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Orthopaedic Pathology (Bone Neoplasm (Chondroid Tumours:
Benign:
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Orthopaedic Pathology
Bone Neoplasm
Clinical Presentation of primary malignant bone tumour
- Pain, mass & swelling of affected area, fracture and loss of function
- May also have systemic symptoms:
- Fever
- Anemia
- Weight loss
- Elevated WBC and ESR
- 20-25% present with metastatic disease:
- Lungs (38%)
- Bone (31%)
- Bone marrow (11%)
Common Investigations used for bone tumours:
- X-ray
- MRI (or CT scan)
- Accurately outlines the bone tumours and its relationship with other structures (e.g .artery, nerves etc) for pre-operative assessment and surgery planning
- Bone radionuclide bone scan
- Detect tumour spread to other bones
- Positron emission tomography (PET) scan:
- Highly sensitive test that scans the whole body for tumour spread
- Sometimes can be helpful in determining whether a tumour is more likely to be benign or malignant esp in follow up post surgery cases
- Biopsy (Needle or incisional surgical biopsy)
- Gold standard in diagnosing the tumour, or at least typing the tumour (benign vs malignant, low vs high grade)
General Prognostic Factors for malignant bone tumours:
- Size
- Grade
- Location of the tumours and margin clearance
- Certain metastatic sites have worse prognosis (e.g.. liver and bone worse than lung)
- Response to chemotherapy (good, >90% necrosis)
- Specific molecular aberrations confer different prognosis (due to varying response to chemotherapy)
Precursor lesion of bone malignancy
- Most cases are sporadic
- High risk:
- Ollier disease (enchondromatosis and Maffuci syndrome)
- Familial retinoblastoma syndrome
- Rothmund-Thomson syndrome
- Moderate risk:
- Multiple osteochondroma
- Polyostotic Paget disease
- Radiation osteitis
- Low risk:
- Fibrous dysplasia
- Bone infarct
- Chronic osteomyelitis
- Implants
- Giant cell tumour
- Osteoblastoma
- Chondroblastoma
- Osteogenesis imperfecta
Treatment: General Principles
- Surgery:
- Local control (remove entire tumour with negative margins and minimal healthy tissue)
- Radical surgical procedures (ie, amputation - very rare) vs limb sparing surgery (maximise limb function)
- Chemotherapy:
- Impt adjuvant therapy in major malignant bone tumours (except chondrosarcoma) for control of micro metastases
- Radiation therapy:
- Local control (esp in advanced tumours and surgical excision is incomplete)
- These modalities are often used in combination. Multidisciplinary approach essential.
Bone-forming tumours:
- Benign:
- Osteoid osteoma/osteoblastoma
- Osteoma
- Malignant:
Osteosarcoma (35%)
- A mostly high-grade malignant bone tumour that produces osteoid directly from tumour cells
- Epidemiology and Associations:
- 60% male
- Usually ages 10-25 years
- 75% between 10 and 20 yrs
- Older patient often associated with precursor lesion (e.g. Paget’s disease)
- X-ray findings:
- Large, destructive, lytic or blastic mass with permeative margins
- May break through cortex and elevate periosteum
- Sunburst pattern due to new bone formation in soft tissue
- Sites:
- Metaphysis of long bones (distal femur, proximal tibia, proximal humerus)
- Gross:
- Fleshy appearance with necrosis and haemorrhage
- Usually arises within medullary cavity and extends to cortex
- Histology:
- Lace-like pattern of osteoid is produced by eosinophilic matrix entrapping anaplastic tumour cells
- Histological Variants:
- Osteoblastic OS
- Fibroblastic OS
- Chondroblastic OS
- Low-grade OS
Ewing sarcoma (16%)
- Epidemiology and Associations:
- Represents a family of tumours including:
- Ewing sarcoma of bone
- Extraosseous Ewing sarcoma
- Peripheral neuroectodermal tumor (PNET) of bone or soft tissue
- 2nd most common malignant bone tumor in children.
- Occurs most commonly in 2nd decade
- 80% occur between ages 5 and 25
- Most common bone tumor in children < 10 yrs
- M:F 1.3:1 < 10 yrs, 1.6:1 > 10 yrs
- Rare in African-Americans and Asians
- Radiography:
- Poorly marginated, permeative, destructive lytic tumour
- Onionskin appearance (concentric layers of new
bone formation incited by permeating of cortex by
tumour)
- Histology:
- Sheets of small, round, uniform cells
- Homer-Wright rosettes (central fibrillary space) or pseudo rosettes (cells arrange themselves around vessels)
- Positive immune stains: CD99 (MIC2)
- Molecular Pathogenesis:
- Unique translocation t(11,22)(q24;q12) EWS / FLI in at least 90%
- Useful molecular pathology tests
- FISH, PCR, DNA sequencing
- Diferential diagnoses (other small round blue cell tumours)
- Lymphoma/Leukemia
- Rhabdomyosarcoma
- Metastatic Carcinoma
- Neuroblastoma
- Small cell osteosarcoma
Chondroid Tumours:
- Benign:
- Chondroma (enchondroma)
- Osteochondroma
- Chondroblastoma
- Chondromyxoid fibroma
- Malignant:
Chondrosarcoma (25%)
- Malignant bone tumour that produces cartilage (but not osteoid)
- Epidemiology and Associations:
- Usually ages 30-60 years, 75% males
- Often large painful tumors of long bones or ribs that grow rapidly during adolescence and reach 8 cm or larger
- May be associated with preexisting bone tumour e.g. enchondroma or osteochondroma.
- Not chemo sensitive
- Gross:
- Large lobulated tumour with pearly white or light blue, often with focal calcification
- Myxoid change is more common and suggestive of malignancy
- Areas of hemorrhagic necrosis may be present
- Histology:
- Cartilaginous matrix
- Cytological atypia (low to high grade)
- Permeation of bone trabeculae
- Soft tissue and marrow invasion
Osteochondroma/exostosis
- Most common benign bone tumours arising in the long bones
- Bone extension containing cortex and periosteum covered in a thin cartilaginous cap
- Rarely undergoes malignant transformation (chondrosarcoma)
Chondroma
- Enchondroma (inside bone within medullary cavity)
- Subperiosteal chondroma (surface of bone)
- Soft tissue chondroma (inside soft tissue and no communication with adjacent bone)
Giant cell rich lesions of bone and joint
- Giant cell tumour
- Giant cell reparative granuloma
- Giant cell tumour of joint (pigmented villonodular synovitis)
- Brown tumour (hyperparathyroidism)
- All benign (may be locally recurrent) with very rare malignant cases
Giant cell (reparative) granuloma
- Young patients (first two decades of life)
- Benign but potentially and locally aggressive
- Gross:
- Central giant cell lesion primarily of jaw, and also other craniofacial bones and short tubular bones of hands and feet
- Histology:
- Numerous giant cells with haemorrhages, haemosiderin-laden macrophages and reactive bone
- No atypia
Giant cell tumour of bone
- Benign but locally aggressive neoplasm with frequent recurrences
- Very rare malignant transformation
- Epidemiology and Associations:
- 3rd to 5th decades
- More common in Oriental countries
- Females > male (1.2: 1)
- Prototype of giant cell rich neoplasms of the skeleton
- 4-5% of all primary bone tumours and represents almost 23% of benign skeletal neoplasms
- Site:
- Long tubular bones (Almost one-half of cases - knee)
- Epiphyseal- metaphyseal region
- Usually solitary. (<1% of cases they are multifocal - hands and feet)
- Histology:
- Abundant giant cells often with numerous nuclei (50-100 per cell)
- Stromal cells similar to giant cells
- No atypic and no bone formation
Langerhan's Histiocytosis
- A benign bone tumour (aka eosinophilic granuloma of the bone)
- More common in young or paediatric patients, due to the clonal proliferation of neoplastic Langerhans cells
- Histology:
- LH cell is a specialized macrophage characterised by oval nuclei with longitudinal grooves (coffee bean)
- Often asc with eosinophils
- LH cells are always positive for CD1a
- Sites:
- Skull, jawbones, ribs, long bones are vertebrae
- Clinical Features:
- Maybe syndrome (Hand- Schüller-Christian and Letterer-Siwe disease) with multifocal with or without multiorgan involvement.
- Worse prognosis in multi systemic disease
- Clinically may be confused with infection or metastases
Metabolic Bone Diseases
Osteoporosis
- Reduction in bone mass and increased bone porosity
Primary Causes/Idiopathic:1. Old age (senile osteoporosis)
- Decreased replicative ability of osteoprogenitor
- Decreased synthetic ability of osteoblasts
- Decreased biologic activity of matrix-bound growth factors
- Reduced physical activity (as mechanical forces are needed to induce bone remodelling)
2. Menopause
- Decreased serum oestrogen
- Increased IL-1, IL-6, TNF levels
- Increased expression of RANK, RANKL which increases osteoclast generation and activity
Secondary Causes (identifiable):
- Endocrine
- Cushing syndrome, Hyperparathyroidism, Hyperthyroidism, Hypogonadism, Type I DM
- Gastrointestinal causes (malnutrition):
- Vit C & D deficiency
- Liver insufficiency
- Drugs
- Corticosteroids
- Chemotherapy
- Immobilisation
- Bone diseases:
- Multiple myeloma
- Osteogenesis imperfecta
Sites Affected
- Spongy bone of vertebral bone
- Affected first (high surface area for osteoclast action)
- Causes loss of vertical height in elderly, leading to dowager's hump
- Cortex in hip & waist
- Thinning of cortex (subperiosteal and endosteal resorption with widening of haversian systems)
Histology
- Abnormally thinned and reduced bone trabeculae
- Normal mineralization
Prevention
- Maximise peak bone mass attained during early adulthood by ensuring adequate calcium intake during adolescence
- Regular exercise to promote bone remodelling
Treatment
- Hormone replacement therapy
- Biphosphonates (binds to bone to inhibit osteoclast)
- Vit D + calcium supplements
Osteomalacia & Rickets
- Defect in matrix mineralization due to abnormal Vitamin D metabolism or deficiency
- Rickets (children) and osteomalacia (adults)
Causes:
- Vit D deficiency:
- Dietary insufficiency, malabsorption
- Lack of sun exposure --> Inadequate body synthesis (i.e. skin)
- Abnormal Vit D metabolism:
- Increased degradation (drugs)
- Chronic liver disease (diminished 25-hydroxylation)
- Renal failure (diminished 1-hydroxyation)
- Abnormal bone mineralization:
- Low bone alkaline phosphatase (hypophosphatasia)
- Chemicals, drugs (aluminium toxicity)
Clinical Presentation:
- Rickets: bowing of legs
- Lumbar lordosis
- Distortion of skull (bossing)
Hyperparathyroidism
- Excessive osteoclastic activity (bone resorption) as a result of increased amount of parathyroid hormones or its activity
- Due to primary or secondary hyperparathyroidism
- Increased parathyroid hormone secretion results in diffuse bone resorption and demineralisation
- Diffuse bone resorption by osteoclastic giant cells will result in osteolytic lesion
- "Brown tumours" developed when there are masses of osteoclastic giant cells
Paget's Disease
- Disorderly bone formation due to a mixture of excessive bone resorption and uncoordinated bone formation resulting in poorly made bone (bulk w/o quality)
- More common in elderly and caucasian. Cause is still unknown
- Sites:
- 85% - polyostotic (pelvis, spine, skull)
- 15% - monoostotic (tibia, ilium, femur, skull, vertebrae, humerus)
- Morphology:
- Bone architecture greatly distorted due to haphazard and uncoordinated osteoclastic and osteoblastic activity
- Mosaic pattern of lamellar bone, resembles jigsaw puzzle
with prominent irregular cement lines
- Reflection of disorganization of collagen fibres
- Complications:
- Bone overgrowth in the craniofacial skeleton and heavy cranium (becomes difficult for the patient to hold the head erect)
- Severe secondary osteoarthritis
- Fractures (vertebrae and long bones)
- Nerve compression injury and deafness (skull)
- The hypervascularity of paretic bone behaves as an arteriovenous shunt leading to high-output heart failure or exacerbation of underlying cardiac disease
- Most dangerous complication is the development of sarcoma (0.7-0.9% of all patients)
Arthritis
Osteoarthritis
Clincal Presentation:
- 1. Primary generalised OA
- Most common in post-menopausal women
- 2. Erosive inflammatory OA
- Severe destructive disease with rapid progression
- 3. Hypertrophic OA:
- Florid osteophyte formation, bone sclerosis with slow progression
Pathogenesis:
- Multiple factors e.g.
- Increased unit load on joint
- Degradation of articular cartilage * Biochemical abnormalities – reduction of proteoglycans, protein synthesis and chondrocyte replication
- Genetic abnormalities (familial mutation of type II collagen COL2A1).
- Most common degenerative joint disease
- Involves chronic progressive destruction of articular cartilage of joints
- Primary or secondary disease
- Secondary - due to other joint disease, trauma, congenital abnormality & avascular necrosis
- Degenerative, inflammatory and reparative activity involving articular cartilage & subarticular bone, with secondary effects on synovium, muscle and nerves.
- Pain, limitation of movements, swelling and osteophytes
- Cervical spondylosis spinal nerve compression
Pathological Findings:
- Destruction of articular cartilage
- Leading to narrowing of joint space
- Thickening of subarticular bone
- Due to constant friction between two naked bone surfaces leading to eburnation (smooth polished surface)
- Formation of subchrondral cyst
- Formation of osteophytes
- Due to irregular outgrowths of bone
- Reactive thickening of synovium
- Secondary changes to surrounding tissue (eg. muscle atrophy)
Radiological Features:
- Narrowing of joint space
- Sclerosis (increased thickness of subchondral bone)
- Subchondral cyst
- Osteophytes (peripheral growths of bone and cartilage)
Rheumatoid Arthritis
- Multi-systemic chronic inflammatory disease that involves joints symmetrically and bilaterally
- Commonly involves the joints of the hand (PIP and MCP joints), wrist, elbows and knees
- More common in women (3:1). 4th to 6th decade
- Clinical Features:
- Pain, swelling, warmth, redness and loss of function/movement
- Class II MHC molecules play an impt role in the pathogenesis of RA
- RA is strongly associated with HLA-DR4
- Seropositive arthritis
- Important autoantibodies for diagnosis:
- Rheumatoid Factor (RF)
- Not specific for RA and occurs in a number of other non-rheumatic diseases
- Anticitrullinated Protein Antibody (ACPA)
Key Pathological Features:
- Synovial Inflammation
- Formation of the pannus and destruction of the articular cartilage
- Vascular granulation tissue that grows across the cartilage surface
- Destruction of adjacent bone
- Due to the pannus
- Results in joint deformity
- Formation of rheumatoid nodules
- Specific type of granuloma characterised by a central zone of fibrinoid necrosis
RA: a systemic disease
- Rheumatoid nodules can be found in other organs (eg. lung)
- Vasculitis may affect any organ
- Amyloidosis
Seronegative arthritis
- Ankylosing spondylitis, Reiter syndrome, Psoriatic arthritis and inflammatory bowel disease associated arthritis
- Ankylosing spondylitis: destruction and fusion of vertebral column and sacroiliac joints
- Psoriatic arthropathy: DIP joint
- Reiter syndrome: conjunctivitis, polyarthritis and urethritis
- Sero-negative (lack of rheumatoid factor) with high incidence of HLA B27 antigen in these patients
- Preferential onset in young men
- Axial location (e.g. vertebral column and pelvic) and asymmetric involvement of few peripheral joints)
- Systemic involvement of other organs
-
Infectious Bone Diseases
-
Chronic Osteomyelitis
- Chronic persistent osteomyelitis often with recurrent exacerbation
Forms:
- Progression from acute osteomyelitis
- 5-25% of acute osteomyelitis progresses to chronicity
- Due to delay in diagnosis, extensive bone necrosis, inadequate antibiotic treatment, incomplete surgical debridement of necrotic bone or weakened immunity
- Tuberculous osteomyelitis
- Seen in the young, old, immunocompromised, AIDS, developing nations & lower socioeconomical group
- Usually blood borne or lymphatic drainage
- Very difficult to treat as it tends to be more destructive with extensive necrosis
- Chronic inflammation, epithelioid granulomas and caseating necrosis
- Sites affected:
- Vertebrae, especially thoracic & lumbar (vertebrae TB is known as Pott’s disease)
- Hip, knee, ankle
- Elbow, wrist
Complications:
- Pathological fractures
- Can cause severe scoliotic & kyphotic deformities & neurological deficits due to cord & nerve compression (tuberculous osteomyelitis in vertebral spine)
- Permanent deformities, fractures & neurological deficits
- Abscesses & discharging sinuses
- Secondary amyloidosis
- Sclerosis of the bones
- Malignant transformations:
- Osteosarcoma in the bone
- Squamous cell carcinoma in the sinuses
Crystal arthropathies
- Deposition of crystals in joints and soft tissue causing arthritis
- Acute pain, swelling and redness in the joints especially foot and big toe
- May be clinically indistinguishable from septic joint. Septic arthritis is a medical emergency
- Joint fluid analysis (gram stain, culture and crystal analysis)
Pseudogout
- Aka chonedrocalcinosis
- Deposition of calcium pyrophosphate dehydrate
- Idiopathic, asc with trauma, hyperparathyroidism and haemochromatosis
- Asymptomatic or present as acute arthritis
- Polarised microscopy:
- Crystals are rhomboid-shaped and weakly birefringent
Gout
- Characterised by increased serum uric acid and urate crystals deposition
- Causes:
- Primary gout: Cause is idiopathic and asc with obesity, alcohol, HTN and fatty diet
- Secondary gout: Due to known conditions that promote hyperuricemia
- Eg. specific drugs, renal failure, familial juvenile hyperuricaemic nephropathy and congenital enzyme defects
- Pathogenesis:
- Problems of purine metabolism - results in increased uric acid production and decreased uric acid elimination
- 1. Overproduction of purines
- Due to high purine diet ie. meat
- Increased de novo synthesis
- 2. Increased catabolism of nuclei acids
- Due to high cell turnover (eg. infection, cancer)
- 3. Decreased uric acid excretion by kidneys
- Complications in long term:
- Deformities
- Erosion of joints
- Gouty tophi
- Interstitial nephritis
- Kidney disease (stones)
- Renal failure
- Polarised microscopy:
- Examination of synovial fluid: Strongly birefringent needle shaped crystals