Minarcik robbins 2013_ch26-ortho

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  • The topics covered will generally be the realm of orthopedic surgeons.
    This is NOT my favorite chapter.
    1) Personality of chapter:
    2) Personality of orthopods:
  • Do you remember all the names?
    Do you remember the histology of the 2 different types?
    Where is red marrow in the adult human? Where is yellow marrow?
  • Left: Intramembranous ossification
    Right: Endochondral ossification, note: 1, Reserve zone. 2, Zone of proliferation. 3, Zone of hypertrophy. 4, Zone of mineralization. 5, Primary spongiosa.
    The shape and strength of any bone is 100% dependent on the forces put upon it (Wolff’s Law)
  • Bone is never static! It is DYNAMIC! Constantly in a homeostatic state between production and resorption. TGF-beta is a key factor in maintaining that equilibrium.
  • This natural and necessary surface-bound molecule found on osteoBLASTS serves to activate osteoCLASTS, which are the cells involved in bone resorption. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis.
    Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.
    RANKL is important in bone metabolism. This natural and necessary surface-bound molecule (also known as CD254) found on osteoblasts serves to activate osteoclasts, which are the cells involved in bone resorption.
  • Just like regular or irregular connective tissue, same principle.
  • Remember the FOUR types of “bone” cells: progenitor cells, osteoBLASTS, osteoCYTES, osteoCLASTS
  • Do osteoclasts look like multinuclated giant cell macrophages? Mebbe that’s because they ARE!
  • Even though BONES are one of the most ANATOMIC structures in the body, most bone diseases are PHYSIOLOGIC.
    If you did nothing more than memorize all these classifications, and a good example of each one, you would have an excellent feel for bone pathology. This is the “cheat sheet” you want to take into Step 1, even though it is a nightmare to look at.
  • Craniorachischisis:
    Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure.
  • You can think of absences or supernumeraries of whole bones as being due, in general, to defects in nuclear proteins or transcription factors.
  • There are many types of dwarfism, achondroplasia any pituitary HGH deficiency are the most common. Most of the true “non-pituitary” dwarfisms are regarded as being due to defects in hormones and signal transduction mechanisms.
    Most of the dwarfs or “munchkins” in “The Wizard of Oz” were hypopituitary dwarfs.
  • Achondroplastic and thanatophoric dwarfs, respectively
  • Review the main functions of collagen 1,2,3,4: bONE, carTWOlage, thREEticulin, basement membrane floor (four).
    Why is OI bone “brittle”? Answer: not enough collagen protein to give the matrix “elasticity”
  • BLUE sclera, many fractures due to BRITTLE bones. Lack of collagen ONE.
  • Because, as you sense, cartilage has a much greater amount of glycosaminoglycans than bone, diseases of macromolecules are primarily CARTILAGE diseases rather than BONE
  • Rather than trying to describe the face, I will ask your temporal lobes to remember the appearance. The mucopolysaccharidoses are diseases due to lack of enzymes needed to break down glycosaminoglycans. Hunter, Hurler, Sanfillipo, Morquio, Maroteaux-Lamy, Sly, Natowicz, etc.
  • “Petra” is the root word for ROCK, like the “petrous” portion of the temporal bone which is rock hard.
  • Diffusely DENSE bone with “Erlenmeyer Flask deformity” of distal humerus. Remember Wolff’s Law!
    CHONG: Mnemonic for Etiologies of Erlenmeyer Flask Deformity
    CHONG
    Craniometaphyseal deformities
    Hemoglobinopathies
    Thalassemia
    Sickle cell disease
    Osteopetrosis
    Nieman Pick Disease
    Gaucher’s Disease
    Other
    Lead poisoning
    Fibrous dysplasia
    Hereditary multiple exostoses
  • Bone is a constant homeostasis between osteoclasts (bone resorption) and osteoblasts (bone deposition), when the -clasts win, we get osteoporosis
  • The main rule is: if you do not USE a bone, it loses mass. A bone is only as big and strong as it has to be (Wolff’s Law of bone)
  • Osteoporosis = DECREASED BONE MASS, therefore DECREASED BONE DENSITY also.
  • An ENTIRE bone showing extremely increased uptake of bone scanning agent is PAGET’s diease (of bone, NOT breast) until proven otherwise.
  • Best way to describe Paget’s Disease of bone in plain English.
    OsteoCLASTS go wild and chew up bone like crazy
    The osteoBLASTS then compensate by going crazy themselves
    Eventually the whole process becomes sclerotic
  • Bone scan activity is DIRECTLY proportional to OSTEOBLASTIC activity.
  • * Due to increased hemosiderin
  • Brown tumors are tumors of bone that arise in settings of excess osteoclast activity, such as hyperparathyroidism.
    BOTH OFS and brown tumors are the result of excessive osteoclast activity due to increased PTH.
  • Hypocalcemia goes hand in hand with renal failure just as reliably as hyperkalemia.
  • With only a few exceptions (which I can’t even recall any more) almost any metabolic disease of bone INCREASES the likelihood of a fracture, rather than DECREASES it. Even pathologic fractures usually occur in association with trauma, perhaps more minor trauma than usual.
    PRINCIPLE: HEALTHY BONE is as strong as it has to be. Anything decreasing that health interferes with its overall strength, hardness, and/or elasticity.
  • A general rule of thumb is that a complete healing of a fracture is about as long as a pregnancy.
  • See the callus? Hard or soft?
  • Whenever you have a list of 14 things associated with osteonecrosis, you might as well highlight the top 3 which cause MOST cases.
    Rather than memorize this list, please simply recall, logically, all the things which might interfere with bone blood flow, which is the single common factor.
  • Osteonecrosis is imaged best by MRI, showing an evolution of phases.
    Necrotic bone is “CRUMBLY” bonr.
  • Note the LACK of osteocytes in lacunae in the diseases bone on the RIGHT. The bone on the LEFT is normal, and has viable osteocytes in lacunae.
  • Sequestrum (dead bone, arrowheads)
    Involucrum (new bone, full arrows)
  • Easy classification, BONE TUMORS.
    No surprises here.
    This list is an UN-logical NIGHTMARE!
  • Easy classification, BONE TUMORS
  • Once again, as we have seen time and time again, the classification of bone tumors, is based on the kinds of tissue which are associated with bone, bone, cartilage, fibrous tissue.
  • “Osteoma” can also be a generic word referring to ANY benign tumor of bone.
  • Because you’ll be damn bored with seeing normal bone.
    Any pathologist who tries to diagnose ANY bone disease without an x-ray, is a damn fool also!
  • Primary = YOUNGER patients, Secondary = OLDER patients
  • What is a periosteal “starburst” effect?
  • Once again, as we have seen time and time again, the classification of bone tumors, is based on the kinds of tissue which are associated with bone, bone, cartilage, fibrous tissue.
  • Osteochondroma
  • Look at cartilage/bone interface. Well defined or jagged?
  • Clockwise from upper left: Hyaline, mesenchymal, myxoid, clear, anaplastic, are the adjectives (i.e., classifications) generally used.
  • Once again, as we have seen time and time again, the classification of bone tumors, is based on the kinds of tissue which are associated with bone, bone, cartilage, fibrous tissue.
  • Don’t let the word “dysplasia” fool you into thinking this is premalignant or has premalignant atypia!
  • Look how the spicule blends in with the fibrous tissue because of the lack of distinct osteoblasts.
  • Fibroblast vs “histio”-cyte? Does it matter?
    “spindly” cells and clear cut malignant nuclear features
  • EXACTLY like the skin MFH we saw
  • GCT occurs in patients, 20s-40-s, and GCT has a MACROPHAGE lineage, as most multinucleated giant cells do.
  • Why are most (90?) metastatic tumors to bone adenocarcinomas?
  • No need for an arrow here.
  • If you were asked to draw a circle around the metastatic area, where would you draw it?
  • Signet ring cells are poorly differentiated adenocarcinoma cells.
    Notice the nuclear size of the tumor cells compared to the normal marrow cells at the top.
  • This is a massively good diagram because it beautifully outlines most joints of the body, which are “synovial” joints.
    The “non synovial” joints, like cranial sutures or synchondroses, have a very limited or no degree of motion.
  • Synovium, like GBM, seems to be a MAGNET for Ag-Ab complexes.
    Note the rather “epithelial” appearance of the synovial cells.
    Synovium is NOT mesothelium.
  • Even the “degenerative” diseases of joints are called “arthridities”, even though they are the most classical examples of degenerative processes.
    Four kinds of joint diseases: 1) Degenerative arthritis, 2) Rheumatoid arthritis, 3) all other arthritis, and 4) tumors.
  • eburnation (e″bәr-na´shәn)   conversion of bone into a hard, ivory-like mass
    In the classical list of DEG-INF-NEO diseases, degenerative arthritis is hard to isolate as pure DEG or INF, but is always used as a classic example of “DEG”, from the pure sense of the word, i.e., “degeneration” means loss of cells, i.e., chndrocytes.
  • Various clinical radiologic and arthroscopic facets of Degenerative Arthritis
    HEBERDEN = DIP, BOUCHARD = PIP
  • Synovium, like GBM, seems to be a MAGNET for Ag-Ab complexes.
    Note the rather “epithelial” appearance of the synovial cells.
    Synovium is NOT mesothelium.
  • The rheumatoid “factor” is an antibody AGAINST the FC portion of IgG, often present in the serum of patients with RA and other autoimmune diseases.
    The MAIN HISTOPATHOLOGY of rheumatoid arthritis is a WHOPPING CHRONIC SYNOVITIS!
  • Rheumatoid nodules can be associated with the joint or in far off places like lung.
    Remember it is a SYSTEMIC auto-immune disease!
  • You can go to any medicine textbook and calculate the factors, MAJOR and minor, to enable the specific diagnosis.
  • ULNAR DEVIATION of MP joints is MOST consistent reliable finding.
    The main area of arthritis in NOT DIP or PIP, but MP
  • What is the HLA-B27 antigen?
    Does it have a wide human variation from <1% to >8%
  • What does “ankylosing” mean?
  • Is it a big surprise that where gout usually develops in joints and soft tissues is also the most likely areas to suffer ischemia of peripheral ASCVD? Ans: NO
  • A TOPHUS is a GRANULOMATOUS response to monosodium urate crystals.
  • Remember Uric acid stones are the THIRD most common type of renal stone after 1) calcium, and 2) magnesium ammonium phosphate.
  • Any surprises?
  • Ochronosis = ↑ homogentisic acid
  • Biurate has the OPPOSITE polarization pattern of pyrophosphate. In GOUT, as seen here, the yellow needles are vertical and the blue needles are horizontal, under polarization. IN PSEUDOGOUT, the OPPOSITE is seen.
  • These diseases are related, but PVNS (Pigmented Villo-Nodular Synovitis) appears as shaggy or “villous” projections of synovium, and GCT is a solid tumor. BOTH are regarded as BENIGN proliferations of synovium and reactive cells.
    Do you think the giant cells come from the macrophage or fibroblast component of synovium?
  • Synovial sarcomas usually have a “BIPHASIC” appearance, i.e., spindly and “epithelial”, but of course there is the monophasic variety also, which looks about like any other spindly sarcoma.
  • I personally would never know this unless I had to teach it.
  • What is the herring bone pattern classically described in fibrosarcomas?
    Why are “reactive” fibromatoses VERY difficult to differentiate from benign tumors of fibrous tissue? (no need for answer)
  • MYOSITOS OSSIFICANS can be thought of as being a METAPLASTIC process, often following inflammation, i.e.:
    Usual scenario:InflammationFibrosis ( sometimes calcification too)
    Myositis Ossificans:InflammationFibrosisOssification
    Remember ossification is a heck of a lot MORE than just calcification!
  • Just like in skin!
    NO difference.
  • Usually tumors of skeletal or cardiac muscle do not look anything like the “normal” tissue from which they emerged. Even the benign ones.
    Therefore, do you think you might see striations on a rhabdomyoma?
  • COUNTING mitoses is MUCH more important than getting a visual feel for pleormorphism and hyperchromasia in the evaluation of soft tissue tumors, as to whether they are benign or sarcomas, i.e., you can have almost normal looking smooth muscle, but an increased mitotic rate of more than a few per 10HPFs (High Power Fields), would be enough criteria for a sarcoma.
    Conversely, you may see extreme pleomorphism, but if the mitotic rate is not increased, it is usually benign! It takes a lot of COURAGE and SAVVY to call a pleomorphic leiomyoma benign.
  • The MAIN difference between leiomyomas and leiomyosarcomas is the number of mitoses per high power field! How many do you see here?
    COUNTING mitoses is MUCH more important than getting a visual feel for pleormorphism and hyperchromasia in the evaluation of soft tissue tumors, as to whether they are benign or sarcomas.
    Please remember this.
  • Same as in chapter 11.
    Jaggedness (invasiveness) of gross specimen
    Jaggedness of endothelial lined spaces
    Ability to see lumina vs. poorly defined cells staining positive for Factor VIII
  • If you see a nucleus within a section of peripheral nerve, what kind of cell is it?
    Ans: Schwann cell.
    Therefore, just about all primary tumors of nerve HAVE TO BE Schwannomas, right? Ans: YES
  • Minarcik robbins 2013_ch26-ortho

    1. 1. BONE JOINT SOFT TISSUE
    2. 2. Modeling/RE-modeling
    3. 3. 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
    4. 4. Proteins (organic) of BONE • Type 1 (TYPE [B]ONE) collagen (90%) • Cell adhesion proteins, i.e. CAMs: Osteopontin, fibronectin, thrombospondin • Calcium-binding proteins: Osteonectin, sialoprotein • Proteins involved in mineralization: Osteocalcin   • Enzymes: Collagenase, Alk. Phos. • Growth factors – IGF-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
    5. 5. Minerals (IN-organic) of BONE HYDROXY-APATITE Ca5(PO4)3(OH) Ca10(PO4)6(OH)2
    6. 6. ADJECTIVES of BONE • Compact – Dense – Cortical • Spongy – Cancellous – Membranous – Endosteal – Spicular
    7. 7. Woven vs. “Lamellar”
    8. 8. -BLASTS/-CLASTS Ca++ Ca++ Calcitonin PTH
    9. 9. 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 • – Type 1 Collagen Diseases (Osteogenesis Imperfecta) – Types 2, 10, and 11 Collagen Diseases 4) DISEASES ASSOCIATED WITH DEFECTS IN FOLDING AND DEGRADATION OF • • • • • • PROTEINS 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 (Ca++) HOMEOSTASIS – Ricketts and Osteomalacia – Hyperparathyroidism – Renal Osteodystrophy
    10. 10. 1) MALFORMATIONS AND DISEASES CAUSED BY DEFECTS IN NUCLEAR PROTEINS AND “TRANSCRIPTION FACTORS” proteinDNAmRNA • Congenital absence of a, usually single, bone: phalanx, rib, clavicle • Supernumerary digit (polydactyly) • Syndactyly • CRANIORACHISCHISIS
    11. 11. 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, hence the term “achondroplastic”; • A MUTATION causes FGFR3 to be constantly activated.
    12. 12. Achondroplastic “dwarf” Thanatophoric “dwarf”, often lethal Short arms and extra folds of skin
    13. 13. 3) DISEASES ASSOCIATED WITH DEFECTS IN EXTRACELLULAR STRUCTURAL PROTEINS • OSTEOGENESIS 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 sequelae
    14. 14. Osteogenesis Imperfecta BLUE SCLERA
    15. 15. 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 AN – KERATAN – HEPAR • Chiefly CARTILAGE disorders: short, chest wall, malformed bones
    16. 16. MUCOPOLYSACCHARIDOSES
    17. 17. 5) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATHWAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS) • OSTEOPETROSIS, 4 types • One common one has a CARBONIC ANHYDRASE deficiency, i.e., ↓ acid • DECREASED osteoclast resorption • “MARBLE” bone, increased bone, brittle, sclerotic bone
    18. 18. OSTEOPETROSIS
    19. 19. 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
    20. 20. Categories of Generalized Osteoporosis Primary Postmenopausal Idiopathic   Senile Secondary Endocrine disorders Rheumatologic disease Hyperparathyroidism   Drugs Hypo-hyperthyroidism   Anticoagulants   Hypogonadism   Chemotherapy   Pituitary tumors   Corticosteroids   Diabetes, type 1   Anticonvulsants   Addison disease   Alcohol   Neoplasia Miscellaneous Multiple myeloma   Osteogenesis imperfecta   Carcinomatosis   Immobilization   Gastrointestinal Pulmonary disease   Malnutrition, Malbs., Hepatic Insuf., Vit C,D   Homocystinuria   Anemia  
    21. 21. OSTEOPOROSIS
    22. 22. 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
    23. 23. PAGET’s DISEASE (of BONE) 85% MONOSTOTIC, WHOLE BONE 15% POLY-OSTOTIC (skull, pelvis) “JIGSAW”, NOT LAMINAR, BONE CLINICAL: PAIN!!! (MICROFRACTURES)
    24. 24. PAGET’s DISEASE NON-Lamellar bone
    25. 25. 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
    26. 26. PRIMARY HYPERPARATHYROIDISM OSTEITIS FIBROSA CYSTICA “BROWN” “TUMOR”
    27. 27. RENAL OSTEODYSTROPHY • • • • • • PHOSPHATE RETENTION HYPOPHOSPHATEMIA HYPOCALCEMIA INCREASED PTH INCREASED OSTEOCLASTS METABOLIC ACIDOSIS  release of HYDROXYAPATITES from matrix
    28. 28. FRACTURES
    29. 29. FRACTURES, adjectives • • • • • Complete, incomplete Closed, open (communicating) Communited (splintered, “greenstick”) Displaced (NON-aligned) PATHOGENIC, (non-traumatic, 2º to other disease, often metastases) • “STRESS” fracture
    30. 30. FRACTURES • THREE PHASES – HEMATOMA, minutes days PDGF, TGF-β, FGF – SOFT CALLUS (“PRO”-CALLUS), ~1 week – HARD CALLUS (BONY CALLUS), several weeks • COMPLICATIONS – PSEUDARTHROSIS (non-union) – INFECTION (especially OPEN [communicating] fractures)
    31. 31. FRACTURES
    32. 32. 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
    33. 33. OSTEONECROSIS Disorders Associated with Osteonecrosis Idiopathic Pregnancy Trauma Corticosteroid administration Gaucher disease Infection Alcohol abuse Dysbarism Chronic pancreatitis Radiation therapy Tumors Connective tissue disorders Epiphyseal disorders Sickle cell and other anemias
    34. 34. OSTEONECROSIS
    35. 35. OSTEONECROSIS
    36. 36. OSTEOMYELITIS • Pyogenic: Staph, E. coli, Pseudom, Kleb, Salmonella – Hematogenous – Contiguous, e.g., from a nearby joint – Direct implantation • TB • Syphilis
    37. 37. OSTEOMYELITIS • DX: X-ray, Bone scan
    38. 38. OSTEOMYELITIS • DX: Histology
    39. 39. OSTEOMYELITIS • COMPLICATIONS – Subperiosteal abscess – Draining sinus – Joint involvement • SEQUESTRUM (dead bone) vs. • INVOLUCRUM (new bone)
    40. 40. OSTEOMYELITIS • Tuberculous – Usually blood borne – TB of spine is known as POTTS disease • Syphilis – CONGENITAL – TERTIARY, “SABRE” shins
    41. 41. POTT’s DISEASE
    42. 42. SABER SHINS
    43. 43. Classification of Primary Tumors Involving Bones Histologic Type Benign Malignant Hematopoietic (40%) Myeloma Chondrogenic (22%) Osteochondroma Malignant lymphoma Chondrosarcoma Chondroma Dedifferentiated chondrosarcoma Chondroblastoma Mesenchymal chondrosarcoma Chondromyxoid fibroma Osteogenic (19%) Osteoid osteoma Osteosarcoma Unknown origin (10%) Osteoblastoma Giant cell tumor tumor Histiocytic origin Fibrous histiocytoma Giant cell tumor Adamantinoma Malignant fibrous histiocytoma Fibrogenic Metaphyseal fibrous defect (fibroma) Desmoplastic fibroma Notochordal Vascular Lipogenic Neurogenic Hemangioma Lipoma Neurilemmoma Fibrosarcoma Chordoma Hemangioendothelioma Hemangiopericytoma Liposarcoma
    44. 44. BONE TUMORS • • • • BONE CARTILAGE FIBROUS MISC. – Ewing’s “sarcoma” – Giant Cell Tumor – METASTASES
    45. 45. BONE- BONE TUMORS • • • • OSTEOMA OSTEOID OSTEOMA (nidus) OSTEOBLASTOMA OSTEOSARCOMA (OSTEOGENIC SARCOMA)
    46. 46. OSTEOMA • SOLITARY • MIDDLE AGE • FROM SUBPERIOSTEAL or ENDOSTEAL surfaces • SKULL, FACE, most common • Totally BENIGN • To be distinguished from REACTIVE BONE, (can be difficult)
    47. 47. FRONTAL SINUS Why am I not showing you HISTOLOGY?
    48. 48. OSTEOID OSTEOMA • At least 2 cm in diameter • Teens, twenties, APPENDICULAR skeleton • M>>F • PAINFUL • Has a NIDUS • Responds to aspirin • Induces a MARKED bony reaction
    49. 49. NIDUS
    50. 50. • • • • OSTEOBLASTOMA AXIAL SKELETON, i.e., SPINE NO nidus NO bony reaction NOT relieved by aspirin
    51. 51. OSTEOSARCOMA (OSTEOGENIC SARCOMA) LATE TEENS KNEES METAPHYSES PAINFUL!!!
    52. 52. 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 (pre-existing 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)
    53. 53. 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
    54. 54. BONE- CARTILAGE TUMORS • OSTEOCHONDROMA (EXOSTOSIS) • CHONDROMA • CHONDROBLASTOMA • CHONDROMYXOID FIBROMA • CHONDROSARCOMA
    55. 55. OSTEOCHONDROMA (EXOSTOSIS) • Common, Cartilage AND Bone present • Often MULTIPLE as a hereditary syndrome • M>>>F • PELVIS, SCAPULAE, RIBS
    56. 56. CHONDROMA • Chondroma vs. EN-chondroma • PURE Hyaline Cartilage • MULTIPLE enchondromas = Ollier’s dis. • Maffucci Synd. if hemangiomas present
    57. 57. CHONDROBLASTOMA • • • • • RARE, in teenagers M>>F KNEES, usually Epiphyses MUCH LESS matrix than a chondroma
    58. 58. CHONDROMYXOID FIBROMA • • • • RAREST of all TEENS, MALES “MYXOID” concept “ATYPIA”
    59. 59. CHONDROSARCOMA • ANATOMY – INTRAMEDULLARY – JUXTACORTICAL • HISTOLOGY – CONVENTIONAL • HYALINE • MYXOID – CLEAR – DE-DIFFERENTIATED – MESENCHYMAL
    60. 60. CHONDROSARCOMA
    61. 61. BONE- FIBROUS TUMORS • FIBROUS CORTICAL DEFECT/NONOSSIFYING FIBROMA • FIBROUS DYSPLASIA • FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA
    62. 62. FIBROUS CORTICAL DEFECT • COMMON, usually LESS THAN 1 CM • CHILDREN >2 • IF MORE THAN 5-6 CM, they are then called NONOSSIFYING FIBROMA
    63. 63. 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
    64. 64. 1) CURVED thin spicules 2) LACK of osteoblastic “rimming”
    65. 65. FIBROSARCOMA/MFH • • • • • METAPHYSES of LONG BONES PELVIC FLAT BONES LYTIC FRACTURES OF COURSE, SARCOMATOUS METASTASIS
    66. 66. FIBROSARCOMA/MFH
    67. 67. MISC. TUMORS of BONE • EWING sarcoma/PNET (Primitive NeuroEctodermal Tumor) • GIANT CELL TUMOR • METASTASES
    68. 68. EWING/PNET • • • • • SAME TUMOR SMALL ROUND BLUE CELL TUMOR NEUROENDOCRINE CELL ORIGIN CHROMOSOME TRANSLOCATION 11&22 SECOND most COMMON bone malignancy in CHILDREN • ARISE IN MEDULLARY CAVITY of BONE • LOOK LIKE LYMPHOMA
    69. 69. GCT (Giant Cell Tumor), BONE
    70. 70. METASTASES MALE: PROSTATE FEMALE: BREAST RENAL, THYROID also seek bone early also LYTIC? BLASTIC?
    71. 71. SYNOVIAL JOINTS
    72. 72. TWO KINDS of cells form the synovial intima • 1) fibroblasts – Hyaluronin – Lubricin • 2) macrophages The SUB-intima is loose CT or fat
    73. 73. 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 (all are of synovium) – Ganglion (Synovial Cyst), non-neoplastic – Giant Cell Tumor (Pigmented VilloNodular Synovitis[PVNS]), benign – Synovial Sarcoma, malignant
    74. 74. “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
    75. 75. HEBERDEN’S NODES DIP, NOT MP or PIP
    76. 76. 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.
    77. 77. TWO KINDS of cells form the synovial intima • 1) fibroblasts – Hyaluronin – Lubricin • 2) macrophages The SUB-intima is loose CT or fat
    78. 78. 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IgG-Fc,
    79. 79. HANDSWRISTELBOWS The rheumatoid “nodule” shows “palisading” fibroblasts
    80. 80. 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
    81. 81. “JUVENILE” Rheumatoid Arthritis • Begins BEFORE age 16, by definition • Generally LARGER joints than RA • Often POSITIVE ANA
    82. 82. “SERONEGATIVE” ARTHRITIDES • ANKYLOSING SPONDYLITIS (aka, “rheumatoid” spondylitis, or MarieStrumpell 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]
    83. 83. Ankylosing Spondylitis
    84. 84. INFECTIOUS ARTHRITIS • From OSTEOMYELITIS • USUALLY SUPPURATIVE • GC, staph, strep, H. flu, E. coli, (Salmonella in sicklers) • 4 cardinal signs, fever, leukocytosis, ESR
    85. 85. INFECTIOUS ARTHRITIS • TB • LYME Disease, i.e., Borrelia burgdorferi, from Ixodes ticks • VIRAL – Parvovirus B19 – Rubella – Hepatitis C
    86. 86. 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
    87. 87. Classification of Gout Clinical Category Metabolic Defect Primary Gout (90% of cases) Enzyme defects unknown (85%–90% of primary gout) ■ Overproduction of uric acid Normal excretion (majority)   Increased excretion (minority)   Underexcretion of uric acid with normal   production Known enzyme defects—e.g., partial HGPRT deficiency (rare) ■ Overproduction of uric acid Secondary Gout (10% of cases) Associated with increased nucleic acid turnover—e.g., leukemias ■ Overproduction of uric acid with increased urinary excretion Chronic renal disease ■ Reduced excretion of uric acid with normal production Inborn errors of metabolism—e.g., complete HGPRT deficiency (LeschNyhan syndrome) ■ Overproduction of uric acid with increased urinary excretion HGPRT, hypoxanthine guanine phosphoribosyl transferase.
    88. 88. HYPERURICEMIA GOUT • Age of the individual and duration of the • • • • • hyperuricemia are factors. Gout rarely appears before 20 to 30 years of hyperuricemia. M>>F 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 gout
    89. 89. FEATURES • TOPHACEOUS ARTHRITIS • GOUTY NEPHROPATHY
    90. 90. GOUTY NEPHROPATHY
    91. 91. GOUT • Associated with ATHEROSCLEROSIS • Associated with HYPERTENSION
    92. 92. 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
    93. 93. GOUT vs. PSEUDOGOUT
    94. 94. JOINT TUMORS • BENIGN – GANGLION (SYNOVIAL CYST) – GIANT CELL TUMOR of TENDON SHEATH, aka PVNS, Pigmented VilloNodular Synovitis • MALIGNANT – SYNOVIAL SARCOMA
    95. 95. GANGLION
    96. 96. PVNS/GCT
    97. 97. Synovial Sarcoma
    98. 98. “SOFT TISSUE” TUMORS • • • • • • • • FAT FIBROUS TISSUE FIBROHISTIOCYTIC SKELETAL MUSCLE SMOOTH MUSCLE VASCULAR PERIPHERAL NERVE UNCERTAIN: SYNOVIAL SARCOMA, ALVEOLAR SOFT PART SARCOMA, EPITHELIOD SARCOMA
    99. 99. 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
    100. 100. Chromosomal and Genetic Abnormalities in Soft Tissue Sarcomas Tumor Extraosseous Ewing sarcoma and primitive neuroectodermal tumor Cytogenetic Abnormality Genetic Abnormality t(11:22)(q24;q12) FLI-1-EWS fusion gene t(21:22)(q22;q12) ERG-EWS fusion gene t(7;22)(q22;q12) ETV1-EWS fusion gene Liposarcoma—myxoid and round cell type t(12:16)(q13;p11) 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
    101. 101. SOFT TISSUE TUMORS • ALL “SPINDLY” • Deep (desmoid) vs. Superficial (skin) • Importance of counting MITOSES • Importance of STAGING • Importance of IMMUNOPEROXIDASE • Importance of CONSULTATION
    102. 102. FAT • LIPOMA • LIPOSARCOMA NORMAL FAT LIPOMA, encapsulated LIPOSARCOMA, often retroperitoneal
    103. 103. FIBROUS TISSUE • NODULAR FASCIITIS (pseudosarcomatous) • FIBROMATOSES (plantar, palmar, penile) • FIBROSARCOMA
    104. 104. MYOSITIS OSSIFICANS • BENIGN FIBROUS TISSUE PROLIFERATION PLUS OSSEOUS “METAPLASIA”
    105. 105. FIBROHISTIOCYTIC • FIBROUS HISTIOCYTOMA • DERMATOFIBROSARCOMA PROTUBERANS • MALIGNANT FIBROUS HISTIOCYTOMA
    106. 106. SKELETAL MUSCLE • RHABDOMYOMA • RHABDOMYOSARCOMA
    107. 107. SMOOTH MUSCLE • LEIOMYOMA • LEIOMYOSARCOMA
    108. 108. VASCULAR • • • • • HEMANGIOMA LYMPHANGIOMA HEMANGIOENDOTHELIOMA HEMANGIOPERICYTOMA ANGIOSARCOMA
    109. 109. PERIPHERAL NERVE • • • • NEUROFIBROMA SCHWANNOMA GRANULAR CELL TUMOR MALIGNANT (SCHWANNOMA)
    110. 110. UNCERTAIN • SYNOVIAL SARCOMA • ALVEOLAR “SOFT PART” SARCOMA • EPITHELIOD SARCOMA

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