Download Musculoskeletal

Diseases of the musculoskeletal
system
D S O’Briain
February 2009
Medical disease of bone and joint
• Metabolic disorders
• Arthritis
Medical disease of bone and joint
(1) Metabolic diseases
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Vitamin D and parathyroid hormone
Rickets and osteomalacia
Hyperparathyroidism, renal osteodystropy
Osteoporosis
• Importance of calcium phosphate product
Vitamin D
• Role: bone mineralisation, maintaining serum calcium and
phosphate levels
• Source; skin, 7 dehydrocholesterol (sun) vitamin D3: diet
ergosterol altered to vitamin D2
• Synthesis: travels on binding protein
– to liver (hydroxylase) produces 25 (OH)D
– to kidney (hydroxylase) produces 1.25 (OH)D
• Effects
– GI absorbs calcium and phosphate
– Bone: mobilises calcium phosphate (with PTH)
– Kidney: absorbs calcium, loses phosphate (with PTH)
Parathyroid hormone
• 84 amino acid polypeptide from parathyroid glands, binds to
cell plasma membrane receptor generating cAMP etc
• Supports serum calcium
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Activates osteoclasts to release bone calcium
Increases renal tubular reabsorption of calcium
Increases conversion of vitamin D to 2(OH) in kidney
Increase urinary phosphate excretion
Increases GI calcium absorption
• Excess causes
– Increased osteoclasts that erode bone
– hypercalcemia
Rickets and osteomalacia
• Vitamin D deficiency:
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1) diet (sunlight),
2 malabsorption,
3 metabolism: liver or kidney disease (cyto P450, renal hydroxylase deficiency),
4 end organ resistance
• Phosphate deficiency (aluminium bound, failed renal tubular absorption
• Normal growing cartilage - becomes calcified - stops growing - endochondral
ossification
• Children (rickets): growing cartilage not calcified, abnormal growth and poor
ossification, abnormal bone in skull, ribs, vertebrae, lower limbs
• Adult (osteomalacia): growth finished, excess osteoid, osteopenia, fractures
Hyperparathyroidism
• Primary or secondary hyperparathyroidism
• Increased PTH signals osteoblasts which signal osteoclasts to
resorb bone
• Effects:
– Subperiosteal resorption (hand X-ray)
– Dissecting osteitis: resorption, fibrosis, microfractures of cancellous bone
– Brown tumour (osteitis fibrosa cystica, Von Recklinghausen)
haemorrhage, haemosiderin, inflammatory repair, cystic change
Renal osteodystropy
• Renal failure causes defective 1,25 (OH)D, loss of phosphate
and retention of H (acidosis)
• These induce changes of hyperparathyroidism, osteomalacia,
osteoporosis, osteosclerosis and decreased growth.
• The bone loss may be high, low or mixed turnover
• Excess aluminium and amyloid may add to the effect
Osteoporosis
• Peak bone mass; effect of vitamin D, diet, exercise, hormones
• Normal bone remodeling: bone loss less than 1% a year
• Senile osteoporosis: with age, osteoblasts less effective (diet and
exercise influence) increased slow bone loss mainly in cortex
• Post menopausal osteoporosis: decreased oestrogen allows
increase in cytokines (Il-1, Il-6 and TNF alpha) which mobilizes
osteoclasts; reactive osteoblast mobilisation, high turnover bone
loss, main effects on cancellous bone
• Result: (microfracture) vertebrae—pain, height loss, deformity;
pelvis, hips—fractures (fatal secondary illnesses; pneumonia,
pulmonary embolism)
Medical disease of bone and joint
(2) Arthritis
• Osteoarthritis
• Rheumatoid arthritis
• Other forms of arthritis
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Juvenile rheumatoid arthritis
Ankylosing spondylitis
Reiter syndrome
Infectious arthritis
Lyme arthritis
Gout and pseudogout
Joint Features
• Solid joints: structural, little movement,
– synarthroses (fibrous); symphyses (cartilage)
• Synovial joints: cavity, movement
– Capsule, ligaments, muscles
– Synovial lining, phagocytic or fibroblast-like cells,
hyaluronic acid lubricant
– hyaline cartilage shock absorber, wear resistant
– chondrocytes synthesise and digest matrix of type 2 collagen,
proteoglycans
Osteoarthritis
progressive degeneration of articular cartilage
• Usually age-related and oligoarticular; vertebrae, hips, knees, feet and hands
(DIP, PIP)
• May be secondary to obesity, trauma, or joint disease (haemophilia)
• Pain, morning stiffness, crepitus, decreased movement, root compression,
nerve pressure effects
• Cartilage degenerates, chondrocytes cluster, increased water, decreased
proteoglycans, fibrillation, fragmentation, joint mice, bone exposed,
fractures, cysts, eburnation, osteophytes (Heberden’s nodes), reactive
synovium, fibrous pannus
• Chondrocytes produce Il-1, TNF alpha, Il-6, prostaglandins
Rheumatoid Arthritis
chronic systemic inflammatory disorder
• 1% of population, majority (x5) women, peak
20-40 years
• Involves many sites: skin (rheumatoid nodules),
blood vessels (vasculitis), heart, lungs
• Principally involves joints: hands, feet; later
wrists, elbows, ankles, knees
• Onset: gradual systemic or acute arthritis,
swollen, hot, painful and stiff joints
Rheumatoid Arthritis
• Pathogenesis
– Genetic susceptiblity (HLA Dr4, common motif of antigen binding site of DR
molecule)
– Antigen: microbial? Epstein Barr, mycoplasma, borrelia
– Autoimmunity: to collagen or cartilage proteoglycan, driven by CD4 cells
• Joint damage:
– activated cells cytokine loop,
– B cell activation, IgM autoantibodies to IgG (rheumatoid factor)
– immune complexes
• Effect:
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inflamed synovium, oedema, thickened hyperplastic papillae form
Increased vascularity, lymphocytes, plasma cells, fibrin
Bone eroded, subchondral cysts, osteopenia,
pannus (granulation tissue obliterating synovium); ankylosis
Other forms of arthritis (1)
• Juvenile rheumatoid arthritis: large joints, oligo
involvement, RF negative, ANA+
• Ankylosing spondylitis, HLA B27, males, axial,
sacroiliac joints
• Reiter syndrome: Arthritis, urethritis, conjunctivitis,
autoimmune reaction following infection of GI or
urethra
• Psoriatic arthritis: 5% of psoriasis, like RA
Other forms of arthritis (2)
• Infectious: suppurative, tuberculous
• Lyme arthritis: borrelia burgdorferei, late in disease,
large joints
• Gout: uric acid crystals, giant cell reaction, acute
arthritis, chronic tophaceous arthritis, tophi
• Pseudogout: calcium pyrophosphate, knees
Bone tumours
• Secondary tumours
• Marrow tumours
• Primary bone tumours
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Osteosarcoma
Chondrosarcoma
Ewing sarcoma
Giant cell tumour
Others
Bone Features (1)
• Bone profile: joint - cartilage - epiphysis - plate - metaphysis diaphysis (shaft)
• Bone section: periosteum - cortical bone - cancellous bone medulla
• Growth: at metaphysis, site of most tumours
• Long bone growth: metaphyses near knee (lower femur, upper
tibia) remote from elbow (upper humerus)
• Effects of age: closure of epiphyses
Bone Features (2)
• Periosteum: produces reactive bone if stimulated (causes
Codman’s triangle, sunburst, or onion skin patterns on X-ray)
• Osteoblasts, contain alkaline phosphate, become osteocytes,
produce osteoid (like collagen) which becomes mineralised as
bone (fibres are at first irregular - woven - later become parallel
- lamellar
• Osteoclast: multinucleated cell of monocyte-histiocyte lineage,
contains acid phosphate, lyses bone.
Bone tumours
• Presentation: pain, tenderness, swelling, deformity, pathological
fracture
• 1) secondary tumours: 70% of cancer involves bone; spreads to
bone by blood or vertebral lymphatics
– Deposits are usually: multiple, in axial skeleton, in the red marrow, lytic,
may be sclerotic (prostate, breast)
– (role of vessels, prostaglandins, osteoclast activing factor)
– Effect: hypercalcemia, leukoerythroblastic anaemia
• 2) marrow tumours: leukaemia, lymphoma, myeloma
• 3) primary bone tumours: benign or malignant
Primary bone tumours
• Majors
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Osteosarcoma
Chondrosarcoma
Ewing sarcoma
Giant cell tumour
• Others
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Paget’s disease
Fibrous dysplasia
Other cartilage tumours
Other bone tumours
cysts
Osteosarcoma
• Primary (70%): 10-25 years, males x 2, some familial or follow
retinoblastoma
• Secondary (30%): paget’s disease, enchondromatosis, chronic osteomyelitis,
fibrous dysplasia, bone infarcts or fractures, radiation (radium or external),
alkalating agents
• Aetiology: ? Virus, immunological, genetic, related to bone mass
• Usual findings: in medulla of long bones at metaphysis, 70% about the knee
as bulky mass
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Codman’s triangle on x-ray
25% have metastases (usually lung) at diagnosis, mean survival 3 years
Variants: may be cortical, periosteal, parosteal, extraskeletal
Microscopy: osteoblastic (but also chondroblastic, fibroblastic, angioblastic
areas)
Chondrosarcoma
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Males x 2, age 50s and 60s
Primary (90%)
Secondary (10%) enchondromas etc. as for osteosarcoma
Presentation: lobulated mass with spotty calcification; pelvic
bone (50%) or other central sites
• Correlation of clinical, x-ray and histopathology essential
(malignant central lesion histologically similar to a benign
peripheral lesion)
• Microscopy: most are low grade (grade 1) 90% 5-year survival;
grade 3 have poor survival (40% 5-year survival)
Ewing’s Sarcoma
• Presentation: Pain, tenderness, swelling, systemic symptoms (may simulate
osteomyelitis), age 5-20, males x 2, involves pelvis or long bones, 25% have
metastases (to lung, brain, other bones) at diagnosis
• Begins in medulla of metaphysis or of diaphysis but spreads to periosteum
producing Codman’s triangle and onion layering effect on x-ray
• Microscopy: small round cells with cytoplasmic glycogen (PAS+)
• Cell of origin unknown: ?mesenchymal, related to peripheral
neuroectodermal tumour (PNET) which has neural feature; both have t(1122), produce a fusion gene EWS-FLI1, stain with antibodies to CD99
• Survival: has improved from 10% to 75% with modern chemotherapy
Giant cell tumour
• Microscopy: neoplastic stromal cells with prominent giant cells
• Exclude other lesions which may have giant cells including
brown tumour of hyperparathyroidism, gingival epulis, fibrous
cortical defect, aneurysmal bone cyst, chondroblastoma.
Carcinoma and soft tissue sarcoma may sometimes have
prominent giant cells but rarely cause diagnostic difficulties
• Occur in epiphysis after closure (age 15-55 years), 50% about
knee, more frequent in females
• Most are benign, one-third to one-half recur, 10% are aggressive
or malignant but such behaviour can not reliably be predicted
histologically
Paget’s disease
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Bone disease with osteoclastic (early), mixed , and osteosclerotic (late) stages
May be monostotic or polyostotic; usually involves axial skeleton
Involves 1-3% of the older population, males (4:3) more frequently
Prodominantly a disease of people of N European stock, ? Viral cause, viral
type particles in osteoclasts
• Usually asymptomatic (identified incidentally on x-ray or by raised alkaline
phosphatase). Causes excess production of collagen products
(hydroxyproline)
• May cause pain, deformity, nerve pressure, haemodynamic shunting of blood,
pathological fracture, sarcoma
• Therapy: calcitonin, diphosphonates, mithramycin, fluorides
Fibrous dysplasia
• A developmental defect showing impaired bone formation with
disorganised osseous and fibrous tissue which fractures and
causes deformities
• Usually monostotic, ribs, skull, jaw, femur (in teens and 20s)
• In 25% polyostotic (usually children)
• Occasionally (3%) with pigmentation, precocious puberty
(females) and endocrinopathy (hyperthyroidism,
hyperparathyroidism, hyperpituitarism, diabetes) as Allbright’s
syndrome
Other cartilage tumours
Osteochondroma
• Disordered growth from epiphysis to form abnormal metaphyseal spur
• Mainly a sporadic disorder of long bones in adolescence
• Occasionally multiple as an autosomal dominant disorder
• Rarely sarcoma may supervene
Enchondroma
• Sporadic single lesions, may be asymptomatic or cause deformity
• Multiple (enchondromatosis) (Ollier’s disease) as a non-hereditiary disease
involving hand and feet in childhood
• Multiple with multiple cavernous haemangiomas as a familial disease
(Maffucci’s disease)
Rare lesions: Chondromyxoid fibroma, Chondroblastoma
Other bone tumours
Osteoma
• Rare, usually involves face of skull
• Gardner’s syndrome: osteomas with epidermal cysts, teeth disorders,
desmoid tumours, and colonic adenomatous polyps
Osteoid osteoma
• Tiny (3-10 mm) vascular osteoblastic lesion (nidus), regarded as a benign
neoplasm, surrounded by a large reactive osteosclerotic rim
• Larger, histologically similar lesion in vertebrae and lower limbs is painless
(osteoclastoma)
• Causes severe night pain relieved by aspirin, cured by excision
• Age 5-25, males x 3
• Site: metaphysis of long bones especially of lower limb
Bone Cysts
• Simple: solitary fluid-filled lesions in metaphysis near
epiphyseal plate. Two-thirds in proximal long bones, males x 3,
childhood and adolescence
• Aneurysmal bone cyst: blood-filled spaces separated by fibrous
septae distend bone and may extend into surrounding tissue
(may be secondary to degeneration of another lesion). Involve
vertebrae and flat bones (10-20 years; M=F)
• Fibrous cortical defect (non-ossifying fibroma): Defect of
epiphyseal plate growth extending into the metaphysis, usually
about the knee, in children
Soft tissue tumours
• Muscle, fat, fibrous tissue, vessels, nerves
• Benign (-oma): (leio/rhabdo)myoma, lipoma,
neuroma, angioma, fibroma, neurofibroma
• Malignant (sarcoma): leio/rhabdo myosarcoma,
liposarcoma, fibrosarcoma, angiosarcoma
Connective tissue neoplasms
Leiomyoma
Rhabdomyoma
Lipoma
Fibroma
Chondroma
Osteoma
Synovioma
Angioma
Leiomyosarcoma
Rhabdomyosarcoma
Liposarcoma
Fibrosarcoma
Chondrosarcoma
Osteosarcoma
Synovial sarcoma
Angiosarcoma
Neuroectodermal tumours
Central
• Glial: astrocytoma, oligodendroglioma,
ependyoma
• Neural: medulloblastoma, neuroblastoma,
ganglioneuroma, meningoma
Peripheral
• Schwannoma, Neurofibroma,
• Naevus, Melanoma
Vascular Tumours
• Haemangioma, benign. capillary, cavernous, granuloma pyogenicum, Lindau
von Hipple glomus, telangiectasia, spider naevus, naevus flammeus (simple
birthmark). port-wine stain (disfiguring birthmark), Sturge Weber, Osler
Weber Rendau
• Malignant.
• Haemangioendothelioma: Skin (spleen, liver), low grade malignancy.
• Epithelioid: soft tissue, lung - 20% metastasise.
• Haemangiopericytoma: lower extremites, retroperitoneal - 50% metastasise
• Angiosarcoma: Skin, soft tissue, breast, liver (arsenic, thorotrast, PVC) .
High grade malignancy
• Kaposi’s sarcoma: immune deficiency, herpes HHV8
Some varieties of soft tissue
tumours (1)
• Synovial sarcoma: biphasic, t(X:18), metastasise to
lymph nodes (most sarcomas spread to lung)
• Small round blue cells (broad differential, children)
• Spindle cell (broad differential; use of
immunohistochemistry, grade 1-3)
• Fibrohistiocytic tumours: classification problem
Some varieties of soft tissue
tumours (2)
• Nodular fasciitis: a reactive pseudosarcomatous
proliferation
• Myositis ossificants: a reactive proliferation
forming bone
• Fibromatosis (Dupuytren of hand, deeper
desmoids, locally infiltrative)
• Lipoma: commonest soft tissue tumour
• Haemangioma: wide variety