26 Bones Joints And ST Flashcards

Question

Treat osteopetrosis

Answer 1

HSC transplant | Osteoclasts are produced from donor stem cells and may reverse many of the skeletal anomalies

Answer 2

bones of endochondral origin, most commonly at the metaphysis of long bones (especially near the knee) If they arise from the pelvis, scapula, or ribs they are sessile and have short stalks

Answer 3

Sporadic: CDKN2A, IDH1/2 mutations Syndromic: EXT, IDH1/2 mutations

Answer 4

Non-epithelial tissue excluding the skeleton, joints, CNS, hematopoietic and lymphoid tissues Benign tumors >> malignant sarcomas (100x), exception: skeletal muscle neoplasm sarcomas == 2% of cancer mortality in the US (ie they are highly aggressive) majority of sarcomas are sporadic Tumors often occur in extremities (thigh) 15% occur in children, incidence ↑ with age

Answer 5

Common with open fractures | Malnutrition and skeletal dysplasia hinder healing

Answer 6

Cox-2 inhibitors, trk inhibitors tamoxifen

Answer 7

Diagnosis: DEXA, or quantitative CT measure bone density. NO LABS for diagnosis Treatment: exercise, Ca++/vitamin D intake, prescription (bisphosphonates, denosumab (anti-RANKL) bisphosphonates reduce osteoclast activity and induce apoptosis HRT → DVT, stroke

Answer 8

Ollier disease and Maffucci syndrome non-hereditary disorders characterized by multiple enchondromas Maffucci syndrome is, in addition, distinguished by presence of spindle cell hemangiomas and patients are at increased risk of developing ovarian carcinomas and brain gliomas enchondromas are sometimes more cellular than sporadic enchondromas and exhibit cytologic atypia Tumors may be numerous and large → severe deformities Patients are mosaics (IDH1/2 mutations) increased potential for sarcomatous transformation most likely site of metastasis with malignant transformation == lung

Answer 9

Herniation of synovium through a joint capsule OR massive enlargement of a bursa eg Baker Cyst of the popliteal fossa in rheumatoid arthritis Synovial lining may be hyperplastic and contain inflammatory cells and fibrin

Answer 10

Morphology Edematous granulation tissue containing lots of plasma cells and necrotic bone Spirochetes are seen with silver stains Gummas can also form

Answer 11

``` Definition Malignant tumor of adipose tissue Scattered atypical spindle cells 50-60 year olds Relatively indolent Location Deep extremity, retroperitoneum Mutations Amplification of 12q13-q15 = MDM2 encodes an inhibitor of p53 ```

Answer 12

Ewing Sarcoma: arises in the medullary cavity, invades the cortex, periosteum, and soft tissue Sheets of primitive round cells without much differentiation, rich in glycogen small, round blue cells with scant cytoplasm Tumor contains areas of hemorrhage & necrosis Homer Wright rosettes: Round groupings of cells with central fibrillary core. indicate neuroectodermal differentiation Periosteal reaction: layers of reactive bone deposited in an "onion-skin" fashion characteristic

Answer 13

Chronic inflammatory arthropathy associated with psoriasis that affects peripheral and axial joints and entheses (tissue connecting ligaments and tendons to bones) Develops in 10% of patients concurrently or after onset of skin disease HLAB27, HLA-Cw6 confer susceptibility 30-50 years old when signs and symptoms manifest

Answer 14

Benign: giant cell tumor, giant cell reparative granuloma, extraosseous hematopoietic tissue Sarcoma: osteosarcoma or fibrosarcoma of the long bones, pelvis, skull, spine

Answer 15

systemic, chronic, autoimmune etiology (females > males) 20-40 year olds, HLA-DR4 Chronic inflammatory disorder of autoimmune origin that may affect many tissues/organs, primarily affects small joints → non-suppurative proliferative and inflammatory synovitis Skin, heart, vessels, lungs (can resemble other autoimmune diseases) Can progress to destruction of articular cartilage and ankyloses Commonly happens after an infection (trigger

Answer 16

On the matrix surface Synthesize, transport and assemble matrix, regulating mineralization May become inactive over time which is indicated by ↓ cytoplasm Some may remain on the surface of trabecula, others become embedded in the matrix (osteocytes) produce monocyte colony stimulating factor (M-CSF) that activates osteoclast precursors to become osteoclasts

Answer 17

amantinoma from the table Malignant, primary bone tumor of unknown origin Cortical, fibrous bone matrix with epithelial islands Location: tibia 30-40 year olds

Answer 18

Lesions occur due to degeneration of articular cartilage + disordered repair in weight bearing joints Three phases Chondrocyte injury (genetics, biochemical) Early OA: proliferation for remodeling of cartilaginous matrix and secondary inflammatory changes Late OA: chondrocyte drop out due to repetitive injury and chronic inflammation → extensive subchondral bone changes All extracellular components are affected Proteoglycan composition is altered Sparse inflammatory cells, but many other inflammatory factors are present: TGFβ (induces MMPs), TNF, prostaglandins, and nitric oxide

Answer 19

Diaphysis of long bones (femur + flat bones of pelvis) and shoulder

Answer 20

Mutations affect acidification of the osteoclast resorption pit, which is necessary for the dissolution of calcium hydroxyapatite within the matrix ahem CA2 (carbonic anhydrase 2) autosomal recessive: acidification of urine is blocked with the lack of acidification of the pit --> metabolic acidosis CLCN7: encodes the proton pump on the surface of osteoclasts

Answer 21

Definition Malignant tumor of uncertain histology 40-70 year olds largest category of adult sarcomas no reproducible genetic changes Location Thigh, deep soft tissue of extremities Morphology Sheets of high grade anaplastic polygonal, round or spindle cells Bizarre nuclei, atypical mitoses, necrosis Treatment and prognosis Aggressive malignancies treated with surgery and chemo +/- radiation Poor prognosis; 30-50% rate of metastases

Answer 22

Staph Aureus: 80-90% of culture positive cases of osteomyelitis. Cell wall proteins bind bone matrix components (collagen) facilitating adhesion staph == coagulase positive (aureus only), catalase positive coagulase positive == staph aureus and nothing else strep == coagulase negative, catalase negative E. Coli, Pseudomonas, Klebsiella: patients with genitourinary infections or IV drug users Mixed infection: Direct spread or inoculation of organisms during surgery or into open fractures Neonatal: H. Influenzae, group B strep Sickle cell: Salmonella typhi 50% of cases = no organism can be isolated

Answer 23

Formation of bone by tumor cells is diagnostic Large, destructive, grey-white, gritty +/- hemorrhage and cystic degeneration Large, hyperchromatic, pleomorphic, mitotically active tumor cells Neoplastic bone has a fine, lace-like pattern Osteoblastic, chondroblastic, or fibroblastic differentiation

Answer 24

Malignant tumors producing cartilage Conventional (90%): hyaline cartilage producing 2nd most common malignant matrix producing tumor of bone (half as common as osteosarcoma) patients older than 40 years, males 2X

Answer 25

Age: Diminished capacity to form bone (senile form aka low turnover variant) Reduced physical activity: Mechanical forces stimulate bone remodeling.: Weight training (load magnitude) exercise is better Genetics: RANKL, RANK, OPG, HLA locus, estrogen receptor Calcium nutritional state: impacts the bone density peak that can be achieved, especially affected are adolescent females Hormones

Answer 26

Typically regresses spontaneously | If excised: rarely recurs

Answer 27

fundamental abnormality == too little bone → extreme skeletal fragility Blue sclera: ↓ collagen = translucent sclera and partial visualization of the underlying choroid Hearing loss: related to both sensorineural deficit and impeded conduction due to bone abnormalities in the middle and inner ear Dental imperfections: Small, misshapen, blue-yellow teeth secondary to deficiency in dentin

Answer 28

Polyostotic disease unilateral bone disease, with café-au-lait pigmentation ipsilateral dark, irregular serpiginous borders on neck, back, chest, shoulder, and pelvic areas skin pigmentation is usually limited to the same side of the body Precocious puberty is the most common clinical presentation, especially in girls treat with aromatase inhibitors Endocrinopathies: hyperthyroidism, growth hormone excess, primary adrenal hyperplasia GNAS1 mutation

Answer 29

Benign tumor of skeletal muscle frequent in individuals with tuberous sclerosis Polygonal rhabdomyoblasts, "spider cells" Location: head & neck 0-60 year olds

Answer 30

One of the most common sarcomas of adulthood

Answer 31

Variant of embryonal rhabdomyosarcoma Develops in the walls of hollow, mucosal lined structures: Nasopharynx, common bile duct, vagina, bladder Form cambium layer (submucosal zone of hypercellularity) on organ mucosa Best outcome of all subtypes

Answer 32

Adolescents knee

Answer 33

Typically multifocal Kidney, thyroid cancers may be solitary Most involve the axial skeleton: Red marrow has rich capillary network and slow blood flow allowing implantation and growth of tumor cells Hand or foot involvement is uncommon (lung, kidney, colon

Answer 34

Definition Benign tumor of smooth muscles 20 year olds uterine leiomyomas are the most common neoplasm in women Location Extremities, uterus, erector pili muscles (pilar) of skin, nipples, scrotum, labia, gut Pilar = multiple & painful Morphology Uniform, plump, eosinophilic cells in fascicles intersecting at right angles Blunt ended elongated nuclei Minimal atypia, few mitotic figures Treatment Solitary = easily cured Multiple: complete surgical removal may be impractical

Answer 35

RB (70% of sporadic) 1,000x ↑ risk TP53: the guardian of the genome Li-Fraumeni patients have ↑ risk INK4a: encodes p16 (negative regulator of CDKs) and p14 (augments p53 function) MDM2 (inhibits p53) & CDK4 (inhibits RB): overexpressed in low grade osteosarcomas via amplification of 12q13-q15

Answer 36

Originate from HSCs rather than mesenchymal stem cells Specialized multinucleated macrophages derived from circulating monocytes Responsible for bone resorption Attach to bone matrix via integrins → resorption pit (sealed extracellular trench) Dissolution of bone components occurs due to secretion of acid and neutral proteases (MMPs) into the pit

Answer 37

Excess levels of this hormone occur due to autonomous secretion (primary) OR Renal disease (secondary): inadequate 1,25(OH)2D synthesis (altered GI absorption) & hyperphosphatemia suppression of α1-hydroxylase Secondary hyperPTH is typically milder Significant skeletal change due to unabated osteoclast activation Entire skeleton affected Bone changes are completely reversible with reduction of hormone levels

Answer 38

Manifests somewhat earlier and may cause problems into adulthood May require corrective orthopedic surgeries, bisphosphonates Affects femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, vertebra 50% with craniofacial involvement, 100% in patients with extensive skeletal disease Progressive deformities & fractures when involvement of the shoulder or pelvic girdles occurs Rare complication == malignant transformation of a lesion into sarcoma can occur

Answer 39

Malignant tumors producing cartilage, more aggressive Low grade tumor with a second, high grade component that does not produce cartilage Treatment: widely excised + additional chemotherapy because of more aggressive course

Answer 40

efinition Most common type of joint disease Degeneration of articular cartilage and disordered repair→structural and functional failure of synovial joints biomechanical causes == wear and tear (eg increased age, obesity, and trauma) biochemical causes == injury to chondrocytes or abnormal matrix formation Females: knees & hands Males: hips

Answer 41

``` Definition Malignant tumor of skeletal muscles 5-15 year olds Location Extremities, sinuses Genetics Genetically heterogenous FOXO1 fusion to PAX3 or PAX7 t(2;13) or t(1;13) Morphology Uniform, round, discohesive cells with little cytoplasm between septae (look like alveoli) Discohesive center with peripheral cells adherent to the septae No cross striations ```

Answer 42

Hips, knees, lower lumbar & cervical vertebra, proximal & distal interphalangeal joints of fingers, 1st carpometacarpal & 1st tarsometatarsal joints Wrists, elbows and shoulders are spared

Answer 43

Bone involvement is infrequent due to earlier diagnosis and treatment Bone lesions appear in the 5th months of gestation and are fully developed at birth Spirochetes localize to areas of active enchondral ossification (osteochondritis) and in the periosteum (periostitis) Saber shin: massive reactive periosteal bone deposition on the medial & anterior surfaces of the tibia (don't forget about Hutchinson teeth) If acquired, bone disease manifests 2-5 years after initial infection and involves the nose, palate, skull and extremities (long bones

Answer 44

ormonal Control of Bone Growth Growth hormone stimulates chondrocytes to induce and maintain proliferation Thyroid hormone (T3) stimulates chondrocyte proliferation Indian Hedgehog coordinates chondrocyte proliferation and differentiation and osteoblast proliferation PTHrP activates PTH receptor and maintains proliferation of chondrocytes Wnt activates β-catenin signaling; can promote both proliferation and maturation of chondrocytes Wnt proteins produced by osteoprogenitor cells bind to the LRP5 and LRP6 receptors on osteoblasts and trigger the activation of β-catenin and the production of OPG sclreostin (produced by osteocytes) inhibits WNT/β-catenin signaling SOX9 is essential for differentiation of precursor cells into chondrocytes RUNX2 controls terminal chondrocyte and osteoblast differentiation Fibroblast Growth Factors act on hypertrophic chondrocytes to inhibit proliferation and promote differentiation Bone Morphogenic Proteins have diverse effects on chondrocyte proliferation and hypertrophy

Answer 45

Benign, bone forming tumor < 2cm Severe nocturnal pain due to osteoblast production of PGE2, relieved by ASA metaphysis of long bones (femur, tibia = 50%) Thick rind of reactive cortical bone radiographically 10-20 year olds, male predominance Presentations: severe nocturnal pain that is relieved by aspirin Treatment: radiofrequency ablation

Answer 46

Most common benign bone tumor Benign, cartilage capped tumor attached to the underlying skeleton via a bony stalk Slow growing solitary masses Painful if impinge on a nerve or stalk is fractured, but generally found incidentally Male predominance Late adolescence and early adulthood

Answer 47

Due to bacterial infection reaching the bone via hematogenous spread (most common in children), extension from a contiguous site, direct implantation

Answer 48

Mostly malignant

Answer 49

Neoadjuvant chemotherapy and surgical excision +/- irradiation because ESFT are aggressive malignancies 75% 5 year survival, 50% long term cure Chemotherapy induced necrosis = important prognostic factor

Answer 50

Definition Malignant tumor of adipose tissue Myxoid matrix, 'chicken wire' vessels, round cells, lipoblasts Abundant basophilic extracellular matrix, arborizing capillaries and primitive cells at various stages of differentiation (fetal fat) 30 year olds Intermediate malignant behavior Location Thigh, leg Mutation t(12;16) -- chromosome 12q == MDM2 gene (potent inhibitor of p53

Answer 51

Alveolar Embryonal (most common) sarcoma botyroides == variant embryonal rhabdomyosarcoma with the best prognosis Pleomorphic: seen predominantly in adults often fatal

Answer 52

Areas not physically stressed are resorbed, reducing the callus in size and shape The outline of the fractured bone is reestablished as lamellar bone Healing is complete with restoration of the medullary cavity

Answer 53

most common lethal form of dwarfism micromelic shortening of the limbs, frontal bossing, relative macrocephaly, a small chest cavity (--> respiratory insufficiency), and a bell-shaped abdomen gain-of-function mutations in FGFR3 that differ from those in achondroplasia

Answer 54

morning joint stiffness, worsens with use Insidious disease that presents >50 years old. Young patients likely have an underlying condition Deep, achy pain in 1-2 joints that worsens with use Morning stiffness, joint crepitus, limited range of motion, joint swelling Osteophytes may impinge on spinal foramina → cervical & lumbar nerve root compression = radicular pain, muscle spasms, muscle atrophy, and neurological deficits X-ray: joint narrowing Heberden nodes: prominent osteophytes at distal interphalangeal joints that are common in females Bouchard nodes more proximal than Heberden nodes Deformity may occur but fusion does not occur (rheumatoid arthritis == fusion/ankylosis

Answer 55

Painful, progressively enlarging mass, may present as a fracture Extends from medulla to lift periosteum = reactive periosteal bone formation Radiographically: large, destructive, lytic & blastic mass with infiltrative margins Codman triangle: triangular shadow between the cortex & raised ends of the periosteum; indicates an aggressive tumor; non-specific (characteristic but not diagnostic)

Answer 56

Can occur in any bone, but most commonly occur in the metaphysis of distal femur or proximal tibia, especially in the growth plate since there is faster cell proliferation there

Answer 57

symmetric arthritis principally affecting the small joints of the hand and feet Synovial hyperplasia and proliferation Dense inflammatory infiltrates of CD4 T helper cells, B cell, plasma cells, dendritic cells, and macrophages ↑ vascularity due to angiogenesis Fibrinopurulent exudate on the synovial & joint surfaces Osteoclast activity in underlying bone = synovium penetration of bone → periarticular erosions and subchondral cysts pannus: mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblasts that grows over the articular cartilage and causes its erosion in time, the pannus bridges the apposing bones to form a fibrous ankylosis, which eventually ossifies and results in fusion of the bones, called bony ankylosis pannus == granulation tissue --> bony ankylosis blood vessels fibroblasts myofibroblasts contract and lead to joint deviations/deformity Joint Deformity == Rheumatoid Arthritis ulnar deviation of the fingers, radial deviation of the wrist Swan Neck and Boutonniere deformities

Answer 58

Subchondral infarction: triangular/wedge shaped segment of tissue that has the subchondral bone plate as its plate undergoes necrosis The overlying articular cartilage remains viable from nutrients in the synovial fluid Dead bone is recognized as empty lacunae that are surrounded by ruptured adipocytes, which can have associated fat saponification (may remain for life) Creeping substitution with new bone occurs from the margin of the infarct, but is too slow and collapses upon itself

Answer 59

due to deficient osteoclast activity, bone lacks a medullary canal ends of long bones are bulbous (Erlenmeyer flask deformity) neural foramina are small, compressing exiting nerves II, VII, and VIII primary spongiosa is not removed, filling the medullary cavity leading to no hematopoietic marrow and preventing the formation of mature trabeculae woven architecture of newly deposited bone diffuse skeletal sclerosis (bones look wider but they are brittle because increased woven bone) = fractures

Answer 60

Somatic GNAS1 gain-of-function mutation same gene is mutated in pituitary adenoma Constitutively active GS protein, activating cAMP→ cellular proliferation Extent of phenotype depends on stage in which the mutation occurs and the fate of cell harboring the mutation McCune Albright occurs when mutations happens during embryogenesis monostotic fibrous dysplasia happens when mutation occurs in one osteoblast precursor during or after skeletal formation

Answer 61

Large, infiltrative masses that frequently recur (no metastases) Benign fibrous tumor Teens-30s Female predominance

Answer 62

Variable clinical presentation based on extent and site of disease Most are asymptomatic and discovered incidentally 85% of cases are poly-ostotic (involve more than one bone) 80% involve the axial skeleton (head/trunk) or proximal femur Pain localizes to the affected bone due to microfractures or bone overgrowth compressing spinal and cranial nerve roots Bone pain/deformity (bowing of tibia) and/or nerve entrapment Leontiasis ossea (lion face): enlargement of craniofacial skeleton (frontal bone) and a cranium so heavy that it is difficult to hold up Platybasia: invagination of the skull base → compression of the posterior fossa Weight bearing = anterior bowing of femurs and tibia → distortion of femoral heads --> 2˚ osteoarthritis in the absence of malignant transformation, Paget disease is usually not a serious or life-threatening disease

Answer 63

``` Benign, bone forming tumor >2cm (larger) No bony reaction involves the posterior spine (laminae & pedicles) 10-20 year olds Pain is not responsive to aspirin Treatment: curetted or excised in bloc ```

Answer 64

t(1;2)(p13;q37): Type VI collagen α-3 promoter with M-CSF = M-CSF overproduction --> proliferation of macrophages (similar to giant cell tumor of bone

Answer 65

Sharply demarcated radiolucencies with a long axis of bone parallel to the cortex, surrounded by a thin rim of sclerosis Fibroblasts are arranged in a storiform (pinwheel) pattern Macrophages are clustered together with foamy cytoplasm or giant cells Limited growth potential, and spontaneously regress

Answer 66

Older adults pelvis and proximal extremities

Answer 67

Conventional Clear cell Dedifferentiated Mesenchymal

Answer 68

< 1% of all bone disease 50% are lethal Found from bone pain or pathological fractures Treatment is often disfiguring Goal: optimize survival & maintain function of affected body parts bone tumors are classified according to the normal cell or matrix they produce lesions that do not have normal tissue counterparts are grouped according to their clinicopathologic features Risk factors Chronic injury and inflammation: bone infarcts, chronic osteomyelitis, Paget disease, radiation, metal prostheses

Answer 69

Arthritis may be accompanied by inflammation of tendons, ligaments and adjacent skeletal muscles Radial deviation of wRist, ulNar deviation of fiNgers -- RR and NN Swan-neck deformity: PIP extension + DIP flexion Boutonniere deformity: PIP flexion + DIP extension Characteristic rheumatoid nodules that can present in places like the lung or skin

Answer 70

AKA pseudogout or chondrocalcinosis patients > 50 years old, incidence increases with age Sporadic (idiopathic) or hereditary Causes Autosomal dominant mutation of pyrophosphate transport channel Secondary form: previous joint damage, hyperparathyroidism, hemochromatosis (HFE mutation), hypothyroidism, diabetes, ochronosis Pathogenesis Proteoglycans (normally inhibit mineralization) are likely degraded, allowing crystallization around chondrocytes Inflammation is caused by activation of inflammasome in macrophage Morphology Crystals first develop in the articular cartilage, menisci, intervertebral discs Crystals are chalky, white, friable deposits Crystals are rhomboid and positively birefringent

Answer 71

Palmar Fibromatosis (Dupuytren Contracture) Irregular or nodular thickening of the palmar fascia uni- or bi-laterally Puckering and dimpling of the skin may occur over years Slow, progressive flexion contracture affects the 4th and 5th digits of the hand 25% do not progress

Answer 72

Intramembranous ossification is responsible for the development of flat bones and facial bones unaffected in achondroplasia

Answer 73

Purine catabolism → uric acid ↑ uric acid likely due to abnormal purine production Most primary causes are due to this

Answer 74

Occurs during early adolescence Stops enlarging at the time of growth plate closure Asymptomatic lesion of a single bone, incidentally discovered Femur, tibia, ribs, jaw, calvarium, humerus Can cause pain, fracture, limb length discrepancies Radiographic: ground glass appearance, well defined margins If symptomatic: treat with curettage (curative

Answer 75

Contain complex karyocytes without reproducible genetic abnormalities Sheets of anaplastic cells Bizarre nuclei Variable number of immature adipocytes (lipoblasts) Aggressive tumor that frequently metastasizes Liposarcoma treatment

Answer 76

Mechanical injury to blood vessels: thromboembolism, external pressure on vessels, venous occlusion Often due to fracture or corticosteroid administration Alcohol abuse, Bisphosphonates (especially jawbones), pregnancy

Answer 77

Rickets (children) Vitamin D deficiency or abnormal metabolism Impaired mineralization → accumulation of under-mineralized matrix disease of children (called osteomalacia in adults) Interferes with deposition of bone in the growth plates

Answer 78

Osteopenia ↓ bone mass Bone mass 1-2.5 standard deviations below mean peak bone mass in young adults

Answer 79

Curettage (40-60% recur) 4% metastasize to lungs, but spontaneously regress -- do not usually undergo malignant transformation RANKL inhibitor (denosumab) as adjuvant therapy

Answer 80

ocalized problems in the migration and condensation of mesenchyme; transcription factors, homeobox genes, cytokines and cytokine receptors aplasia: complete absence of a bone or entire digit supernumerary digit: extra bones or digits syndactyly, craniosynostosis: abnormal fusion of bones

Answer 81

Multiloculated, hemorrhagic, cystic spaces separated by cellular, fibrous septae Lesions are completely lytic with a thin shell of reactive bone at the periphery Plump uniform fibroblasts and reactive woven bone that is lined by osteoblasts and follows the contours of the fibrous septa 1/3 contain a densely calcified matrix call "blue bone

Answer 82

Attempt at healing Chronic inflammatory infiltrates stimulate osteoclastic bone resorption, ingrowth of fibrous connective tissue and deposition of reactive tissue after the first week Involucrum: sub-periosteal new bone encasing the inflammatory focus; newly deposited bone can form a shell of living tissue, known as the involucrum Brodie abscess: small, walled off intracortical abscess Sclerosing osteomyelitis of Garre: extensive new bone formation of the jaw obscuring the underlying osseous structure

Answer 83

Insidious onset of malaise, fatigue, generalized musculoskeletal pain mediated by IL1 and TNF Joints become involved weeks-months later Small joints affected before large joints (hands and feet followed by wrists, ankles, elbows, knees) OA == PIP and DIP, Bouchard and Heberden = osteophytes at those joints RA == MCP and PIP Lumbosacral region & hips are usually spared Symmetric, progressive joint enlargement & ↓ ROM bilateral Swollen, warm, painful, stiff in morning or after inactivity (progresses to ankylosis) Periods of remission: recurrence involves previously unaffected joints Baker cyst of posterior knee: develop due to ↑ intraarticular pressure → herniation of the synovium

Answer 84

Cortex is thinned by sub-periosteal and endosteal resorption | Haversian systems are widened

Answer 85

ay appear as Lytic (bone destroying) due to secretion of prostaglandins, cytokines, PTHrP upregulating RANKL carcinomas of the kidney, lung, and gastrointestinal tract and malignant melanoma produce lytic lesions; do not directly resorb bone Blastic (bone forming) prostatic adenocarcinoma is predominantly -blastic ^^outlier

Answer 86

Malignant tumors producing cartilage, more aggressive Occur in younger patients (teens-20s) Islands of well-differentiated hyaline cartilage surrounded by sheets of small round cells Treatment: widely excised + additional chemotherapy because of more aggressive course

Answer 87

Synovium contains germinal centers with secondary follicles + abundant plasma cells that produce antibodies (some vs. self-antigens) many of the autoantibodies produced are specific for citrullinated peptides (CCPs) in which arginine residues are post-translationally converted to citrulline (de-aminated?) Rheumatoid Factor: serum IgM or IgA auto-antibodies specific for the Fc portion of self-IgG non-specific Antigen/Antibody complexes deposit in the joints Anti-CCP antibodies and T-cell response to citrullinated proteins → chronic disease CCPs are produced during inflammation (smoking, infection may promote citrullination of self-proteins

Answer 88

↑ but disordered and structurally unsound bone mass Progresses through three stages: Osteolytic stage Mixed osteoclastic-osteoblastic stage --> ends with predominant osteoblastic activity burned out quiescent osteosclerotic stage

Answer 89

Chondrocyte clusters (cloning) while the water content of the matrix increases and the proteoglycans decrease Joint mice: articular surface is soft with dislodged fragments of cartilage and subchondral bone forming loose bodies Bone eburnation: exposed subchondral bone is burnished by opposing degenerated articular surface Underlying cancellous bone becomes sclerotic Cystic space formation due to small fractures -- subchondral bone cysts Mushroom-shaped osteophytes (bony outgrowths) develop at edges of articular cartilage subchondral bone sclerosis

Answer 90

typically located near joints --> frequently causes arthritis-like symptoms Epiphysis (the only one) of long bones (may extend to metaphysis) Common around the knee (distal femur, proximal tibia) Solitary (multicentric in distal extremities

Answer 91

Arthritic signs and symptoms within weeks of inciting urethritis or diarrhea low back pain and joint stiffness (ankles, knees, feet), asymmetric Arthritis waxes and wanes over weeks to months 50% have recurrent arthritis, tendonitis and lumbosacral pain red, swollen joint == get a tap, stick a needle in it will see sterile synovial fluid (no bacteria in the joint space

Answer 92

Subchondral infarcts: Pain initially associated with activity then becomes persistent. Articular cartilage collapses → severe, secondary osteoarthritis Medullary infarcts: small, clinically silent except when they arise in the setting of Gaucher disease, dysbarism (the "bends"), and sickle cell anemia Gaucher disease: inborn error of metabolism that leads to problems with glucocerebrosidase more than 10% of the 500,000 joint replacements performed annually in the United States are for treatments of complications of osteonecrosis

Answer 93

60-70% 5 year survival Hematogenously spread to lungs (seen at diagnosis in 10-20%) Of those who die: 90% have metastases to the lungs, bones, brain, etc Outcome with metastases, recurrence or secondary disease is poor (< 20% 5 year survival

Answer 94

Often asymptomatic Can produce acute, subactue or chronic arthritis (confused with osteoarthritis or rheumatoid arthritis) Joint involvement lasts days-weeks Monoarticular or polyarticular, knees and wrists 50% experience significant joint damage Treatment Supportive there is no known treatment that prevents or slows crystal formation

Answer 95

Rheumatoid arthritis == small joints, symmetrical, improves with use x-ray == juxta-articular osteoporosis and bone erosion osteoarthritis == weight bearing joints, asymmetrical, improves with rest fuck it

Answer 96

Joint effusions juxta-articular osteopenia with erosions and narrowing of joint space loss of articular cartilage

Answer 97

Osteopenia that is severe enough to significantly ↑ risk of fracture Bone mass 2.5 standard deviations below mean peak bone mass in young adults (2.5 and lower) Can also be indicated by the presence of an atraumatic or vertebral compression fracture May be primary or secondary Most common types: senile and postmenopausal May be localized (disuse) or involve the entire skeleton (manifestation of a metabolic disease

Answer 98

Painful, progressively enlarging masses Direct correlation between grade & biologic behavior Most are grade 1 with 80-90% 5 year survival Grade 1: rarely metastasize Grade 3: 70% metastasize (lungs

Answer 99

APC or β-catenin mutations = ↑ Wnt signaling Usually sporadic individuals with familial adenomatous polyposis (Gardner syndrome) who have germline APC mutations are predisposed to deep fibromatosis

Answer 100

Giant cell inflammation Inflammation is triggered by monosodium urate crystals in the joints which produces cytokines that recruits leukocytes macrophages phagocytose the crystals Inflammasome recognizes crystals activating caspase1 → IL1 IL1 = accumulation of neutrophils, leukotrienes, & macrophages into the joint, which promote further recruitment of leukocytes, damaging the joint Crystals may also activate complement Attack spontaneously remits in days to weeks

Answer 101

Hematogenous seeding of joints, direct inoculation or via contiguous spread from soft tissue abscess/osteomyelitis Can cause rapid joint destruction → permanent deformities single, red, hot, swollen, painful joint that shows >50,000 WBCs, no crystals, and positive for microbes

Answer 102

Chalk stick-type fractures: occur in long bones Compression fracture of spine → kyphosis High output cardiac failure may arise in severe cases Hypervascularity of bone warms overlying skin (acts as arterio-venous shunt

Answer 103

↑ expression of RANKL (promotes proliferation of osteoclasts) Normal feedback that regulates osteoclast activation is absent → highly destructive, localized resorption Destroys medulla and cortex

Answer 104

Most common form of skeletal malignancy Direct extension, lymphatic or hematogenous spread, or intraspinal seeding (Batson plexus of veins) 75% in adults originate from prostate, breast, kidney and lung (especially adenocarcinomas) Children: Neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma Dim prognosis (indicates widely disseminated cancer

Answer 105

Gout (monosodium urate) needle-shaped crystals negative birefringent Pseudogout (calcium pyrophosphate dehydrate) rhomboid-shaped crystals (weakly) positive birefringent: yellow under parallel light, blue under perpendicular light associated with underlying metabolic diseases (eg diabetes, hypothyroidism) Calcium phosphate Exogenous crystals Corticosteroid ester crystals, talcum, polyethylene, methyl methacrylate Some are used in artificial joints and accumulate with long use → joint failure

Answer 106

Morphology | Histologically normal bone, but decreased quantity of trabecular bone

Answer 107

Abdominal wall (musculoaponeurotic structures), limb girdle, mesenteries

Answer 108

Ganglions Synovial cysts Osteochondral loose bodies usually result from trauma or degenerative processes; much more common than neoplasms neoplasms (rare) are benign and tend to recapitulate cells and tissue types native to joints

Answer 109

Benign, cartilage forming tumor Circumscribed, pericellular calcification Location: epiphysis of long bones 10-20 year olds

Answer 110

Loss of bone integrity due to mechanical injury and/or diminished bone strength Simple: overlying skin intact Compound: bone communicates with skin surface Comminuted: bone is fragmented Displaced: ends of bone at site are not aligned Stress: slowly develops with physical activity and repetitive loads Greenstick: extending only partially through the bone, common in infants when bones are soft Pathologic: associated with an underlying disease process (tumor

Answer 111

Discrete nodule attached to a tendon sheath Well circumscribed with the tumor cells growing in a solid aggregate attached with a pedicle Affects small joints like the hand

Answer 112

Arise in the synovial lining of joints, tendon sheaths and bursae Can either be diffuse or localized types patients are 20-40 years old

Answer 113

Conversion of the procallus activated osteoprogenitor cells deposit subperiosteal trabeculae of woven bone that are oriented perpendicular to the cortical axis and within the medullary cavity Fibrocartilage and hyaline cartilage are also produced Undergoes enchondral ossification → newly deposited bone in the medulla and beneath the periosteum Allows fracture site stabilization by the end of the 2-3rd week with maximal girth Fracture ends are bridged: as it mineralizes stiffness and strength of the callus increases allowing controlled weight bearing

Answer 114

Disfiguring and disabling Occasionally painful if infiltrative, complete resection is difficult Marked infiltration of surrounding muscles, nerves, and fat pops up in Gardner syndrome intestinal polyps, multiple osteomas, and soft tissue tumors Gardner Syndrome == when the extra-intestinal manifestations are more prominent

Answer 115

↑ RANKL on osteoblasts Osteoclast activation -- hyperparathyroidism leads to significant skeletal changes related to unabated osteoclast activity ↑ bone resorption and calcium mobilization ↑ resorption of calcium by renal tubules ↑ urinary excretion of phosphates ↑ synthesis of active vitamin D by the kidneys ↑ calcium absorption from the gut Net: ↑ serum calcium

Answer 116

Wide surgical excision

Answer 117

group of lysosomal storage disease that are caused by deficiencies in the acid hydrolases that degrade dermatan sulfate, heparan sulfate, and keratan sulfate mucopolysaccharides from the extracellular matrix accumulate inside the chondrocytes causing apoptosis skeletal manifestations result from abnormalities in hyaline cartilage

Answer 118

Amenable to surgery, recurrence is common Pain, locking & recurrent swelling (similar to monoarticular arthritis) Tumor progression = limited ROM and stiff, firm joint Aggressive: erode into adjacent bones and soft tissue Clinical features of localized type Solitary, slow growing, painless mass of tendon sheaths (wrists/fingers) Most common mesenchymal neoplasm of the hand Cortical erosion of bone happens in 15% of cases Treatment Local excision, recurrence is common M-CSF antagonists potentially

Answer 119

Method of spread Bacterial infection enters the joint via hematogenous spread Neonates: contiguous spread from underlying epiphyseal osteomyelitis Causative bacteria: Children < 2: Haemophilus Influenzae Older children/adults: Staphylococcus Aureus (most common overall) diagnosis: +ve gram stain with cocci in clusters Late adolescent/young adult (sexually active females): Gonococcus (Neisseria gonorrhea) patients with MAC deficiencies: disseminated gonococcal infections Sickle cell patients: Salmonella (typhi) Presentation Sudden development of acutely painful and swollen joint with restricted ROM Systemically: fever, leukocytosis, ↑ESR 90% of all non-gonococcal = single joint (knee is the most common) IV drug users: axial joints Diagnosis and Treatment Joint aspiration with purulent fluid helps to identify causal agent Effective antimicrobial therapy prevents joint destruction

Answer 120

Diagnosed at 70 years old (many are asymptomatic) Whites in England, France, Austria, Germany, Australia, NZ, USA Rare: Scandinavia, China, Japan, Africa

Answer 121

Asymptomatic hyperuricemia (puberty: males; post-menopause: females) Acute arthritis: Sudden onset of excruciating joint pain and localized hyperemia & warmth First attacks are monoarticular, 50% in 1st metatarsophalangeal joint (then affect insteps, ankles, heels, knees, wrists, fingers, elbows) Asymptomatic inter-critical period: Without adequate treatment, the attacks occur at shorter intervals and may become polyarticular Chronic tophaceous gout Develops ∼ 12 years after the initial acute attack and the appearance of chronic tophaceous arthritis Chronic Tophaceous Arthritis Radiographs show juxta-articular bone erosion due to osteoclastic bone resorption and loss of joint space; progression leads to severe, crippling disease gout does not materially shorten life span but it may impair the quality of life

Answer 122

Neoadjuvant chemotherapy + surgery | assume that all patients have occult metastases at the time of diagnosis

Answer 123

Too much bone

Answer 124

Woven bone: Rapidly produced (fetal development, fracture) with less structural integrity due to haphazard arrangement of collagen and always abnormal in adults

Answer 125

Surgical (curettage or en bloc resection) | Low recurrence, and if incomplete excision spontaneous regression may occur

Answer 126

I’ll-6 receptor antibody systemically

Answer 127

anglion Cyst Small (1-1.5cm), multi-loculated, cystic lesions of connective tissue near joint capsules (wrist) or tendon sheaths Firm, fluctuant, pea-sized, translucent nodule that contains synovial fluid Due to cystic or myxoid degeneration of connective tissue (lacks cell lining) No communication with joint spaces

Answer 128

Lamellar bone: Slowly produced with parallel fibers and more strength

Answer 129

Sporadic forms exhibit ↓ EXT1, EXT2 ↓ or abnormal synthesis of glycosaminoglycans = abnormal diffusion of Indian Hedgehog (Ihh), which regulates cartilage growth

Answer 130

Develop in instances of delayed diagnosis, extensive bone necrosis, inadequate antibiotic therapy or surgical debridement, or due to weakened host defenses May experience acute flare ups spontaneously after years of dormancy May also have pathologic fractures, secondary amyloidosis, endocarditis, sepsis, squamous cell carcinoma development in draining sinus tracts and sarcoma of the infected bone

Answer 131

Proximity of tumors to joints → arthritis like signs and symptoms May present with pathologic fractures

Answer 132

Gray-white, firm, poorly demarcated masses (1-15cm) Rubbery & tough Histologically resembles a scar Dense collagen, long, unidirectional fascicles

Answer 133

Hyperuricemia (>6.8 mg/dl) is necessary, but not sufficient levels to develop gout Can be due to too much synthesis or too little excretion Repeated attacks of acute arthritis → chronic tophaceous arthritis Formation of tophi in synovial membranes and periarticular tissue = severe damage to cartilage, compromising joint function

Answer 134

Suppurative Mycobacterial Lyme Viral

Answer 135

resentation Similar to rheumatoid arthritis, except involves DIP, is not as severe, more frequent remissions and less frequent joint destruction Predominantly peripheral arthritis of hands and feet DIP involvement → "pencil in cup" deformity Rheumatoid Arthritis == PIP, not the DIP Osteoarthritis == DIP and PIP, not the MCP 20% involve SI joints -- least associated with SI joint involvement

Answer 136

Mutations of Types II, IX, I, XI collagen type mutations are related to abnormal hyaline cartilage synthesis Severe disorders: absence of type II leads to insufficient bone formation Mild disorders: reduced synthesis of type II

Answer 137

Hyaline cartilage == elastic shock absorber and wear resistant surface water, Type II collagen, and proteoglycans avascular, does not have a lymphatic drainage, and is not innervated

Answer 138

50% of familial cases & 10% of sporadic SQSTM1 mutations (familial) → ↑ NFκB activity = ↑ osteoclast activity Juvenile cases Activating RANK mutations Inactivating OPG mutations Chronic infection by measles or other RNA viruses affect vitamin D sensitivity and IL6 secretion by infected osteoclasts

Answer 139

Definition Borrelia burgdorferi Transmitted via Ixodes ricinus deer ticks Leading arthropod borne disease in USA Presentation Initial skin infection progresses to other organs, particularly large joints in days to weeks 60-80% of untreated patients develop late stage arthritis of large joints (knees, shoulders, elbows ankles) 1-2 joints affected at a time, attacks for weeks-months then migrates to a different site which dermatologic manifestation is most likely associated == erythema migrans Diagnosis and Treatment Spirochetes identified in 25%, confirmed with serology antibodies antibiotics Chronic, Antibiotic Refractory Develops in 10% of patients Organism is not detected in joint fluid even via PCR Infected synovium → chronic synovitis with synovocyte hyperplasia, fibrin deposition, mononuclear cell infiltrates (CD4+), onion skin thickening of arterial walls Morphology often resembles rheumatoid arthritis

Answer 140

Children and young adults = perfect unions are the norm | Older adults may require surgical immobilization for adequate repair

Answer 141

Changes are dependent on the chronicity and location Entrapped bone becomes necrotic within 48 hours Bacteria and inflammation percolate within the shaft and along the haversian systems to involve the periosteum Lifting of the periosteum further compromises the vascular supply → zone of bone necrosis Dead bone = sequestrum Periosteum rupture → soft tissue abscess and a draining sinus to the skin

Answer 142

Polyostotic fibrous dysplasia presents in childhood with multiple deformities Intramuscular myxomas present in adulthood in the same areas as the fibrous dysplasia Benign, but can cause compression signs and symptoms treatment: surgery is curative

Answer 143

Type II collagen: frictionless movement | Proteoglycans: resistance to tension & compression

Answer 144

Painful, enlarging masses: tenderness, warmth and swelling Systemic signs and symptoms mimicking infection may be present: fever, elevated ESR, anemia, and leukocytosis Radiographs: destructive, lytic tumor with permeative margins extending into soft tissues

Answer 145

Malignant tumors producing cartilage Seen in younger patients (teens-20s) unique in that it originates in the epiphyses of long tubular bones Sheets of large, malignant chondrocytes with abundant, clear cytoplasm Numerous osteoclast-type giant cells Intralesional reactive bone formation

Answer 146

inflammatory bowel disease: ulcerative colitis or Crohn's disease + arthritis treating the IBD resolves the arthritis Due to gastrointestinal infection (eg Yersinia, Salmonella, Shigella, Campylobacter, etc) LPS of the organisms outer membrane stimulates immunologic response Arthritis appears abruptly Involves knees and ankles (sometimes wrists, fingers, toes) Lasts ∼ 1 year then clears Rarely accompanied by ankylosing spondylitis if treat the IBD and the arthritis persists, likely have one of the other seronegative spondyloarthropathies (ie ankylosing spondylitis

Answer 147

Very common benign tumor of mature adipose tissue Subclassified based on morphology or molecular features: conventional lipoma (most common subtype), fibrolipoma, angiolipoma, spindle cell lipoma, myelolipoma Soft, mobile, painless (except angiolipoma) and cured by simple excision, and encapsulated Location: superficial extremities and the trunk 40-60 year olds, most common soft tissue tumor of adulthood

Answer 148

Malignant, large, bulky, cartilage producing tumors Transluscent cartilage with gelatinous or myxoid matrix (may ooze from cut surfaces) Spotty calcifications Central necrosis → cystic spaces Infiltrates surrounding muscle/fat and marrow space, surrounds preexisting bony trabeculae Grade ranges from 1 (low cellularity) to 3 (high cellularity

Answer 149

Ewing Sarcoma Family Tumors (ESFT) == Ewing sarcoma and Primitive NeuroEctodermal Tumor (PNET) Definition Tumors of unknown origin 6-10% of malignant primary bone tumors (second most common group of bone sarcomas in children) Small blue cell tumor Aggressive

Answer 150

Abnormally short proα1(1) chain Abnormal or insufficient proα2(1) Unstable triple helix Autosomal recessive (some dominant or new mutations) Perinatal lethal: Death in utero or within days of birth Skeletal deformity with excessive fragility and multiple in utero fractures Blue sclera

Answer 151

Fibrous cortical defect (small) Non-ossifying fibroma (5-6cm) Fibrous dysplasia Metastatic tumors

Answer 152

Triad: Arthritis, nongonococcal urethritis or cervicitis, conjunctivitis can't see, can't pee, can't climb a tree Typically affects males in their 20-30's or HIV+ patients 80% are HLAB27 (+) Autoimmune reaction to a prior infection of genitourinary tract (eg Chlamydia) or gastrointestinal tract (eg Shigella, Salmonella, Yersinia, or Campylobacter) -- following STD or bloody diarrhea (bacillary dysentery

Answer 153

AKA rheumatoid spondylitis or Marie-Strümpell disease (Dobson will use Marie-Strümpell disease) Destruction of articular cartilage and bony ankyloses (fusion) Particularly of the SI joints and apophyseal joints (between tuberosities and processes) Peripheral joints (hips, knees, shoulders) are involved in 1/3 of cases Signs and symptoms arise in 2-3rd decades as low back pain and spinal immobility 90% are HLAB27 (+) -- very sensitive; most sensitive for HLA-B27 IL-23 gene associations also found Increased erythrocyte sedimentation rate BAMBOO SPINE from fusion of the vertebrae

Answer 154

Definition Malignant mesenchymal tumor with skeletal muscle differentiation alveolar and embryonal == most common soft tissue sarcoma of childhood/adolescence Aggressive neoplasms that require surgery and chemo +/- radiation

Answer 155

Pain & swelling | If vertebral involvement neurological signs and symptoms if nerves are compressed

Answer 156

Benign, primary bone tumor of unknown origin Eccentric, expansile lesion with well-defined margins CT/MRI can show internal septa and fluid filled levels Radiographic & histological findings are typical of secondary reactions to primary bone tumors (especially giant cell tumor and chondroblastoma) 10-20 year olds

Answer 157

Well-circumscribed, intramedullary masses Curvilinear trabeculae of woven bone that resemble Chinese characters Cystic degeneration, hemorrhage and foamy macrophages 20% may also show nodules of hyaline cartilage with a disorganized growth plate

Answer 158

Benign tumors of hyaline cartilage that usually occur in bones of enchondral origin more likely to be multiple Enchondroma: in medullary cavity (most common) Juxtacortical chondroma: on the surface of bone 20-50 year olds

Answer 159

AKA: Marble Bone Disease or Albers-Schonberg Disease Bones are "stone-like", brittle and fracture easily like chalk ↓ bone resorption with diffuse symmetric skeletal sclerosis due to impaired formation or function of osteoclasts

Answer 160

CD4+ T helper cells react with an arthritogenic agent (microbial or self-antigen) → cytokines & stimulate inflammatory cells IFNγ activates macrophage & resident synovial cells IL17 recruits neutrophils & monocytes TNF (most important) & IL1 induces protease secretion → hyaline cartilage break down TNF == firmly implicated in the pathogenesis; TNF inhibitors == effective therapy Etanercept, adalimumab, infliximab == TNF inhibitors RANKL → bone resorption

Answer 161

Imaging: foci of flocculent densities | Slow growing, reactive thickening of the cortex

Answer 162

Radiographic findings Enlarged bone with thick, coarsened cortices and cancellous bone Active disease: wedge shaped lytic leading edge progressing along the bone 1cm/year ahem ↑ serum ALK phosphatase -- most common cause of isolated elevated ALP Normal calcium, phosphorous

Answer 163

the most common skeletal dysplasia major cause of dwarfism gain-of-function mutations in the FGF receptor 3 (FGFR3); autosomal dominant; retarded cartilage growth shortened proximal extremities, a trunk of relatively normal length, and an enlarged head with bulging forehead and conspicuous depression of the root of the nose no changes in longevity, intelligence, or reproductive status

Answer 164

Common in the axial skeleton: pelvis, shoulder, ribs | Extremities are rarely involved (vs enchondroma

Answer 165

Chronic progressive monoarticular infection Complication of adjoining osteomyelitis or hematogenous spread from visceral infection (ie pulmonary) Seeding of joint → confluent granulomas with central caseous necrosis Synovium may grow as pannus over articular cartilage, eroding bone along joint margins All age groups (especially adults) Presentation Affects weight bearing joints (hips, knees, ankles) Insidious onset with gradual, progressive pain Systemic signs and symptoms may be present or absent Chronically: fibrous ankylosis + joint space obliteration

Answer 166

Affects the bones/parts that have more surface area (eg cancellous compartment of vertebral bodies) Trabecular plates become perforated, thinned and lose their interconnections leading to progressive micro-fractures and vertebral collapse

Answer 167

Endochondral ossification is responsible for the development of long bones this is what is defective in achondroplasia (activating mutations in FGFR3

Answer 168

extremely common, seen in 30-50% of children > 2 years old Asymptomatic, detected incidentally, biopsy rarely needed Arise in metaphysis of distal femur, proximal tibia (eccentric) 50% are bilateral or multiple Small (∼0.5cm) Rarely progress to non-ossifying (5-6cm) fibromas, and exclusion of other tumors may be necessary

Answer 169

``` 15% of primary tumors involving bone Benign Giant cell tumor == the only one of the epiphysis "soap bubble" appearance on x-ray Aneurysmal bone cyst Malignant Ewing sarcoma Adamantinoma ```

Answer 170

nfarction of bone and marrow | Cortex is typically not affected because there is collateral blood flow

Answer 171

Peaks in 2-4th decades | 3x more prevalent in females

Answer 172

Relieve pain/inflammation and slow progression. Corticosteroids, disease modifying agents (MTX, TNF) Systemic amyloidosis and infections may occur due to immunocompromised state (from anti-TNF or immunosuppressant therapy) Differences from Osteoarthritis

Answer 173

Type 1 Collagen Diseases == Osteogenesis Imperfecta (brittle bone disease) Definition Most common inherited disorder of connective tissue Improper collagen formation leads to brittle bones (brittle bone disease) places where type I collagen is found: joints, eyes, ears, skin, and teeth four subtypes vary in severity based on location of the mutation in the protein Type I == normal life span but experience childhood fracture that decrease following puberty Type II == uniformly fatal in utero or during the perinatal period

Answer 174

Hematogenous: acute systemic illness presentation with malaise, fever, chills, leukocytosis, and throbbing pain over infected region Others may present with unexplained fever (children) or localized pain (adults

Answer 175

Definition Skeletal changes associated with renal disease (ie dialysis) Manifestations are not unique and include things like: Osteopenia/osteoporosis, Osteomalacia, secondary hyperPTH, and growth retardation

Answer 176

Cleidocranial Dysplasia: patent fontanelles, delayed closure of cranial sutures, Wormian bones (extra bones that occur within a cranial suture) delayed eruption of secondary teeth, primitive clavicles, and short height loss of function mutations in the RUNX2 autosomal dominant Dustin from Stranger Things

Answer 177

Sheets of multinucleated osteoclast type giant cells Destroy overlying cortex → bulging soft tissue mass with a thin shell of bone Large, red-brown tumors with cystic degeneration Uniform mononuclear cells with osteoclast giant cells that have 100+ nuclei & prominent ovoid nucleoli Necrosis and mitotic activity Do not synthesize bone or cartilage, although reactive bone may be present "soap bubble" appearance on x-ray

Answer 178

Seen in the deep dermis, subcutis or muscles Plump, immature fibroblasts & myofibroblasts Gradient of maturation is seen (zonation) Cells vary in shape and size (spindle to stellate) Conspicuous nucleoli Abundant mitotic figures lymphocytes and extravasated RBCs are common, neutrophils are unusual

Answer 179

chromosome 17p13 rearrangements → USP6 overexpression | = ↑ NFκB activity = ↑ MMPs & cystic bone resorption

Answer 180

two subtypes: Central (intramedullary) or peripheral (juxtacortical) conventional central chondrosarcomas == 90% of chondrosarcomas 15% are secondary tumors (preexisting endochondroma or osteochondroma

Answer 181

Radiographic level of disease is not proportional to signs and symptoms No effective means to prevent or halt disease progression Pain management, activity modification, arthroplasty for severe cases Corticosteroids can lead to avascular (osteo)necrosis

Answer 182

Complications Involvement of digital tendon sheath → sausage finger/toe (dactylitis) Ossification of tendoligamentous insertions → calcaneal spurs and bony outgrowths Severe chronic disease: Spinal involvement, indistinguishable from ankylosing spondylitis Extraarticular involvement: Inflammatory balanitis (swelling of foreskin/penile head), conjunctivitis, cardiac conduction anomalies, aortic regurgitation

Answer 183

Help control calcium and phosphate levels Detect mechanical forces translating them to biologic activity (mechanotransduction) These cells are interconnected via a network of canaliculi (dendritic cytoplasmic processes passing through tunnels

Answer 184

acture Healing: Delayed or nonunion Occurs with inadequate immobilization and movement of the callus Nonunion persistence = cystic degeneration of callus with the luminal surface lined by synovial like cells → pseudoarthrosis (false joint

Answer 185

Involves large joints (knee) (then hip, ankle, calcaneocuboid joints) Joint synovium → tangled mat by red-brown folds, finger like projections and nodules The tumor cells spread along the surface and infiltrate the subsynovial tissue

Answer 186

Bones of endochondral origin | Small bones of hands & feet

Answer 187

Tubular dysfunction: the major tubular disease that affects the skeleton is renal tubular acidosis low pH --> demineralization --> osteomalacia Generalized renal failure: chronic hyperphosphatemia, hypocalcemia, secondary hyper-PTH ↓ production of secreted factors: Vitamin D3, BMP7, FGF-23, Klotho BMP-7: produced by renal tubular cells to induce osteoblast differentiation and proliferation Klotho: membrane bound protein made by the kidney to cause osteocytes to make FGF-23 and help regulate phosphate and vitamin D in the kidney aluminum from dialysis, oral phosphate binders, iron deposition, and diabetes mellitus may indirectly contribute to bone disease in the setting of renal failure

Answer 188

Brachydactyly types D and E: shortening of the terminal phalanges of the thumb and big toe gene: HOXD13

Answer 189

``` Site of origin (intramedullary, intracortical, surface) Primary (underlying bone is unremarkable) or secondary (signs of past chronic disease) Histologic grade (low, high) Histologic features (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, giant cell) Most common subtype: primary, intramedullary, osteoblastic and high grade arising in the metaphysis of long bones ```

Answer 190

Translucent gray-blue tumors, < 3cm with limited growth potential Well-circumscribed nodules of benign hyaline cartilage Peripheral portion of the nodules may undergo enchondral ossification and the center can calcify and infarct Treatment Observation or curettage

Answer 191

Malignant tumor of uncertain histology fourth most common sarcoma (10% of all soft tissue sarcomas) 15-40 years old Location Thigh, leg, locations that lack synovium (chest wall, head, neck) Deep seated mass of several years Mutation t(x;18) → SS18 - SSX1/SSX2/SSX4 encoding chimeric transcription factors ^^ the only one involving a sex chromosome SS == Synovial Sarcoma Morphology Monophasic: Uniform basophilic spindle cells with scant cytoplasm and dense chromatin in short, tightly packed fascicles that may calcify Biphasic: Monophasic + gland like structures of cuboidal to columnar epithelium (+) for epithelial markers (eg keratins) -- different from most other sarcomas Treatment and prognosis Aggressively with limb sparing therapy and frequent chemotherapy Metastasis common to lung and regional lymph nodes Prognosis is 25-62% based on stage

Answer 192

Chondrosarcoma (conventional) | Formation of hyaline or mixed cartilage

Answer 193

Osteoporosis: Most severe in the phalanges, vertebrae, and proximal femur Osteoclasts more prominent in cortical bone (subperiosteal and endosteal) Dissecting osteitis: tunnels along the length of the trabeculae (railroad tracks) Brown tumors: Reactive tissue mass due to influx of macrophages and fibrous tissue that leads to hemorrhage and hemosiderin deposition. May have cystic degeneration. generalized osteitis fibrosa cystica (von Recklinghausen disease of bone): increased bone cell activity, peri-trabecular fibrosis, and cystic brown tumors hallmark of severe hyperparathyroidism Now rare due to early treatment

Answer 194

``` Vertebral fracture (thoracic, lumbar): May be multiple and painful. Loss of height, altered lordosis and kyphosis that can lead to “dowager’s hump” fractures of the femoral neck, pelvis, or spine → pulmonary embolism and pneumonia ```

Answer 195

Primary tumors are far outnumbered by metastatic tumors and hematopoietic tumors Benign tumors are much more common than malignant tumors Benign tumors are more common in the first three decades, but malignant tumors are more common in adults Of the malignant tumors: Osteosarcoma > chondrosarcoma > Ewing sarcoma

Answer 196

Autosomal dominant Germline loss-of-function chromosome 1q42 (fumarate hydratase - Krebs cycle enzyme) Uterine leiomyomas + Renal cell carcinoma == fumarate hydratase enzyme deficiency

Answer 197

``` Involvement Oligoarthritis is more common Systemic disease is more frequent Large joints are affected more often than small joints Rheumatoid nodules & Rheumatoid Factor are usually absent ANA ANA seropositivity is common ```

Answer 198

Monostotic: involvement of a single bone Polyostotic: involvement of multiple bones Mazabraud syndrome: fibrous dysplasia (polyostotic) and soft tissue myxomas (intramuscular) McCune Albright: Polyostotic disease associated with café-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty. GNAS mutation in embryogenesis

Answer 199

Inflammation of bone and marrow secondary to infection | Pyogenic bacteria and mycobacteria are most common

Answer 200

Vitamin D deficiency or abnormal metabolism Impaired mineralization → accumulation of unmineralized matrix Disease of adults (called rickets in children) Bone formed during remodeling is under-mineralized → predisposition to fractures

Answer 201

Autosomal dominant mutations of COL1A1 and COL1A2 mutations (α1 and α2 chains of type I collagen) Many mutations replace glycine with another amino acid in the triple helical domain → defective assembly of higher order collagen peptides Loss of function due to misfolding of the polypeptides and improper assembly of wild type collagen chains

Answer 202

Acute arthritis associated with crystallization of monosodium urate in and around joints Hyperuricemia is seen in primary and secondary single, red, hot, swollen, painful joint that shows < 50,000 WBCs, +ve for crystals, and -ve for microbes Primary (90%): cause unknown Secondary: ↑ uric acid due to underlying condition (eg high cell turnover rate as in leukemia/lymphoma, renal insufficiency, tumor lysis syndrome

Answer 203

Malignant tumor of skeletal muscles in adults Numerous, large, multinucleated, bizarre eosinophilic tumor cells Often fatal Genetically heterogenous Requires immunohistochemistry for definitive diagnosis

Answer 204

Generally stop growing at the time of growth plate closure | Symptomatic: simple excision (curative

Answer 205

Common in young pts, unilateral, and no contractures 25% do not progress More likely to recur after excision

Answer 206

RANK: transmembrane receptor; receptor activator for NFκB; expressed on osteoclast precursors RANK signaling activates the transcription factor NF-κB NF-κB is essential for the generation and survival of osteoclasts RANKL: expressed on osteoblasts and marrow stromal cells OPG (osteoprotegrin): a secreted "decoy" receptor made by osteoblasts and several other types of cells that can bind RANKL and thus prevent its interaction with RANK RANKL and OPG oppose one another; RANK-to-OPG ratio determines bone resorption vs formation PTH, estrogen, testosterone, and glucocorticoids, vitamin D, inflammatory cytokines (eg IL-1), and growth factors alter the ratio

Answer 207

Primary bone tumor of unknown origin uncommon, benign, but locally aggressive 20-40 year olds

Answer 208

Polygonal tumor cells (minority of the cell pop) Heavily infiltrated by macrophages that can contain hemosiderin or foamy lipid Scattered giant cells and patchy fibrosis are common

Answer 209

Benign tumor likened to localized developmental arrest All components of bone are present, but do not differentiate into mature structures Arise during skeletal development

Answer 210

Due to overproduction or under excretion (>6.8 mg/dl) primary manifestations due to over production some patients may have identifiable enzyme defects HGPRT most common location associated with first attack of primary gout == great toe another location == gouty tophus on the helix of outer ear HGPRT deficiency interrupts purine salvage pathway so they are instead degraded (enzyme is absent in Lesch-Nyhan syndrome and neurological symptoms dominate the clinical picture, along with gout) mental retardation and self-mutilation "orange sand" in diapers as an infant -- CIS ??? sand material is high uric acid in the diaper that cools off and crystallizes in the diaper X-linked; deficiency == recessive Secondary manifestations may be due to either over production (tumor lysis syndrome) or under excretion (chronic renal disease

Answer 211

Neonates: metaphyseal vessels penetrate the growth plate → infection of metaphysis, epiphysis or both. Children: trivial mucosal injury (defecation, chewing), minor skin infection. Metaphysis localization. Adults: open fracture, surgical procedure, diabetic infections of feet. Epiphyses and subchondral regions

Answer 212

Associated with HLA-DRB1 (shared epitope) & PTPN22 | FA2018, Pathoma == HLA-DR4

Answer 213

``` Definition Self-limited fibroblastic & myofibroblastic proliferation Benign fibrous tumor 20-30 year olds 25% have a history of trauma Tumors grow rapidly over weeks-months (< 5cm) Location Arm, forearm (UE) Mutation t(22;17)→ MYH9-USP6 fusion ABC also contains a USP6 fusion gene Clonal, but self-limited proliferation proliferating cells lack some key hallmark of cancer (perhaps ability to avoid senescence ```

Answer 214

Manage signs and symptoms and limit further spread | Systemic chemotherapy, localized radiation, bisphosphonates +/- surgery (fracture stabilization

Answer 215

``` Definition Malignant tumor of skeletal muscles 15 year olds Location genitourinary tract Morphology Tumor cells mimic skeletal muscle at various stages of embryogenesis Sheets of primitive round and spindle cells, "strap cells" Cross striations may be present ```

Answer 216

Extracellular component of bone 35% osteoid: Type I collagen and other proteins (ie osteopontin allows formation and is measurable in serum) 65% mineral: Hydroxyapatite, causes bone to be hard and stores 99% of bodies calcium, 85% of phosphorous

Answer 217

``` ↓ synthesis of proα1(1) chain Abnormal proα1(1) or proα2(1) chains ahem Autosomal dominant Normal life-span with childhood fractures that decrease at puberty Postnatal fracture Blue sclera Normal stature, skeletal fragility, joint laxity Dentinogenesis imperfecta Hearing impairment ```

Answer 218

t(11;22)(q24;q12) → EWS-FLI1 | in-frame fusion of the EWS gene on chromosome 22 to the FL1 gene on chromosome 11

Answer 219

Most endochrondromas of large bones are detected incidentally, occasionally they are painful and cause pathologic fracture x-ray: circumscribed marrow lucencies with central, irregular calcifications, sclerotic rim & intact cortex Pathogenesis IDH1, IDH2 mutations Acquired synthesis of 2-hydroxyglutarate which interferes with regulation of DNA methylation (transformation by association may occur

Answer 220

Glomerulus filters uric acid, which is then completely resorbed in the proximal tubule Small fraction is secreted into the urine by the distal nephron

Answer 221

dysplasia: global disorganization of bone and/or cartilage; mutations in genes that control development or remodeling of the entire skeleton

Answer 222

mild symptoms readily suppressed with calcitonin and bisphosphonates

Answer 223

Rheumatoid subcutaneous skin nodules occur in 25% of patients (severe disease) that are firm, nontender, round/oval. Seen in areas subjected to pressure (ulnar forearm, elbows, occiput, lumbosacral) and resemble necrotizing granulomas. rheumatoid nodules == central fibrinoid necrosis surrounded by palisading epithelioid histiocytes arise in the skin and visceral organs Dobson == ulnar aspect of the forearm Vasculitis of small or large arteries can lead to obliterating endarteritis → peripheral neuropathy, ulcers, gangrene Leukocytoclastic vasculitis: purpura, cutaneous ulcers, and nail bed infarction Ocular changes: uveitis and keratoconjunctivitis Felty Syndrome == Rheumatoid Arthritis + Splenomegaly + Neutropenia Caplan Syndrome == Rheumatoid Arthritis + pneumoconiosis (eg asbestos, coal-workers, chlamydia psittaci) Secondary Amyloidosis == Rheumatoid Arthritis is one of the most common causes of secondary amyloidosis caused by chronic inflammation --> SAA protein (acute phase protein) --> cleaved into AA and deposited in tissue

Answer 224

RA-small joints PIP MCP Osteoarthritis-weight bearing joints

Answer 225

Acute Arthritis morphology Dense neutrophilic infiltrate in the synovium & synovial fluid Slender, negatively birefringent monosodium urate crystals in the edematous and congested synovium and within neutrophils -- monosodium urate crystals found in cytoplasm of neutrophils When the episode of crystallization abates and the crystals are resolubilized, the acute attack remits Chronic Tophaceous Arthritis Urates encrust the articular surfaces → grossly visible synovial deposits Synovium becomes hyperplastic and fibrotic ↑ inflammatory infiltrates Synovial plannus extends from the cartilage into juxtaarticular bone Causes erosions & fibrosis, eventually producing bony ankylosis Tophi Pathognomonic lesion Masses of urates (crystalline or amorphous) surrounded by intense mononuclear inflammation with foreign body giant cells Occur in joints, or less commonly, ear, in the olecranon or patellar bursa and in periarticular ligaments and connective tissue white, chalky deposits; fibrotic tissue with giant cell reaction -- similar to rheumatoid nodules Gouty nephropathy Renal medullary monosodium urate deposition (tophi) and uric acid stones Obstruction can cause secondary pyelonephritis Can manifest as renal colic with the passage of gravel and stones 20% with chronic gout die of renal failure

Answer 226

Malignant, bone forming tumor Most common primary malignant bone tumor, exclusive or myeloma and lymphoma Epidemiology Bimodal: 10 - 20 year olds (growth spurt), and older adults who suffer from conditions known to predispose to osteosarcoma (Paget's, bone infarcts, and prior radiation) Think Chondrosarcoma in adults, Osteosarcoma in kids Male predominance peak in incidence around the time of the adolescent growth spurt and occur most frequently in the region of the growth plate in bones with the fastest growth

Answer 227

Definition Malignant tumor of smooth muscle 10-20% of all soft tissue sarcomas 40-60 year olds Location Deep soft tissues of thigh (extremities), retroperitoneum "large intra-abdominal mass arising in the retroperitoneum and encasing organs" retroperitoneal organs == SAD PUCKERS anywhere there is smooth muscle Great vessels: IVC = deadly -- anywhere there is smooth vessels Morphology Pleomorphic eosinophilic spindle cells Blunt-ended hyperchromatic nuclei in interweaving fascicles Bundles of thin filaments with dense bodies and pinocytic vesicles Individual cells are surrounded by basal lamina Stain for smooth muscle actin and desmin all cells stain for actin, mesenchyme derived cells stain for desmin Treatment and prognosis Superficial/cutaneous: good prognosis Retroperitoneum: large, not entirely excised, death by spread to lungs

Answer 228

Too little bone

Answer 229

``` Subtype III Altered structure of propeptides of proα2(1) Impaired formation of triple helix 75% autosomal dominant Progressive, deforming disease Growth retardation, progressive kyphoscholiosis Multiple fractures Blue sclera at birth → white Hearing impairment Dentinogenesis imperfecta ```

Answer 230

types recur locally and often repeatedly unless adequately excised

Answer 231

acture Healing: Soft Tissue Callus /Procallus -- WEEK 1 Fracture site hematomas are organized by an influx of inflammatory cells, fibroblasts and new vessels Platelets and inflammatory cells release PDGF, TGFβ, FGF and IL's to trigger osteoprogenitor cells and stimulate osteoclast and osteoblast activity Matrix production in adjacent tissues has occurred by the end of the first week The fracture ends of the bone have been remodeled Some anchorage between the ends of the fracture bones but not structural rigidity for weight bearing

Answer 232

Seen with displaced and comminuted fractures

Answer 233

Round, oval masses of hemorrhagic, gritty, tan tissue Well circumscribed nodules of radiologically translucent cortical, interlacing woven bone (nidus) rimmed by osteoblasts Surrounded by highly vascular (congested, dilated), loose connective tissue enclosed by radiologically dense, reactive, sclerotic bone Seen in the diaphysis of bone

Answer 234

Autosomal dominant, seen in children Germline loss of function EXT1 or EXT2 and loss of remaining wild type chondrocytes of the growth plate Accounts for 15% of osteochondromas Multiple lesions Underlying bones may be bowed & shortened Reflects an associated disturbance in epiphyseal growth 5-20% progress to chondrosarcoma

Answer 235

Sessile or pedunculated, 1-20cm Cap: benign hyaline cartilage covered peripherally by perichondrium Cartilage looks like a disorganized growth plate and undergoes enchondral ossification, with the newly made bone forming the inner portion of the head and stalk The cortex of the stalk merges with the cortex of the host bone so that the two medullary cavities are continuous Treatment Generally stop growing at the time of growth plate closure Symptomatic: simple excision (curative

26 Bones Joints And ST Flashcards

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