Bones, Joints, and Tumors Flashcards
Infectious arthritis joint seeding
- Hematogenous spread
- Contiguous sites
- Direct extension
IA contiguous sites joint seeding (periarticular)
- Osteomyelitis
- Soft tissues
IA direct extension joint seeding
- Penetrating trauma
- Arthrocentesis
Suppurative infectious arthritis etiologies
- Gonococcus
- Staphylococcus (MRSA)
- Streptococcus
- Haemophilus influenzae
- Pasteurella multocida
- Eikenella corrodens
- Fungi
Haemophilus ingluenzae
- Gram-negative bacilli
- Pseudomonas aeruginosa
Pathophysiology of IA
- Synovial membrane contamination (1st)
- Synovial fluid contamination (2nd)
Pathologic features of IA
- Synovial membrane edema
- Synovial membrane hypertrophy
- Purulent exudate accumulation
- Cartilage destruction
- Fibrin deposition on cartilage
- Joint destruction / Erosion
Predisposing conditions to acute bacterial arthritis (IA)
- Immune deficiencies
- Debilitating illness
- Joint trauma
- Chronic arthritis
- Intravenous drug abuse
Definitive diagnosis of single/multi joint involvement acute bacterial arthritis
- History
- Aspiration of Synovial Fluid / culture
- CBC
- Rapid joint destruction (without treatment)
Aspiration of acute bacterial arthritis synovial fluid
- Non-inflammatory effusions (Leukocytes < 3k/uL)
- Inflammatory effusions (Leukocytes 3k – 75k/uL)
- Purulent (infectious) effusions (Leukocytes > 50k/uL)
- Hemorrhagic Effusions
Clinical presentation of infectious arthritis
- Single joint involvement
- Restricted ROM
- Fever
- Leukocytosis
- Elevated ESR
Differential diagnosis of infectious arthritis
- Cellulitis
- Bursitis
- Acute osteomyelitis
Single joint infectious arthritis joints/symptoms
- Knee, hip, shoulder, elbow
- Acutely painful
- Hot, swollen, erythema
Infections with variable clinical presentation
- Disseminated Gonococcal Infection (DGI)
- Symptoms are subacute
- Single joint involvement
Gonococcal arhtritis
- Bacteremic Infection (Stage): Migratory polyarthritis, tenosynovitis, dermatitis
- Septic Arthritic: Joint localized (Stage)
Manifestations of disseminated gonococcal infection
- Myalgias
- Fever
- Chills
- Rash
Joint fluid in disseminated gonococcal infection
- 20k + (> 50) leukocytes / ul
- Synovial culture (-)
- Blood cultures (+)
Single joint/oligoarthritic pattern of disseminated gonococcal infection
- Subacute
- Knee
- Ankle
- Hip
- Shoulder
- Elbow
- Wrist
- Sternoclavicular joints
Axial articulations affected in intravenous drug abuse
- Spine
- Sacroiliac
- Sternoclavicular
Tuberculous arthritis clinicopathological characteristics
- Hematogenous dissemination (visceral, usually pulmonary, site of infection; adjoining osteomyelitis)
- Chronic progressive
- Monoarticular disease
- Insidious in onset
- Gradual progressive pain
- Systemic symptoms vary
Tuberculous arthritis symptoms
- Large weight baring joints
- Monoarticular pain and swelling (variable time frame)
- +90% synovial culture
- Mycobacterium stain red (Fite stain)
Tuberculous arthritis clinicopathological characteristics
- Chronic progressive
- Monoarticular disease
- Systemic symptoms variable
Tuberculous arthritis joint fluid
- 20k / uL ~ 50% neutrophils
- Acid fast staining
- Synovial culture
- PCR
Mycobacterial seeding of joints in tuberculous arthritis
- Confluent granulomas
- Central caseous necrosis
- Pannus over the articular cartilage
- Bone erosions along the joint margins
- Fibrous ankylosis and obliteration of the joint space
- Severe destruction
- Weight-bearing joints
Pott’s Disease (associated wwith tuberculous arthritis)
- Extrusion of disc after collapse of vertebra
- Tuberculous pus and granuloma with lysis and collapse of bone
- Anterior extrusion of pus to form psoas abscess
- Posterior extrusion of pus into dura
- Bamboo spine
Seronegative spondyloarthropathies: Ankylosing Spondylitis (AS)
- Reactive Arthritis (ReA)
- Psoriatic Arthritis (PsA)
- Ulcerative colitis
- Crohn disease
Ankylosing spondylitis primary sites of involvement
- Vertebrae
- Sacro – iIio – lumbar and areas (prominent region of tendon and ligament insertions)
- Enthesis (point of tendon, ligament or muscle insertion into bone)
Enthesitis
- Inflammation at tendon/ligament/muscle insertion sites
Ankylosing spondylitis
- Chronic inflammatory joint disease
- Sacroiliac infiltration (CD4 and CD8+ T cells, macrophages and high [TNF-α])
Ankylosing spondylitis symptoms
- Usually 2nd and 3rd decades of life
- Men 2-3x > frequently than woman
- 80 - 90% of individuals are HLA-B27 positive
- No specific lab test
AS pathogenesis
- Enthesopathy (inflammation)
- Mononuclear cell infiltrate
- PMN
- Tumor Necrosis Factor (high levels)
- CD4+ T cells
- CD8+ T cells
- Macrophages
AS pathology
- Chronic synovitis
- Destruction of articular cartilage
- Bony ankylosis
- Tendinoligamentous inflammation and ossification
- Bony outgrowths (syndesmophytes) –> severe spinal immobility
Syndesmophytes
- Osseous excrescence attached to a ligament
- Bamboo Spine
- Feature of AS
Ankylosing Spondylitis
clinicopathologic features
- Chronic progressive
- Low back pain
- Peripheral joints (hips, knees, and shoulders)
Ankylosing spondylitis complications
- Fracture of the spine
- Uveitis
- Aortitis
Reactive arthritis (formerly Reiter Syndrome) associations
- Genitourinary (Chlamydia)
- Gastrointestinal tract infections (Shigella, Salmonella, Yersinia, Campylobacter)
- Symptoms emerge 2-3 wks after infection
- 80% + HLA-B27
Reactive arthritis triad
- Arthritis
- Urethritis / Cervicitis
- Conjunctivitis
Reactive arthritis autoimmune reaction (prior infection)
- Organisms associated with enteric Infections
- Immunologic responses against lipopolysaccharide components
Pathology of reactive arthritic autoimmune response
- Enthesitis
- Macrophage infiltration of fibrocartilage
Reactive arthritis clinicopathological conditions
- Arthritic symptoms (painful)
- Develop within weeks of urethritis or diarrhea
- Joint stiffness and low back pain
- Asymmetrical (additiveknee/ankle)
- Synovitis
- Ossifications
- Severe
Reactive arthritis is indistinguishable from
- Ankylosing spondylitis
Extra-articular involvement of reactive arthritis
- Circinate Balanitis
- Keratoderma blenorrhagica
- Plaques / erosions of tongue
- Painful erosions on hands / fingers
- Conjunctivitis
- Cardiac conduction abnormalities
- Aortic regurgitation
Circinate balanitisis
- Serpiginous ring-shaped dermatitis of the glans penis
- One of the most common cutaneous manifestations of reactive arthritis
- However,balanitiscircinata can also occur independently
Keratinized skin, mucousy discharge (also called keratoderma blennorrhagica)
- Skin lesions commonly found on the palms and soles in reactive arthritis
- May spread to the scrotum, scalp and trunk
- Lesions may resemble psoriasis
Reactive arthritis prognosis
- Self-limiting (resolution 3-12 months)
- Arthritis waxes and wanes (several weeks to months)
50% of patients with reactive arthritis experience
- Recurrent arthritis
- Tendonitis
- Fasciitis
- Lumbosacral back pain
Crystal-Induced Arthritis
- Deposition of calcium pyrophosphate crystals within joint space
- Occurs in patients > 50 years old; both sexes affected equally
- Knee most commonly affected joint
Crystal-induced arthritis diagnostic findings
- Chondrocalcinosis (cartilage calcification) on x-ray
- Crystals are rhomboid and weakly ⊕ birefringent under polarized light (blue when parallel to light)
Crystal-induced arthritis treatment and prophylaxis
- Acute treatment: NSAIDs, colchicine, glucocorticoids
- Prophylaxis: colchicine
Gout
- Caused by precipitation of monosodium urate crystals in joints
Risk factors for gout
- Male sex
- Hypertension
- Obesity
- Diabetes
- Dyslipidemia
- Hyperuricemia (strongest risk factor)
Causes of gout
- Underexcretion of uric acid (90% of patients)
- Overproduction of uric acid (10% of patients)
Underexcretion of uric acid
- Idiopathic
- Potentiated by renal failure
- Exacerbated by certain medications (eg, thiazide diuretics)
Overproduction of uric acid
- Lesch-Nyhan syndrome
- Increased cell turnover (eg, tumor lysis syndrome)
- von Gierke disease
Uric acid crystals in gout
- Needle shaped and ⊝ birefringent under polarized light
- Yellow under parallel light, blue under perpendicular light
Osteoarthritis (DJD) characteristics
- Degeneration of cartilage
- Structural and functional failure of synovial joints
3 phases of chondrocyte changes in OA
- Chondrocyte injury
- Early OA
- Late OA
Chondrocyte injury (phase 1 OA)
- Genetic
- Biomechanical factors
Early OA (phase 2)
- Chondrocyte proliferation
- Secrete inflammatory mediators
- Remodeling of cartilaginous matrix
- Initiation secondary inflammatory changes in the synovium and subchondral bone
Late OA (phase 3)
- Repetitive injury and chronic inflammation
- Chondrocyte drop out
- Marked loss of cartilage
- Extensive subchondral bone changes
OA morphology (1)
- Fissures and clefts at the articular surface occur
- Chondrocytes die
- Full-thickness portions of the cartilage are sloughed
- Dislodged pieces of cartilage and subchondral bone tumble into the joint, forming loose bodies (joint mice)
OA morphology (2)
- Exposed subchondral bone plate becomes the new articular surface
- Bone eburnation
- Fracture gaps force synovial fluid into the subchondral
- Fibrous-walled cysts develop
- Bony outgrowths develop at the margins
OA clinical course
- Insidious disease
- Asymptomatic until 50s
Characteristic symptoms of OA
- Deep, achy pain that worsens with use, morning stiffness , 20min
- Crepitus, limitation ROM
- Only one or a few joints are involved (asymmetrical)
Joints commonly involved in OA
- Hips, Knees, lower lumbar, cervical vertebrae
- Proximal and distal interphalangeal joints of the fingers
- First carpometacarpal joints, first tarsometatarsal joints
Heberden nodes
- Prominent osteophytes at the DIP joints (common in women)
- Feature of OA
Impingement on spinal foramina by osteophytes (OA)
- Results in cervical and lumbar nerve root compression
- Radicular pain
- Muscle spasms
- Muscle atrophy
- Neurologic deficits
Rheumatoid Arthritis
- Chronic inflammatory disorder of autoimmune origin
- Affect many tissues and organs
- Principally attacks the joints
Rheumatoid arthritis produces
- Non-suppurative proliferative and inflammatory synovitis
Pathogenesis of rheumatoid arthritis
- Mediated by antibodies against self-antigens
- Cytokine-mediated inflammation (secreted by CD4+ T-cells)
- Autoantibodies generated specific for citrullinated peptides (CCPs)
Citrullination
- Arginine residues are post-translationally converted to citrulline
- Antigen-antibody complexes containing citrullinated fibrinogen, type II collagen, α-enolase and vimentin deposit in the joints
Joint involvement in rheumatoid arthritis
- Symmetric arthritis
- Small joints of the hand and feet
- Synovium
Joint presentation of rheumatoid arthritis (bulbous villi)
- Edematous
- Thickened, hyperplastic
- Dense inflammatory infiltrates
- Lymphoid follicles
- Increased vascularity
- Fibrinopurulent exudate on the synovial and joint surfaces
Rheumatoid arthritis effect on joints
- Periarticular erosions and subchondral cysts
- Pannus formation
- Pannus bridges the apposing bones to form a fibrous ankylosis
- Ossification and fusion of bone = bony ankylosis
Rheumatoid subcutaneous nodules
- Most common cutaneous lesions of RA
- Approximately 25% of individuals with severe disease
Regions of the skin most affected by rheumatoid subcutaneous nodules
- Ulnar aspect of the forearm
- Elbows
- Occiput
- Lumbosacral area
RA effects on blood vessels
- Acute necrotizing vasculitis (small and large arteries)
- Obliterating endarteritis (peripheral neuropathy, ulcers, gangrene)
- Leukocytoclastic vasculitis (purpura, cutaneous ulcers, nail bed infection)
- Ocular changes (such as uveitis and keratoconjunctivitis)
Clinical presentation of RA
- Symptoms usually develop in the hands (MCP, PIP)
- Feet, followed by the wrists, ankles, elbows, and knees
- Progressive joint enlargement
- Decreased range of motion
- Ankylosis
Diagnosis of RA
- Characteristic radiographic finding
- Sterile, turbid synovial fluid
- Combination of rheumatoid factor and anti-CCP antibody (80% of patients)
Tumors and tumor-like lesions involving joints and tendons
- Reactive (2° trauma or degenerative processes)
- Neoplastic (cytogenetic studies reveal consistent chromosomal aberrations)
- Benign neoplasms
Giant cell tumor (benign)
- 20–40 years old
- Epiphysis of long bones (often in knee region)
- Locally aggressive benign tumor
- Significant bone destruction, local recurrence, and occasionally metastasis
Giant cell tumor neoplastic mononuclear cells
- Express high levels of RANKL
- Promotes proliferation of reactive multinucleated giant (osteoclast-like) cells
Characteristics of giant cell tumor
- Feedback between osteoblasts and osteoclasts is absent
- “Osteoclastoma”
- “Soap bubble” appearance on x-ray
Morphology of giant cell tumor
- Destroy the overlying cortex
- Large, red-brown masses
- Cystic degeneration
Giant cell tumor make up
- Sheets of uniform oval mononuclear cells
- Numerous osteoclast-type giant cells
- Necrosis and mitotic activity prominent
Giant Cell Tumor of tendon Sheath (GCTTS)
- Common localized form of GCTs
- GCT of the tendon sheath
- Often found in the hands and feet
GCTTS characteristics
- Discrete nodule on a tendon sheath (wrist, fingers)
- Arise in the 20s – 40s
- Affect the sexes equally
GCTTS clinical presentation
- Solitary
- Slow-growing
- Painless mass
- Cortical erosion
- Often recurs locally
- Surgery
Morphology of GCTTS
- Localized
- Well circumscribed (walnut shaped)
Microscopic presentation of GCTTS
- Polyhedral
- Histiocytes
- Multinucleated Giant Cells
- Resemble synoviocytes
Peripheral nerve sheath tumors
- Tumors that show evidence of Schwann cell differentiation
- Schwannomas (Neurilemmoma)
- Neurofibromas
- Malignant Peripheral Nerve Sheath Tumors
- Neurofibromatosis Type 1 Type 2
Schwannomas
- Arise directly from peripheral nerves
- Benign
- Encapsulated
2 most common benign peripheral nerve sheath tumors
- Schwannomas
- Neurofibromas
Ewing sarcoma
- Most common in boys (< 15 years old)
- Anaplastic small blue cells (neuroectodermal origin)
- “Onion skin” periosteal reaction in bone
- Aggressive with early metastases
- Responsive to chemotherapy
Ewing sarcoma location
- Diaphysis of long bones (especially femur)
- Pelvic flat bones
Anaplastic small blue cells of Ewing sarcoma differentiate from
- Conditions with similar morphology
- Lymphoma, chronic osteomyelitis
Testing for Ewing sarcoma
- T (11;22) (fusion protein EWS-FLI1)
Osteosarcoma pathogenesis (molecular mutations)
- 70% have acquired genetic abnormalities
- RB
- TP53
- INK4a
- MDM2 and CDK4
Presentation of osteosarcoma
- Painful (particularly pain with activity)
- Progressively enlarging masses
- Sudden fracture of the bone is the first symptom
Osteosarcoma radiographs usually show
- Mixed lytic and blastic mass with infiltrative margins
- Tumor breaks through the cortex and lifts the periosteum
- Codman triangle
Codman triangle (feature of osteosarcoma radiograph)
- Shadow between the cortex and raised ends of periosteum
Osteosarcoma (osteogenic sarcoma) occurence
- All age groups
- Bimodal age distribution
- 75% in persons younger than 20
- Second peak occurs in older adults (Paget disease, bone infarcts, prior radiation)
- Men affected more than women (1.6 : 1)
Osteosarcoma (osteogenic sarcoma) often found in
- Metaphysis of long bones (often in knee region)
- Pleomorphic osteoid-producing cells (malignant osteoblasts)
Morphology of osteosarcoma
- Arises in the metaphysis of long bones
- Destroy the surrounding cortices and produce soft tissue masses
- Spread extensively in the medullary canal, infiltrating and replacing hematopoietic marrow
Osteosarcoma description
- Bulky tumors that are gritty, gray-white
- Often contain areas of hemorrhage and cystic degeneration
- Tumor cells vary in size and shape and frequently have large hyperchromatic nuclei
- Bizarre tumor giant cells are common, as are abnormal mitoses
- Vascular invasion is usually conspicuous
Formation of bone by the tumor cells is diagnostic for
- Osteosarcoma
Diagnosis of osteosarcoma
- X-ray
- Biopsy
Osteosarcoma prognosis
- Spread hematogenously to the lungs
- Approximately 10% to 20% have pulmonary metastases at diagnosis
- Outcome for patients with metastases, recurrent disease or secondary osteosarcoma is poor (<20% 5-year survival rate)
