BONE JOINT SOFT TISSUE

Transcription

1 BONE JOINT SOFT TISSUE

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3 Modeling/RE-modeling

4 CELLS of BONE OSTEOPROGENITOR ( STEM ) (TGFβ) OSTEOBLASTS (surface of spicule), under control of calcitonin to take blood calcium and put it into bone. OSTEOCYTES (are osteoblasts which are now completely surrounded by bone) OSTEOCLASTS (macrophage lineage), under control of PTH to chew up the calcium of bone and put it into blood

5 Proteins (organic) of BONE Type 1 collagen (90%) Cell adhesion proteins Calcium-binding proteins Proteins involved in mineralization Enzymes Growth factors GF-1, TGF-β, PDGF Cytokines Prostaglandins, IL-1, IL-6, RANKL Proteins Concentrated from Serum β2 microglobulin Albumin IGF, insulin-like growth factor TGF, transforming growth factor PDGF, platelet-derived growth factor IL, interleukin RANKL, RANK ligand

6 Minerals (IN-organic) of BONE HYDROXY-APATITE Ca5(PO4)3(OH) Ca10(PO4)6(OH)2

7 ADJECTIVES of BONE Compact Dense Cortical Spongy Cancellous Membranous Endosteal Woven Lamellar Spicular

8 Woven vs. Lamellar

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10 -BLASTS/-CLASTS Ca++ PTH Ca++ Calciton.

11 BONE DISEASES 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS IN NUCLEAR PROTEINS AND TRANSCRIPTION FACTORS, polydactyly, syndactyly, absence of a bone 2) DISEASES CAUSED BY DEFECTS IN HORMONES AND SIGNAL TRANSDUCTION MECHANISMS, achondroplasia, thanatophoria 3) DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL PROTEINS Type 1 Collagen Diseases (Osteogenesis Imperfecta) Types 2, 10, and 11 Collagen Diseases 4) DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF MACROMOLECULES Mucopolysaccharidoses 5) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATHWAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS) Osteopetrosis 6) DISEASES ASSOCIATED WITH DECREASED BONE MASS Osteoporosis 7) DISEASES CAUSED BY OSTEOCLAST DYSFUNCTION Paget Disease (Osteitis Deformans) 8) DISEASES ASSOCIATED WITH ABNORMAL MINERAL HOMEOSTASIS Ricketts and Osteomalacia Hyperparathyroidism Renal Osteodystrophy

12 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS IN NUCLEAR PROTEINS AND TRANSCRIPTION FACTORS Congenital absence of a, usually single, bone: phalanx, rib, clavicle Supernumerary digit (polydactyly) Syndactyly CRANIORACHISCHISIS

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14 2) DISEASES CAUSED BY DEFECTS IN HORMONES AND SIGNAL TRANSDUCTION MECHANISMS Achondroplasia, dwarf (non-lethal) Thanatophoria, dwarf (lethal, FGF-3 mutations) a point mutation (usually Arg for Gly375) in the gene that codes for FGF receptor 3 (FGFR3), which is located on the short arm of chromosome 4. In the normal growth plate, activation of FGFR3 inhibits cartilage proliferation; A MUTATION causes FGFR3 to be constantly activated.

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16 3) DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL PROTEINS OSTEOGENESS IMPERFECTA TYPES ( Brittle bone disease, too LITTLE bone), BLUE sclerae Mutations in genes which code for the alpha-1 and alpha-2 chains of COLLAGEN 1 Mutations of COLLAGEN 2,10, 11 manifest themselves as CARTILAGE diseases, ranging from joint cartilage destruction to fatal

17 Osteogenesis Imperfecta

18 4) DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF MACROMOLECULES (glycosaminoglycans) MUCOPOLYSACCHARIDOSIS (one of MANY lysosome storage diseases) DECREASES in ENZYMES which degrade: DERMATAN HEPARAN KERATAN Chiefly CARTILAGE disorders: short, chest wall, malformed bones

19 MUCOPOLYSACCHARIDOSES

20 5) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATHWAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS) OSTEOPETROSIS, 4 types One common one has a CARBONIC ANHYDRASE deficiency DECREASED osteoclast resorption MARBLE bone, brittle, sclerosis

21 OSTEOPETROSIS

22 6) DISEASES ASSOCIATED WITH DECREASED BONE MASS OSTEOPOROSIS PEAK bone mass is early adulthood Normal decline, slow Osteoporosis is accelerated bone loss Factors: AGE Physical activity Estrogen withdrawal (menopause) Nutrition (Ca++) Genetics

23 Primary Postmenopausal Senile Secondary Endocrine disorders Categories of Generalized Osteoporosis Idiopathic Rheumatologic disease Hyperparathyroidism Drugs Hypo-hyperthyroidism Anticoagulants Hypogonadism Chemotherapy Pituitary tumors Corticosteroids Diabetes, type 1 Anticonvulsants Addison disease Alcohol Neoplasia Multiple myeloma Carcinomatosis Gastrointestinal Malnutrition, Malbs., Hepatic Insuf., Vit C,D Miscellaneous Osteogenesis imperfecta Immobilization Pulmonary disease Homocystinuria Anemia

24 OSTEOPOROSIS

25 7) DISEASES CAUSED BY OSTEOCLAST DYSFUNCTION Paget Disease (Osteitis Deformans) Matrix madness, Osteoblasts/-cytes gone wild THREE PHASES: 1) Increased osteoclast resorption 2) Increased hectic bone formation (osteoblasts) 3) Osteosclerosis ELEVATED ALKALINE-PHOSPHATASE ELEVATED urine HYDROXYPROLINE

26 PAGET s DISEASE (of BONE) 85% MONOSTOTIC, WHOLE BONE 15% POLY-OSTOTIC (skull, pelvis) JIGSAW, NOT LAMINAR, BONE CLINICAL: PAIN!!! (MICROFRACTURES)

27 PAGET s DISEASE

28 8) DISEASES ASSOCIATED WITH ABNORMAL MINERAL HOMEOSTASIS Ricketts and Osteo malacia VITAMIN D deficiency/dysfunction Hyperparathyroidism, PRIMARY (PTH ADENOMA) ENTIRE SKELETON OSTEITIS FIBROSIS CYSTICA (von Recklinghausen s disease (of bone) BROWN TUMOR Hyperparathyroidism, SECONDARY (RENAL) (NOT AS SEVERE AS 1º) Renal Osteodystrophy = ANY bone disorder due to chronic renal disease

29 PRIMARY HYPERPARATHYROIDISM OSTEITIS FIBROSA CYSTICA BROWN TUMOR

30 RENAL OSTEODYSTROPHY PHOSPHATE RETENTION HYPOPHOSPHATEMIA HYPOCALCEMIA INCREASED PTH INCREASED OSTEOCLASTS METABOLIC ACIDOSIS release of HYDROXYAPATITES from matrix

31 FRACTURES

32 FRACTURES, adjectives Complete, incomplete Closed, open (communicating) Communited (splintered, greenstick ) Displaced (NON-aligned) PATHOGENIC, (non-traumatic, 2º to other disease, often metastases) STRESS fracture

33 FRACTURES THREE PHASES HEMATOMA, minutes days PGDF, TGF-β, FGF SOFT CALLUS ( PRO -CALLUS), ~1 week HARD CALLUS (BONY CALLUS), several weeks COMPLICATIONS PSEUDARTHROSIS INFECTION (especially OPEN [communicating] fractures)

34 FRACTURES

35 OSTEONECROSIS Also called AVASCULAR necrosis Also called ASEPTIC necrosis CAUSE: ISCHEMIA Trauma Steroids Thrombus/Embolism Vessel injury, e.g., radiation INCREASED intra-osseous pressure vascular compression Venous hypertension too

36 OSTEONECROSIS Disorders Associated with Osteonecrosis Idiopathic Trauma Corticosteroid administration Infection Dysbarism Radiation therapy Connective tissue disorders Pregnancy Gaucher disease Sickle cell and other anemias Alcohol abuse Chronic pancreatitis Tumors Epiphyseal disorders

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38 OSTEONECROSIS

39 OSTEOMYELITIS Pyogenic: Staph, E. coli, Pseudom, Kleb Hematogenous Contiguous Direct implantation TB Syphilis

40 OSTEOMYELITIS DX: X-ray, Bone scan

41 OSTEOMYELITIS DX: Histology

42 OSTEOMYELITIS COMPLICATIONS Subperiosteal abscess Draining sinus Joint involvement SEQUESTRUM (dead bone) vs. INVOLUCRUM (new bone)

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44 OSTEOMYELITIS Tuberculous Usually blood borne TB of spine is known as POTTS disease Syphilis CONGENITAL TERTIARY, SABRE shins

45 POTT s DISEASE

46 SABER SHINS

47 Classification of Primary Tumors Involving Bones Histologic Type Benign Malignant Hematopoietic (40%) Myeloma Malignant lymphoma Chondrogenic (22%) Osteochondroma Chondrosarcoma Chondroma Chondroblastoma Dedifferentiated chondrosarcoma Mesenchymal chondrosarcoma Chondromyxoid fibroma Osteogenic (19%) Osteoid osteoma Osteosarcoma Osteoblastoma Unknown origin (10%) Giant cell tumor tumor Giant cell tumor Adamantinoma Histiocytic origin Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Metaphyseal fibrous defect (fibroma) Desmoplastic fibroma Fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma Hemangiopericytoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma

48 BONE TUMORS BONE CARTILAGE FIBROUS MISC. Ewing s sarcoma Giant Cell Tumor METASTASES

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50 BONE- BONE TUMORS OSTEOMA OSTEOID OSTEOMA OSTEOBLASTOMA OSTEOSARCOMA (OSTEOGENIC SARCOMA)

51 SOLITARY MIDDLE AGE OSTEOMA FROM SUBPERIOSTEAL or ENDOSTEAL surfaces SKULL, FACE, most common Totally BENIGN To be distinguished from REACTIVE BONE, (can be difficult)

52 FRONTAL SINUS Why am I not showing you HISTOLOGY?

53 Induces a MARKED bony reaction OSTEOID OSTEOMA At least 2 cm in diameter Teens, twenties, APPENDICULAR skeleton M>>F PAINFUL NIDUS Has a Responds to aspirin

54 NIDUS

55 OSTEOBLASTOMA AXIAL SKELETON, i.e., SPINE NO Nidus NO bony reaction NOT relieved by aspirin

56 OSTEOSARCOMA (OSTEOGENIC SARCOMA) LATE TEENS KNEES METAPHYSES PAINFUL!!!

57 TYPES of OSTEOSARCOMAS The anatomic portion of the bone from which they arise (intramedullary, intracortical, or surface) Degree of differentiation Multicentricity (synchronous, metachronous[not synchronous]) Primary (underlying bone is unremarkable) or secondary (e.g., osteosarcoma associated with pre-existing disorders such as benign tumors, Paget disease, bone infarcts, previous irradiation) Histologic variants (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, and giant cell)

58 The most common subtype is osteosarcoma that arises in the metaphysis of long bones; is primary, solitary, intramedullary, and poorly differentiated; and produces a predominantly bony matrix

59 BONE- CARTILAGE TUMORS OSTEOCHONDROMA (EXOSTOSIS) CHONDROMA CHONDROBLASTOMA CHONDROMYXOID FIBROMA CHONDROSARCOMA

60 OSTEOCHONDROMA (EXOSTOSIS) Common, Cartilage AND Bone present Often MULTIPLE as a hereditary syndrome M>>>F PELVIS, SCAPULAE, RIBS

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62 CHONDROMA Chondroma vs. EN-chondroma PURE Hyaline Cartilage MULTIPLE enchondromas = Ollier s dis. Maffucci synd. if hemangiomas present

63 CHONDROBLASTOMA RARE, in teenagers M>>F KNEES, usually Epiphyses MUCH LESS matrix than a chondroma

64 CHONDROMYXOID FIBROMA RAREST of all TEENS, MALES MYXOID concept ATYPIA

65 CHONDROSARCOMA ANATOMY INTRAMEDULLARY JUXTACORTICAL HISTOLOGY CONVENTIONAL HYALINE MYXOID CLEAR DE-DIFFERENTIATED MESENCHYMAL

66 CHONDROSARCOMA

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68 BONE- FIBROUS TUMORS FIBROUS CORTICAL DEFECT/NON- OSSIFYING FIBROMA FIBROUS DYSPLASIA FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA

69 FIBROUS CORTICAL DEFECT COMMON, usually LESS THAN 1 CM CHILDREN >2 IF MORE THAN 5-6 CM, they are then called NON- OSSIFYING FIBROMA

70 FIBROUS DYSPLASIA BENIGN TUMOR THREE TYPES SINGLE BONE (70%) POLY-OSTOTIC (27%) POLY-OSTOTIC (3%) with café-au-lait and endocrine disorders, especially precocious puberty

71 1) CURVED spicules 2) LACK of osteoblastic rimming

72 FIBROSARCOMA/MFH METAPHYSES of LONG BONES PELVIC FLAT BONES LYTIC FRACTURES OF COURSE, SARCOMATOUS METASTASIS

73 FIBROSARCOMA/MFH

74 MISC. TUMORS of BONE EWING sarcoma/pnet (Primitive NeuroEctodermal Tumor) GIANT CELL TUMOR METASTASES

75 EWING/PNET SAME TUMOR SMALL ROUND NEUROENDOCRINE IDENTICAL CHROMOSOME TRANSLOCATION SECOND most COMMON bone malignancy in CHILDREN ARISE IN MEDULLARY CAVITY of BONE LOOK LIKE LYMPHOMA

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77 GCT (Giant Cell Tumor), BONE

78 METASTASES MALE: PROSTATE FEMALE: BREAST RENAL, THYROID also seek bone early also LYTIC? BLASTIC?

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83 SYNOVIAL JOINTS

84 JOINT DISEASES ARTHRITIS DEGENERATIVE (OSTEOARTHRITIS) RHEUMATOID JUVENILE RHEUMATOID NON-INFECTIOUS: Ankylosing Spond., Reactive, Psoriasis, IBD INFECTIOUS: Supp., TB, Lyme, Viral GOUT (URATE) PSEUDOGOUT (PYROPHOSPHATE) Tumors Ganglion (Synovial Cyst) Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS]) Synovial Sarcoma

85 DEGENERATIVE ARTHRITIS aka, OSTEO ARTHRITIS Etiology/Risk Factors: Age, Trauma, Genes Pathogenesis: Progressive EROSION of articular cartilage Morphology: X-Ray, eburnation, joint mice, osteophytes Clinical Expression: PAIN, Limitation of motion

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88 HEBERDEN S NODES DIP, NOT MP or PIP

89 RHEUMATOID ARTHRITIS Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs skin, blood vessels, heart, lungs, and muscles but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints.

90 TWO KINDS of cells form the synovial intima 1) fibroblasts Hyaluronin Lubricin 2) macrophages The SUB-intima is loose CT or fat

91 RHEUMATOID ARTHRITIS Etiology/Risk Factors: Autoimmune Pathogenesis: Progressive SYNOVITIS Morphology: Synovial lymphocytes, macrophages, plasma cells, neutrophils, osteoclasts, pannus, hyperemia, rheumatoid nodules, vasculitis Clinical Expression: PAIN, Limitation of motion, malaise, fatigue, rheumatoid factor IgM-IgGFc,

92 HANDS WRIST ELBOWS The rheumatoid nodule shows palisading fibroblasts

93 DIAGNOSIS CLINICAL FEATURES (1% of population F>>M) MORNING STIFFNESS, MEAN AGE 45 YRS ARTHRITIS in MORE THAN 3 JOINT AREAS TYPICAL hand findings, MP ULNAR deviation SYMMETRIC ARTHRITIS SERUM RHEUMATOID FACTOR TYPICAL X-RAY findings

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95 JUVENILE Rheumatoid Arthritis Begins BEFORE age 16, by definition Generally LARGER joints than RA Often POSITIVE ANA

96 SERONEGATIVE ARTHRITIDES ANKYLOSING SPONDYLITIS (aka, rheumatoid spondylitis, or Marie- Strumpell Disease [HLA-B27] (M>>F) REACTIVE ARTHRITIS (FOLLOWS GU or GI INFECTIONS) REITER SYDROME (urethral & conjunctival inflammation too) [HLA-B27] Arthritis associated with IBD PSORIATIC ARTHRITIS [HLA-B27]

97 Ankylosing Spondylitis

98 INFECTIOUS ARTHRITIS From OSTEOMYELITIS USUALLY SUPPURATIVE GC, staph, strep, H. flu, E. coli, (Salmonella in sicklers) 4 cardinal signs, fever, leukocytosis, ESR

99 INFECTIOUS ARTHRITIS TB LYME Disease, i.e., Borrelia burgdorferi VIRAL Parvovirus B19 Rubella Hepatitis C

100 GOUT Endpoint of HYPERURICEMIA from ANY cause resulting in JOINT deposition of monosodium urate crystals (TOPHI) ACUTE CHRONIC 10% of population has hyperuricemia (>7 mg/dl), but only 1/20 of these has gout

101 Clinical Category Primary Gout (90% of cases) Enzyme defects unknown (85% 90% of primary gout) Known enzyme defects e.g., partial HGPRT deficiency (rare) Secondary Gout (10% of cases) Associated with increased nucleic acid turnover e.g., leukemias Chronic renal disease Inborn errors of metabolism e.g., complete HGPRT deficiency (Lesch- Nyhan syndrome) Classification of Gout Metabolic Defect Overproduction of uric acid Normal excretion (majority) Increased excretion (minority) Underexcretion of uric acid with normal production Overproduction of uric acid HGPRT, hypoxanthine guanine phosphoribosyl transferase. Overproduction of uric acid with increased urinary excretion Reduced excretion of uric acid with normal production Overproduction of uric acid with increased urinary excretion

102 HYPERURICEMIA GOUT Age of the individual and duration of the hyperuricemia are factors. Gout rarely appears before 20 to 30 years of hyperuricemia. Genetic predisposition is another factor. In addition to the well-defined X-linked abnormalities of HGPRT, primary gout follows multifactorial inheritance and runs in families. Heavy alcohol consumption predisposes to attacks of gouty arthritis. Obesity increases the risk of asymptomatic gout. Certain drugs (e.g., thiazides) predispose to the development of gout. Lead toxicity increases the tendency to develop saturnine gout

103 FEATURES TOPHACEOUS ARTHRITIS GOUTY NEPHROPATHY

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107 GOUTY NEPHROPATHY

108 GOUT Associated with ATHEROSCLEROSIS Associated with HYPERTENSION

109 Pseudo-GOUT Gout: Monosodium Urate Pseudo-GOUT: Calcium Pyrophosphate PSEUDOGOUT is also called CHONDROCALCINOSIS, or CPPD (Calcium Phosphate Deposition Disease) IDIOPATHIC, HEREDITARY, SECONDARY Secondary joint damage, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, ochronosis, and diabetes

110 GOUT vs. PSEUDOGOUT

111 JOINT TUMORS BENIGN GANGLION (SYNOVIAL CYST) GIANT CELL TUMOR of TENDON SHEATH, aka PVNS, Pigmented VilloNodular Synovitis MALIGNANT SYNOVIAL SARCOMA

112 GANGLION

113 PVNS/GCT

114 SOFT TISSUE TUMORS FAT FIBROUS TISSUE FIBROHISTIOCYTIC SKELETAL MUSCLE SMOOTH MUSCLE VASCULAR PERIPHERAL NERVE UNCERTAIN: SYNOVIAL SARCOMA, ALVEOLAR SOFT PART SARCOMA, EPITHELIOD SARCOMA

115 CAUSES MOSTLY UNKNOWN RADIATION association CHEMICAL BURN association THERMAL BURN association TRAUMA association VIRUS association (HHV8 for Kaposi) GENETICS Parts of many SYNDROMES MANY TRANSLOCATIONS

116 Chromosomal and Genetic Abnormalities in Soft Tissue Sarcomas Tumor Cytogenetic Abnormality Genetic Abnormality Extraosseous Ewing sarcoma and primitive neuroectodermal tumor Liposarcoma myxoid and round cell type t(11:22)(q24;q12) t(21:22)(q22;q12) t(7;22)(q22;q12) t(12:16)(q13;p11) FLI-1-EWS fusion gene ERG-EWS fusion gene ETV1-EWS fusion gene CHOP/TLS fusion gene Synovial sarcoma t(x;18)(p11;q11) SYT-SSX fusion gene Rhabdomyosarcoma alveolar type t(2;13)(q35;q14) PAX3-FKHR fusion gene t(1;13)(p36;q14) PAX7-FKHR fusion gene Extraskeletal myxoid chondrosarcoma t(9;22)(q22;q12) CHN-EWS fusion gene Desmoplastic small round cell tumor t(11;22)(p13;q12) EWS-WT1 fusion gene Clear cell sarcoma t(12;22)(q13;q12) EWS-ATF1 fusion gene Dermatofibrosarcoma protuberans t(17:22)(q22;q15) COLA1-PDGFB fusion gene Alveolar soft part sarcoma t(x;17)(p11.2;q25) TFE3-ASPL fusion gene Congenital fibrosarcoma t(12;15)(p13;q23) ETV6-NTRK3 fusion gene

117 SOFT TISSUE TUMORS ALL SPINDLY Deep (desmoid) vs. Superficial Importance of counting MITOSES Importance of STAGING Importance of IMMUNOPEROXIDASE Importance of CONSULTATION

118 LIPOMA LIPOSARCOMA FAT NORMAL FAT LIPOMA, encapsulated LIPOSARCOMA, often retroperitoneal

119 FIBROUS TISSUE NODULAR FASCIITIS (pseudosarcomatous) FIBROMATOSES (plantar, palmar, penile) FIBROSARCOMA

120 MYOSITIS OSSIFICANS BENIGN FIBROUS TISSUE PROLIFERATION PLUS OSSEOUS METAPLASIA

121 FIBROHISTIOCYTIC FIBROUS HISTIOCYTOMA DERMATOFIBROSARCOMA PROTUBERANS MALIGNANT FIBROUS HISTIOCYTOMA

122 SKELETAL MUSCLE RHABDOMYOMA RHABDOMYOSARCOMA

123 SMOOTH MUSCLE LEIOMYOMA LEIOMYOSARCOMA

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126 VASCULAR HEMANGIOMA LYMPHANGIOMA HEMANGIOENDOTHELIOMA HEMANGIOPERICYTOMA ANGIOSARCOMA

127 PERIPHERAL NERVE NEUROFIBROMA SCHWANNOMA GRANULAR CELL TUMOR MALIGNANT (SCHWANNOMA)

128 UNCERTAIN SYNOVIAL SARCOMA ALVEOLAR SOFT PART SARCOMA EPITHELIOD SARCOMA