LECOM Path Ch 26 Bone Joints connective tissue
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| noncollagenous protein measured in the serum for osteoblast activity | osteocalcin
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| Mutation in HOXD13 gene leads to what? | extra finger between 3rd and 4th
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| What is the most common disease of the growth plate? Gene Mutated? Transmission? And phenotype? | Achondroplasia; FGFR3 constant actiivation; AD; short limbs, normal torso, “mid face” sunken
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| Outlook for Pt’s with the most common disease of the growth plate? | Achondroplasia Pts have normal longevity, reproduction and intelligence
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| Most common form of lethal dwarfism is called? Mutation? Distinguishing phenotype? | Thanatophoric dwarfism; GOF FGFR3; small chest cavity, bell shaped abdomen
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| GOF mutations in LPR5 causes what? And name 3 diseases. | increased bone mass; endosteal hyperostosis; Van Buchen disease; AD osteopetrosis type I
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| Inactivation of LPR5 gene causes what? Name of Dx? What else is a diagnostic feature of this disease? | decreased bone density and formation; Osteoporosis-pseudoglioma syndrome; congenital or infantile loss of sight
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| 5 types of collagen important to bone or cartilage | types 1, 2, 9, 10, 11
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| Disease caused by defective or decreased Type 1 collagen | osteogenesis imperfecta types I-IV
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| What is the most common inherited disorder of connective tissue? Mode of inheritance? | osteogenesis imperfecta; AD
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| Mutations in these 2 genes cause the 3 rare variants of Osteogenesis Imperfecta. | CRTAP and LEPRE1
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| Most mutations in osteogenesis imperfecta result from substitutions of what? | glycine residues in the triple helix
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| Type of OI that is always fatal in utero. Inheritance? | OI type II; AR causing short pro-alpha 1(1) chains
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| Type I OI, common findings? | blue sclera, post natal fractures, hearing loss, dental imperfections
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| Standout to differentiate Type I from Types III and IV OI | Type I has normal height
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| Type III vs Type IV OI | Type III has blue sclera at birth, growth retardation, progressive disease w/ hearing impairment.
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| 2 most common modes of Osteopetrosis | Severe Autosomal Recessive and Mild Autosomal Dominant
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| Bulbous ends of long bones on x-ray, bone microscopically shows a woven architecture. Name of deformity and Dx? | Erlenmeyer flask deformity; Osteopetrosis
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| Severe autosomal recessive Osteopetrosis can be caused by mutations in what 3 genes? | CA2 (w/ kidney problems); CLCN7; TCIGR1
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| Baby with multiple fractures, anemia, hydrocephaly, hepatosplenomegaly, death after multiple infections. Dx and inheritance | Severe Infantile malignant Osteopetrosis; Autosomal Recessive
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| When and how are mild autosomal dominant forms of Osteopetrosis Diagnosed? | on x-ray later in life after multiple fractures, anemia, and CN issues
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| MC Osteopetrosis Tx? | bone marrow transplant
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| Most common forms of osteoporosis | senile and postmenopausal
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| As people age their osteoblasts decrease their potential for action as well as the extracellular matrix proteins lose “their punch”. Dx? And variant type? | Senile osteoporosis and low turnover variant
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| What builds more bone, running or weight lifting? | Weight lifting; increased bone loading stress
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| % of the variation in bone density that is genetically determined? Top 3 genes associated? | 60-80%; RANK; RANKL; OPG
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| % of cortical and cancellous bone lost per year in post-menopausal women | 2% cortical and 9% cancellous
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| Major effector in post-menopausal osteoporosis | low estrogen levels
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| What levels are increased and decreased in post-menopausal osteoporosis due to estrogen deficiency? | increased IL-1, IL-6, TNF; increased RANK-RANKL; decreased OPG
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| What variant type is post-menopausal osteoporosis? | High-turnover form
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| Affects bones with larger surface area i.e. vertebral bodies; loss of horizontal trabeculae with vertebral fractures and collapse. Type of osteoporosis? | Post-menopausal.
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| Thinned bone cortex, widening of Haversian system. Type of osteoporosis? | Senile
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| You can’t see osteoporosis on x-ray till how much of the bone is gone? | 30-40%
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| 3 phases of Paget’s Disease | 1. Osteolytic 2 Mixed ending in oseoblastic 3. Burnt out/ osteosclerotic
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| Net effect of Paget’s Disease on bone? | increased bone mass but disordered, architecturally unsound bone
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| Average age of Dx in Paget’s Disease? | 70yo
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| Pathognomonic: mosaic pattern of lamellar bone | Paget’s Disease
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| Bone biopsy shows numerous resorption pits, with extremely large osteoclasts that have up to 100 nuuclei, and very few osteoblasts are noted. Dx and stage? | Paget’s disease; 1. Osteolytic stage
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| What would you see during Mixed stage of Paget’s Disease? | bone with many osteoblasts and even some large osteoclasts persist. Marrow is replaced by highly vascularized loose connective tissue filled with osteoprogenator cells
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| MC location of involvement with Paget’s disease? | axial skeleton or proximal femur 88%
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| Hear condition associated with Paget’s | high-output heart failure
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| Anterior bowing of femur and tibia with abnormally thick bone on X-ray Dx? | Paget's disease
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| Increased bone cell activity, peritrabecular fibrosis, cystic brown tumors. Dx? Cause? Other names? | Hyperparathyroidism/osteitis fibrosa cystica/von Recklinghausen disease of bone; increased PTH
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| Primary vs Secondary hyperparathyroidism | Primary: autonomous or tumor secretion; Secondary: compensatory due to hypocalcemia
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| Cause of Secondary Hyperparathyroidism with hyperphosphatemia | Chronic Renal Failure
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| Hypocalcemia with increased 25-(OH)D3 | decrease in renal hydroxylase to form 1-25…
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| Renal failure induces release of hydroxyapatite leads to what acid-base disorder | metabolic acidosis
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| Fx classification: all the way through bone | complete
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| Fx classification: goes through skin | compound
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| Fx classification: overlying skin intact | simple or closed
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| Fx classification: bone is splintered | comminuted
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| Fx classification: broken because of medical condition | pathologic
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| How long to see “soft tissue callus” or “procallous” at fx site? | 1 week
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| Maximum repair tissue girth in uncomplicated Fx is seen when? | 2nd or 3rd week
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| Osteonecrosis in the absence of fracture can be caused by what drug? | corticosteroids
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| Visible characteristic of subchondral bone infarct | wedge shaped necrosis
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| How does bone change microscopically when “dead” | empty lacunae surrounded by necrotic adipose cells or calcium soaps
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| Clinical presentation of subchondral infarct | chronic pain, first with activity then constant
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| Clinical presentation of medullary infarcts | silent unless large
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| 3 diseases that can cause massive medullary infarcts | Gauchers; dysbarism (Bends); Sickle Cell
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| Osteomyelitis is most commonly cause by what 2 types of bugs | pyogenic bacteria and mycobacteria
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| MCC of pyogenic osteomyelitis | Staph Aureus
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| MCC of (2)Neonatal pyogenic osteomyelitis | H. flu and group B strep
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| Pt with pyogenic osteomyelitis and GU infection. What bugs are suspect? | pseudomonas, E.coli, Klebsiella (PEK)
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| Sickle cell Pt with pyogenic osteomyelitis. MCC | salmonella
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| Children get pyogenic osteomyelitis from | mucosal injury, harmless in initial origin
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| Periosteal abscesses between the periosteum and bone are mmost like seen in what age group? | children
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| Adults contracts pyogenic osteomyelitis by what MC 3 ways | diabetic feet, surgical procedure, open fracture
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| Neonate-Child-Adult: MC locations of osteomyelitis | metaphysis/epiphysis -> metaphysis-> epiphysis/subchondral
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| Who would you expect to see with extension of pyogenic infection from epiphyseal osteomyelitis along a tendon to a joint: infant, child, or adult? | Infant
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| After one week what changes in pyogenic osteomyelitis | chronic inflammatory cells take over, bone resorption and deposition of fibrous tissue
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| What is a Brodie abscess? | osteomyelitis abscess involving the cortex walled off by new bone
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| What is sclerosing osteomyelitis of Garre? | huge jaw bone caused by new bone deposition
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| Lytic bone lesion with surrounding zone of sclerosis. Dx? | osteomyelitis
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| MCC of Psoas abscess that tracts down the muscle | Potts Disease- tuberculosis osteomyelitis
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| Congenital skeletal syphilis likes to be where? | around active enchondral ossification and periosteal
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| Massive bone deposition noted on medial and anterior tibiaon x-ray. Dx and Buzz word? | syphilis “saber shin”
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| Early tertiary syphilis likes what bones? | long bones of the extremity, nose, palate, and skull
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| Granulation tissue noted around bone containing plasma cells and necrotic bone Dx? | syphilis
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| MC primary bone cancer (excluding hematopoietic tumors)(and the next 2) | osteosarcoma; Chondrosarcoma; Ewing Sarcoma
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| Young vs Old: bone tumors in each are likely to be malignant or benign? | Young- benign Old Malignant
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| Benign bone forming tumor, usually solitary on the face or skull. Bone laid in cortical fasion w. haversian system dx? | osteoma
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| Osteoid osteoma: size? Gender? Age? Location? | less than 2cm; younger than 25; male; appendicular skeleton (50% femur/tibia) or postior spine
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| Osteoblastoma: size? Location? | greater than 2cm; spine usually
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| Difference in pain between osteoid osteoma vs osteoblastoma | asprin works for os.osteoma and it is nocturnal and sever
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| Well-circumscribed round mass; hemorrhagic gritty and tan; shows random trabeculae of woven bone surrounded by osteoblasts; benign cytoplasm DDx? | osteoid osteoma vs osteoblastoma
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| MC primary bone cancer. Dx? Age? Location? | osteosarcoma; younger than 20 then some old people; long bone metaphysis; 50% around the knee
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| 3 genes mutated often in osteosarcoma | RB, p53, INK4a
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| MC subtype of osteosarcoma | metaphyseal long bone, primary, solitary, intramedullary, poorly differentiated
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| Gross appearance of osteosarcoma | big bulky gritty white grey w/ hemorrhage and cystic changes
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| Suspected osteosarcoma: micro shows multitude of malignant cartilage Dx? | chondroblastic osteosarcoma
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| Codman triangle: what is it and characteristic of? | triangle on x-ray coming off the bone. Periosteal Osteosarcoma
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| MC benign bone tumor? Age? Sex? Location? | osteochondroma; sessile with cartilage cap; pre-adolescent; men; metaphysis of long bones
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| Osteochondroma with EXT2 mutation. Sporadic or hereditary? | hereditary
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| Describe the architecture of osteochondroma | sessile capped with benign “growth plate” hyaline cartilage; cortex and medullary cavity are continuous with bone
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| MC intraosseous cartilage tumor? Age? Location? | enchondromas; 20-40; long bones of the hands and feet
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| Pt with Ollier disease has? | multiple enchondromas
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| Enchondromatosis w/ soft tissue hemangiomas is called | Maffucci syndrome
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| C or O ring signs on x-ray with multiple large deforming radioluscencies in the long bones of the hands and feet DDx? | Maffucci or Ollier syndromes
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| rare, benign cartilaginous tumor most commonly around the knee in young males; chicken-wire pattern of mineralization, tons of compact chondroblasts with little cartilage and usually centers of necrosis and mitotic activity. Dx? | chondroblastoma
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| rarest cartilage tumor, variable morphology, most often young males, in metaphysis of long tubular bones; on x-ray, eccentric lucency, well delineated from adjacent bone by rim of sclerosis | chondromyxoid fibroma
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| MC subclass of Chondrosarcoma | conventional (hyaline/myxoid) central tumor
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| rarest cartilage tumor, variable morphology, most often young males, in metaphysis of long tubular bones; on x-ray, eccentric lucency, well delineated from adjacent bone by rim of sclerosis | chondrosarcoma
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| Chondrosarcoma grading possibilities | Grades 1-3; Grade 1 w/ some 2 is “dedifferentiated”
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| Sheets of large malignant chondrocytes that have abundant clear cytoplasm, osteoclast-like giant cells and includes reacti bone formation.Dx? | Clear cell chondrosarcoma
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| Where does clear cell variant chondrosarcoma like to grow? | epiphysis of long tubular bones, all else central skeleton
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| Difference in cortical reaction in high grade vs low grade tumors? | high grade destroys cortex low grade induces reactive thickening
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| 5cm elongated, sharply demarcated radioluscency surrounded by a rim of thin sclerosis. Biopsy shows bland fibroblasts in pinwheel pattern and multinucleated giant cells and foamy macrophages in an asymptomatic 17yo boy. Dx? | Fibrous cortical defect now a Non-ossifying Fibroma
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| Multiple fibrous dysplasias are found in a young woman. Testing shows GNAS mutations. What else is likely to be found about the girl? | café-au-lait spots, neuroendocrine disorder, most likely precocious puberty; Mcune-Albright syndrome
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| Hard lump in mandible biopsy: intramedullary tan-white tissue with curvilinear trabecular woven bone with moderately cellular fibroblastic proliferation around. Some bone looks like Chinese letters. Dx? | Fibrous dysplasia
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| Middle age-> elderly Pt; mataphyseal mass; large, tan-white, hemorrhagic, destroying the bone and soft tissue around it; in femur; micro: malignant fibroblasts in herringbone storiform pattern. Dx? | Fibrosarcoma
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| 2nd most common sarcoma in children with the youngest average presentation age | Ewing sarcoma/PNET
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| Difference between Ewing Sarcoma and PNET | neural differentiation is PNET
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| Mutation in ewing Sarcoma | t(11;22) FLI1 and it’s TF are cocreated
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| Ewing sarcoma is rarely seen in this age group and this race | above 20 and blacks
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| Invasive tumor from medullary cavity in diaphysis of long bones, soft tan-white, tons of necrosis and hemorrhage, tons of uniform, small, round cells, in sheets or rosette around fibrillary space. Little stroma present, few mitotic bodies Dx? | Ewing Sarcooma/PNET
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| Mass with periosteal reaction with layers of reactive bone in “onion skin” fashion | Ewing Sarcoma
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| benign but locally aggressive tumor at epiphysis/metaphysisof long bones esp around knee; peak age 20-40; uniform oval mononuclear cells w/ multinucleated (around 100) giant cells; large, red-brown cystic mass Dx? | Giant-cell tumor aka osteoclastoma
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| Mutation in aneurismal bone cysts | 17p13; up regulation of USP6
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| Rapidly growing tumor in Pt 0-20yo, posterior element of vertebraor metaphysis of long bone; shows cystic, blood filled spaces, with fibrous/giant cell/reactive woven bone septa; some have “blue bone” cartilage matrix; Dx? | aneurismal bone cyst
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| MC metastatic cause of bone CA in adults (4) | prostate, breast, kidney, lung
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| MC mets to bone in children (5) | neuroblastoma; Wilms Tumor; osteosarcoma; Ewing sarcoma; rhabdomyosarcoma
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| Solitary bone met lesion. 2 MCC | carcinoma of kidney and thyroid
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| MC joint disease | OA
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| progressive erosion of articular cartilage | OA
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| the pathology of this disease of joints is d/t intrinsic breakdown of cartilage, not inflammation | OA
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| deep, achy pain that worsens with use, morning stiffness, crepitus and limitation of ROM. Dx? | OA
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| what joints are typically spared in osteoarthritis? | wrists, elbows, shoulders
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| Heberden nodes are seen where? In who? With what disease? | DIP; Women; OA
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| Free-floating pieces of cartilage in joints are called what? And seen in what disease? | joint mice/loose bodies; OA
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| What is contained in cystic lesions in OA? | synovial fluid
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| Is there any bone deposition in OA? If so describe | mushroom shaped osteophytes periphery of articular surfaces
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| chronic, inflammatory disorder producing nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the cartilage and ankylosis of the joints? | RA
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| RA presents at what age range in what population | 40-70yo women
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| RA has strong association with what HLA antigen? | HLA-DR4
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| what causes the joints to be red and warm in RA? | increased vascularity in joints 2ndary to angiogenesis
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| where is pannus formation most often seen in RA? | PIP and MCP
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| what joints are characteristically spared in RA? | DIP, lumbosacral spine, hips
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| purpura, cutaneous ulcers and nail bed infarction d/t leukocytocastic venulitis is seen in what disease? | RA
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| how does JIA differ from RA in adults? | oligoarthritis, systemic involvement, and larger joint involvement increased, no RF, ANA+
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| how does the wrist and fingers deviate in RA? | Wrist->Radial; Fingers <- ulnar
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| remitting, high spiking fevers, migratory and transient skin rash, hepatosplenomegaly, and serositis in young. Dx? | Systemic arthritis type JIA
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| antibody other than RF used in dx of RA? | anti-CCP-Ab
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| seronegative spondyloarthropathies have strong association with what? | HLA-B27
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| triad of conjuctivitis/anterior uveitis, urethritis, and arthritis; caused by autoimmune rxn initiated by GI or chlamydial infxn | Reiter syndrome
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| pt presents with thick red patches of skin with silvery-white scales, asymmetric dactylitis of DIPs and swelling of ankles, knees, hips, or wrists. Dx? And 2 HLA types? | Psoriatic arthritis; HLA-B27 and HLA-Cw6
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| MCC of bacterial arthritis in Sickle cell Pt? | salmonella
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| MCC of bacterial arthritis in Pt under 2yo? | H. Flu
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| MCC of bacterial arthritis in older children and adults | S. aureus
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| MCC of bacterial arthritis in late adolescence and young adults | gonococcus.
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| This disease is characterized by males with hyperuricemia, mental retardation, neurological defects, and self mutilation. What enzyme is absent? | Lesch-Nyham syndrome; HGPRT
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| Long slender, needle like crystals, negatively birefringent. Associated disease and are phagocytosed by what 2 cells? | Gout, macrophages and neutrophils
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| This precipitates in pseudo-gout. Describe crystals | calcium pyrophosphate; rhomboid, blue-purple weakly birefringent
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| chronic, progressive monoarticular disease w/ confluent granulomas w/ central caseous necrosis most commonly in hips, knees, or ankles? Causative agent | tuberculosis
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| 2 systemic diseases associated with Gout? | CV disease and renal diseases
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| chronic, progressive monoarticular disease w/ confluent granulomas w/ central caseous necrosis in hips benign neoplasms of synovial linings, tendon sheaths and bursae; heavily infiltrated by macrophages may form multinucleated giant cells? | tenosynovial giant-cell tumor
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| solitary, slow-growing, painless mass often on tendon sheaths of wrists and fingers, most common mesenchymal neoplasm of the hand? | localized tenosynovial giant-cell tumor
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| Synovium of joint appears red-orange, mottled, with tangled mat with fingerlike projections. | diffuse tenosynovial giant-cell tumor
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| malignant fat tumor that can be large. Cells with supernumary rings and giant rod chromosomes Dx? Where? And genetic mutation? | liposarcoma; deep proximal extremities or retroperitoneum; 12q amplification and t(12;16) in myxoid/round cell variant
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| 2 week history of rapid growing madd in forearm of adult. Biopsy shows plump-immature fibroblasts, tons of mitotic bodies, and RBC/lymphs in stroma. Turns out to be non-neoplastic. Dx? | Psuedosarcoma fasciitis
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| Painless, hard, well demarcated mass, visible on x-ray in thigh of high school football player. Non-neoplastic. Dx? | Myositis ossificans
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| benign nodular or broad fascicles of fibroblasts and myofibroblasts surrounded by abundant dense collagen, leading to contractures of the 4th and 5th digits of the hand and abnml curvature of the penis and urethral constriction | superficial fibromatosis
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| what is Peyronie disease? | superficial fibromatosis of the penis
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| large infiltrative mass that grows back after incomplete excision. Made up of banal, well differentiated fibroblasts that do not metastasize | desmoid tumor
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| abdominal desmoid tumor is most common in who | pregnant women on abdominal aponeurosis
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| non-encapsulated, infiltrative soft, “fish-fleshed” mass w/ hemorrhage and necrosis, herringbone growth pattern | fibrosarcoma
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| MC soft-tissue sarcoma in childhood and adolescence | rhabdomyosarcoma
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| Small round cell tumor that stains with desmin, MYOD1, or myogenin | rhabdomyosarcoma
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| MC type of rhabdomyosarcoma | embryonic; younger than 10yo and can be treated
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| Large round or elongated cells with abundant eosinophilic cytoplasm. What is this diagnostic tumor cell? | rhabdomyoblast[
Tumor in deep musculature of extremity in adolescence; tumor w/ network of fibrous septa, cells moserate in size, with little cytoplasm. Dx? And mutation imposing poorer outcome?
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| Malignant spindle cells with cigar shaped nuclei with interweaving fascicles Dx? And where is a location with poor prognosis? | leiomyosarcoma; retroperitoneum
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