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Jatuwit Howannapakorn M D

Musculoskeletal System

Jatuwit Howannapakorn, M.D.

ContentsBones

Developmental and acquired abnormalitiesOsteoporosisRickets, osteomalacia, hyperparathyroidism, renal osteodystrophyy p yFractureOsteonecrosis (Avascular necrosis)InfectionsBone tumors and tumor-like lesions

ContentsJoints

Arthritis and osteoarthritisTumor and tumor-like lesions of joints

Soft tissue tumors and tumor-like lesions

Developmental & Acquired abnormalities in bone cells, matrix & structure

Dysostoses: localized problems in migration of mesenchymal cells and their formation of condensations

Limited structure abnormalitiesMutation in transcription factors (Homeobox genes)

Dysplasia: mutations in regulators of skeletal organogenesisAffect bone and cartilage globallyMutation in cellular signaling and matrix components

Defects in nuclear proteins and transcription factors

Failure of development of bone

Formation of extra bones (supernumerary)

Fusion of two digits (syndactyly)

Development of long spider-like digits (arachnodactyly)

Failure closure of spinal column and skull (Craniorachischisis) MeningiomyeloceleMeningioencephalocele

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Defects in hormones and signal transduction

Achondroplasia:Major cause of dwarfismAutosomal dominant (80% new mutation)Point mutation of FGFR3

Thanatophoric dwarfism:Thanatophoric dwarfism:Most common lethal form of dwarfism1 in 20,000 live birthsMutation of FGFR3Shortening of limbs, frontal bossing, small chest cavity, bell-shaped abdomen

Defects in extracellular structural proteins

Type 1 collagen diseases (osteogenic imperfecta)Deficiency in the synthesis of type 1 collagenBone (too little bone), joint, eyes (blue sclerae), ears (hearing loss), skin, teeth (dental imperfections)Four major subtypes:

T II f l i Type II: fatal in uteroType I: normal life span with increased fracture

Type 2, 10, and 11 collagen diseaseEarly destruction of joint (osteoarthritis)

OsteoporosisIncreased porosity of skeleton resulting from reduced bone mass

Localized: disused osteoporosisGeneralized: metabolic bone disease

Primary: Senile, postmenopausal, idiopathicy , p p , p

Secondary: Vit D deficiency, Steroids

Most common:Senile osteoporosispostmenopausal osteoporosis

OsteoporosisPathogenesis

Age-related change:Osteoblast replication and biosynthesis ↓Low turnover variant

Reduced physical activity:Mechanical force ↓ bone remodeling ↓

Genetic factors:Type of Vitamin D receptor maximal peak mass

Body calcium nutritional state:Calcium deficiency ↓ bone mass

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OsteoporosisPathogenesis

Hormonal influences:Menopause ↓ estrogen ↑IL-1, IL-6, TNF from monocytes and bone marrow cells ↑osteoclast activity (30-40 yrs 35-50% bone loss)High turnover variant

↑ ↓Glucocorticoids ↑bone resorption & ↓bone formationBiphosphonate prevent bone loss

OsteoporosisClinical course:

Veterbral fractures: thoracic and lumbar regions, painful

Multiple fractures loss of height, lumbar lordosis and kyphoscoliosis

Diagnosis:Diagnosis:30-40% bone loss detected by radiographsDual-energy absorption and quantitative CTBiopsy

OsteoporosisPrevention and treatment:

ExerciseCalcium and vitamin D intakeEstrogen replacementBiphosphonateBiphosphonateRecombinant PTH

Rickets and OsteomalaciaDefect in matrix mineralization

Lack of vitamin D or disturbance of its metabolism

Children “rickets”Skeletal deformities

d l “ l ”Adults “osteomalacia”Osteopenia fracture

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HyperparathyroidismPTH ↑osteoclastic activity

Osteitis fibrosa cystica (brown tumor)

Clinical features:Fracture, bone deformitiesJ i t i d d f tiJoint pain and dysfunction

Renal OsteodystrophySkeletal changes of chronic renal disease:

High turnover osteodystrophy↑Osteoclastic bone resorption (osteoporosis)

Low turnover or aplastic disease↓Matrix mineralization (osteomalacia)

Pathogenesis:Vitamin D def. hypocalcemia PTH ↑Hyperphosphatemia PTH ↑Metabolic acidosis bone resorption ↑Aluminum deposit bone mineralization ↓

FracturesClassification:

Complete vs. incompleteClosed (simple) vs. Opened (compound)Comminuted (splintered)Displaced Displaced Pathologic fracture (underlying bone dis.)Stress fracture (repetitive loads)

FracturesReparative process:

1st week organizing hematoma (soft tissue callus, procallus)

2nd or 3rd week bony callus (cartilage and bone formation)

Delayed healing: nonunionDisplaced, comminuted, compound fractures

Inadequate immobilization

Infections

Calcium↓, phophorus↓, Vitamin def. diabetics, vascular insufficiency

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Osteonecrosis (AVN)Ischemia infarction

Mechanisms:Vascular interruption (fracture)CorticosteroidsThrombosis and embolism (nitrogen bubbles dysbarism)Thrombosis and embolism (nitrogen bubbles, dysbarism)Vessel injury (vasculitis, radiation)

↑ Intraosseous pressure and vascular compressionVenous hypertension

Osteonecrosis (AVN)Clinical course:

Subchondral infarcts chronic pain, 2nd osteoarthritisMedullary infarcts clinically silent, painful, collapse

Infections—Osteomyelitis Pyogenic osteomyelitis

Bacterial infections: S. aureus (80-90%)

E. coli, Pseudomonas, Klebsiella: IVDU, GU tract

Mixed organisms: fracture, direct spread

H. influenzae: neonatal period

Salmonella: sickle cell anemia

Spread: hematogenous, extension from contiguous sites, direct implantation

Infections—OsteomyelitisPyogenic osteomyelitis

Sites:Neonate: Metaphysis, epiphysis

Children: Metaphysis

Adult: Epiphysis, subchondral

Clinical course:Acute systemic illness, fever, malaise, leukocytosis, throbbing pain

X-ray: lytic bone destruction

Threatment: antibiotics and surgical drainage

5-25% chronic osteomyelitis

Infections—OsteomyelitisTuberculous osteomyelitis

1-3% of patients with pulmonary or extrapulmonary TB have osseous infectionHematogenous spread from visceral organs or direct extensionSpine infection (Pott disease): thoracic and lumbar vertebraep ( )More destructive and resistance to therapy than pyogenic osteomyelitis

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Bone tumors and Tumor-like lesionsHematopoietic (40%)

Chondrogenic (22%)

Osteogenic (19%)

Unnown origin (10%): giant cell tumor

Micellaneous:Fibrous and histiocyticVascularLipogenicNeurogenic

Bone tumors and Tumor-like lesionsCharacteristic:

Osteosarcoma:Adolescence, metaphysis around the knees

ChondrosarcomaAdulthood, trunk, limb girdle, proximal long bones

Giant cell tumors and chondroblastoma:Epiphysis of long bones

Ewing sarcoma, osteofibrous dysplasia, adamantinomaDiaphysis

Bone-forming tumorOsteoma:

skull, facial bonesMiddle-aged adultsObstruction of sinuses, cosmetic problems

Osteoid osteoma osteoblastoma:Osteoid osteoma, osteoblastoma:Osteoid osteoma: <2 cm in size

Teens and twenties, femur, tibia, painful lesion

Osteoblastoma: >2 cm in sizeSpine, dull pain

X-ray: nidus

Bone-forming tumorOsteosarcoma:

Most common primary bone tumorAge: 75% (children, <20 yo) 25% (elderly)Secondary osteosarcoma: Paget disease, bone infarct, irradiationSites: metaphyseal region of long boneSites: metaphyseal region of long boneClinical: painful enlarging massX-ray: destructive, lytic and blastic mass with permeative margin, “Codman Triangle”Treatment: Chemotherapy, limb salvage

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Cartilage-forming tumorOsteochondroma:

ExostosisSolitary and multiple (hereditary)Late adolescence and early adulthoodMetaphysis of long bonesMetaphysis of long bones

Clinical: slow-growing mass, can be painful, rare (<1%) chondrosarcoma

Cartilage-forming tumorChondroma:

Intramedullary: enchondromaMetaphysis of short tubular bones of hands & feet

Surface of bone: Subperiosteal or juxtacortical chondromaClinical: asymtomatic, painful, pathologic fracturey , p , p gX-ray: well-circumscribed oval lucencies (O ring sign)

Cartilage-forming tumorChondrosarcoma:

Second most common malignant matrix-producing tumor of bonesAge 40 or olderMalignant transformation from enchondroma,

t h d h d bl tosteochondroma, chondroblastomaSites: central portions of skeleton, pelvis, shoulder, and ribsClinical: painful enlarging mass, fractureX-ray: Destructive radiolucent massTreatment: Surgical excision, chemotherapy

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Fibrous and Fibro-osseous tumorsFibrous cortical defect

30-50% of all children older than age 2 yearsEccentric in metaphysis of distal femur and proximal tibiaSmall size, 0.5 cm in diameterSpontaneous resolutionSpontaneous resolution

Nonossifying fibromaLarge size tumor, 5 to 6 cm in sizeMay present with pathologic fracture

Fibrous and Fibro-osseous tumorsFibrous dysplasia

Localized developmental arrestClinical pattern:

Single bone (Monostotic)

Multiple bones (Polyostotic)

Polyostotic disease with café au lait skin pigmentation and endocrine abnomalities (precocious puberty)

Monostotic fibrous dysplasia:Early adolescence

Ribs, femur, tibia, jawbones, calvaria, humerus

Enlargement and distortion of bone (craniofacial)

Fibrous and Fibro-osseous tumorsFibrous dysplasia

Polyostotic fibrous dysplasia:Femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, vertebrae

Polyostotic fibrous dysplasia with café au lait skin pigmentation and endocrinopathies:

McCune-Albright syndrome

Sexual precocity, hyperthyroidism, pituitary adenoma

X-ray: ground glass appearanceTreatment: conservative surgery

Metastatic diseaseAdults:

Prostate, breast, kidney, and lung

Children:Neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomosarcomarhabdomosarcoma

X-ray:Multifocal or solitary (kidney, thyroid)

Lytic: Kidney, lung, GI and melanoma

Blastic: Prostate

JointsOsteoarthritis:

Degenerative joint diseaseProgressive erosion of articular cartilageIdiopathic (primary OA): aging phenomenonSecondary oateoarthritis (5%): diabetics ochronosis Secondary oateoarthritis (5%): diabetics, ochronosis, hemochromatosis, obesityWomen: knees and handsMen: hips

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OsteoarthritisPathogenesis:

Aging and mechanical effectsGenetic factors: high bone density

Clinical course:Primary OA: old age (>50 yr)Primary OA: old age (>50 yr)Secondary OA: younger age, underlying dis.Deep achy pain, worsen with useMorning stiffness, crepitus, limitation of movementNerve root compression (osteophytes)

Rheumatoid arthritisChronic systemic inflammatory disorder: skin, blood vessels, heart, lungs, muscles, joints

Pathogenesis:Autoimmune disease: arthritogenic antigen CD4+ helper T cells inflammatory cytokinescells inflammatory cytokinesGenetic susceptibility: HLA-DR1*0401, *0404Antigens: unknown

Rheumatoid arthritisClinical course:

50%, slow and insidious onset: malaise, fatigue, musculoskeletal pain, joint pain10% acute onset with sever symptomsSite: small joints > large joints: MCP, PIP, MTP, IP, wrists,

kl lb kankles, elbows, knees20%, partial or complete remission periodJoint destruction, deformity: swan neck, boutonniere of fingersX-ray: juxta-articular osteopenia, bone erosion with narrowing of joint space

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Rheumatoid arthritisLaboratory tests and Dx:

Serum rheumatoid factor (IgM to Fc portion): not specificSynovial fluid analysis: inflammatory exudateClinical criteria: 4 criteria

Morning stiffnessA h i i i h j iArthritis in three or more jointsArthritis of typical hand jointsSymmetric arthritisRheumatoid nodulesSerum rheumatoid factorTypical radiographic changes

Rheumatoid arthritisTreatment:

Anti-inflammatory drugs (aspirin, NSAIDs)SteroidsAnti-TNF antibody, soluble TNF receptor

Infectious arthritisSuppurative arthritis:

Bacteria: gonococcus, Staphylococcus, Strepcoccus, Haemophilus influenza, E. coli, salmonella, PseudomonasChildren <2 yr: H. InfluenzaeAdults: S. aureusYoung women: GonococcusSickle cell anemia: SamonellaPainful joint, fever, leukocytosisKnees, hip, shoulder, elbow, wrist

Gout and Gouty arthritisTransient attacks of arthritis initiated by crystallization of monosodium urates (needle shape, neg. birefringent) within jointsPathogenesis: hyperuricemia gout

Age: 20-30 yr after hyperuricemiaGenetic: Lesch-Nyhan syndromeHeavy alcohol consumptionObesityDrugs: thiazidesLead toxicity

Gout and Gouty arthritisClinical course: four stages

Asymptomatic hyperuricemia: puberty male or menopause womenAcute gouty arthritis: 50% MTP joint, ankles, heels, knees, wrists, fingers, elbowsgIntercritical goutChonic tophaceous gout: 12 years after first attackExtra-articular: atherosclerosis, hypertension, renal colic, gouty nephropathy

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PseudogoutCalcium pyrophosphate crystal deposit disease (CPPD)Age: over age 50Type: Idiopathic, hereditary and secondary (joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism)Clinical: aymptomatic, acute, sunacute, chronic arthritis of knees, wrists, elbows, shoulder, ankles

Tumor and Tumor-like lesionsGanglion cysts:

Size: 1 to 1.5 cm near joint capsule or tendonSite: wrists, fingersEtiology: Cystic degeneration

Synovial cysts:Synovial cysts:Baker cyst of knees in RA patientsSynovial protrusion (diverticulum)

Soft tissue tumors and tumor-like lesions

Mesenchymal proliferations that occur in the extraskeletal, nonepithelial tissue

Classification: muscle, fat, fibrous, vesels, nerves

Location: lower ext. (40%), upper ext. (20%), head&neck (10%) trunk&retroperitoneum (30%)(10%), trunk&retroperitoneum (30%)

Prognosis: histologic classification, grade I-III, Staging, superficial vs. deep-seated

Fatty tumorsLipoma:

Most common soft tissue tumor of adultWell-encapsulated mass, mature adipocytesSoft, mobile, painless (exp. Angiolipoma)

Liposarcoma:Liposarcoma:Most common sarcoma of adult (40s-60s)Deep seat soft tisueWell-differentiated (indolent), myxoid (intermediate), round cell, pleomorphic (aggressive)

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Fibrous tumors and tumor-like lesionsReeactive pseudosarcomtous proliferations

Nodular fasciitis, proliferative fasciitis, proliferative myositisMyositis ossificans

Fibromatoses:Superficial fibromatosis (palmar plantar penile)Superficial fibromatosis (palmar, plantar, penile)Deep-seated fibromatosis (desmoid tumors)

Fibrosarcoma:Aggressive tumors with recur and metastasis

Fibrohistiocytic tumorsBenign fibrous histiocytoma (dermatofibroma):

Painless, slow growing tumor of dermis and subcutisAdequate treatment: simple excision

Malignant fibrous hisiocytoma:Undifferentiated pleomorphic sarcomaUndifferentiated pleomorphic sarcomaDeep-seat soft tissue, superficial (atypical fibroxanthoma)Aggressive, recur and metastasis

Tumors of skeletal muscleRhabdomyoma:

Hamartomatous?Heart, tongue, external genitalia

Rhabdomyosarcoma:Most common soft tissue sarcoma of childhood and adolescenceMost common soft tissue sarcoma of childhood and adolescenceMost occur in head& neck or genitourinary tractType: embryonal, alveolar, pleomorphicAggressive tumor, also chemotherapy Rx

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Tumors of smooth muscleLeiomyoma:

Often arise in the uterusErector pili: skin, nipples, scrotum, labiaSurgical removal

Leiomyosarcoma:Leiomyosarcoma:10 to 20% of soft tissue sarcomaAdult, W>M

Superficial or cutaneous lesion good prognosisDeep soft tissue local extension, metastasis

ReferenceKumar, Kabbas, fausto: Robbins and Cotran Pathologic Basis of Disease: 7th ed

http://www.pathguy.com/lectures/bones.htm