Bones Joints Soft Tissues Robbins Chapter 26 Skeletal

Bones, Joints, & Soft Tissues Robbins Chapter 26

Skeletal System NORMAL • Number of bones: 206 • Function: • • • Structural support Movement Protection Metabolism (Ca & P) Erythropoiesis Special senses

Bone Cell Types • Osteoprogenitor cells: Pluripotent mesenchemal stem cells • Osteoblasts: Produce collagen-rich osteoid matrix; surface • Osteocytes: Metabolically active; incorporated into lacunae • Osteoclasts: Bone resorption; multinucleated giant cells

Osteoid Matrix • Produced by osteoblasts • Type I collagen & other proteins • Serves as “template” on which mineralization occurs • May be “woven” or “lamellar”

Bone Development • Endochondral Ossification: • Hyaline cartilage template • Long bones • Epiphysis, Diaphysis, Metaphysis • Intramembranous Ossification: • No cartilage template • Flat bones (skull, sternum)

Cartilage • Chondrocytes: produce cartilage • Matrix: Type II collagen • 3 types of cartilage: • Hyaline: joints, ribs, trachea • Elastic: epiglottis • Fibrous: intervertebral discs, tendons & ligaments

Developmental Disorders • Malformations • Achondroplasia • Thanatophoric Dwarfism

Malformations • Incidental: • Absent rib • Absent clavicle • Cosmetic: • Absent phalanx • Extra phalanx • Serious: • Craniorachisis

Achondroplasia • • • Clinical: dwarfism Autosomal dominant 80% of cases are new mutations Mutation of FGF receptor 3 gene Defective epiphyseal plate, with premature calcification of long bones (head & spine spared)

Thanatophoric Dwarfism • Most common lethal form of dwarfism; natal/neonatal death • Different mutation of FGFR 3 • Shortened limbs & underdeveloped chest cavity

Disorders with Abnormal Matrix • Osteogenesis imperfecta (type I collagen disease) • Other collagen disorders • Mucopolysaccharidoses • Osteoporosis

Osteogenesis Imperfecta • • • “BRITTLE BONE DISEASE” A group of disorders a 1 & a 2 collagen gene mutations Net result: too little bone 4 major subtypes (type II: fatal) Blue sclerae; hearing deficit; dental imperfections; fractures

Abnl Metabolism of Types 2, 10, & 11 Collagen • Spectrum of disorders • Severe forms: lethal • Less severe forms: chronic destruction of joints

Mucopolysaccharidoses • Chapter 6 • Lysosomal storage disorders • Deficiencies in the enzymes that degrade dermatan sulfate, heparan sulfate, & keratan sulfate • Abnormal hyaline cartilage • Short stature; chest wall abnls

Osteoporosis • Age-related disorder • Reduced bone density with proportional deficit of osteoid and mineralization • Risk of fractures • Elderly; F>M; decreased activity

Disorders with Osteoclast Dysfunction • Osteopetrosis (Albers-Schonberg dz) • Paget disease of bone (osteitis deformans)

Osteopetrosis ALBERS-SCHONBERG DISEASE or MARBLE BONE DISEASE • Group of rare hereditary d/os • Defective osteoclast function • Reduced bone resorption • Oversized, brittle bones • Erlenmyer flask deformity • Primary spongiosa fills medulla

Paget Disease OSTEITIS DEFORMANS • “Matrix metabolic madness” • 3 stages: • Osteolytic • Mixed osteolytic / osteoblastic • Osteosclerotic • ? Slow-virus infection; risk of OS • Pain, facial changes, chalkstick frxs • Mosaic pattern of lamellar bone

Diseases with Abnormal Mineral Homeostasis • Rickets & osteomalacia • Hyperparathyroidism • Renal osteodystrophy

Rickets & Osteomalacia • • • Vitamin D deficiency Rickets in children Osteomalacia in adults Failure of bone mineralization Wide osteoid seams (unmineralized osteoid matrix)

Osteitis Fibrosa Cystica • Bone changes in hyper. PT • PTH leads to increased osteoclast activity & marked bone resorption • Peritrabecular fibrosis & cyst formation (“brown tumors”)

Renal Osteodystrophy • Bone changes in renal failure • Includes changes similar to osteitis fibrosa cystica, osteomalacia, & osteosclerosis • Related to secondary hyper. PT & vitamin D deficiency

Fractures • Types based on bone breakage: • Complete (simple) • Incomplete (greenstick) • Comminuted (splintered) • Types based on skin involvement: • Closed (intact overlying skin) • Compound (open, lacerated skin)

Osteonecrosis AVASCULAR NECROSIS • • • Ischemic infarction of bone Variety of underlying mechanisms Chronic pain & bony destruction Rx: joint replacement Necrosis of cancellous bone and bone marrow

Osteomyelitis • Inflammation of bone & marrow • Pyogenic osteomyelitis: • Bacterial infection; +/- draining sinuses • Sickle cell dz: Salmonella • TB osteomyelitis (Pott disease) • Skeletal syphilis (saber shin)

Bone Tumors & Tumor-like Lesions • M. C. bone tumor: metastasis • Types of bone tumors: • • • Osteoblastic / osteogenic Chondromatous / chondrogenic Histiocytic / fibrogenic Hematopoietic Others / Unknown

Bone-Forming Tumors • Osteoma • Osteoid Osteoma • Osteoblastoma • Osteosarcoma

Osteoma • • • Benign bony projection Skull & face Any age; M>F Gardner syndrome Composite of woven & lamellar bone

Osteoid Osteoma • • • Painful, benign neoplasm Less than 2 cm Ends of tibia or femur < 25 yrs; M>F Excess prostaglandin E 2: pain WC, woven trabeculae rimmed with osteoblasts

Osteoblastoma • • • Similar to osteoid osteoma Osteolytic rather than osteoblastic Larger; dull, achy pain Most common in spine +/- malignant transformation Similar microscopically

Osteosarcoma • The M. C. primary bone cancer • < 20 yrs; M>F; pain & tenderness • Long bone metaphysis (especially distal femur & proximal tibia) • “Codman’s triangle” (x-ray) • Osteoid & bone formation • Several variants (fibroblastic, chondroblastic, osteoblastic)

Cartilage-Forming Tumors • • • Osteochondroma Chondroblastoma Chondromyxoid Fibroma Chondrosarcoma

Osteochondroma EXOSTOSIS • Benign, cartilage-capped bony outgrowths; endochondral bones • Developmental aberrations • The M. C. benign bone tumor • Hereditary forms • Mushroom-shaped

Chondroma • • • ENCHONDROMA Benign tumor of hyaline cartilage Usually solitary; asymptomatic Hands & feet; any age; M=F Ollier’s disease Maffucci’s syndrome Mature hyaline cartilage

Chondromyxoid Fibroma • • Benign tumor Lower femur / upper tibia 10 -30 yrs; M>F Chondroid, fibrous, & myxoid components

Chondroblastoma • Rare benign tumor • 10 -20 yrs; M>F; knee; pain • Background of immature chondrocytes with scattered multinucleated giant cells & islands of chondroid matrix

Chondrosarcoma • • • Malignant cartilage-making tumor Slow clinical evolution Middle to late life; M>F Central skeleton & knee Malignant hyaline & myxoid cartilage; several variants

Fibrous & Fibro. Osseous Tumors • • • Fibrous Cortical Defects Non-ossifying Fibroma Fibrous Dysplasia Fibrosarcoma Malignant Fibrous Histiocytoma

Fibrous Cortical Defect NON-OSSIFYING FIBROMAS • • Common; 30 -50% children >2 yrs Developmental defects Metaphyses of knee region Usually small; larger lesions are called “non-ossifying fibromas” • X-ray radiolucency • Benign storiform fibroblasts

Fibrous Dysplasia • Benign, tumor-like condition • 3 patterns: • Monostotic: 70%; early adolescence; incidental; usually asymptomatic • Polyostotic: 25%; earlier age; face, shoulder & pelvic girdles; fractures • Mc. Cune-Albright syndrome: polyostotic; café-au-lait; endocrinopathies • WC, intramedullary fibrosis

Fibrosarcoma & MFH • Fibroblastic, collagen-producing sarcomas of bone • Overlapping features • Middle-aged & elderly • Large, hemorrhagic • FS: herringbone pattern • MFH: spindle cells & giant cells

Miscellaneous Bone Tumors • Ewing Sarcoma • Primitive Neuroectodermal Tumor (PNET) • Giant Cell Tumor of Bone • Aneurysmal Bone Cyst

Ewing Sarcoma PRIMITIVE NEUROECTODERMAL TUMOR • • • Small blue cell malignancies Medullary cavities of long bones < 30 yrs; M>F “Onion-skinning” on x-ray c-myc oncogene; t(11; 22) PNET: neural differentiation

Giant Cell Tumor • • • Benign & malignant varieties Most (90 -97%) are benign High recurrence rate Epiphyses of long bones (knee) 20 -40 yrs; F>M ! Multinucleated giant cells

Aneurysmal Bone Cyst • Benign bone tumor • Multiloculated blood-filled cystic spaces • Rapidly-growing cystic tumor, typically in persons <20 yrs; no sex predilection • Pain & swelling; metaphyses, vertebrae • 17 p 13 translocations up-regulation of USP 6, a deubiquitinating enzyme

Bone Metastases • The most common bone tumor • Most common primaries: • Adults: prostate, breast, kidney, lung • Children: NB, Wilms, OS, Ewing, RMS • Most mets are multifocal • Solitary: kidney & thyroid

Joints • Connective tissue structures which join bones • Synarthroses: Joints which allow little or no movement • Diarthroses: Joints which permit free movement of bones:

Diarthrosis Joints • Joint capsule surrounds joint • Hyaline cartilage covers articular surfaces of bones • External fibrous capsule • Internal synovial membrane • Synovial fluid fills joint space

Joint Pathology • Inflammation (arthritis): • • Osteoarthritis Rheumatoid arthritis & related d/os Infectious arthritis (bacterial, TB, etc…) Gout & pseudogout • Tumors: • • Ganglions & synovial cysts Giant cell tumor of tendon sheath Pigmented villonodular synovitis Synovial sarcoma

Osteoarthritis DEGENERATIVE JOINT DISEASE • Progressive deterioration of joint with loss of articular cartilage • “Wear & tear” plus cytokine role • Impaired mobility • Deep, achy pain; morning stiffness • Weight-bearing joints, IP, TM 1 & CM 1

Osteoarthritis • • • Two types: primary & secondary Osteophytes Bone eburnation Joint mice Heberden’s nodes (osteophytes of DIP in women)

Rheumatoid Arthritis • Multisystem, chronic, relapsing inflammatory d/o (joints, skin, blood vessels, heart, lungs, muscles) • Unpredictable; F>M; HLA-DR 4 & 1 • AI disorder triggered by microbe (EBV, other virus, mycobacteria, mycoplasma) • Rheumatoid factor: Ig. M which binds Fc portion of Ig. G

Rheumatoid Arthritis JOINT MANIFESTATIONS • Small joints of hands & feet • Ulnar deviation; Baker cyst • Pain, tenderness, stiffness, with eventual ankylosis • Morning stiffness; symmetric • Synovium: perivascular lymphs, fibrin, PMNs, & pannus (fibrosis)

Rheumatoid Arthritis OTHER ORGANS • Skin: rheumatoid nodules (nontender, SQ inflammatory nodules) • Vessels: vasculitis • Other organs: rheumatoid nodules & vasculitis

Conditions Related to RA • • • Juvenile RA Felty syndrome Ankylosing spondylitis Reiter syndrome Psoriatic arthritis Enteropathic arthritis

Juvenile RA STILL’S DISEASE • Often begins with acute febrile systemic illness • Knees, wrists, elbows & ankles • Assymetric; oligoarthritis • RF & nodules are rare • Antinuclear Ab positive

Felty Syndrome • • • Polyarticular arthritis Splenomegaly Leukopenia Leg ulcers RA frequently negative

Ankylosing Spondylitis MARIE-STRUMPELL DISEASE • • • Localized to spine Predominantly affects men Strong association with HLA-B 27 RF is frequently negative +/- uveitis, aortitis, amyloidosis

Reiter Syndrome • Triad of findings: arthritis, conjunctivitis, & urethritis • Typically s/p NG urethritis or bacillary dysentery; RF negative • M. C. arthritis in young men • Strong association with HLA-B 27 • Ankles, knees & feet

Other RA Variants • Enteropathic arthritis: • 10 -20% of patients with IBD • Usually HLA-B 27 positive • RF negative • Psoriatic arthritis: • 5% of psoriasis patients • Strongly associated with HLA-B 27 • RF negative

Infectious Arthritis • Suppurative arthritis • Tuberculous arthritis • Lyme disease • Viral arthritis

Suppurative Arthritis • Painful & swollen joint (large joints) • Bacteria (staph, strept, neisseria, hemophylis, GN rods) • Children: H. influenzae • Sickle cell: Salmonella • Sexually active F: Gonococcal

Tuberculous Arthritis • • Usually monoarticular M. C. site: spine (Pott’s disease) Other sites: hip, knee, ankle Very destructive

Lyme Disease • Borrelia burdorferi (spirochete) • Vector: Ixodid ticks • 3 stages: • Skin lesions • Cardiac & nervous system • Chronic, symmetric polyarthritis • Lg joints (knees, shoulders, elbows, ankles)

Gout • Recurrent attacks of acute arthritis caused by monosodium urate crystals • Hyperuricemia; many causes • Tophus: Nontender mass of urates surrounded by inflammation • Urate crystals: yellow when parallel with polarized light rays • Alcohol, obesity, drugs, lead

Pseudogout CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DZ • • Caused by a variety of conditions Acute vs. chronic Mono- vs. polyarticular Crystals are blue when parallel to polarized light rays

Joint Tumors • Ganglion • Synovial cyst • Giant cell tumor of tendon sheath • Pigmented villonodular synovitis

Ganglion • Small cyst near joint capsule or tendon sheath • Myxoid degeneration of connective tissue • No communication with joint space

Synovial Cyst • Herniation of synovium through a joint capsule or… • Massive enlargement of a bursa • +/- hyperplastic synovium • +/- inflammation

Villonodular Synovitis • Neoplastic process of synovial lining of joints, tendon sheaths, & bursae • Giant cell tumor of tendon sheath: localized form; single; WC; hand • Pigmented villonodular synovitis: diffuse form; one or more joints; multiple fingerlike projections; knee • “giant cell tumor of tendon sheath” • “pigmented villonodular synovitis”

Synovial Sarcoma • • Synovial malignancy Knee & ankle; rarely within joint WC, firm, gray-pink; +/- Ca++ Biphasic pattern: • Glandular areas • Stromal areas • t(x; 18)

Soft Tissue Tumors GENERAL FEATURES • Congenital tumors rarely behave malignantly (even if anaplastic) • Many sarcomas have characteristic molecular abnormalities • Certain architectural patterns are characteristic for certain types

Soft Tissue Tumors GENERAL FEATURES • Grading of malignancies is of great importance (I: WD; II: MD; III: PD) • Staging determines prognosis • Superficial tumors tend to have a better prognosis than deeper tumors • Larger sarcomas are worse

Soft Tissue Lesions • • Fatty tumors Reactive fibrous lesions Fibromatoses Fibrosarcoma Fibrohistiocytic tumors Skeletal muscle tumors Smooth muscle tumors

Fatty Tumors • Lipoma: • Benign, WC fatty tumor; trunk & neck • F>M; 5 th & 6 th decades • The M. C. soft tissue tumor • Liposarcoma: • Malignant adipose tissue tumor • Legs; retroperitoneum • Lipoblasts; multiple variants

Reactive Lesions • Nodular Fasciitis: • Rapidly growing small mass • Arms, trunk, & neck • Zonation (central: hypocellular; myxoid; outer hypercellular) • Myositis Ossificans: • Rapidly growing, painful lesion • Extremities; young males • Zonation with peripheral metaplastic bone

Fibromatoses • Superficial fibromatosis: • Palmar - Dupuytren contracture • Plantar - Uncommon • Penile - Peyronie disease • Deep fibromatosis (Desmoid): • Extra-abdominal (chest, back, thigh) • Abdominal (anterior wall) • Intra-abdominal (mesentery, pelvic wall)

“Malignant Fibrous Histiocytoma” • Once considered the most common soft tissue malignancy • Composed of malignant cells with considerable pleomorphism • Being dropped as a diagnostic category • Most former MFHs have been found to be variant fibrosarcomas

Fibrosarcoma • • Malignant tumor of fibroblasts Any age; any site Often WC; soft; +/- necrosis Highly cellular; herringbone pattern is classic • A variety of other subtypes may occur, including “pleomorphic fibrosarcoma”

Rhabdomyosarcoma • • Skeletal muscle cell malignancy M. C. sarcoma of childhood Desmin, myoglobin, myosin, actin Variants: • Embryonal: H/N, GU, retroperitoneum; “sarcoma botryoides; ” “Strap cells” • Alveolar: Thorax, extremities; worse • Pleomorphic: Rare; adults

Leiomyoma • • • Benign smooth muscle tumor Small except uterine variety WC, yellow-pink, firm Fascicles of smooth muscle cells +/- pleomorphism No necrosis, hemorrhage, mitoses

Leiomyosarcoma • • • Malignant smooth muscle tumor Adults; extremities, viscera, retro Tend to be large; +/- WC + hemorrhage, necrosis, mitoses Fascicular growth

Miscellaneous Tumors • Chordoma: notochord; physaliferous cells • Granular cell tumor: PAS+; any site; tongue • Alveolar soft part sarcoma: Young women; alveolar pattern; EM crystals with cross-grid • Epithelioid sarcoma: Hands; adolescence • Clear cell sarcoma: S-100+ • Rhabdoid tumor: intermediate filaments