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

Joints-normal histology

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

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

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

Non-neoplastic disease

Baker’s cyst

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

Bursitis

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 syndrome

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

Cystic meniscus

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

Disc material

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

Ganglion

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

Implant related changes

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)

Meniscal tears

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

Morton’s neuroma

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)

Osteochondritis dissecans

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

Sarcoidosis

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

Spondylosis deformans

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

Synovial cyst

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

Arthritis-general

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

General

Usually granulomatous

Lyme arthritis

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

Micro: chronic papillary synovitis with hyperplasia, fibrin deposition, mononuclear cell infiltrates, onion skin thickening of arterial walls; resembles rheumatoid arthritis

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)

Spondylodiskitis

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

Micro: vascularization, myxoid degeneration, necrosis of disk, chronic osteomyelitis; variable acute osteomyelitis (25%), granulation tissue; tuberculous infection has caseating granulomas

References: Archives 2000;124:712, more information

Suppurative arthritis

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)

Tuberculous arthritis

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

Viral arthritis

Variable clinical manifestations

Usually parvovirus B19, Hepatitis C, rubella

Non-infective arthritis

Ankylosing spondyloarthritis

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

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

DD crystal deposition: gout, deposition of calcium phosphate, talc, methyl methacrylate (prosthetic joints)

References: Hum Path 1995;26:587 (tophaceous pseudogout)

Degenerative joint disease

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

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)

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)

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

Enteropathic arthritis

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

Gout and gouty arthritis

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

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

DD crystal deposition: deposition of calcium pyrophosphate, calcium phosphate, talc, methyl methacrylate (prosthetic joints)

Juvenile rheumatoid arthritis

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

Psoriatric arthritis

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

Reiter’s syndrome

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

Rheumatoid arthritis

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

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

Scleroderma

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

Systemic lupus erythematosus

Micro: changes resemble rheumatoid arthritis, but with more intense surface fibrin deposition and less synovial proliferation

Joint tumors

Joint tumors-general

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

EM: synovial cells, fibroblasts, histiocytes, lymphocytes

DD: epithelioid sarcoma (granuloma-like formations, necrosis, invasive, epithelioid features, keratin+)

Malignant variant of fibrous histiocytoma of tendon sheath

High number of mitotic figures, marked nuclear hyperchromasia, few multinucleated giant cells

Juxta-articular myxoma

Often associated with cystic changes resembling ganglion cyst

Median age 43 years, range 16-83 years

72% male

Sites: knee (88%), also shoulder, elbow, ankle, hip

Often recurs, up to 4 times

References: Hum Path 1992;23:639

Pigmented villonodular synovitis (PVNS)

Rare neoplastic-like villonodular hyperplasia of synovium and tendon sheaths in young adults composed of mononuclear cells and multinuclear giant cells with hemosiderin deposition

May be similar to diffuse form of tenosynovial giant cell tumor

Develops in synovial lining of joints, tendon sheaths and bursae, usually of knee (80%), ankle, hip, shoulder, elbow joint; nodular variant occurs in hands and wrists

Almost always monoarticular

Occasionally invades underlying bone

May cause bone cyst formation, loss of bone and cartilage

Consists of CD68+ histiocytes with osteoclastic giant cell differentiation, may be hyperplastic, not neoplastic (Hum Path 2003;34:65)

Locally aggressive; may recur, but only rarely has malignant behavior (AJSP 1997;21:153)

Treatment: excision, but may recur locally if not completely excised; radiation therapy may be useful for recurrences

Case reports: 36 year old man with tumor at temporomandibular joint (Archives 2002;126:195), vertebral column (Archives 1984;108:228), rare cases of malignant behavior (Archives 2000;124:1636)

Gross: focal or diffuse; brown-yellow spongy tissue with variable color and firm nodular consistency

Micro: hyperplastic synovium with papillary projections composed of foamy cells and hemosiderin containing macrophages; also large clefts, pseudoglandular or alveolar spaces lined by synovial cells, multinucleated (10-70 nuclei) giant cells, epithelioid cells; abundant collagen may be present, but lymphocytes and plasma cells are sparse; no/rare mitotic figures

Malignant if nodular and solid invasive growth pattern are coupled with large round or oval cells with large nuclei, prominent nucleoli, necrotic areas, atypical mitotic figures

Cytology: round, spindled and multinucleated cells without atypia; round cells have minimal cytoplasm and eccentric nuclei; occasional cytoplasmic hemosiderin; no mitotic figures

Positive stains: CD68 (stromal and giant cells)
Negative stains: S100, CD45/LCA, EMA, keratin, HMB45, CD34, desmin, smooth muscle actin

Molecular: trisomy 5 and 7

DD: hemosiderotic synovitis (associated with hemophilia and intraarticular bleeding, no mononuclear or giant cell nodular cellular proliferation, hemosiderin primarily in synovial lining cells), fibrosarcoma, synovial sarcoma

Synovial chondromatosis

Also called synovial chondrometaplasia, synovial osteochondromatosis

Mean age 41 years, range 17-64 years, 2/3 male

Primary disease is uncommon, unknown etiology, aggressive

Usually monoarticular, affecting knee, hip, elbow and communicating bursae; may affect adjacent soft tissue

Aggravated by infection and trauma

Xray: usually calcific densities within joint; may be negative or show diffuse joint swelling

May be extra-articular (tenosynovial chondromatosis)

Treatment: excision, but frequently recurs; 5% become malignant

Gross: numerous round osteocartilaginous nodules cover a thickened synovial surface or float freely within the joint space

Micro: cartilage cells with variable atypia or binucleated forms within synovium; clusters of chondrocytes are often arranged in lobules; no underlying arthritis

DD: secondary synovial chondrometaplasia due to degenerative joint disease, neuropathic arthropathy or osteochondritis dissecans (no lobulation, clustering or atypia), chondrosarcoma (not within a joint, no characteristic clustering pattern, marked myxoid change, spindling of nuclei), cartilaginous loose bodies (more common, but associated with arthritis)

References: Hum Path 1998;29:683, Hum Path 1979;10:439, more information

Secondary disease

Associated with degenerative joint disease - growth of fragments of articular cartilage

Initially intrasynovial disease without loose bodies; then intrasynovial proliferation and free loose bodies, then multiple free osteochondral bodies without intrasynovial disease

No atypia

Synovial chondrosarcoma

Very rare

Gross: may be more expansile than synovial osteochondromatosis

Micro: cartilage cells have cytologic features of malignancy

Synovial giant cell tumor

Axial skeleton tumor; often cervical spine

<50 cases reported

Mean age 32 years, range 17-44 years

Xray: mass of posterior aspect of adjoining vertebrae, often involving facet joints, with bone abnormalities present

Treatment: resection; may persist if incompletely excised; no metastases reported

Case reports: malignant synovial giant cell tumor (Hum Path 1989;20:765)

Gross: 1-6 cm

Micro: epithelioid cells with mixed osteoclast-like giant cells, hemosiderin containing macrophages, xanthoma cells, fibroblasts, lymphocytes; often with infiltrative growth; variable mitotic activity

Positive stains: CD68, CD163, vimentin

DD: giant cell tumor of bone (10% involve spine, usually sacrum, giant cells have abnormally large number of nuclei), osteoblastoma (well circumscribed, surrounded by cortical bone or periosteum, osteoblastic rimming with scattered osteoclasts), aneurysmal bone cyst (younger patients, well demarcated, lytic lesion bordered by thin rim of new bone, cavernous blood filled spaces), schwannoma

References: Hum Path 2003;34:670

Synovial hemangioma

Uncommon; usually young adults, more common in males

Sites: knee, elbow, finger

Gross: tumor usually confined to intra-articular synovium, may be in adjacent bursa

Micro: resembles either cavernous hemangioma, lobular capillary hemangioma, arteriovenous hemangioma or venous hemangioma

DD: pigmented villonodular synovitis, organizing hemorrhage

References: Hum Path 1993;24:737

Synovial lipomatosis

Also called Hoffa’s disease

Rare; usually knee but may occur in any joint

Gross: enlargement of infrapatellar fat pad with pain in anterior compartment of knee; synovium is papillary, yellow and fatty

Micro: synovial hyperplasia with unremarkable fat extending to synovial lining; occasional chronic inflammatory infiltrate

Tenosynovial chondromatosis

Rare; may be extraarticular counterpart of synovial chondromatosis

Mean age 46 years, range 20-86 years

Painless mildly tender mass present for median 2 years

Usually recurs, perhaps due to subclinical micronodules

Sites: fingers (50%), feet (20%); also wrists, ankles, palm, knee, forearm

Treatment: complete excision in a conservative, function-preserving fashion

Micro: multinodular cartilaginous proliferation arising from tenosynovial membranes; often mild or moderate atypia similar to chondroma of soft parts or synovial chondromatosis; occasionally has prominent mineralization; often minute cartilaginous nodules; cartilaginous matrix more intensely basophilic than chondroma of soft parts

DD: chondroma of soft parts (not multinodular, younger patients overall although overlap exists)

References: AJSP 2003;27:1260

End of Joint chapter/outline

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