• Junction between adjacent bones that provide painless range of motion and stability
• 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 and maintains stability during use
    
    
    Different types of synovial joints
  
  
• Nonsynovial joints:
  • Also called solid joint or synarthrosis
  • No joint space present
  • Provides structural integrity and minimal movement
  • May be fibrous / synarthrosis (cranial sutures, bonds between roots of teeth and jaw bones) or cartilaginous / amphiarthrosis (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

Structure of joint synarthrosis and symphysis

Shoulder joint

Synovial joints - distal phalanx (interphalangeal joint) - H&E

• Mcgraw-Hill (pdf)

• 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

Normal synovium

Hyaline cartilage

Joint

Tendon

• Also called popliteal 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

Popliteal Cyst

• 44 year old woman with lower extremity pain and swelling (Int J Emerg Med 2010;3:469)
• 45 year old man with rheumatoid arthritis and pain in calf (N Engl J Med 2009;361:1098)

• Treat cause of excess fluid, sclerotherapy (Pain Physician 2008;11:375)

Baker's cysts

Left popliteal fossa

• Lined by synovium, may have cartilage in cyst wall

• Pain, erythema, swelling around bursae that lie between muscles, tendons and bony prominences
• Usually due to chronic trauma (professional athletes in shoulders, pre- and infrapatellar bursae of those who kneel); rheumatoid arthritis
• Rarely associated with infection, gout
• Associated with cysts, fluid and loose bodies
• Chronically inflamed bursa may develop extensive calcification
• Subdeltoid bursitis: degeneration of muscle/tendon in shoulder rotator cuff, followed by deposition of calcium in necrotic collagenous tissue, which stimulates inflammatory reaction

• Common sites: shoulder, knee, elbow and hip
• Infrequent sites: interspinous, ischio gluteal, retrocalcaneal

• 18 year old woman with interspinous bursitis (J Bone Joint Surg Br 2004;86:1062)
• 45 year old man with subacromial bursitis related to HIV infection (Braz J Infect Dis 2010;14:645)

• Varies based on cause of bursitis and changes in bursa
• Includes aspiration, antibiotic irrigation, incision and drainage (for abscess), excision (for thickened bursa)

Elbow

Knee

Foot

• Thickened, erythematous and shaggy bursal wall with fibrinous exudates

• Chronic inflammation, scarring

• Carpal tunnel: space between flexor retinaculum (transverse carpal ligament) and carpal bones, through which median nerve travels
• Syndrome is an entrapment neuropathy
• Symptoms due to compression of median nerve by trauma, masses within canal (hemangioma, lipoma, ganglia), rheumatoid arthritis, amyloidosis

• Pain, often accompanied by parasthesia in distribution of median nerve
• Rarely wasting of thenar muscles

• 48 year old man with giant lipoma causing carpal tunnel syndrome (Pan Afr Med J 2011;9:29)
• 64 year old woman with periarticular calcification causing acute carpal tunnel syndrome (J Orthop Surg (Hong Kong) 2009;17:234)

• Surgical; division of transverse carpal ligament

Untreated

Lesion with incision marking

Giant lipoma stretching median nerve

2 years follow up

• Nerve appears constricted and pale

Resected giant lipoma

• Transverse carpal ligament shows nonspecific fibrosis

• Lesion similar to ganglion, but in menisci of knee
• Either at lateral or medial joint margin (AJR Am J Roentgenol 2001;177:409)
• Either confined to meniscus or extends beyond capsule
• Almost always associated with meniscal tears; may be due to trauma
• Cyst caused by simple extrusion of synovial fluid through meniscal tear
• Usually pain and swelling

• 27 year old man with symptomatic posterior cruciate ganglion cyst (Knee Surg Relat Res 2012;24:52)
• 66 year old woman with tumor-like medial meniscal cyst (Clinics (Sao Paulo) 2008;63:411)

Resected cyst

Arthroscopic finding

External aspect of cyst

Cyst resection

• Cyst lined by synovial epithelium with nonspecific inflammation and focal hemorrhage

• 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
  • Can rarely disappear spontaneously
• Prolapse:
  • Rupture of nucleus pulposus through annulus but not the posterior or anterior longitudinal ligament
  • Associated with neovascularization at edges of fibrocartilaginous fragments (Hum Pathol 1988;19:406)
  • Usually in lumbar region
  • May occur in thoracic or cervical disc
• 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
  • Clinical symptoms depend on severity of herniation and position of offending disc
  • Patient may develop Cauda equine syndrome in severe cases

• 45 year old woman with low back ache and sciatica (Br J Gen Pract 2008;58:646)

• 52 year old woman with abdominal pain (Ann R Coll Surg Engl 2009;91:W4)
• 60 year old man with brucellosis masquerading as spondylodiscitis with multiple intervertebral disc prolapse (J Glob Infect Dis 2012;4:184)

• 53 year old woman with spontaneous regression of large lumbar disc extrusion. (J Korean Neurosurg Soc 2010;48:285)
• 68 year old man with extrusion of C7-D1 intervertebral disc associated with intradiscal hematoma (Turk Neurosurg 2011;21:446)

• 49 year old man with sequestered L5-S1 disc (Cox® Technic Case Report #63 sent August 2008 (pdf))

• Annular fibrosis: collagen (pink)
• Nucleus pulposus: pure cartilage (blue)
• Herniated disk: vascular ingrowth
• Also chondrocyte proliferation, structural alterations in form of tears and clefts, granular changes and mucous degeneration (BMC Res Notes 2011;4:497)

Intervertebral disc

Disc degeneration

• Common tumor-like lesion arising from soft tissue, caused by mucoid degeneration of joint capsule, tendon or tendon sheath
• Small cyst-like mass (no epithelial lining) near joint capsule or tendon sheath
• Common site is wrist, also hand and foot, rarely in intratendinous region
• 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

• 43 year old woman with intratendinous ganglion cyst of semimembranosus tendon (Br J Radiol 2010;83:e79)
• 57 year old man with subperiosteal ganglion cyst of tibia (J Bone Joint Surg Br 1999;81:643)
• 63 year old woman with ganglion cyst of temporomandibular joint with intracranial extension (J Neurosurg 2012;116:310)

• Usually does not communicate with joint space; rarely is intraosseus (medial malleolus of tibia)

• Dense fibrous tissue, with no synovial or epithelial lining; inflammation may be associated with cyst rupture

Ganglion cyst

Cystic space lined by histiocytes and granulation tissue with moderate acute and chronic inflammation of cyst wall

• Tissue around failed implants is often submitted for examination
• Causes of joint failure are infection (usually Staphylococci, also inflammatory cells) and 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
• Implants can result in aggressive metallosis eroding bone and causing joint failure (Acta Orthop 2010;81:402)
• Frozen section: assessment of infected joint based on 5+ neutrophils / HPF (excluding surface fibrin and inflammatory exudates) in 5+ separate fields is 43% sensitive and 97% specific for infection compared to culture (Mod Pathol 1998;11:427)

Various images - due to polyethylene

Metallosis surrounding implant and cervical neck

Prosthetic synovitis: hyperplastic synovial membrane adjacent to prosthesis

Methylmethacralate debris (linear webs) surrounded by giant cells

Polyethylene flakes (shiny linear material) surrounded by foreign body giant cell reaction (polarized microscopy)

• Patients age 40+ years have fewer cells in meniscus and are more prone to degeneration and tears (Am J Sports Med 2007;35:103)
• Most common site is medial meniscus; tears arise as clefts along circumferential collagen fibers that may extend to medial margin and create a tag
• Surgery required for young active patients with tears due to athletics and older individuals with tears due to degeneration

• Fibroblast proliferation, synovial hypertrophy and increased cellularity
• Neovascularization of peripheral zone (Kerala Journal of Orthopaedics 2011;24(1))

Meniscus tear

• Thickening (perineural fibrosis) and degeneration of interdigital nerve of foot, usually between third and fourth metatarsal heads (eMedicine)
• Usually women due to poorly fitting shoes
• Sharp shooting pains, worse when standing, that begin in sole of foot and radiate to exterior surface
• Prevalence of 30-33% (Korean J Radiol 2007;8:148)
• Lesions >5mm are more symptomatic than smaller ones

Neuroma removed

• Fusiform swelling proximal to bifurcation of plantar interdigital nerve

• Endarterial thickening of digital artery, often with thrombosis
• Fibrosis around and within nerve
• Schwann cell and fibroblast proliferation
• Also loss of myelinated nerve fibers

• Bursitis, intermetatarsal: see Semin Musculoskelet Radiol 2005;9:175
• Traumatic neuroma: rare, but also in interdigital nerves of feet

• Benign noninflammatory condition affecting young adults, with 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, bone dies but cartilage remains viable through synovial fluid nutrients
• Probably due to trauma, although familial autosomal dominant (Clin Orthop Relat Res 1979;(140):131) and bilateral symmetric cases have been described
• Symptoms include joint pain, joint effusions, locking of joint

• Usually at lateral aspect of medial femoral condyle near intercondylar notch; also ankle and elbow joints

• Well demarcated defect in articular surface of joint

• 14 year old with pain, swelling and inability to move right knee joint (J Orthopaedic Case Reports 2012;2:3)
• 26 year old housewife with chronic ankle pain (BMJ Case Rep 2009;2009 Epub 2009 Apr 14)

• Reattachment (if possible) or excision

• Flat, smooth nodule of avascular bone with overlying articular cartilage
• Layer of fibrocartilage is usually present on bony surface

Head of femur

Osteochondritis of left humeral head with secondary deformation of bone, eighth to ninth century from Iona

• Articular cartilage, often with calcification; 50% have subchondral bone

Pathological specimen of Danish sow

• 10% of patients have joint involvement, usually polyarticular
• Most common involvement is acute polyarthritis / periarthritis (Jansen and Geusens: Sarcoidosis: joint, muscle and bone involvement (pdf))
• Usually resolves quickly, but occasionally progresses to chronic granulomatous arthritis resembling tuberculosis but without caseation or lymphocytes

C: sarcoidosis

• Common form of spinal disease seen radiographically or at autopsy, due to anterior protrusion of disc
• Present in 50% of population at age 50, affects lumbar spine
• Associated with heavy physical labor; due to traction forces acting on weak anterior ligament which causes tears (Arch Orthop Trauma Surg 1984;103:201)

• Herniation of synovium through joint capsule
• Usually present in joint of extremeties
• In spine, referred to as spinal cyst
• Called Baker cyst if in popliteal space
• May bleed and become a mass-like lesion

Baker's cyst

• Baker's cyst: palisading histiocytes and fibrinoid necrosis, similar to rheumatoid pericarditis and rheumatoid nodules

• Soft tissue mass located extradurally along medial border of degenerated facet joint
• Usually at L4-5, rarely in cervical or thoracic spine
• Filled with clear or xanthochromic fluid
• Causes back and radicular pain
• Rarely results in cauda equina syndrome (Pain Physician 2012;15:435)

Cystic mass in L2-L3 facet joint

• 14 year old girl with synovial cyst of thoracic spine (Arq Neuropsiquiatr 2007;65:838)
• 63 year old woman with intradural invasion of lumbar synovial cyst (Neurol Med Chir (Tokyo) 2012;52:234)
• 71 year man with synovial cyst of thoracic spine (BMJ Case Rep 2009;2009 Epub 2009 Feb 16)
• 72 year old woman with hemorrhagic lumbar synovial cyst (J Korean Neurosurg Soc 2012;52:567)
• 84 year old man with cervical brachyalgia (Eur Spine J 2010;19:S100)

Extradural cystic lesion

Hemorrhagic synovial cyst

Thin fibrous wall

• Lined by metaplastic synovial tissue
• May be due to local trauma

• 51 year old woman with cutaneous metaplastic synovial cyst of first metatarsal head area.(Ann Dermatol 2011;23:S165)

• Surgical excision; recurrence is rare

Solitary, well-demarcated 3 cm mass

Cystic lesion filled with gelatinous material

• Cystic structure with papillary projections lined by epithelium resembling synovium

Numerous villous-like structures

Villous structures lined by membrane of varying cellularity

Vimentin+ CD34- CD68-

• Joint pain, limitation of motion or instability, due to dysfunctional 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

Carpometacarpal joint

• If etiology is not known, examine synovial fluid before biopsy to detect TB or other granulomatous lesions

"Fibrillation"

Loose body

• 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)

"Osteophytes"

• Findings are related to either injury or reparative change

• 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 and may grow into enormous size
• Endochondral ossification can occur in loose bodies
• Subchondral bone has superficial bone necrosis, microfractures, replacement of bone by solid or cystic fibromyxomatous tissue

• 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 (evidence of bleeding)
• Polarized microscopy demonstrates discontinuity between collagen network of repair cartilage and preexisting cartilage

Sheep with cylindrical metal implant

Pentachrome-stained knee joint of rabbit

• Usually granulomatous
• Most cases are not infectious (Ann Rheum Dis 1999;58:661)

• Due to infection with Borrelia burgdorferi, a spirochete transmitted by Ixodes tick; joints affected weeks to years later
• Causes chronic arthritis of large joints with pannus formation in 10%
• Also affects skin, heart, nervous system
• Precise pathophysiology of disease unknown, but involves intricate network of vector, bacterial and host factors (Clin Vaccine Immunol 2008;15:21)
• "Amber theory": disease due to infection of structures close to joint space, followed by entry of nonviable bacteria and debris into joint space, eliciting inflammatory response (Clin Rheumatol 2012;31:989)

Erythema migrans skin lesion

Lyme arthritis of right knee

• Chronic papillary synovitis with hyperplasia, fibrin deposition, mononuclear cell infiltrates, onion skin thickening of arterial walls; resembles rheumatoid arthritis
• Perineuritis may be present

Borrelia burgdorferi

Borrelia spirochetes identified on silver stain

Joint capsule, elbow

Chronic lyme disease - perineuritis

• Silver stain highlights bacteria

• 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 Pathol 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 (since involves lumbar segments), ages 50+ years, male predominance
• Spondylodiskitis commonly involves lumbar (45%), thoracic (35%), and cervical (10-20%) spine; causes secondary epidural abscess most commonly in cervical spine, also thoracic and lumbar spine
• Increased frequency of diagnosis due to magnetic resonance imaging
• Most cases are due to pyogenic organisms (Staph, Strep); also Candida, Aspergillus, Cryptococcus, Mycobacterium tuberculosis; rarely Enterococcus

• Culture usually positive (78%), special stains are usually negative

Destruction of vertebral bodies and disk tissue

• 14 year old girl with fungal thoracic spondylodiskitis (J Nippon Med Sch 2009;76:265)
• 35 year old man with tuberculous spondylodiskitis with lumbar tumor (Reumatol Clin 2012;8:292)
• 42 year old man with chronic hemodialysis and Aspergillus fumigatus spondylodiskitis (Exp Clin Transplant 2011;9:265)
• 62 year old man with sigmoid carcinoma and Candida tropicalis spondylodiskitis (Cases J 2008 Jul 29;1:66)
• 70 year old man with recurrent infective endocarditis associated with pyogenic spondylodiskitis (Korean Circ J 2011;41:167)

Intervertebral disc (top center) destroyed by vertebral abscess

Spinal cord compressed by abscess

• Vascularization, myxoid degeneration, necrosis of disk, chronic osteomyelitis
• Variable acute osteomyelitis (25%), granulation tissue
• Tuberculous infection has caseating granulomas

Primary Aspergillus spondylodiscitis in liver transplant recipient

G/H: inflammatory cells and bacteria

C. tropicalis

• Arch Pathol Lab Med 2000;124:712, eMedicine

• Due to seeding of joint during bacteremia, most commonly Staphylococcus, Streptococcus, gram negative rods; rarely syphilis
• Also due to postsurgical infection
• Neonates: often due to osteomyelitis; hip more common than ankle or knee
• Young women: usually gonorrhea, associated with multiple joint involvement, including 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

• Usually single joint (knee, hip, shoulder)

• Aspiration of joint under radiologic guidance

• 38 year old man with septic arthritis due to Staphylococcus warneri (Open Rheumatol J 2012;6:310)
• 40 year old man with septic arthritis of hip due to Salmonella typhi (Case Rep Infect Dis 2012;2012:464527)
• 53 year old woman with isolated septic facet joint arthritis (Pol J Radiol 2012;77:72)
• 66 year old man with septic arthritis of knee associated with calf abscess (J Orthop Surg (Hong Kong) 2012;20:272)

• Immediate surgical incision and drainage, immobilization and antibiotics

Ankle joint

• Neutrophils (also Bechet's disease, familial Mediterranean fever)

Pyogenic osteomyelitis and suppurative arthritis leading to joint destruction

• Insidious onset of chronic progressive arthritis, usually monoarticular in knee and hip; usually after osteomyelitis
• More common in children
• First, synovial membrane secretes excessive fluid; then proliferation, thickening, studding of its inner surface with tubercles; finally fibrosis of outer surface
• Leads to fibrous ankylosis of joint with obliteration of joint space
• Can detect from culture, examination of synovial fluid, PCR (apparent false positives in clinically negative patients may represent early disease, Arch Pathol Lab Med 2004;128:205)

• Marginal erosion of hip and knee joints, with destruction of subchondral bone on both sides of joint and loss of joint space

• 2 year old girl with limping of right lower extremity (Reumatol Clin 2011;7:417)
• 34 year old woman from Burma with wrist swelling, initially AFB negative with negative cultures, but subsequent diagnosis of TB tenosynovitis (Hum Pathol 2004;35:1044)
• 40 year old woman with pain and swelling in shoulder (Int J Surg Case Rep 2012;3:164)
• 57 year old woman with swelling and pain in elbow (Korean J Intern Med 2009;24:397)

Arthroscopic view of elbow joint

• Granulomas with caseous necrosis; AIDS patients often have histiocytes with numerous acid-fast organisms but no granulomas

1B: typical caseating tuberculous granuloma

Synovial tissue

Synovial biopsy showing granuloma

• Presents with joint pain and swelling; symptomatic treatment is sufficient
• Resolves on its own without any sequelae
• Usually parvovirus B19, Hepatitis A, B & C, rubella
• Also enterovirus, dengue virus, HIV, alphaviruses & human parvovirus

General
=========================================================================

• Chronic inflammatory disease of axial joints, especially sacroiliac
• Affects teenage boys, 90% are HLA-B27 positive
• M:F: 2-3:1

Pathophysiology
=========================================================================

• Typically involves sacroiliac joints and slowly ascends
• Chronic synovitis destroys articular cartilage and causes bony ankylosis
• Inflammation of tendinoligamentous insertion sites cause osteophytes
• CD3+ T cells and CD68+ macrophages are main inflammatory cells

Clinical features
=========================================================================

• Symptoms: low back pain that gets progressively worse
• Reactive bone formation may be seen in ring apophysis with erosions of margins
• Calcification of posterior longitudional ligament is seen
• In later stages, spine appears fused with fixed kyphosis (Bamboo spine)
• Complications: uveitis, aortitis, amyloidosis

Diagrams
=========================================================================

Ankylosing spondylitis

Case reports
=========================================================================

• 30 year old woman with coexisting ankylosing spondylitis and rheumatoid arthritis (Chin Med J (Engl) 2011;124:3430)
• 47 year old man with coexisting CML (Tunis Med 2012;90:901)
• 55 year old man with associated foraminal synovial cyst (J Korean Neurosurg Soc 2011;50:54)
• 57 year old man with 30 year history and recent onset cauda equina syndrome and dural ectasia (Br J Radiol 2011;84:e123)

Clinical images
=========================================================================

Anterior flexion

General
=========================================================================

• Also called pseudogout, chondrocalcinosis
• Common finding in arthritic joints

Pathophysiology
=========================================================================

• Calcium pyrophosphate dehydrate (CPPD) crystals develop first in menisci and intervertebral discs, may seed the joint and elicit neutrophilic response (Hum Path 1995;26:587)
• 50% get significant joint damage
• CPPD deposition may also cause symptoms similar to septic arthritis, polyarticular inflammatory arthritis or degenerative osteoarthritis

Diagrams
=========================================================================

Pathogenesis

Sites
=========================================================================

• Knee is common site; 50% have involvement of several joints at diagnosis

Clinical features
=========================================================================

• Age 50+ years, 30% of patients are at least 85 years old
• Hereditary variant: symptoms early in life, associated with severe osteoarthritis
• Secondary: associated with prior joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, diabetes mellitus

Diagnosis
=========================================================================

• Radiographic or microscopic detection of CPPD crystals
• Ultrasound is very sensitive (Ann Rheum Dis 2005;64:638)

Laboratory
=========================================================================

• Synovial fluid has high white count (2000-8000 cells/mm3), 80% neutrophils with intracellular crystals; later mononuclear cells with intra- or extracellular crystals

Radiology images
=========================================================================

Pyrophosphate arthropathy

Meniscal chondrocalcinosis

Case reports
=========================================================================

• 65 year old woman with crystal deposition in knee (Arch Pathol Lab Med 2001;125:705)
• 78 year old woman with pseudogout at craniocervical junction (Arch Pathol Lab Med 2003;127:895)
• Massive total body disease, including vertebral disks (Arch Pathol Lab Med 1982;106:352)

Treatment
=========================================================================

• Supportive (Ther Adv Musculoskelet Dis 2012;4:121)

Gross description
=========================================================================

• Chalky white deposits in articular tissue

Micro description
=========================================================================

• Small rectangular (rhomboid) crystals that are weakly positive birefringent; may have histiocytic and giant cell reaction around these crystals
• CPPD crystals have rhomboid or parallelelipedic morphology

Micro images
=========================================================================

H&E (A-C), Shiddam staining (figure 2)

High magnification

Compensated polarised light microscopy

H&E, polarized light

Differential diagnosis
=========================================================================

• Crystal deposition: gout, deposition of calcium phosphate, talc, methyl methacrylate (prosthetic joints)

General
=========================================================================

• Also called osteoarthritis (OA) (inaccurate since not due to inflammation)
• Nonneoplastic disorder of progressive erosion of articular cartilage associated with aging, trauma, occupational injury

Sites
=========================================================================

• Men-hips, women-knees and hands; also first metatarsophalangeal joint, lumbar spine; usually one joint or same joint bilaterally, at least initially
• Also common in small joints of hands and wrist, particularly first carpometacarpal joint

Clinical features
=========================================================================

• Either no prior arthritis (primary or idiopathic OA) or due to severe arthritis (secondary OA)
• Usually age 50+ years (present in 80% at age 65 years)
• 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); includes knees of basketball players
• Chondromalaciae patellae: softening, fibrillation, fissuring and erosion of articular cartilage of patella (Wikipedia)
• Charcot 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; occurs in femoral head, degenerative and regenerative changes are present, but only mild osteomalacia and ebernation (Hum Pathol 1985;16:117); characterized by two distinct abnormalities, protrusio acetabuli that mainly affects females and increases in frequency with age, and hip dysplasia that is more frequent with age (Joint Bone Spine 2010;77:399)
• 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

Radiology
=========================================================================

• 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

Radiology images
=========================================================================

Euplastic bilateral arthrosis with large osteophytes

Case reports
=========================================================================

• 55 year old diabetic man with Charcot joint (J La State Med Soc 2002;154:246)
• 61 year old woman with chronic pain and stiffness in multiple joints (Am Fam Physician 2011;83:1203)
• 66 year old man with rapidly destructive osteoarthritis of the hip (Reumatol Clin 2011;7:56)
• Case with mucinous synovial transformation (Hum Pathol 1982;13:946)

Treatment
=========================================================================

• Medication for pain
• May have sinus histiocytosis of pelvic lymph nodes after hip replacement due to metal microparticles of implants (Am J Surg Pathol 1994;18:83)

Clinical images
=========================================================================

Swelling around distal interphalangeal joints

 

Charcot joints

Joint mice-loose body

Gross description
=========================================================================

• 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 Pathol 1984;15:79)

Gross images
=========================================================================

Bone eburnation

Advanced osteoarthritis of hip

Micro description
=========================================================================

• 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 (Am J Surg Pathol 1999;23:192)

Micro images
=========================================================================

Reactive changes with increased cellularity and multilayering of synovial cells

Areas of uninjured bone tissue (A), necrotic bone tissue (B) and cartilage (C)

Synovial area with granulation tissue and chronic inflammation

   

Microscopic changes

Virtual slides
=========================================================================

Degenerative joint disease

Molecular / cytogenetics description
=========================================================================

• Clonal aberrations in HMGIC gene at 12q13-15 in synovia of 5% of patients (Mod Pathol 2001;14:311)

General
=========================================================================

• Subset of spondyloarthritides and seronegative arthritis
• Lipopolysaccharide antigens stimulate immune system and cause abrupt onset of arthritis in knees and ankles, lasts only 1 year
• Can be associated with inflammatory bowel disease, Crohn disease and ulcerative colitis (J Postgrad Med 2005;51:273, World J Gastroenterol 2009;15:2456)
• Also associated with celiac disease, Whipple disease, collagenous colitis, intestinal bypass surgery

Epidemiology
=========================================================================

• More common in males, with peak incidence at 15-35 years

Etiology
=========================================================================

• Due to bowel infection with Yersinia, Salmonella, Shigella, Campylobacter

Clinical features
=========================================================================

• Usually asymmetric, oligoarticular arthritis involving the lower limbs along with gastrointestinal manifestations of IBD

Prognostic factors
=========================================================================

• IBD related arthritis usually carries worse prognosis

Case reports
=========================================================================

• 58 year old Malay woman with 17 year history of ulcerative colitis with persistent knee effusion (J Med Case Rep 2012;6:10)

Micro images
=========================================================================

Synovial tissue of knee

General
=========================================================================

• 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

Pathophysiology
=========================================================================

• 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)
• Uric acid/urate is product of metabolic breakdown of purine nucleotides
• 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 (The Medical Biochemistry Page)
• 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
• Lesch-Nyan syndrome: rare; men with HGPRT deficiency causing hyperuricemia, severe neurologic deficits with mental retardation, self-mutilation, gouty arthritis (chart; OMIM 300322)
• 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

Clinical features
=========================================================================

• Males more commonly affected
• In women, onset occurs at very late age (Clin Rheumatol 2010;29:575)
• Risk factors for gout with hyperuricemia are age > 30 years, familial history of gout, alcohol use, obesity, thiazide administration, lead
• Aspirate: grossly white-gray and granular; strongly negative birefringent needle-shaped crystals under polarized light; foreign body giant cells

Case reports
=========================================================================

• 55 year old man with 10 year history of pain in ankle joints followed by involvement of first metatarsophalangeal joint (Indian J Med Sci 2004;58:349)
• 59 year old Chinese man with 30 year history of psoriasis vulgaris, 13 year history of polyarthralgia and 5 year history of painful mass on foot (Eur J Dermatol 2009;19:184)
• 66 year old obese woman suffering from a systemic polyarthritis for 3 years (J Orthop Surg (Hong Kong) 2005;13:203)
• 73 year old man with elbow pain (Arch Pathol Lab Med 2002;126:621)

Clinical images
=========================================================================

Milky effusion associated with gout

Various images

Various images

Fingers

Chalky white appeareance

Gross description
=========================================================================

• Chalky white appearance of gouty deposits

Gross images
=========================================================================

White deposits

Micro description
=========================================================================

• 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
=========================================================================

1. Xray
2. Diff-Quick
3. Pap smear
4. Polarized light
5. H&E

Uric acid crystals

Needle shaped monosodium crystals

Sodium urate crystals - polarized light

Typical granuloma

Differential diagnosis
=========================================================================

• Crystal deposition: deposition of calcium pyrophosphate, calcium phosphate, talc, methyl methacrylate (prosthetic joints)

General
=========================================================================

• Common connective tissue disease in children age 15 years or less - most common chronic rheumatic illness in children (Dermatology Online Journal 2001;7(2):19)
• Worldwide incidence varies from 0.008 to 0.226 per 1,000 children

Sites
=========================================================================

• Knees, wrists, elbows, ankles

Pathophysiology
=========================================================================

• Pathogenesis: oligoarthritis and polyarthritis group are T helper 1 cell mediated disorders; precise mechanisms are unclear, but proinflammatory cytokines are responsible for part of clinical symptoms (Korean J Pediatr 2010;53:921)

Diagrams
=========================================================================

Cytokine signaling pathways

Clinical features
=========================================================================

• 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
• Usually seronegative for rheumatoid factor
• Symptoms: systemic onset with fever, rash, hepatosplenomegaly, serositis; also warm and swollen joints; pericarditis, myocarditis, pulmonary fibrosis, glomerulonephritis, uveitis, growth retardation

Case reports
=========================================================================

• 4 year old girl with limping and swelling of knee (University of Hawaii 2003)
• 6 year old boy with knee and heel pain (Rev Med Inst Mex Seguro Soc 2006;44:355)
• 8 year old girl with knee pain (Arch Dis Child 2005;90:1038)
• 9 year old boy with painful swelling of knee and elbow joints (Bangladesh Journal of Child Health 2010;34:31)

Treatment
=========================================================================

• NSAIDs initially (Korean J Pediatr 2010;53:936)

Clinical images
=========================================================================

Flesh-colored, subcutaneous nodules

Swelling and flexion contracture

Polyarticular disease

Systemic onset disease

Micro description
=========================================================================

• Similar morphologic changes as adult rheumatoid arthritis but less severe

Micro images
=========================================================================

Degenerated fibrin with surrounding palisading histiocytes

Destruction of articular cartilage of femoral head

Proliferative and exudative synovitis

Typical pannus formation

General
=========================================================================

• Affects 5-10% of psoriasis population, usually ages 35-45 years
• Onset or exacerbation may be associated with trauma (Can Fam Physician 2012;58:e636)
• 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

Case reports
=========================================================================

• 29 year old woman with psoriasis and painful and swollen distal and proximal interphalyngeal joints (J Zhejiang Univ Sci B 2010;11:779)

Clinical images
=========================================================================

Psoriasis rash

Psoriatic arthritis of hands

Swollen and erythematous third digit

Swollen joints

Micro description
=========================================================================

• Similar to rheumatoid arthritis but tends to be more fibrotic

General
=========================================================================

• Aseptic arthritis triggered by infective agent located outside the joint (Am Fam Physician 1999;60:499, UpToDate )
• Also called reactive arthritis

Clinical features
=========================================================================

• Patients present with asymmetric oligoarthritis
• Articular and extraarticular manifestations are similar regardless of organisms causing this disorder
• Synovitis of digital tendon sheath produces sausage fingers or toes, causes spurs
• Triad of arthritis, uveitis/conjunctivitis, non-gonococcal urethritis/cervicitis is not always present
• 80% are HLA-B27 positive

Epidemiology
=========================================================================

• Typically affects men or women in 20-30's

Sites
=========================================================================

• Affects ankles, knees, feet

Etiology
=========================================================================

• Occurs after GI infections (Salmonella, Shigella, Campylobacter, Yersinia), Chlamydia, Escherichia coli, Clostridium difficile, Chlamydia pneumoniae

Case reports
=========================================================================

• 35 year old Nigerian man with fever, dysentery, dysuria and joint pains (Afr Health Sci 2004;4:136)
• 36 year old man with progressive myelopathy (J Clin Neurol 2007;3:215)
• 46 year old HIV+ man with Reiter's syndrome (Braz J Infect Dis 2002;6:40)

Treatment
=========================================================================

• Doxycycline

Clinical images
=========================================================================

Onychodystrophy

Swollen "sausage" toe / inflamed ankle

Radiograph: periosteal reaction at plantar fascia insertion

General
=========================================================================

• Chronic systemic inflammatory disorder affecting synovial lining of joints, bursae and tendon sheaths; also skin, blood vessels, heart, lungs, muscles (Davidson College)
• Produces nonsuppurative proliferative synovitis, may progress to destruction of articular cartilage and joint ankylosis

Epidemiology
=========================================================================

• 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 Pathol 2003;16:811)

 

Pathogenesis

Clinical features
=========================================================================

• 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

Diagnosis
=========================================================================

• Morning stiffness, arthritis in 3+ joint areas, arthritis in hand joints, symmetric arthritis, rheumatoid nodules, rheumatoid factor, typical radiographic changes

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), increased protein, low mucin
• Other antibodies include antikeratin antibody (specific, not sensitive), antiperinuclear factor, anti-rheumatoid arthritis associated nuclear antigen (RANA)

Radiology
=========================================================================

• 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

Case reports
=========================================================================

• 30 year old woman with 7 year history of pain in lumbosacral area and 1 year history of pain in joints of both hands (Chin Med J (Engl) 2011;124:3430)
• 49 year old woman with chief complaint of restricted mouth opening without pain, lasting approximately 4 months (Braz Dent J 2012;23:779)
• 72 year old woman with 6 month history of progressive painful swelling of wrists (Int J Surg Case Rep 2011;2:208)
• Woman with pain and edema in second, third and fourth proximal interphalangeal (PIP) joints of hands and wrists (Rev Bras Reumatol 2012;52:648)

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)

Clinical images
=========================================================================

Yellowish discharge of altered synovial fluid

Gross description
=========================================================================

• Joints have edematous, thick, hyperplastic synovium, covered by delicate and bulbous fronds
• Osteophytes and new bone formation are not prominent

Gross images
=========================================================================

Swollen and erythematous finger

Knee joint

Micro description
=========================================================================

• 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

Micro images
=========================================================================

 

Chronic inflammation, plasma cells, lymphocytes

 

Lymphoid follicles

 

Amorphous, pink, necrotic material

Pannus

Rheumatoid nodule

Virtual slides
=========================================================================

Rheumatoid nodule

Cytology description
=========================================================================

• May have inflammatory exudate with neutrophils, suggesting an infectious arthritis

Molecular / cytogenetics description
=========================================================================

• More than 20 genetic risk factors
• HLA-DR4, DR1 (65%); PADI4 (Immunogenetics 2011;63:459)
• T-cell antigen receptor motif Q(K/R)RA in 75%
• IL2 signalling pathway involved in T cell activation and proliferation (Curr Opin Rheumatol 2010;22:109)

Molecular / cytogenetics images
=========================================================================

HLA-DR4 molecule

Clinical features
=========================================================================

• Also called progressive systemic sclerosis
• Initially presents with nonspecific joint pains, which can lead to arthritis
• Joint mobility may be restricted by calcinosis or skin thickening
• May be accompanied or even dominated by arthritis and arthralgia
• Serum positive for rheumatoid factor and anticentromere antibodies (Br J Rheumatol 1995;34:831)

Micro description
=========================================================================

• Superficial fibrin deposition in synovial membrane, mild mononuclear infiltrate, mild synovial hyperplasia, proliferation of collagen fibers, focal obliteration of small vessels

General
=========================================================================

• Autoimmune disease that usually presents with mild arthritis or joint effusions
• Destructive joint disease is rare except for those on steroid therapy who rarely can develop aseptic necrosis
• Occasionally there is a progression to rheumatoid-like nonerosive hand deformities (Jaccoud's syndrome, Rheum Dis Clin North Am 1988;14:99, Ann Rheum Dis 1974;33:204)
• Synovial fluid shows less inflammation than rheumatoid arthritis

Clinical images
=========================================================================

Correctable swan-neck deformities and ulnar deviation

 

Readily correctable swan-neck deformities and subluxation of right fifth MCP

Metacarpal heads-no cartilage damage seen

Non-correctable deformities of PIP joints

Mild ulnar deviation, especially on right

Micro description
=========================================================================

• Changes resemble rheumatoid arthritis, but with more intense surface fibrin deposition and less synovial proliferation and less intense inflammation
• Occasional vasculitis can be seen (Ann Intern Med 1971;74:911)

Micro images
=========================================================================

Synovial membrane

General
=========================================================================

• Usually direct extension of bone tumors

General
=========================================================================

• Lobular, circumscribed fibroblastic process of extremities (Stanford University)
• Rarely originates from synovial membrane of joint capsule
• May be related to fibrous histiocytoma of tendon sheath due to similar location, clinical presentation and recurrence rate

Terminology
=========================================================================

• Also called tenosynovial fibroma

Epidemiology
=========================================================================

• Any age, peaks at 20-30 years, usually males

Case reports
=========================================================================

• 17 year old boy with large, tense knee effusion following trauma (Indian J Orthop 2011;45:276)
• 20 year old woman with two month history of difficulty extending ring finger (J Hand Microsurg 2010;2:31)
• 58 year old man with 2 year history of progressive localized swelling of ankle joint (J Orthop Traumatol 2009;10:147)

Gross description
=========================================================================

• Smooth, dense, multinodular mass, pearly white, 0.5-5.5 cm

Gross images
=========================================================================

Multilobular mass

3.5×2cm mass

Micro description
=========================================================================

• 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

Micro images
=========================================================================

H&E

Various images

General
=========================================================================

• Also called tenosynovial giant cell tumor, giant cell tumor of tendon sheath, nodular tenosynovitis, xanthogranuloma, benign synovioma
• Ages 20-40's, usually women
• Develops in synovial lining of joints, tendon sheaths and bursae
• Usually knee (80%); also ankle, hip, shoulder or elbow joint and foot
• Almost always monoarticular, painful swelling
• May actually be hyperplastic / reactive, not neoplastic (Hum Pathol 2003;34:65)
• Occasionally invades underlying bone; may cause bone cyst formation, loss of bone and cartilage
• Locally aggressive; often recurs, but only rarely has malignant behavior (see below)
• 15% erode adjacent bone by pressure
• May be related to tendon sheath fibromas

Case reports
=========================================================================

• 9 year old girl with nodule in right index finger (Dermatol Online J 2011;17:9)
• 15 year old boy with swelling in knee (Oncol Lett 2012;3:718)
• 30 year old man with pain in ankle (J Med Case Rep 2009;3:9331)
• 32 year old woman with 2 year history of slowly growing firm, nodular, and nontender thumb mass (Eplasty 2013;13:ic36)
• 73 year old man with mass on thumb (Int J Clin Exp Pathol 2012;5:374)

Treatment
=========================================================================

• Excision (benign), but may recur locally

Gross / clinical images
=========================================================================

Foot

Palmar aspect of middle phalanx of index finger

Firm, nodular, nontender thumb mass

Excised giant cell tumor

Dome-shaped nodule

Well-demarcated yellowish lobulated tumor

Gross description
=========================================================================

• 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 description
=========================================================================

• Polymorphic infiltrate of small histiocytes, multinucleated giant cells within dense fibrous tissue with hemosiderin and foamy macrophages
• Mitotic figures and focal hyalinized areas; tumor margins are more cellular

Micro images
=========================================================================

2A: H&E with multinucleated giant cells and mononuclear cells; B: mononuclear cells are HAM56+; C: giant cells and some mononuclear cells are TRAP+; 3: differentiation sequence of giant cell tumor

Giant cell

Low power and high power

Circumscribed lobulated nodule

Histiocytes with abundant eosinophilic cytoplasm

Low power view of thumb tumor

High power view of cellular zone

High power view of hypocellular zone

CD68 immunostaining of cellular zone

Ki-67 immunostaining of peripheral zone

CD45 immunostaining of peripheral zone

Electron microscopy description
=========================================================================

• Synovial cells, fibroblasts, histiocytes, lymphocytes

Differential diagnosis
=========================================================================

• Epithelioid sarcoma: granuloma-like formations, necrosis, invasive, epithelioid features, keratin+

General
=========================================================================

• Mean 61 years, no gender preference
• Usually extra-articular, near large joints or extremities
• Most common location is knee joint
• High number of mitotic figures, marked nuclear hyperchromasia, few multinucleated giant cells

Micro images
=========================================================================

Radiological, histologic, and FISH/ISH findings in malignant tumors

General
=========================================================================

• Myxoid lesion arising adjacent to large joint (Hum Pathol 1992;23:639, Stanford University)
• Often associated with cystic changes resembling ganglion cyst
• Often recurs, up to 4 times

Epidemiology
=========================================================================

• Median age 43 years, range 16-83 years
• 72% male

Sites
=========================================================================

• Knee (88%), also shoulder, elbow, ankle, hip

Case reports
=========================================================================

• 5 year old boy with palpable mass on medial side of knee proximal to knee joint (Eur Radiol 2010;20:764)
• 63 year old male runner with suprapatellar symptoms (Orthopedics 2009;32:527, free full text)
• 68 year old athletic woman with several month history of progressing pain, swelling, and loss of motion in knee (Arthroscopy 2003;19:E6)

Clinical images
=========================================================================

Arthroscopic image of lesion within suprapatellar pouch

Gross description
=========================================================================

• Myxoid, mucoid or slimy mass with pale white to yellow color

Gross images
=========================================================================

Glassy appearance

Micro description
=========================================================================

• Loosely arranged spindle cells in hypovascular myxoid matrix; variable cystic spaces can be seen

Micro images
=========================================================================

Myxoid stroma and spindle cells

Knee joint

Bland myxoid neoplasm without
mesenchymal atypia or hypercellularity

General
=========================================================================

• Rare neoplastic-like villonodular hyperplasia of synovium and tendon sheaths in young adults composed of mononuclear cells and multinuclear giant cells with hemosiderin deposition (bonetumor.org, Am Fam Physician 1999;60:1404)
• May be similar to diffuse form of tenosynovial giant cell tumor

Clinical features
=========================================================================

• 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 Pathol 2003;34:65)
• Locally aggressive; may recur, but only rarely has malignant behavior (Am J Surg Pathol 1997;21:153)

Case reports
=========================================================================

• 15 year old with new onset of fatigue, diffuse arthralgia, butterfly rash, tenosynovitis of wrist, lymphopenia and thrombocytopenia (J Med Case Rep 2011;5:443)
• 28 year old woman with painful swelling in ankle (Intern Med 2013;52:1149)
• 36 year old man with tumor at temporomandibular joint (Arch Pathol Lab Med 2002;126:195)
• 38 year old man with 3 year history of nontraumatic pain in knee joint (J Ultrasound 2011;14:167)
• 56 year old woman with malignant tumor (Open Orthop J 2011;5:13)
• 62 year old man with gradually worsening pain and stiffness in knee (J Med Case Rep 2009;3:121)
• 66 year old woman with long history of back pain (Turk Neurosurg 2010;20:251)
• 2 cases involving vertebral column (Arch Pathol Lab Med 1984;108:228)
• 2 rare cases of malignant behavior (Arch Pathol Lab Med 2000;124:1636)

Treatment
=========================================================================

• Excision, but may recur locally if not completely excised; postoperative external beam radiotherapy may be useful for recurrences (Acta Orthop 2012;83:256)
• Also Imatinib mesylate (Cancer 2012;118:1649)

Clinical images
=========================================================================

Knee arthroscopy

Stained synovium

Gross description
=========================================================================

• Focal or diffuse; brown-yellow spongy tissue with variable color and firm nodular consistency

Gross images
=========================================================================

Brownish synovium

Micro description
=========================================================================

• 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

Micro images
=========================================================================

Pseudoglandular or cleft-like spaces

Proliferation of polygonal cells

Multinucleated giant cells

Hemosiderin-laden macrophages

Hemosiderin-laden and lipid-laden macrophages

Lipid-laden macrophages

Low power

Medium power

Malignant cases

Hemosiderin deposits, foamy histiocytes and giant cells

Extensive histiocytic proliferation

Virtual slides
=========================================================================

48 year old woman with synovial polyp

54 year old man with tissue from knee joint

Cytology description
=========================================================================

• Round, spindled and multinucleated cells without atypia
• Round cells have minimal cytoplasm and eccentric nuclei
• Occasional cytoplasmic hemosiderin
• No mitotic figures

Cytology images
=========================================================================

H&E

Positive stains
=========================================================================

• CD68 (stromal and giant cells), HAM56, and vimentin

Negative stains
=========================================================================

• S100, CD45/LCA, EMA, keratin, HMB45, CD34, desmin, smooth muscle actin

Molecular / cytogenetics description
=========================================================================

• Trisomy 5 and 7
• Translocation and expression of CSF1 (Stanford University)

Molecular / cytogenetics images
=========================================================================

FISH: trisomy 5 and 7

Differential diagnosis
=========================================================================

• Fibrosarcoma
• Hemosiderotic synovitis: associated with hemophilia and intraarticular bleeding, no mononuclear or giant cell nodular cellular proliferation, hemosiderin primarily in synovial lining cells
• Synovial sarcoma

General
=========================================================================

• Also called synovial chondrometaplasia, synovial osteochondromatosis
• Mean age 41 years, range 17-64 years, 2/3 male (Hum Pathol 1998;29:683)
• Primary disease is uncommon, unknown etiology, aggressive (Hum Pathol 1979;10:439)
• Usually monoarticular, can be bilateral rarely (JCDR 2012;6:475), affecting knee, hip, elbow and communicating bursae; may affect adjacent soft tissue
• Aggravated by infection and trauma
• May be extra-articular (tenosynovial chondromatosis)

Radiology
=========================================================================

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

Case reports
=========================================================================

• 11 year old girl with persistent left elbow pain 2 months after roller skating accident (Indian J Orthop 2011;45:181)
• 13 year old girl with progressive swelling over thumb (Hand (N Y) 2012;7:98)
• 26 year old man with chronic bilateral ankle pain (Chiropr Osteopat 2007;15:18)
• 32 year old man with unilateral spinal claudication and tenderness of sacroiliac joint (Acta Orthop 2011;82:246)
• 36 year old man with knee pain (Sports Med Arthrosc Rehabil Ther Technol 2009;1:6)
• 36 year old woman with pain and swelling in both knee joints (IJHSR 2012;2:87)
• 49 year old man with progressively worsening knee pain (J Med Case Rep 2010;4:113)

Treatment
=========================================================================

• Excision, but frequently recurs; 5% become malignant

Clinical images
=========================================================================

Loose bodies in synovial chondromatosis

Multiple loose osteocartilaginous fragments

Smooth white nodule

Showing extent of disease

Gross description
=========================================================================

• Numerous round osteocartilaginous nodules cover a thickened synovial surface or float freely within joint space

Micro description
=========================================================================

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

Micro images
=========================================================================

Metaplastic cartilage in synovium

Clusters of chondrocytes

Resembles Grade 1 chondrosarcoma

Nodule of cartilage

Lobular structure

Medium power

Loose bodies

Subsynovial cartilaginous nodule

Moderate atypia of chondrocytes

 

Osteochondral loose body

Cartilaginous tissue enclosed by synovial tissue

Differential diagnosis
=========================================================================

• Cartilaginous loose bodies: more common, but associated with arthritis
• Chondrosarcoma: not within a joint, no characteristic clustering pattern, marked myxoid change, spindling of nuclei
• Injury-related soft-tissue calcification
• Lipoma arborescence with osseous metaplasia
• Neuropathic arthropathy or osteochondritis dissecans: no lobulation, clustering or atypia
• Pigmented villonodular synovitis
• Secondary synovial chondrometaplasia due to degenerative joint disease
• Synovial vascular malformation

General
=========================================================================

• 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

General
=========================================================================

• Very rare
• Very difficult to distinguish low grade chondrosarcoma from chondromatosis (Sarcoma 2003;7:69)

Case reports
=========================================================================

• 38 year old woman with hip pain and difficulty in ambulation (Radiographics 2011;31:1883)
• Chondrosarcoma developing in synovial chondromatosis (J Bone Joint Surg Br 1987;69:137)

Gross description
=========================================================================

• May be more expansile than synovial osteochondromatosis

Gross images
=========================================================================

       

Various images of extracapsular hip specimen after fixation and bisection

Chondromatosis with chondrosarcoma

Micro description
=========================================================================

• Cartilage cells have cytologic features of malignancy

Micro images
=========================================================================

   

Tumor tissue permeating cortical bone and filling marrow spaces

General
=========================================================================

• Benign neoplasm characterized by proliferating histiocytes containing lipid and hemosiderin intermingled with multinuclear giant cells

Terminology
=========================================================================

• Synovial-type giant cell tumor, pigmented villonodular synovitis

Epidemiology
=========================================================================

• Usually adults over 30 years old

Sites
=========================================================================

• Frequently tendon sheaths in hand, rarely axial skeleton (thoracic vertebrae, lumbar or cervical spine)

Pathophysiology
=========================================================================

• Most tumors appear to be clonal neoplastic proliferations driven by CSF1 production (Arch Pathol Lab Med 2012;136:901)

Clinical features
=========================================================================

• Mechanical derangement of joint; with knee joint, meniscal symptoms and locking are often present
• May have joint effusion without previous trauma
• Vertebral involvement presents with pain localized to spinal region or radicular pain

Case reports
=========================================================================

• 7 year old Thai girl with back pain, progressive paraparesis (J Med Case Rep 2013;7:178)
• 18 year old man with 2 year history of mild knee pain (Orthopedics 2012;35:e1116)
• Malignant synovial giant cell tumor (Hum Pathol 1989;20:765)

Treatment
=========================================================================

• Complete surgical resection

Gross description
=========================================================================

• 1-6 cm, circumscribed, solid or diffuse

Micro description
=========================================================================

• Polyhedral stromal cells with numerous multinucleated giant cells
• Stroma can be hyalinized
• Siderophages, xanthoma cells, lymphocytes, and some spindled fibroblast-like cells
• Rarely classic villiform architecture of pigmented villonodular synovitis is noted

Micro images
=========================================================================

Histiocytes, foam cells, and multinucleated giant cells

Histiocyte-like tumor cells, lymphocytes,
hemosiderin-laden macrophages and
osteoclast-like giant cells

Positive stains
=========================================================================

• CD68, CD163, vimentin
• Rarely muscle actin (HUC1-1)

Differential diagnosis
=========================================================================

• Other primary bone lesions such as aneurysmal bone cyst, osteoblastoma and osteoclastoma should be considered in differential diagnosis of lesion involving posterior vertebral elements

General
=========================================================================

• Uncommon; usually young adults, more common in males
• Presents as nontraumatic joint swelling with recurrent effusions

Sites
=========================================================================

• Knee, elbow, finger

Xray images
=========================================================================

MRI of knee of 32 year old man

Case reports
=========================================================================

• 4 year old boy with pain and swelling of knee (Indian J Pathol Microbiol 2001;44:353)
• 10 year old girl with pain and swelling in knee joint (Indian J Pathol Microbiol 2008;51:257)
• 12 year old boy with pain and swelling in knee joint (J Med Case Rep 2010;4:105)
• 25 year old man with knee pain (Acta Orthop Traumatol Turc 2004;38:224)
• 30 year old woman with elbow swelling (The Internet Journal of Pathology 2008;7(2))

Gross description
=========================================================================

• Tumor usually confined to intra-articular synovium, may be in adjacent bursa

Gross images
=========================================================================

Various images

Heavily pigmented soft tissue mass

Micro description
=========================================================================

• Resembles either cavernous hemangioma, lobular capillary hemangioma, arteriovenous hemangioma or venous hemangioma

Micro images
=========================================================================

Figure 1

Figure 2

Figure 3

Hip

Hyperplastic synovium

Dilated vascular spaces

Cavernous blood vessels

Differential diagnosis
=========================================================================

• Organizing hemorrhage (Hum Pathol 1993;24:737)
• Pigmented villonodular synovitis

General
=========================================================================

• Also called Hoffa's disease, villous lipomatous proliferation of synovium, lipoma arborescens
• Pseudotumor of synovium with distinct histomorphology, possibly due to inappropriate fat deposition and degenerative articular diseases of joints (J Lab Physicians 2011;3:84)

Clinical features
=========================================================================

• Rare; usually knee but may occur in any joint
• Unknown etiology
• Males commonly affected with pain and swelling of joint

Treatment
=========================================================================

• Arthroscopy and excision

Gross description
=========================================================================

• Enlargement of infrapatellar fat pad with pain in anterior compartment of knee; synovium is papillary, yellow and fatty

Micro description
=========================================================================

• Synovial hyperplasia with unremarkable fat extending to synovial lining; occasional chronic inflammatory infiltrate

Micro images
=========================================================================

Villi-like structures

Papillary architecture

Mature adipocytes

Focal hyperplasia

Few mature lipocytes

Definition
=========================================================================

• Tenosynovial chondromatosis is a multinodular cartilaginous proliferation that arises from tenosynovial membranes, due to synovial metaplasia

Terminology
=========================================================================

• Also called tenosynovial or bursal chondromatosis

Epidemiology
=========================================================================

• M > F; ages 20-86 years (mean and median age are 46 years)

Sites
=========================================================================

• Fingers (50%), feet (20%)
• Also wrists, ankles, palm, knee, forearm

Clinical features
=========================================================================

• May present as painless mass, mass with mild tenderness with pressure, loss of motion of affected area

Radiology
=========================================================================

• Multiple calcifications; may have erosion of underlying bone

Radiology images
=========================================================================

Multiple calcifying nodules

Case reports
=========================================================================

• 23 year old man with 6 month history of pain and swelling of right middle finger (J Orthop Surg (Hong Kong) 2012;20:406)
• 48 year old woman with mass and pain in first web space of hand dorsum (Oman Med J 2012;27:316)
• 59 year old woman with pain and swelling in right ring finger (AJR Am J Roentgenol 2005;184:1223)

Treatment
=========================================================================

• Complete excision recommended, 24-88% recur

Clinical images
=========================================================================

Dorsal first web space

Multiple rice bodies within synovial sheath

Gross description
=========================================================================

• Bluish white subsynovial nodules, mm to cm in size, which conglomerate into lobulated mass attached to synovial membranes

Micro description
=========================================================================

• Multinodular cartilaginous proliferation involving tenosynovium or subsynovial connective tissue
• Cartilaginous matrix more intensely basophilic than chondroma of soft parts
• Often minute cartilaginous nodules
• May have mild or moderate atypia
• Occasionally prominent mineralization
• Rarely crystalline deposits mimic tophi (APMIS 2004;112:624)
• Rarely malignant transformation, which resembles synovial chondrosarcoma

Micro images
=========================================================================

Nodule surrounded by tenosynovial membrane

Differential diagnosis
=========================================================================

• Differential diagnosis of extra-osseous tenosynovial chondromatosis includes chondroma (periosteal or soft tissue), hemangiomatosis, tumoral calcinosis / hydroxyapatite deposition disease

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