Last revised 8 July 2008
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See also Bone, Mandible/maxilla, bone marrow-nonneoplastic
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Table of contents for Joints
Joints: normal anatomy, normal histology
Joint non-neoplastic disease: Baker’s cyst, bursitis, carpal tunnel syndrome, cystic meniscus, disc material, ganglion, implant related changes, meniscal tears, Morton’s neuroma, osteochondritis dissecans, sarcoidosis, spondylosis deformans, synovial cyst
Arthritis: general
Infectious arthritis: general, Lyme disease, spondylodiskitis, suppurative, tuberculous, viral
Non-infective arthritis: ankylosing spondylitis, calcium pyrophosphate deposition, degenerative joint disease, enteropathic arthritis, gout, juvenile rheumatoid arthritis, psoriatic arthritis, Reiter’s syndrome, rheumatoid arthritis, scleroderma, systemic lupus erythematosus
Joint tumors: general, fibroma of tendon sheath, fibrous histiocytoma of tendon sheath, juxta-articular myxoma, pigmented villonodular synovitis, synovial chondromatosis, synovial chondrosarcoma, synovial giant cell tumor, synovial hemangioma, synovial lipomatosis, tenosynovial chondromatosis
Primary references
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), March 1977 to June 2005
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to May 2005
Human Pathology, March 1970 to April 2005
Modern Pathology, Jan 1988 to May 2005
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); C. V. Mosby, 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
UMDNJ (New Jersey, USA)-case studies 1-20
University of Pittsburgh cases 1-431
Journal search terms: joint
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Please refer to these primary references for more detailed discussions and photographs
JOINTS
Synovial or nonsynovial
Synovial joints: also called diarthroses; contain joint space between ends of bones formed by endochondral ossification; joints covered by hyaline cartilage, strengthened by dense fibrous capsule continuous with periosteum of bones and an inner synovial membrane; joint is reinforced by ligaments and muscles; presence of joint space allows wide range of motion
Nonsynovial joints: also called solid joint or synarthrosis; no joint space present; provides structural integrity and minimal movement
May be fibrous (cranial sutures, bonds between roots of teeth and jaw bones) or cartilaginous (manubriosternalis and pubic)
Bursae: found when muscles, tendons and skin glide over bony prominences; subject to same diseases as large joint spaces
Menisci: composed of collagen arranged circumferentially with some radial fibers; in young adults, are white, translucent and supple; become more opaque, yellow, less supple in elderly
Physiology: joints provide painless range of motion and stability
Drawings: Diagram of joint structures; hip joint #1; #2; knee joint #1; #2; ankle joint; shoulder joint
Synovial membrane forms boundary of joint space, is firmly anchored to capsule; smooth contour except has numerous villous folds near osseous insertion
Synovial lining lacks basement membrane, overlies vascularized loose connective tissue stroma; allows for quick exchange between blood and synovial fluid
Synoviocytes: 1-4 cells deep over synovial membrane; fibroblast-like cells also associated with macrophages; not present over articular cartilage; produce proteins, hyaluronic acid (lubricant, nutrition for cartilage); positive for VCAM-1, vimentin; negative for keratin
Micro images: normal synovium #1; #2; #3
Hyaline cartilage: no blood supply, no lymphatics, no innervation; thickest at periphery of concave surfaces and in central portions of convex surfaces; composed of type 2 collagen, water, proteoglycans, chondrocytes
Micro images: hyaline cartilage #1; #2
Chondrocytes: synthesize and digest matrix; secrete inactive enzymes and enrich matrix with enzyme inhibitors
Tendons: composed of closely packed type 1 collagen fibers and surrounded by connective tissue tendon sheath
Collagen: arranged in arches to allow cartilage to resist tensile stresses and to transmit vertical loads
Micro images: hyaline cartilage-various images; elastic cartilage (epiglottis) and fibrocartilage (intervertebral disc)
Non-neoplastic disease
Synovial cyst in popliteal space
Due to herniation of synovial membrane through posterior joint capsule or escape of joint fluid from bursae
Associated with degenerative joint disease, neuropathic arthropathy, rheumatoid arthritis
Treatment: treat cause of excess fluid
Micro: lined by synovium, may have cartilage in cyst wall
References: more information
Pain, erythema, swelling around bursae that lie between muscles, tendons and bony prominences
Usually due to chronic trauma (professional athletes in shoulders, pre- and infra-patellar bursae of those who kneel)
Also a complication of rheumatoid arthritis, rarely associated with infection
Associated with cysts, fluid and loose bodies
Subdeltoid bursitis: degeneration of muscle/tendon in shoulder rotator cuff, followed by deposition of calcium in necrotic collagenous tissue, which stimulates inflammatory reaction
Gross: thickened, erythematous and shaggy bursal wall with fibrinous exudate
Micro: chronic inflammation, scarring
Carpal tunnel: space between flexor retinaculum (transverse carpal ligament) and carpal bones, through which median nerve travels
Syndrome is symptoms due to compression of median nerve by trauma, masses within canal (hemangioma, lipoma, ganglia), rheumatoid arthritis, amyloidosis
Lesion similar to ganglion, but in menisci of knee
Most commonly in lateral meniscus
May be confined to meniscus or extend beyond capsule
May be due to trauma
Normal intervertebral disc contains central nucleus pulposus (water, proteoglycans) within an annulus of obliquely oriented collagen fibers and a cartilaginous end plate
Elderly have shrunken, yellowed and dehydrated nucleus pulposus
Common surgical specimen, obtained after intervertebral disc prolapse or herniation, which is most common in ages 20-39 years
Anterior herniation usually is asymptomatic; posterior herniation puts pressure on nerve roots or spinal canal and produces symptoms
Posterior herniation present in 50% of older individuals at autopsy, usually in lumbar spine
Herniation refers to either prolapse, protrusion or extrusion
Protrusion: bulging of nucleus pulposus through weakened annulus fibrosus, usually posterior or posteriolateral
Prolapse: rupture of nucleus pulposus through annulus but not the posterior or anterior longitudinal ligament; associated with neovascularization at edges of fibrocartilaginous fragments (Hum Path 1988;19:406)
Extrusion: rupture of nucleus pulposus through annulus and posterior or anterior longitudinal ligament
Sequestration: fragmentation of extruded segment, may extend into spinal canal or far from site of rupture
Annular fibrosis: collagen (pink)
Nucleus pulposus: pure cartilage (blue)
Herniated disk: vascular ingrowth
Small cyst-like (no cell lining) mass, near joint capsule or tendon sheath (wrist common)
Due to cystic/myxoid degeneration
May cause pain, weakness, bone changes, partial disability of joint
May be due to injury or overuse of joint
May be multilocular, fluid is similar to synovial fluid
Gross: usually does not communicate with joint space; rarely is intraosseus (medial malleolus of tibia)
Micro: dense fibrous tissue, with no synovial or epithelial lining; inflammation associated with cyst rupture
Tissue around failed implants is often submitted for examination
Causes of joint failure are infection (inflammatory cells) or mechanical (granulomatous reaction to debris in joint)
Debris: due to metallic component of joint (gray-black irregular fragments, often within histiocytes, particularly with titanium implants), polyethylene component of joint (thread-like particles up to 20 microns within histiocytes, visible only under polarized light), methyl methacrylate “grout” (dissolution during routine process reveals irregular holes from 1-100 microns), silicone rubber (bosselated, faintly yellow, refractile but not birefringent); all are associated with histiocytes and giant cells
Frozen section: assessment of infected joint based on 5+ PMN/HPF (excluding surface fibrin and inflammatory exudates) in 5+ separate fields is 43% sensitive and 97% specific for infection compared to culture (Mod Path 1998;11:427)
Images: Xray and micro images due to polyethylene
Tears require surgical treatment in (a) young active patients with tears due to athletics or (b) older individuals with tears due to degeneration
Most common site is medial meniscus, as clefts along circumferentially directed collagen fibers that may extend to medial margin and create a tag
Thickening and degeneration of interdigital nerve of foot, usually between third and fourth metatarsal heads
Usually women due to poorly fitting shoes
Sharp shooting pains, worse when standing, that begin in sole of foot and radiate to exterior surface
Gross: fusiform swelling proximal to bifurcation of plantar interdigital nerve
Micro: endarterial thickening of digital artery, often with thrombosis; fibrosis around and within the nerve; Schwann cell and fibroblast proliferation; also loss of myelinated nerve fibers
DD: traumatic neuroma (rare, but also in interdigital nerves of feet)
References: more information
Benign noninflammatory condition affecting young adults
Necrosis of subchondral bone and adjacent articular cartilage causing separation from adjacent structures
Subchondral bone may remain attached to joint surface / synovium; if attached, both bone and cartilage remain viable; if detached, then bone dies but cartilage remains viable through synovial fluid nutrients
Probably due to trauma, although familial cases and bilateral symmetric cases have been described
Symptoms include joint pain, joint effusions, locking of joint
Sites: most commonly at lateral aspect of medial femoral condyle near intercondylar notch
Xrays: well demarcated defect in articular surface of joint
Treatment: reattachment (if possible) or excision
Gross: flat, smooth nodule of avascular bone with overlying articular cartilage; layer of fibrocartilage is usually present on bony surface
Micro: articular cartilage, often with calcification; 50% of cases have subchondral bone
10% of patients have joint involvement, usually polyarticular
Usually resolves quickly, but occasionally progresses to chronic granulomatous arthritis resembling tuberculosis but without caseation or lymphocytes
Micro images: giant cells in A: osteopetrosis; B: foreign body reactions; C: sarcoidosis; D: giant cell tumor; E: chondroblastoma
Due to anterior protrusion of disc
Common form of spinal disease seen radiographically or at autopsy
Present in 50% of population at age 50
Associated with heavy physical labor, affects lumbar spine
Herniation of synovium through a joint capsule
Baker’s cyst (above) if in popliteal space
May bleed and become a mass-like lesion
Micro: Baker’s cyst - palisading histiocytes and fibrinoid necrosis, similar to rheumatoid pericarditis and rheumatoid nodules
Arthritis
Definition: joint pain, limitation of motion or instability
Due to dysfunction in or of articulating surfaces, loss of integrity of muscles/tendons around joint or their innervation, or mechanical properties of cartilaginous or bony extracellular matrix
When specimen is received, disease is usually advanced, making precise cause difficult to determine
Biopsy: when etiology of arthritis is in doubt; examine synovial fluid before biopsy to detect TB or other granulomatous lesions
Gross: cartilage has irregular surface with pitting and loss of cartilage; subchondral bone shows eburnation (polishing due to friction of bone against bone in joint), fractures; bony spurs (osteophytes), loose bodies (detached cartilage or cartilage/bone within joint space with necrotic calcified centers, may become attached to synovial membrane, revascularize and convert to viable bone)
Micro: findings are related to either injury or reparative change
Injury - death of chondrocytes (no visible nuclei) or necrotic chondrocytes, marked irregularity and thickening of tidemark (indicates disturbed calcification) or duplication of tidemark; surface of cartilage may be intact; diminution of basophilic staining due to proteoglycan depletion; vertical and horizontal clefts within cartilage matrix extending from articular surface; if rapid injury, synovium often contains pieces of bone or cartilage and chronic inflammatory cells; loose bodies may have concentric rings of calcification; subchondral bone has superficial bone necrosis, microfractures, replacement of bone by solid or cystic fibromyxomatous tissue
Repair - see chondrocyte proliferation within damaged cartilage or from underlying bone and periphery of joint; bone/joint proliferative cartilage is cellular fibrocartilage, more coarse and disorganized with polarized light; usually marked osteoblastic activity, new bone formation, thickening of superficial trabeculae; marked synovial cell hyperplasia with multilayering or papillary folds, often containing hemosiderin
Infectious arthritis
Usually granulomatous
Due to infection with Ixodes tick borne spirochete Borrelia burgdorferi; joints affected after weeks to years
Causes chronic arthritis of large joints with pannus formation in 10%
Also affects skin, heart, nervous system
Gross images: erythema migrans skin lesion
Micro: chronic papillary synovitis with hyperplasia, fibrin deposition, mononuclear cell infiltrates, onion skin thickening of arterial walls; resembles rheumatoid arthritis
Micro images: Borrelia burgdorferi
Positive stains: silver stain highlights bacteria
EM: surface fibrin-like material, thickened synovial lining cell layer, evidence of vascular injury, Borrelia-like structures in synovial membranes and some synovial fluid cell samples (Hum Path 1996;27:1025)
Inflammation of intervertebral disk tissue and adjacent vertebrae, which are normally resistant to infection due to avascularity
Usually associated with back pain, involves lumbar segments, ages 50+ years, male predominance
Increased frequency of diagnosis due to magnetic resonance imaging
Most cases are due to pyogenic organisms (Staph, Strep)
Diagnosis: culture usually positive (78%) although special stains are usually negative
MRI images: destruction of vertebral bodies and disk tissue
Micro: vascularization, myxoid degeneration, necrosis of disk, chronic osteomyelitis; variable acute osteomyelitis (25%), granulation tissue; tuberculous infection has caseating granulomas
Micro images: G/H: inflammatory cells and bacteria
References: Archives 2000;124:712, more information
Due to seeding of joint during bacteremia, most commonly due to Staphylococcus, Streptococcus, gram negative rods; rarely syphilis
Also due to postsurgical infection
Neonates: often due to osteomyelitis
Young women: most commonly due to gonorrhea (gram negative intracellular diplococci, which is associated with multiple joint involvement, including the knee)
Sickle cell disease: Salmonella
Risk factors: immune deficiencies, severe illness, joint trauma, chronic arthritis, intravenous drug abuse
Symptoms: sudden development of acutely painful and swollen joint with restricted range of motion, systemic findings
Sites: usually single joint (knee, hip, shoulder)
Micro: neutrophils (also Bechet’s disease, familial Mediterranean fever)
Insidious onset of chronic progressive arthritis, usually monoarticular in knee and hip; usually after osteomyelitis
Leads to fibrous ankylosis of joint with obliteration of joint space
Can detect from culture and examination of synovial fluid
PCR is sensitive; apparent false positives in clinically negative patients may represent early disease (Archives 2004;128:205)
Xrays: marginal erosion of hip and knee joints, with destruction of subchondral bone on both sides of joint and loss of joint space
Case reports: 34 year old woman from Burma with wrist swelling, initially AFB negative with negative cultures, but subsequent diagnosis of TB tenosynovitis (Hum Path 2004;35:1044)
Micro: granulomas with caseous necrosis; AIDS patients often have histiocytes with numerous acid-fast organisms but no granulomas
Variable clinical manifestations
Usually parvovirus B19, Hepatitis C, rubella
Non-infective arthritis
Chronic inflammatory disease of axial joints, especially sacroiliac
Affects teenage boys, 90% are HLA-B27 positive
Chronic synovitis destroys articular cartilage and causes bony ankylosis
Inflammation of tendinoligamentous insertion sites cause osteophytes
Symptoms: low back pain that gets progressively worse
Complications: uveitis, aortitis, amyloidosis
Drawing of cervical spondylosis
Calcium pyrophosphate crystal deposition disease
Also called pseudogout, chondrocalcinosis
Common finding in arthritic joints
Age 50+ years, 30% of patients are at least 85 years old
Calcium pyrophosphate crystals develop first in menisci and intervertebral discs, may seed the joint and elicit neutrophilic response
Knee is common site; 50% have involvement of several joints at diagnosis
50% get significant joint damage
Hereditary variant: symptoms early in life, associated with severe osteoarthritis
Secondary: associated with prior joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, diabetes mellitus
Laboratory: synovial fluid has high white count (2000-8000 cells/mm3), 80% neutrophils with intracellular crystals; later mononuclear cells with intra- or extracellular crystals
Treatment: supportive
Case reports: 78 year old woman with pseudogout at craniocervical junction (Archives 2003;127:895), 65 year old woman with crystal deposition in knee (Archives 2001;125:705), massive total body disease, including vertebral disks (Archives 1982;106:352)
Gross: chalky white deposits in articular tissue
Micro: small rectangular (rhomboid) crystals that are weakly positive birefringent; may have histiocytic and giant cell reaction around these crystals
Micro images: H&E, polarized light; H&E (A-C), Shiddam method (figure 2)
DD crystal deposition: gout, deposition of calcium phosphate, talc, methyl methacrylate (prosthetic joints)
References: Hum Path 1995;26:587 (tophaceous pseudogout)
Also called osteoarthritis (inaccurate since not due to inflammation)
Nonneoplastic disorder of progressive erosion of articular cartilage associated with aging, trauma, occupational injury
Usually age 50+ years (present in 80% at age 65 years)
Cartilage degradation may be mediated by IL-1
May have sinus histiocytosis of pelvic lymph nodes after hip replacement due to metal microparticles of implants (AJSP 1994;18:83)
Sites: men-hips, women-knees and hands; also first metatarsophalangeal joint, lumbar spine; usually one joint or same joint bilaterally, at least initially
Symptoms: pain worse with use of joint, crepitus, limited range of motion, nerve root compression; Heberden nodes in fingers of women only (osteophytes at DIP joints)
Secondary degenerative joint disease: younger patients with predisposing condition (trauma, congenital, diabetes, obesity, ochronosis, hemochromatosis), such as knees of basketball players
Chondromalaciae patellae: softening, fibrillation, fissuring and erosion of articular cartilage of patella (more information #1; #2)
Charcot’s joint (neuropathic arthropathy): progressive (slow or rapid), destructive variant with large amounts of dead bone and cartilage particles embedded in synovium; severe subluxation or dislocation of joint with extreme deformity; also fibroblastic proliferation, reactive new bone formation; may be due to peripheral neuropathy associated with diabetes or syringomyelia
Mseleni joint disease: familial disorder of South Africa, causes severe precocious, progressive degenerative osteoarthropathy; in femoral head, degenerative and regenerative changes are present, but only mild osteomalacia and ebernation (Hum Path 1985;16:117)
Xray: deformity of joint with loss of bone substance and cartilage, loss of joint space, migration of joint, osteophyte formation, sclerosis of subchondral bone, subchondral bone cysts
Xray images: femoral head
Treatment: medication for pain
Case reports: with mucinous synovial transformation (Hum Path 1982;13:946)
Gross: early changes are even degeneration of hyaline cartilage of articular surface, with fibrillation of cartilaginous matrix and possible cartilage fragmentation; later thinning of cartilage and overgrowth of apposing joint surface; at time of resection, articular surface is often soft and granular with altered shape, sloughing of cartilage, bone eburnation (friction smoothes and burnishes the exposed bone to resemble ivory), joint mice (dislodged pieces of cartilage and subchondral bone), cysts (synovial fluid forced into fractures via ball valve-like mechanism), osteophytes (bony outgrowths at margins of articular surface), pannus (fibrous synovium that covers periphery of articular surface); rarely secondary infarcts / osteonecrosis (Hum Path 1984;15:79)
Gross images: femoral head #1; #2 with subchondral cysts; #4 and normal; knee
Loose bodies: may form if portion of articular cartilage breaks off; has the tide mark of articular cartilage, has evidence of prior structure; normally loose body is nourished by synovium and continues to grow, has a tree ring appearance; no clumped atypical chondrocytes; no unevenly distributed chondrocytes
Micro: ghost chondrocytes (no nuclei) or necrotic chondrocytes, marked irregularity of tidemark; irregular thinning, fragmentation and fibrillation of thinned cartilage; subchondral cysts with mucoid fluid surrounded by sclerotic bone; usually no significant inflammatory component although advanced cases have synovial hyperplasia with lymphoid follicles; may have associated sterile acute subchondral inflammation (AJSP 1999;23:192)
Micro images: (1) reactive changes with increased cellularity and multilayering of synovial cells; (2) cartilaginous fragmentation
Virtual slides: degenerative joint disease
Molecular: clonal aberrations in HMGIC gene at 12q13-15 in synovia of 5% of patients
References: Mod Path 2001;14:311 (HMGIC gene), more information
Due to bowel infection with Yersinia, Salmonella, Shigella, Campylobacter
Patients usually HLA-B27 positive
Lipopolysaccharide antigens stimulate immune system and cause abrupt onset of arthritis in knees and ankles, lasts only 1 year
Transient attacks of acute arthritis initiated by crystallization of urates and neutrophils, followed by chronic gouty arthritis with tophi in joints and urate nephropathy
Causes 2-5% of chronic joint disease
Sites: 50% have initial attack in first metatarsophalangeal joint; also ankles, heels, knees, wrists, fingers, elbows
Primary gout (90%): idiopathic (85%) with overproduction of uric acid (may have normal excretion) or known enzyme defects (partial hypoxanthine-guanine phosphoribosyl transferase deficiency [HGPRT])
Secondary gout (10%): increased nucleic acid turnover due to leukemia/lymphoma, chronic renal disease, HGPRT deficiency
Pathophysiology: there are two pathways for purine synthesis: de novo (creates purines) and salvage pathway (HGPRT)
HGPRT deficiency causes increased synthesis via de novo pathway, leading to hyperuricemia
Drawing #1 - XO is xanthine oxidase, more information
Lesch-Nyan syndrome: rare; men with HGPRT deficiency causing hyperuricemia, severe neurologic deficits with mental retardation, self-mutilation, gouty arthritis; chart; OMIM 300322
Gout is due to hyperuricemia (present in 10% of population, although only half develop gout) and deposition of monosodium urate crystals in joints and viscera and uric acid kidney stones
Need serum urate > 7 mg/dl for deposition (saturation threshold for urate at 98.6 F)
Risk factors for gout with hyperuricemia are age > 30 years, familial history of gout, alcohol use, obesity, thiazide administration, lead
Arthritis: synovial fluid is poorer solvent for sodium urate than plasma, so with hyperuricemia, urates in joint fluid crystallize, particularly in ankle due to lower temperature; crystals develop in synovial lining cells, stimulate formation of antibodies, which accelerates formation of new crystals; release of crystals attracts neutrophils and complement, generates C3a, C5a, attracts more neutrophils, releases free radicals, releases lysosomal enzymes which eventually causes acute arthritis that last days to weeks without treatment; repeated attacks of acute arthritis cause chronic arthritis and formation of tophi in synovial membranes and periarticular tissue, which eventually damages joints
Aspirate: grossly white-gray and granular; strongly negative birefringent needle-shaped crystals under polarized light; foreign body giant cells
Case reports: 73 year old man with elbow pain (Archives 2002;126:621)
Gross: chalky white appearance of gouty deposits
Micro: early - edematous synovium with acute and chronic inflammatory infiltrate; late - tophi (large aggregates of urate crystals, granulomatous inflammation, hyperplastic fibrotic synovium); gout crystals are long, slender, needle shaped, but difficult to visualize with routine staining because they are dissolved during formalin processing (crystals are water soluble); easier to identify on scrape or with alcohol fixation
With chronic disease, urate deposits may be present in soft tissue, ligaments, skin
Gouty deposits may be surrounded by fibrous tissue and be rimmed by histiocytes and giant cells
Micro images: A: Xray; B: Diff-Quick; C: Pap smear; D: polarized light; E: H&E
DD crystal deposition: deposition of calcium pyrophosphate, calcium phosphate, talc, methyl methacrylate (prosthetic joints)
Common connective tissue disease in children age 15 years or less, 65% male
Either oligoarticular (<5 joints), polyarticular (5 or more joints) or systemic
Compared to classic rheumatoid arthritis, oligoarthritis is more common; systemic large joints are affected more than small joints
Associated with HLA-DRB1, infections by mycobacteria, bacteria, viruses
70% recover, 10% have residual severe joint deformities
Symptoms: systemic onset with fever, rash, hepatosplenomegaly, serositis; also warm and swollen joints; pericarditis, myocarditis, pulmonary fibrosis, glomerulonephritis, uveitis, growth retardation
Sites: knees, wrists, elbows, ankles
Micro: similar morphologic changes as rheumatoid arthritis
Micro images: degenerated fibrin with surrounding palisading histiocytes
References: more information
Affects 5% of psoriasis population, usually ages 35-45 years
First affects DIP of hands and feet; similar to rheumatoid arthritis but milder
Inflammation of digital tendon sheaths causes sausage fingers
Also causes conjunctivitis, iritis
Also called reactive arthritis
Triad of arthritis, uveitis/conjunctivitis, non-gonococcal urethritis/cervicitis is not always present
Typically affects men or women in 20-30's
80% are HLA-B27 positive
Occurs after GI infections (Salmonella, Shigella, Campylobacter, Yersinia), Chlamydia
Affects ankles, knees, feet
Synovitis of digital tendon sheath produces sausage fingers or toes, causes spurs
Treatment: doxycycline
Chronic systemic inflammatory disorder affecting synovial lining of joints, bursae and tendon sheaths; also skin, blood vessels, heart, lungs, muscles
Produces nonsuppurative proliferative synovitis, may progress to destruction of articular cartilage and joint ankylosis
1% of adults, 75% are women, peaks at ages 10-29 years; also menopausal women
Sites: small bones of hand affected first (MCP, PIP joints of hands and feet), then wrist, elbow, knee
Pathophysiology: triggered by exposure of immunogenetically susceptible host to arthitogenic microbial antigen; autoimmune reaction then occurs with T helper activation and release of inflammatory mediators and cytokines that destroys joints; circulating immune complexes deposit in cartilage, activate complement, cause cartilage damage
Parvovirus B19 may be important in pathogenesis (Mod Path 2003;16:811)
Genetics: HLA-DR4, DR1 (65%); T-cell antigen receptor motif Q(K/R)RA in 75%
Laboratory: 80% have IgM autoantibodies to Fc portion of IgG (rheumatoid factor), which is not sensitive or specific; synovial fluid has increased neutrophils (particularly in acute stage), protein, low mucin
Other antibodies include antikeratin antibody (specific, not sensitive), antiperinuclear factor, anti-rheumatoid arthritis associated nuclear antigen (RANA)
Clinical course: variable; malaise, fatigue, musculoskeletal pain, then joint involvement; joints are warm, swollen, painful, stiff in morning; 10% have acute onset of severe symptoms, but usually joint involvement occurs over months to years; most damage occurs in first 5 years, joints are unstable with minimal range of motion; 50% have spinal involvement
Reduces life expectancy by 3-7 years, death due to amyloidosis, vasculitis, GI bleeds from NSAIDs, infections from steroids
Xray: joint effusions, juxta-articular osteopenia, erosions and narrowing of joint space; destruction of tendons, ligaments and joint capsules produce radial deviation of wrist, ulnar deviation of digits, swan neck finger abnormalities
Diagnosis: morning stiffness, arthritis in 3+ joint areas, arthritis in hand joints, symmetric arthritis, rheumatoid nodules, rheumatoid factor, typical radiographic changes
Treatment: nonsteroidal anti-inflammatory drugs (NSAIDs); immunosuppressive drugs; joint replacement (synovitis tends to lessen), synovectomy (inflamed synovium may recur and disease may continue to progress)
Gross: joints have edematous, thick, hyperplastic synovium, covered by delicate and bulbous fronds
Gross images: hand deformity
Micro: dense perivascular inflammatory infiltrate of T lymphocytes, plasma cells (often with eosinophilic cytoplasmic inclusions called Russell bodies), macrophages; inflammation extends to subchondral bone (relatively specific for rheumatoid arthritis); proliferative synovitis with synovial cell hyperplasia and hypertrophy, lymphoplasmacytic infiltrate with variable germinal centers, necrobiotic nodules and fibrosis; increased vascularity with hemosiderin deposition; organizing fibrin floating in joint space as rice bodies; neutrophils present on synovial surface; osteoclasts present in bone forming cysts; erosions, osteoporosis; pannus formation (synovium, synovial stroma with inflammatory cells, granulomatous tissue, fibroblasts), progressing to fibrous ankylosis (bridges joints), then ossifying to form bony ankylosis; minimal evidence of repair (proliferative cartilage, sclerotic bone or osteophytes)
Weichselbaum’s lacunae: enlarged chondrocyte lacunae within articular cartilage due to dead chondrocytes
Skin: rheumatoid nodules in 25%, usually those with severe disease in skin subject to pressure (ulnar forearm, elbows, occiput, lumbosacral area); also present in viscera; firm, nontender, with central fibrinoid necrosis surrounded by palisading epithelioid histiocytes, lymphocytes, plasma cells; obliterative endarteritis in vasa nervorum and digital arteries causes ulcers, neuropathy, gangrene
Blood vessels: small to medium size vessels in vital organs (not kidney) affected by severe erosive disease; rheumatoid nodules present, high titers of rheumatoid factor
Cytology: may have inflammatory exudate with neutrophils, suggesting an infectious arthritis
Also called progressive systemic sclerosis
May be accompanied or even dominated by arthritis and arthralgia
Micro: superficial fibrin deposition in synovial membrane, mild mononuclear infiltrate, mild synovial hyperplasia, proliferation of collagen fibers, focal obliteration of small vessels
Micro: changes resemble rheumatoid arthritis, but with more intense surface fibrin deposition and less synovial proliferation
Joint tumors
Usually direct extension of bone tumors
Fibroma of tendon sheath
May be related to fibrous histiocytoma of tendon sheath (below) due to similar location, clinical presentation and recurrence rate
Micro: lobulated, with lobules divided by narrow cleft like spaces; nodules composed of fibroblasts; narrow vessels, large amounts of dense collagenous tissue, markedly hyalinized; may have foci of myxoid change; compared to fibrous histiocytoma of tendon sheath is less cellular with no xanthoma cells and no giant cells
Fibrous histiocytoma of tendon sheath
Also called tenosynovial giant cell tumor, giant cell tumor of tendon sheath, nodular tenosynovitis, xanthogranuloma, benign synovioma
Ages 20-40's, usually women
Solitary, slow-growing, painless nodule on tendon sheaths of flexor surfaces of wrists/fingers, ankle/toes
15% erode adjacent bone by pressure
May be related to tendon sheath fibromas
Unclear if reactive or neoplastic
Treatment: excision (benign), but may recur locally
Gross: discrete encapsulated nodule, 1-3 cm on tendon sheath, may be attached to synovium by a pedicle; red-brown to orange-yellow, localized, well circumscribed, resembles small walnut; diffuse form may be larger and infiltrative
Micro: polymorphic infiltrate of small histiocytes, multinucleated giant cells within dense fibrous tissue with hemosiderin and foamy macrophages; mitotic figures and focal hyalinized areas