Bones and joints.Bones and joints.

Markéta HermanováMarkéta Hermanová

Achondroplasia, hypochondroplasia Achondroplasia, hypochondroplasia (short stature,rhizomelic shortening of (short stature,rhizomelic shortening of the limbs, frontal bossing, midface deficiency)the limbs, frontal bossing, midface deficiency)

OsteopetrosisOsteopetrosis- reduced osteoclast bone resorption, diffuse symmetric skeletal sclerosisreduced osteoclast bone resorption, diffuse symmetric skeletal sclerosis- bones abnormaly brittle (osteosclerosis fragilis generalisata)bones abnormaly brittle (osteosclerosis fragilis generalisata)- AR malignant type and AD benign typeAR malignant type and AD benign type- Anemia (reduced bone marrow space), extramedullar hemopoiesis – Anemia (reduced bone marrow space), extramedullar hemopoiesis –

hepatosplenomegaly, repeated infections, fractures, cranial nerves problems – hepatosplenomegaly, repeated infections, fractures, cranial nerves problems – the result of nerve compression (optic atrophy, deafness, facial paralysis)the result of nerve compression (optic atrophy, deafness, facial paralysis)

mucopolysacharidosesmucopolysacharidoses- enzymes (acid hydrolases) degrading dermatan, heparan, and keratan sulphates enzymes (acid hydrolases) degrading dermatan, heparan, and keratan sulphates

deficiences deficiences - chondrocytes (playing a role in the metabolism of extracellular matrix chondrocytes (playing a role in the metabolism of extracellular matrix

mucopolysacharides) most severly affectedmucopolysacharides) most severly affected- abnormalities of hyaline cartilage result in short stature, chest wall abnormalities of hyaline cartilage result in short stature, chest wall

abnormalitites, malformed bonesabnormalitites, malformed bones- type I (Hurler disease) and IV type I (Hurler disease) and IV

type 1 collagen disease (osteogenesis imperfecta types 1-4)type 1 collagen disease (osteogenesis imperfecta types 1-4)- phenotypically related disorders: bone fragility, hearing loss, blue sclerae, phenotypically related disorders: bone fragility, hearing loss, blue sclerae,

dentinogenesis imperfecta; variable severity of the disease within the typesdentinogenesis imperfecta; variable severity of the disease within the types type 2, 10, and 11 collagen diseasestype 2, 10, and 11 collagen diseases- achondrogenesis II (short trunk, severely shortened extremities, relatively achondrogenesis II (short trunk, severely shortened extremities, relatively

enlarged cranium, flattened face)enlarged cranium, flattened face)- hypochondrogenesis (similar phenotype) hypochondrogenesis (similar phenotype) - multiple epiphyseal dysplasia (short or normal stature, small epiphyses, early multiple epiphyseal dysplasia (short or normal stature, small epiphyses, early

onset osteoarthritis)onset osteoarthritis)- metaphyseal chondrodysplasia (coxa vara, bowing of lower extremitites, metaphyseal chondrodysplasia (coxa vara, bowing of lower extremitites,

metaphyseal flaring)metaphyseal flaring)

Hyperparathyreoidism: fibrous Hyperparathyreoidism: fibrous osteodystrophy, osteitis cystica osteodystrophy, osteitis cystica

fibrosa, von Recklinghausenfibrosa, von Recklinghausen disease of bonesdisease of bones HyperparathyreoidismHyperparathyreoidism

- primary: hyperplasia, tumor (adenoma)primary: hyperplasia, tumor (adenoma)- secondary: in hypocalcemia resulting in increased secondary: in hypocalcemia resulting in increased

secretion of PTHsecretion of PTH entire skeleton affected, osteitis fibrosa cystica entire skeleton affected, osteitis fibrosa cystica

now very rarenow very rare Osteoclastic resorption – dissecting osteitis Osteoclastic resorption – dissecting osteitis

(increased number of osteoclast – osteoclastic (increased number of osteoclast – osteoclastic resorption; activation of osteoblasts)resorption; activation of osteoblasts)

thin cortex, osteopenia, fibrovascular tissue within thin cortex, osteopenia, fibrovascular tissue within bone marrow spaces, hemorrhages, organisation bone marrow spaces, hemorrhages, organisation of hematoms, pseudocysts, brown tumors (mass of of hematoms, pseudocysts, brown tumors (mass of reactive tissue)reactive tissue)

Pathologic fracture and Pathologic fracture and brown tumorbrown tumor

Renal osteodystrophyRenal osteodystrophy high turnover osteodystrophy (high osteoclastic and high turnover osteodystrophy (high osteoclastic and

osteoblastic activity)osteoblastic activity) low turnover osteodystrophy (low activity; adynamic, aplastic low turnover osteodystrophy (low activity; adynamic, aplastic

disease)disease) osteomalaciaosteomalacia mixed picture of the renal osteodystrophymixed picture of the renal osteodystrophy

chronic renal diseases:chronic renal diseases:- phosphate retention and hyperphosphatemiaphosphate retention and hyperphosphatemia- hypocalcemia (avitaminosis D)hypocalcemia (avitaminosis D)- secondary hyperparathyreoidism secondary hyperparathyreoidism - metabolic acidosis stimulating also bone resorptionmetabolic acidosis stimulating also bone resorption- aluminium deposition at the site of mineralization (dialysis aluminium deposition at the site of mineralization (dialysis

solution); Al interferes with the deposition of calcium solution); Al interferes with the deposition of calcium hydroxyapatite promoting osteomamacia hydroxyapatite promoting osteomamacia

- amyloid deposition in bones and periarticular structures (amyloid deposition in bones and periarticular structures (ββ2 2 mikroglobulin) in patients on long-term dialysismikroglobulin) in patients on long-term dialysis

Rickets (growing children) and Rickets (growing children) and osteomalacia (adults)osteomalacia (adults)

defect in matrix mineralisation (in sites of enchondral, defect in matrix mineralisation (in sites of enchondral, endostal and periostal ossification) results in excess of endostal and periostal ossification) results in excess of unmineralized matrixunmineralized matrix

in children: inadequate provisional calcification of epiphyseal in children: inadequate provisional calcification of epiphyseal cartilage, persisted masses of cartilage, osteoid matrix on cartilage, persisted masses of cartilage, osteoid matrix on inadequately mineralized cartilaginous remnants, abnormal inadequately mineralized cartilaginous remnants, abnormal overgrowth of capillaries and fibroblasts in the disorganized overgrowth of capillaries and fibroblasts in the disorganized zones because of microfractures, deformation of skeleton zones because of microfractures, deformation of skeleton (caput quadratum, pigeon breast deformity, rachitic rosary, (caput quadratum, pigeon breast deformity, rachitic rosary, lumbar lordosis, bowing of the legs,…)lumbar lordosis, bowing of the legs,…)

in adults: inadequate mineralization of newly formed osteoid in adults: inadequate mineralization of newly formed osteoid matrix – weak and vulnerable bones (bone trabecules matrix – weak and vulnerable bones (bone trabecules rimmmed by unmineralized osteoid) rimmmed by unmineralized osteoid)

lack of vitamin D or disturbances in metabolism of vit. Dlack of vitamin D or disturbances in metabolism of vit. D vitamin D resistent rickets and osteomalacia vitamin D resistent rickets and osteomalacia

(hypophosphatemic osteomalacia; inhibition of mineralization (hypophosphatemic osteomalacia; inhibition of mineralization by fluor, aluminium, diphosphonates; oncogenic osteomalacia by fluor, aluminium, diphosphonates; oncogenic osteomalacia (small cell carcinoma produces phosphaturic substance) (small cell carcinoma produces phosphaturic substance)

Moller-Barlow disease – Moller-Barlow disease – avitaminosis Cavitaminosis C

vitamin C – hydroxylation of prolin and vitamin C – hydroxylation of prolin and lysin (molecule of procollagen)lysin (molecule of procollagen)

decreased secretion of collagen by decreased secretion of collagen by fibroblasts and osteoblastsfibroblasts and osteoblasts

hemorrhages, subperiostal hematomas, hemorrhages, subperiostal hematomas, bleeding into joint spacesbleeding into joint spaces

decreased production of osteoid and decreased production of osteoid and proliferation of cartilage (mineralization proliferation of cartilage (mineralization normal) – infractions, fractures, lysis normal) – infractions, fractures, lysis epiphyseos, periostitis ossificansepiphyseos, periostitis ossificans

Paget disease (osteitis Paget disease (osteitis deformans)deformans)

1.1. osteolytic stageosteolytic stage2.2. osteoclastic-osteoblastic osteoclastic-osteoblastic

stagestage3.3. osteosclerotic stageosteosclerotic stage

slow virus infection slow virus infection (paramyxovirus) – viral (paramyxovirus) – viral particles seen in osteoclastsparticles seen in osteoclasts

hereditary component hereditary component (linked to locus on 18q)(linked to locus on 18q)

Histology: Histology: mosaic pattern of mosaic pattern of lamelar bonelamelar bone

Macro: Macro: Pagetic bone enlarged Pagetic bone enlarged with thick, coarsened cortices with thick, coarsened cortices and cancellous boneand cancellous bone

Monoostotic – Polyostotic Monoostotic – Polyostotic (15 %)(15 %)

Higher incidence of tumors Higher incidence of tumors and tumor-like lesionsand tumor-like lesions

Osteoporosis – increased porosity Osteoporosis – increased porosity of the skeleton resulting from of the skeleton resulting from

reduced bone massreduced bone mass PrimaryPrimary- postmenopausalpostmenopausal- senilesenile SecondarySecondary1. Endocrinopathies1. Endocrinopathies- hyperparathyreoidismhyperparathyreoidism- hypo-hyperthyreoidismhypo-hyperthyreoidism- hypogonadismhypogonadism- pituitary tumorspituitary tumors- type I diabetes mellitustype I diabetes mellitus- Addison diseaseAddison disease2. Neoplasia2. Neoplasia (multiple myeloma, carcinomatosis) (multiple myeloma, carcinomatosis)3. GIT disorders3. GIT disorders (malnutrition, malabsorption, hepatic insufficiency, vit. C,D (malnutrition, malabsorption, hepatic insufficiency, vit. C,D

deficiencies)deficiencies)4. Rheumatologic diseases4. Rheumatologic diseases5. Drugs5. Drugs (anticoagulans, chemotherapy, corticosteroids, alcohol, (anticoagulans, chemotherapy, corticosteroids, alcohol,

anticonvulsants)anticonvulsants)6. Miscellaneous6. Miscellaneous (osteogenesis imperfecta, immobilisation, pulmonary (osteogenesis imperfecta, immobilisation, pulmonary

diseases, homocystinuria, anemia) diseases, homocystinuria, anemia)

Infections - osteomyelitisInfections - osteomyelitis Pyogenic osteomyelitisPyogenic osteomyelitis- hematogenous spread, extension from a contiguous site, direct hematogenous spread, extension from a contiguous site, direct

implantation, in children epihyseal parts implantation, in children epihyseal parts - Staphylococcus a., E. coli, Pseudomonas, Klebsiella, Haemophilus i., Staphylococcus a., E. coli, Pseudomonas, Klebsiella, Haemophilus i.,

Salmonella,…Salmonella,…- acute, subacute, chronicacute, subacute, chronic- acute inflammatory reaction, subperiostal abscess, necrosis, acute inflammatory reaction, subperiostal abscess, necrosis,

sequestrum, draining sinussequestrum, draining sinus- chronic osteomyelitis: reactive periostitis ossificans, involcurumchronic osteomyelitis: reactive periostitis ossificans, involcurum Tuberculous osteomyelitisTuberculous osteomyelitis- hematogenous spread of BK into bones (rarely direct extension or hematogenous spread of BK into bones (rarely direct extension or

lymphogenous spread)lymphogenous spread)- Pott disease in the spinePott disease in the spine Skeletal syphilisSkeletal syphilis- STD, Treponema pallidumSTD, Treponema pallidum- congenital syphilis (spirochetes localized in areas of active enchondral congenital syphilis (spirochetes localized in areas of active enchondral

ossification (osteochondritis) and in the periosteum (periostitis)ossification (osteochondritis) and in the periosteum (periostitis)- acquired syphilis (tertiary stage; reactive periostitis: nose, palate, acquired syphilis (tertiary stage; reactive periostitis: nose, palate,

skull, extremities – tibia – saber shin)skull, extremities – tibia – saber shin)

Avascular necrosis: Avascular necrosis: osteonecrosisosteonecrosis

Idiopathic (m. Perthes – femur, m. Kohler – os naviculare)Idiopathic (m. Perthes – femur, m. Kohler – os naviculare) Traumatic (mechanical vascular interruption, fracture)Traumatic (mechanical vascular interruption, fracture) CorticosteroidsCorticosteroids InfectionsInfections Dysbarism (nitrogen bubbles) Dysbarism (nitrogen bubbles) Radiation therapy (vessel injury)Radiation therapy (vessel injury) Connective tissue disorders (vasculitis, vessel injury)Connective tissue disorders (vasculitis, vessel injury) Pregnancy Pregnancy Gaucher diseaseGaucher disease Sickle cells and other anemiasSickle cells and other anemias Alcohol abuseAlcohol abuse Chronic pancreatitisChronic pancreatitis TumorsTumors Epiphyseal disordersEpiphyseal disorders

Bone tumors and tumor-Bone tumors and tumor-like lesionslike lesions

Bone-forming tumorsBone-forming tumors Cartilage-forming tumorsCartilage-forming tumors Fibrous and fibro-osseous tumorsFibrous and fibro-osseous tumors Ewing sarcoma and primitive neuroectodermal Ewing sarcoma and primitive neuroectodermal

tumor (PNET)tumor (PNET) Giant cell tumor (osteoclastoma)Giant cell tumor (osteoclastoma) Secondary tumorsSecondary tumors (metastases in adults: prostate, (metastases in adults: prostate,

breast, kidney, lung,….; in children: neuroblastoma, breast, kidney, lung,….; in children: neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma,…)rhabdomyosarcoma,…)

- - metastases: lyticmetastases: lytic – secrets (PG, IL, PTHRP,…) – secrets (PG, IL, PTHRP,…) stimulating ostaeoclastic bone resorption (kidney, stimulating ostaeoclastic bone resorption (kidney, lung, GIT, melanoma,…); lung, GIT, melanoma,…); osteoblasticosteoblastic (prostatic (prostatic cancer); cancer); mixed lytic and osteoblasticmixed lytic and osteoblastic

Bone forming tumors - Bone forming tumors - benignbenign

OsteomaOsteoma- facial and skull bonesfacial and skull bones- solitary or multiple (Gardner syndrome: osteomas, intestinal polyps, solitary or multiple (Gardner syndrome: osteomas, intestinal polyps,

benign STT)benign STT)- bosselated round to oval sessile tumors bosselated round to oval sessile tumors - waven and lamelar bone in a cortical patterns with haverian-like systemwaven and lamelar bone in a cortical patterns with haverian-like system Osteoid osteomaOsteoid osteoma- << 2 cm, painful (excess of PG E 2 cm, painful (excess of PG E22 produced by proliferating osteoblasts) produced by proliferating osteoblasts)- teenagersteenagers- appendicular skeleton (femur, tibia,…), cortexappendicular skeleton (femur, tibia,…), cortex>>medulla; M:F=2:1medulla; M:F=2:1- centrally nidus (trabeculae of woven bone rimmed by osteoblasts); centrally nidus (trabeculae of woven bone rimmed by osteoblasts);

rimmed by reactive sclerotic bonerimmed by reactive sclerotic bone OsteoblastomaOsteoblastoma- >> 2 cm 2 cm- no rim of sclerotic bone no rim of sclerotic bone - locally aggressivelocally aggressive- spine and long bonesspine and long bones- pain no responsive to salicylates pain no responsive to salicylates

Bone forming tumors – Bone forming tumors – malignant malignant

OsteosarcomaOsteosarcoma- malignant mesenchymal tumors with neoplastic cells malignant mesenchymal tumors with neoplastic cells

producing bone matrix producing bone matrix - 75 % in patients under 20 75 % in patients under 20 - in older patients often associated with Paget´s disease, bone in older patients often associated with Paget´s disease, bone

infarcts and prior irradiation (secondary tumors)infarcts and prior irradiation (secondary tumors)- metaphyses of long bones (60 % knee)metaphyses of long bones (60 % knee)- intramedullary, intracortical or surfaceintramedullary, intracortical or surface- abnormalities of RB gene, p16, p53, p21, cyclinD1, mdm2, abnormalities of RB gene, p16, p53, p21, cyclinD1, mdm2,

CDK4,…CDK4,…- osteoblastic, chondroblastic, fibroblastic, teleangiectatic, osteoblastic, chondroblastic, fibroblastic, teleangiectatic,

small cell, giant cellsmall cell, giant cell- clinically painful, enlarging masss, pathologic fractureclinically painful, enlarging masss, pathologic fracture- destruction of cortex, soft tissue masses, periostal bone destruction of cortex, soft tissue masses, periostal bone

formation (Codman triangle)formation (Codman triangle)- hematogeneous spreading (metastases in lungs, bones, brain,hematogeneous spreading (metastases in lungs, bones, brain,

…) …)

OsteosarcomaOsteosarcoma

Cartilage-forming Cartilage-forming tumorstumors

Osteochondroma (exostosis osteocartilaginea)Osteochondroma (exostosis osteocartilaginea)- metaphysis of long bones (knee) near the growth platemetaphysis of long bones (knee) near the growth plate- solitary or multiple (hereditary exostosis-AD)solitary or multiple (hereditary exostosis-AD)- mushroom shaped covered by benign hyaline cartilage and mushroom shaped covered by benign hyaline cartilage and

perichondrium, 1-20 cm, growth based on enchondral ossificationperichondrium, 1-20 cm, growth based on enchondral ossification- rarely giving rise to chondrosarcoma rarely giving rise to chondrosarcoma

ChondromaChondroma- enchondroma (within medullar cavity) or juxtacortical enchondroma (within medullar cavity) or juxtacortical

chondromas chondromas (subperiostal)(subperiostal)- Ollier disease - multiple enchondromas with a risk of Ollier disease - multiple enchondromas with a risk of

malignizationmalignization- Maffucci syndrome – multiple enchondromas with a risk of Maffucci syndrome – multiple enchondromas with a risk of

malignization + soft tissue hemangiomasmalignization + soft tissue hemangiomas- Nodules of hyaline cartilage surrounded by a thin layer of Nodules of hyaline cartilage surrounded by a thin layer of

reactive bonereactive bone

ChondroblastomaChondroblastoma- young patients, teens, M:F=2:1young patients, teens, M:F=2:1- epiphyses (knee), pelvis, ribsepiphyses (knee), pelvis, ribs- sheets of compact polygonal chondroblast, hyaline matrix (if sheets of compact polygonal chondroblast, hyaline matrix (if

calcified – chicken-wire pattern of hyalinization) , nodules of hyaline calcified – chicken-wire pattern of hyalinization) , nodules of hyaline cartilage, osteoclast-type giant cells, hemorrhagic cystic cartilage, osteoclast-type giant cells, hemorrhagic cystic degeneration degeneration

Chondromyxoid fibromaChondromyxoid fibroma- teens and twenties, Mteens and twenties, M>>FF- metaphysis of long tubular bones, 3-8 cm, lobular, chondromyxoid metaphysis of long tubular bones, 3-8 cm, lobular, chondromyxoid

tissue with spindle or stellate cells; more cellular at the periphery tissue with spindle or stellate cells; more cellular at the periphery of lobules, often with osteoclast-type cellsof lobules, often with osteoclast-type cells

ChondrosarcomaChondrosarcoma- patients more than 20, usually more than 40patients more than 20, usually more than 40- pelvis, shoulder, ribspelvis, shoulder, ribs- de novo or malignization of enchondromas, osteochondromas, de novo or malignization of enchondromas, osteochondromas,

chondroblastomas, fibrous dysplasia, or setting in Paget´s diseasechondroblastomas, fibrous dysplasia, or setting in Paget´s disease- painful, progressively enlarging mass, thickening of the cortex, painful, progressively enlarging mass, thickening of the cortex,

destruction of the cortex and soft tissue mass; metastatic spread destruction of the cortex and soft tissue mass; metastatic spread into lungs and skeleton (often late metastatic spread) into lungs and skeleton (often late metastatic spread)

- malignant hyaline and myxoid cartilage, nodular arrangement; malignant hyaline and myxoid cartilage, nodular arrangement; variants: juxtacortical, dedifferentiated, clear cellvariants: juxtacortical, dedifferentiated, clear cell

Chondrosarcoma and Chondrosarcoma and chondromachondroma

Fibrous and fibro-Fibrous and fibro-osseous tumorsosseous tumors

Fibrous cortical defect and non-ossifying fibroma (metaphysal fibrous defect)Fibrous cortical defect and non-ossifying fibroma (metaphysal fibrous defect)- distal femur and proximal tibia, also bilateral and multipledistal femur and proximal tibia, also bilateral and multiple- lytic lesionslytic lesions- self-limited FCD; progressively growing NOFself-limited FCD; progressively growing NOF- proliferation of fibroblasts (often storiform pattern), histiocytes proliferation of fibroblasts (often storiform pattern), histiocytes

(multinucleated giant cells, clusters of foamy macrophages) (multinucleated giant cells, clusters of foamy macrophages) Fibrous dysplasiaFibrous dysplasia- monoostotic, polyostotic, McCune-Albright syndrome (polyostotic FD, café au monoostotic, polyostotic, McCune-Albright syndrome (polyostotic FD, café au

lait sin pigmentation, endocrinopathies)lait sin pigmentation, endocrinopathies)- circumscribed, intramedullarycircumscribed, intramedullary- curvilinear trabeculae of woven bone and moderately cellular fibroblastic curvilinear trabeculae of woven bone and moderately cellular fibroblastic

proliferation, sometimes nodules of hyaline cartilage; cystic degeneration, proliferation, sometimes nodules of hyaline cartilage; cystic degeneration, hemorrhages, foamy macrophageshemorrhages, foamy macrophages

FibrosarcomaFibrosarcoma- older people, long bonesolder people, long bones- malignant fibroblast in a herringbone patternmalignant fibroblast in a herringbone pattern Malignant fibrous histiocytomaMalignant fibrous histiocytoma - older patients, long bonesolder patients, long bones- spindle fibroblasts, storiform pattern admixed with bizarre, large, spindle fibroblasts, storiform pattern admixed with bizarre, large,

multinucleated tumor giant cells multinucleated tumor giant cells

Miscellaneous tumorsMiscellaneous tumors Ewing sarcoma and primitive neuroectodermal tumor (PNET)Ewing sarcoma and primitive neuroectodermal tumor (PNET)- small round cell tumors of the bones and soft tissues small round cell tumors of the bones and soft tissues - 6-10 % of primary bone tumors6-10 % of primary bone tumors- 80 % patients under 20, M80 % patients under 20, M>>FF- translocations (t(11;22), t(7;22), t(21;22)); fusion of EWS gene with a member of translocations (t(11;22), t(7;22), t(21;22)); fusion of EWS gene with a member of

ETS family of transcription factor; result in chimeric protein which acts as a ETS family of transcription factor; result in chimeric protein which acts as a constitutively active transcription factor stimulating cell proliferationconstitutively active transcription factor stimulating cell proliferation

- diaphyses of long tubulary bones and pelvis; arising in medullary cavity invading diaphyses of long tubulary bones and pelvis; arising in medullary cavity invading the cortex, periostium and soft tissues the cortex, periostium and soft tissues

- lytic lesion, periostal reaction – reactive bone in an onion-like fashionlytic lesion, periostal reaction – reactive bone in an onion-like fashion- neural differentiation, Homer-Wright rosettes neural differentiation, Homer-Wright rosettes

Giant cell tumor (osteoclastoma)Giant cell tumor (osteoclastoma)- locally agressive, osteolytic, large, red brown, often cystically degenerated; high locally agressive, osteolytic, large, red brown, often cystically degenerated; high

recurrence rate, potentially malignant (5 %)recurrence rate, potentially malignant (5 %)- proliferating mononuclear cells, osteoclast-type giant cells, necrosis, hemorrhage, proliferating mononuclear cells, osteoclast-type giant cells, necrosis, hemorrhage,

hemosiderin deposits, reactive bone formationhemosiderin deposits, reactive bone formation- epiphyses of long bonesepiphyses of long bones- between 20 and 40between 20 and 40- differential diagnosis: brown tumor in hyperparathyreoidism, giant cell reparative differential diagnosis: brown tumor in hyperparathyreoidism, giant cell reparative

granuloma, pigmented villonodular synovitis, chondroblastomagranuloma, pigmented villonodular synovitis, chondroblastoma

Giant cell tumor - Giant cell tumor - osteoclastomaosteoclastoma

Pathology of the Pathology of the JointsJoints

Osteoarthritis (degenerative joint Osteoarthritis (degenerative joint disease)disease)

non-inflammatory degenerative disease; progressive non-inflammatory degenerative disease; progressive erosion of cartilage; secondary changes: erosion of cartilage; secondary changes: inflammatory and reactive changes in synovial inflammatory and reactive changes in synovial membranes and the adjacent bonesmembranes and the adjacent bones

aging and mechanical defects, genetic factorsaging and mechanical defects, genetic factors deep achy pain, morning stiffness, crepitus and deep achy pain, morning stiffness, crepitus and

limitation of range of movement limitation of range of movement proliferation of chondrocytes, biochemical changes of proliferation of chondrocytes, biochemical changes of

matrix, vertical and horizontal fibrillation and matrix, vertical and horizontal fibrillation and cracking of the matrix, degradation of superficial cracking of the matrix, degradation of superficial layers of cartilage, bone eburnation, sclerosis of layers of cartilage, bone eburnation, sclerosis of underlying bone, formation of loose bodies, synovial underlying bone, formation of loose bodies, synovial fluid in subchondral regions – pseudocysts, fluid in subchondral regions – pseudocysts, osteophytes at the margins of the articular surfaceosteophytes at the margins of the articular surface

Rheumatoid arthritisRheumatoid arthritis a chronic systemic inflammatory disorder affecting also a chronic systemic inflammatory disorder affecting also

jointsjoints a nonsuppurative proliferative, inflammatory synovitis a nonsuppurative proliferative, inflammatory synovitis

that often progresses to destruction of the articular that often progresses to destruction of the articular cartilage and ankylosis of the jointscartilage and ankylosis of the joints

autoimmune disease triggered by exposure of a autoimmune disease triggered by exposure of a genetically susceptible host to an unknown artritogenic genetically susceptible host to an unknown artritogenic antigen; 95 % RA patients – positive RF (IgM against antigen; 95 % RA patients – positive RF (IgM against Fc fragment of IgG – immunocomplexes); FFc fragment of IgG – immunocomplexes); F>>MM

small bones of the hands, wrist, ankels, elbows, knees, small bones of the hands, wrist, ankels, elbows, knees, cervical spine, hips, lumbosacral region spared cervical spine, hips, lumbosacral region spared

juvenile rheumatoid arthritis: typical form includes juvenile rheumatoid arthritis: typical form includes oligoarthritis, systemic involvement, large joints oligoarthritis, systemic involvement, large joints affected, RF absent, ANA+ affected, RF absent, ANA+

Immune reaction and morphology Immune reaction and morphology of RAof RA

Seronegative Seronegative spondylarthropathiesspondylarthropathies

genetical predisposition (HLA-B27), enviromental factors (exposition genetical predisposition (HLA-B27), enviromental factors (exposition to infections, Ag unknown,…)to infections, Ag unknown,…)

peripheral or axial (sacroilialcal) arthritis and inflammation of peripheral or axial (sacroilialcal) arthritis and inflammation of tendinous attachmentstendinous attachments

ankylosing spondyloarthritisankylosing spondyloarthritis- - MM>>F (3:1); axial, sacroiliacal joints; 90 % HLA-B27+; chronic F (3:1); axial, sacroiliacal joints; 90 % HLA-B27+; chronic

synovitis, destruction of cartilage, bony ankylosis (sacroiliac and synovitis, destruction of cartilage, bony ankylosis (sacroiliac and apohyseal joints), ossification of tendinoligamentous insertion; apohyseal joints), ossification of tendinoligamentous insertion; uveitis, aortitis, amyloidosis,…uveitis, aortitis, amyloidosis,…

reactive arthritisreactive arthritis- infections of genitourinary (Chlamydia) and GIT (Shigella, infections of genitourinary (Chlamydia) and GIT (Shigella,

Salmonella, Yersinia, Campylobacter)Salmonella, Yersinia, Campylobacter)- Reiter syndrome: arthritis + nongonococcal urethritis or cervicitis + Reiter syndrome: arthritis + nongonococcal urethritis or cervicitis +

uveitisuveitis- 80 % HLA-B27+; autoimmune reaction initiated by prior infection80 % HLA-B27+; autoimmune reaction initiated by prior infection psoriatic arthritispsoriatic arthritis others others (e.g. UC, MC or CS complicated by arthritis) (e.g. UC, MC or CS complicated by arthritis)

Infectious arthritisInfectious arthritis suppurative arthritissuppurative arthritis tbc arthritistbc arthritis- - complication of tbc osteomyelitis or hematogenous complication of tbc osteomyelitis or hematogenous

dissemination from a visceral site of infection dissemination from a visceral site of infection Lyme arthritisLyme arthritis- Borrelia burgdorferi (transmitted by ticks)- Borrelia burgdorferi (transmitted by ticks) viral arthritisviral arthritis- parvovirus B19, rubella, HCVparvovirus B19, rubella, HCV

Rheumatic arthritis – rheumatic feverRheumatic arthritis – rheumatic fever: an acute : an acute immunologically mediated multisystem immunologically mediated multisystem inflammatory disease occuring a few weeks after an inflammatory disease occuring a few weeks after an episode of group A streptococcal pharyngitis episode of group A streptococcal pharyngitis (migratory polyarthritis of large joints) (migratory polyarthritis of large joints)

Gout arthritis (arthritis Gout arthritis (arthritis uratica)uratica)

both endogenous (monosodium urate-gout, both endogenous (monosodium urate-gout, hydroxyapatit, calciumpyrophosphatase hydroxyapatit, calciumpyrophosphatase dihydrate,..)or exogenous crystals dihydrate,..)or exogenous crystals (corticosteroid crystal esters, talcum,…) may (corticosteroid crystal esters, talcum,…) may induce joint diseaseinduce joint disease

gout: hyperuricamia (overproduction of uric gout: hyperuricamia (overproduction of uric acid, increased nucleic acid turnover or inborn acid, increased nucleic acid turnover or inborn errors of metabolism: X-linked Lesch-Nyhan errors of metabolism: X-linked Lesch-Nyhan sydnrome), crystallization of urates within sydnrome), crystallization of urates within joints, acute arthritis, chronic gouty arthritis – joints, acute arthritis, chronic gouty arthritis – tophi; matatarsophalangeal joints, sometimes tophi; matatarsophalangeal joints, sometimes gouty nephropathygouty nephropathy

Gout: age, genetic predisposition, alcohol, Gout: age, genetic predisposition, alcohol, obesity, some drughs,….obesity, some drughs,….

Tumor-like lesions of the Tumor-like lesions of the jointsjoints

GanglionGanglion- near a joint capsule, wrist, pea-sized nodulenear a joint capsule, wrist, pea-sized nodule- result of cystic and myxoid degeneration of result of cystic and myxoid degeneration of

connective tisuueconnective tisuue Synovial cystsSynovial cysts- herniation of synovium or enlargement of a herniation of synovium or enlargement of a

bursabursa- poplitesal space – Baker cystpoplitesal space – Baker cyst Osteochondral loose bodiesOsteochondral loose bodies- in degenerative joint diseasein degenerative joint disease

Tumors of the jointsTumors of the joints Pigmented villonodular synovitisPigmented villonodular synovitis- benign neoplasmbenign neoplasm- one or more joints, diffusely involved (knee)one or more joints, diffusely involved (knee)- red brown folds, finger-like projections, nodules, synovialocytes, red brown folds, finger-like projections, nodules, synovialocytes,

hemosiderin deposits, foamy macrophages, multinucleated gint hemosiderin deposits, foamy macrophages, multinucleated gint cells, zones of sclerosis; erosion of the bonecells, zones of sclerosis; erosion of the bone

Giant cell tumor of tendom sheatGiant cell tumor of tendom sheat- - localised nodular tendosynovitis, disrete nodule on a tendon localised nodular tendosynovitis, disrete nodule on a tendon

sheathsheath Synovial chondromatosisSynovial chondromatosis- - multiple intrasynovial chondromas or ossifying chondromasmultiple intrasynovial chondromas or ossifying chondromas

Synovial sarcoma Synovial sarcoma - soft tissue tumorsoft tissue tumor- dual line of differentiation (epithelial-like and spindle cells); rarely dual line of differentiation (epithelial-like and spindle cells); rarely

monophasic monophasic - t(X;18)t(X;18)- metastases into lungsmetastases into lungs