normal iliac crest with tetracycline labeling

 

Woven bone: immature (streamer) bone due to haphazard (random) arrangement of collagen fibers, found during growth, healing, repair, infections or in some neoplasms; highlighted with polarized light or reticulin stain; abnormal in adults and associated with fibrous dysplasia or other causes of accelerated bone turnover

Micro images: developing bone; fetal jaw; under polarized light

 

Bone Histomorphometry: measuring bone formation (% active osteoblastic surface, % osteoid surface, % mineralizing surface), bone mineralization (osteoid volume, mineral apposition rate), bone resorption (% total eroded surface, % active osteoclastic surface).  Bone resorption is identified by numerous osteoclasts in Howship’s lacunae and in bone margins

 

Basic multicellular unit: to fulfill the biological requirements, bone needs to continuously renew itself, which it does at multiple sites called basic multicellular units (BMUs).  Cyclic events involving matrix resorption and formation occur in these BMUs, i.e., activation of osteoprogenitor cells to proliferate and differentiate (A), resorption of bone matrix by osteoclasts (R), quiescent phase for reversing resorption to formation (R) and the formation of bone matrix by osteoblasts (F).  The cellular activities are coupled within each BMU’s remodeling cycle, i.e., A-R-FBone is modeled to reach peak bone mass; then 5-10% is remodeled per year in these BMUs

 

Bone growth

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Growth plate is responsible for interstitial growth of bone (growth within the bone itself)

Bone growth involves resting chondrocytes as they proliferate, mature, orient in a column and degenerate, leaving newly calcified columns for osteoblasts to migrate into

Abnormalities in chondrocyte function disrupt this sequence and produce abnormally short and misshapen bones (example: achondroplasia [short stature], may be due to mutation in fibroblast growth factor)

Chondrocytes of the growth plate behave differently than chondrocytes of articular cartilage; are regulated by Indian hedgehog gene

Limb patterning controls bone development; sonic hedgehog and homeobox genes organize segmentation, anterior-posterior, medial, lateral and longitudional limb patterning during fetal development; gene abnormalities cause extra or missing digits, short or long limbs or congenital amputations

 

Bone production is identified by well-stained small spicules of bone with lacunar cells present and osteoblasts on bone margins

 

Bones are classified based on embryologic development as endochondral (formed by ossification of cartilaginous anlage, such as long bones) and membranous (formed from connective tissue, such as skull)

 

Endochondral bone formation

Primitive mesenchyme differentiates into cartilaginous anlage of future bone, which is degraded, mineralized and removed by osteoclast like cells; allows ingrowth of blood vessels and osteoprogenitor cells; occurs at base of articular cartilage, leading to increase in bone length and diameter

Micro images: formation of finger #1; #2; various images

 

Epiphyseal growth plate: site of endochondral bone formation; area between centers of ossification; chondrocytes here have zones of proliferation, hypertrophy, and mineralization, then primary spongiosa; regulated by PHRP; when bone reaches adult length, epiphysis closes by becoming ossified; closed epiphysis is actually more easily invaded by osteosarcoma than open epiphysis with cartilaginous barrier

Micro images: growth plate; epiphyseal plate #1; #2

 

Periosteum: produces osteoblasts, which deposit beginnings of cortex (primary center of ossification); similar process occurs at epiphysis (secondary center of ossification)

 

Intramembranous bone formation

Cranium, clavicles

Formed from mesenchyme, which differentiates into fibrous tissue containing osteoblasts without an intervening cartilaginous stage

Micro images: various images #1; #2

 

Biopsy

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Frozen sections are useful to document adequacy, to allow quicker definitive treatment (if diagnosis can be made), for assessment of margins, to obtain culture for possible infectious lesions, to differentiate between aseptic and infectious loosing of implants

FNA: helpful for metastatic disease, recurrent tumor or unsuspected malignancy; not helpful for cartilaginous lesions, cystic lesions or obviously benign lesions that require surgical management (chondromyxoid fibroma, giant cell tumor)

References: Archives 2001;125:1463

 

 

Developmental abnormalities

Achondrogenesis

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Type I: rare, lethal; extreme limb shortening, marked discrepancy between head and trunk size, severely delayed ossification

Type IA: autosomal recessive; rib fractures, no ossification of vertebral pedicles; chondrocytes have inclusion bodies, but cartilage matrix is near normal

Type IB: distinctly abnormal cartilage matrix with rarefaction of ground substance and peculiar ringlike pericellular arrangement of collagen fibers

Achondrogenesis type IB is lethal osteochondrodysplasia due to mutations in transporter gene for diastrophic dysplasia sulfate

Genetic defect causes complex derangement in cartilage matrix assembly; impaired decorin deposition causes lack of development of normal interterritorial matrix, preventing necessary structural substrate for proper endochondral bone formation and severe skeletal phenotype

Xray images: short and abnormal long bones in fetus with type IB

Case report of type IB in child of consanguineous (first cousins) parents (Archives 2001;125:1375)

Gross images: 19 week fetus; 21 week fetus

Micro: abnormal endochondral bone formation with curved cartilage-bone junction at growth plates, periosteal bony spurs; spongelike cartilage matrix due to lack of interterritorial matrix; epiphyseal cartilage composed of multiple discrete units of chondrocytes encased in territorial capsule and separated from each other by clefts containing fibroblast-like cells; mosaic of chondrocyte units (chondrons) due to breakdown of usual matrix continuity of epiphyseal cartilage

Micro images: abnormal cartilage bone junction, abnormal matrix

References: more information

 

Achondroplastic dwarfism

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Major cause of dwarfism

Reduction in chondrocytes at growth plate is due to defect in fibroblastic growth factor receptor 3 gene (FGFR3)

FGFR3 inhibits cartilage proliferation, and is constitutively active in these patients

Autosomal dominant, but 80% of cases are new mutations

Clinical: short proximal extremities, normal trunk, enlarged head (bulging forehead, depression of root of nose)

Normal intramembranous bone formation, so bone cortices seem thickened compared to short bone length

Normal life, IQ, reproductive status

Micro: narrow/disorganized zones of proliferation and hypertrophy in growth plates; chondrocytes in clusters, not columns; base of growth plate has prematurely deposited struts of bone which seal the plate

 

Fibrodysplasia ossificans progressiva

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Rare autosomal dominant disorder with congenital malformation of the great toes and progressive heterotopic ossification in defined anatomic patterns

Early preosseous lesions resemble aggressive juvenile fibromatosis

Pathophysiology: spontaneous and post-traumatic flareups heralded by intense connective tissue edema with perivascular lymphocytic infiltration into skeletal muscle, angiogenic fibroproliferative lesions that spread along muscle planes and evolve through endochondral ossification to form mature lamellar bone; leads to immobilization of joints making movement impossible, later death due to starvation (ankylosis of jaw) or from restrictive disease of chest wall

May be mediated by mast cells (Hum Path 2001;32:842)

Treatment: none; surgical trauma induces further bone formation

Case reports: 7 year old girl with 13 cm thoracic tumor (with images)

Gross/clinical images: FOP skeleton

References: Hum Path 1997;28:339; UPOJ (with clinical images)

 

Malformations

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Failure of development of a bone (phalanx, rib, clavicle), supernumerary ribs or digits, syndactyly (fusion of adjacent digits) or arachnodactylism (long, spider-like digits)

Craniorachischisis: failure of closure of spinal column and skull; produces meningomyelocoele or meningoencephalocoele

 

Scoliosis

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Abnormal curvature of vertebral column

Kyphoscoliosis: lateral and posterior curvatures

 

Syndromes

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Maffuci’s syndrome: multiple enchondromas and soft tissue hemangiomas; also ovarian carcinoma, brain gliomas

   Reference: AJSP 1995;19:1029 (with spindle cell hemangioendotheliomas)

McCune-Albright syndrome: polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, endocrine abnormalities; almost exclusively women; also see below

Multiple hereditary exostosis: autosomal dominant disorder of multiple osteochondromas diagnosed during childhood; bowing of underlying bones, wide metaphyses; evolution to chondrosarcoma

Multiple osteomas: associated with Gardner syndrome (autosomal dominant, epidermal cysts, fibromatosis, pigmented ocular fundus lesions, multiple colorectal adenomas with carcinoma at ages 35-40 years)

Ollier’s disease: multiple enchondromas, often ovarian sex-cord tumors

Sapho syndrome: see below

 

Thanatophoric dwarfism

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Also called thanatophoric dysplasia

Thanato”: denoting death

Lethal form of dwarfism, occurs in 1 per 20,000 live births

Type I: short, curved femur; II: straighter femur with cloverleaf skull

Mutation in FGFR3 gene, but different from that in achondroplastic dwarfism

Clinical: micromelia (short limbs), frontal bossing with relative macrocephaly (abnormally large and hyperconvoluted temporal lobes), small chest, bell shaped abdomen

Die at birth or shortly thereafter from respiratory insufficiency due to small thoracic cavity

Case reports: variant in 18 week male fetus (Archives 1993;117:322)

Xray images: shortened long bones

Micro: diminished proliferation of chondrocytes and poor columnization of zone of proliferation

References: more information

 

 

Osteomyelitis

Osteomyelitis-general

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Infection of bone (osteitis) or bone marrow space (myelitis)

Usually pyogenic, fungal or tubercular

HIV+ patients may be infection by unusual organisms

May resemble neoplasms, particularly after antibiotic treatment

Severe osteomyelitis is not associated with grade IV sacral decubitus ulcers in non-septic patients (Archives 2003;127:1599)

May cause secondary AA amyloidosis

Xrays: permeative, destructive lesion with periosteal new bone formation; chronic osteomyelitis may produce focal destruction or focal abscess

Gross images: bone fenestrations

Micro images: various images; mild chronic osteomyelitis-figure 3

References: more information

 

Amebic osteomyelitis

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Case reports: infection of mandibular bone graft by Acanthamoeba castellanii (Hum Path 1981;12:573)

 

Bacterial osteomyelitis (acute)

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Rare due to antibiotics

Usually pyogenic

Hematogenous spread: most common cause; usually long tubular bones of children; usually metaphyseal in children and adults, although involvement of flat bones is more common in adults

Direct extension: less common, may be associated with trauma or rarely iatrogenic implantation of infectious material

In elderly, may affect vertebral column; associated with systemic urinary tract infection, diabetes (affects small bones in feet); in younger adults, associated with immunodeficiency or intravenous drug abuse

50% of cases are due to unknown bacteria

80% of cases with known organisms are due to Staphylococcus aureus, which produces receptors to bone matrix components

Sickle cell patients may have infections by Salmonella choleraesuis, S. paratyphi B and S. typhimurium

Neonates are prone to Treponema (periostitis), gram negative rods, Group B Streptococci, Hemophilus influenzae and Listeria species

Other known organisms are E. coli, Pseudomonas and Klebsiella in intravenous drug addicts (affecting clavicle, sternoclavicular joint, spine or pelvis), Pseudomonas and mixed bacteria in post-traumatic cases

Rarely associated with malakoplakia; cases with draining sinus are rarely associated with malignancy (squamous cell carcinoma)

Designated as acute, subacute or chronic, based on clinical duration of disease, not inflammatory cells present; chronic disease related to delayed diagnosis, inadequate antibiotics or debridement of dead bone, extensive bone necrosis, weakened host defenses; may produce tuberculoid granules with variable central necrosis (AJSP 1985;9:531)

Xrays: may be negative early; three phase bone scans (with Gallium or Indium scanning), MRI or other studies may be necessary; late Xrays show prominent periosteal reaction resembling neoplasm

Pathophysiology: bacteria proliferate in bone, kill osteocytes, cause necrosis, spread along haversian system or medullary cavity within shaft and to periosteum; subperiosteal abscesses impair blood supply, which causes more necrosis and often draining sinuses

Sites: in children, at areas of rapid growth or increased risk of trauma (distal and proximal femur, proximal tibia and humerus, distal radius)

Sequestrum: dead piece of bone; gradually separated from living bone by granulation tissue; may pass through sinus tract; is avascular and dense on Xray

Involucrum: sleeve of living tissue created by periosteum which is deposited around sequestrum

Sclerosing osteomyelitis of Garre': in jaw, associated with extensive new bone formation that obscures underlying osseous structure; also called periostitis ossificans

Xray: lytic bone destruction surrounded by sclerosis; chronic disease may resemble malignant bone tumor due to destructive and regenerative bone changes

Treatment: surgery to remove dead bone (sequestrum), antibiotics (levels in bone may be lower than serum - often Cloxacillin, Nafcillin, third generation cephalosporins, guided by culture and sensitivity reports and drug’s minimum inhibitory concentration)

Complications: may develop sinus tract lined by squamous epithelium that forms large epidermal inclusion cyst within bone; rarely transforms to well differentiated squamous cell carcinoma with excellent prognosis

Case reports: 17 month old immunocompetent black girl with disseminated Mycobacterium avium disease (Hum Path 1980;11:476)

Gross: varies with patient age; infants under age 1 year often have permanent joint and epiphyseal damage sparing metaphysis and diaphysis; children 1 year and older have opposite changes (sparing of joint, damage to metaphysis); adults have joint infection and extensive bone involvement; acute disease has pus tracking through bone, periosteal elevation and shell of reactive periosteal bone around necrotic center; neonates may have considerable subperiosteal spread; chronic disease is accompanied by prominent periosteal bone formation

Micro: neutrophils (may persist for weeks), lymphocytes and plasma cells with bone necrosis, reactive new bone formation, capillary proliferation and fibrosis; subtypes include plasma cell osteomyelitis and xanthogranulomatous osteomyelitis (abundant foamy macrophages); bone marrow space replaced by inflammatory tissue

Micro images: acute osteomyelitis #1; #2; lactobacillus sepsis and osteomyelitis; from extension of soft tissue infection

Virtual slides: osteomyelitis

 

Chronic osteomyelitis

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Develops in 15-30%

Due to lack of treatment, inadequate antibiotic treatment or incomplete surgical debridement of necrotic bone

Brodie abscess: small intraosseous abscess in cortex, walled off by reactive bone with no periosteal reaction; cavity may contain infectious organisms or be sterile; may have late recrudescence

Micro images: chronic osteomyelitis #1; #2

 

Chronic multifocal osteomyelitis

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Recurrent variant of osteomyelitis in children and young adults of unknown origin

Low grade fever, local swelling and pain; periods of exacerbation and remission over years; negative cultures

Sites: metaphyses of tubular bones, clavicle; multiple asymptomatic sites

Associated skin lesion - pustulosis palmoplantaris

Xrays images: images and text

Treatment: non steroidal anti-inflammatory drugs, not antibiotics (since cultures are negative)

Micro: neutrophilic inflammation early; late fibrosis of marrow with chronic inflammatory infiltrate; often plasma cell predominance, fragments of necrotic bone with multinucleated giant cells

DD: rheumatic disease, bacterial osteomyelitis, malignancy

References: Hum Path 1999;30:59

 

Echinococcus osteomyelitis

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Rare; due to infection by larva of Echinococcus tapeworms; usually E. granulosus, also E. multilocularis and E. oligarthrus

Life cycle: tapeworm’s gravid segment breaks off from implantation site in small intestine of dogs, coyotes and wolves (in North America), disintegrates in colon releasing eggs which pass in feces; eggs are ingested by sheep, goats, deer, moose, humans; hatch in small intestine, disseminate via blood; at implantation site, larva secrete hyaline membrane that differentiates into outer acellular laminated structure and inner germinal layer which produces protoscolices; cysts may be ingested by dogs

Cysts may rupture and produce fever, urticaria, anaphylactic shock, dissemination of infection, pathologic fractures if in bone

Sites: 60% liver, 20% lungs, 3% brain, 1% bones (50% in lower vertebrae)

Xray: extensive complex cystic changes

Treatment: excision, albendazole or praziquantel

Case reports: 86 year old woman with draining sinus in tibia (Archives 2002;126:1551)

Gross: ragged surface, multiple cavities filled with red-brown necrotic material and yellow-white cystlike structures

Micro: acellular laminated membranes with germinal layer; rare degenerating scolices and hooklets; intense acute and chronic inflammatory infiltrate may erode bone

Gross/micro images: H&E, PAS, GMS

Cytology: hydatid sand (free daughter cysts, free scolices)

Positive stains: PAS and GMS (membranes)

 

Fungal osteomyelitis

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Case reports: 41 year old man with injury to lumbar/cervical region and Phialemonium obovatum infection (Archives 1993;117:841), Scedosporium apiospermum (Pseudallescheria boydii) osteomyelitis (Hum Path 1998;29:1266)

 

Syphilitic osteomyelitis

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Caused by Treponema pallidum and T. pertenue (yaws)

Bone involvement more common in congenital syphilis; appears at 5th month of gestation in areas of active endochondral ossification (osteochondritis) and periosteum

Acquired syphilis involves bone in tertiary phase, usually nose, palate, skull, tibia, vertebrae, hands/feet

Xray: reactive periosteal bone deposition (“saber shin” of tibia)

Gross: bone destruction and production; necrotic, well-defined bone defects of cortex and periosteum surrounded by sclerotic bone

Micro: edematous granulation tissue, plasma cells, granulomas, necrotic bone and new bone production

Positive stains: silver stains

 

Tuberculous osteomyelitis

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Usually young adults or children

Sites: vertebrae, hip, knee, ankle, elbow, wrist; usually involves synovium, epiphysis or metaphysis

In US, due to immigrants and immunosuppression

1-3% with tuberculosis have bone infection; usually from focus of acute visceral disease, direct extension or lymphatics

Rarely causes inguinal mass with fluctuant psoas abscess

In AIDS patients, bone infection usually multifocal

Advanced cases are associated with cutaneous sinuses, which cause secondary bacterial infections

Associated with fusion of joint, denudation of cartilage, sequestra of medullary cavity

Can detect in synovial fluid by culture and examination

Pott’s disease: involvement of spine (thoracic/lumbar); extensive necrosis of intervertebral discs with extension into soft tissue; may produce significant deformities or neurologic deficits; difficult to treat

DD: foreign body granuloma post-surgery (AJSP 1997;21:563)

 

Xanthogranulomatous osteomyelitis

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Case reports: two cases with prominent foamy macrophages, neutrophils, plasma cells and fibrin (Archives 1984;108:973)

 

 

Non-neoplastic or metabolic disease

Aseptic bone necrosis

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Also called avascular bone necrosis, osteonecrosis

Common; affects almost every bone, including tibial tuberosity (Osgood-Schlatter’s disease), proximal femoral epiphysis (Legg-Calve’-Perthes disease)

>50% of cases are multifocal

Causes 10% of joint replacements

Significant cause of arthritis due to fractures through articular surface of hip, knee and other major joints; also due to collapse of necrotic bone segment with resulting reparative granulomas that destroy bone at margin of infarct, may cause detachment of cartilage and secondary degenerative joint disease

Causes: fracture, dislocation, corticosteroids, nitrogen bubbles in dysbarism, vasculitis, radiation, vascular compression, venous hypertension, thrombosis (sickle cell disease), Gaucher’s disease, alcoholism

Pathophysiology: initially necrosis of epiphysis, with variable necrosis of adjacent cartilage; dead bone is resorped by “creeping substitution” over months/years; new bone is soft, may flatten and cause degenerative joint disease

Creeping substitution: dead trabeculae that are not resorbed by osteoclasts serve as scaffolds for deposition of new living bone

Gross: intact articular cartilage except at edge of necrotic area, which exhibits cracking and folding; necrotic area in cross section is yellow, opaque, chalky with hyperemic fibrous tissue at margin; adjacent bone may be thickened; late changes are breaks in smooth contour of femoral head, destruction of articular cartilage, loose bodies and marginal osteophytes (changes of degenerative joint disease)

Gross images: femoral head #1, #2

Micro: dead trabeculae (empty lacunae) stain deeper blue than nonnecrotic bone; have ragged margins with osteoclasts on one side and osteoblasts on the other; lacunae may be enlarged and cystic or normal size with pyknotic nuclei; calcium salts due to necrotic adipocytes; marrow has fat necrosis and calcium deposits (marrow is a more sensitive indicator of necrosis than bone)

Micro images: osteonecrosis due to metastatic melanoma (melanoma cells are eosinophilic ghost cells)