Pathology of Bones and Joints

Question 1

Achondropolasia

Answer 1

• most common form of inherited dwarfism
• AD pattern, most are sporatic, mutation in fibroblast growth factor receptor (FGFR3) that inhibits chondrocyte proliferation
• effects endochondral ossification ONLY
• short limbs and relatively large head and torso

Question 2

Osteogenesis Imperfecta (OI)

Answer 2

variety of gene defects leading to abnormal development of TYPE 1 Collagen

• brittle bone; recurrent fractures and skeletal deformities
• thin, blue sclera due to Type 1 collagen
• hearing loss (middle ear ossicles abnormal)
• dental imperfections due to deficient dentin
• intra-uterine fractures/deformities possible

Question 3

Osteopetrosis

Answer 3

• Marble Bone Disease, Albers-Schonberg Disease
• failure of osteoclastic bone resorption leads to loss of medullary cavity, loss of marrow function, loss of bone remodelling
• thick, dense brittle bone (chalk-like)
• Anemia, bone deformity causing broad metaphyses (Erlenmeyer flask shape)
• Limited RANKL = less osteoclasts
• Carbonic Anhydrase II enzyme deficiency no acid in resorption pits

Question 4

Paget’s Disease (Osteitis deformans)

Answer 4

• Disorder in bone remodelling
• Excessive bone resoprtion accompianed by disordered bone formation
• Bone is thick but deformed and weak (fracture)
• Genetic; Paramyxovirus
• 15% Monostotic; 85% Polystotic
• in skull, pelvis, proximal femur, vertebrae

Question 5

Paget’s Disease (pathologies)

Answer 5

• INCREASE in serum alkaline phosphotase
• Mosaic bone pattern
• A-V shunts - increase in vascularity so incr warmth, can hear bruits in bone
• Bone pain; fractures
• Deafness - small bones of ear growing so cause compression
• Cranial nerve compression - bone gets thick so compresses neural canals
• osteosarcoma

Question 6

Osteoporosis

Answer 6

• Decreased bone mass resulting in thin, fragile bone prone to fracture
• Normally mineralized bone decreased in mass to point where it no longer provides adequate mechanical support
• enhanced bone resorption relative to bone formation

Question 7

Osteoporosis (pathologies)

Answer 7

• Bone pain
• Loss of height
• Fractures: femoral neck; spine; wrist
• smoking, age, meopause, weight, genetics, diet, exercise all contribrute

Question 8

Osteomalacia and Rickets

Answer 8

• Decreased mineralization of newly formed bone usually caused by Vit D deficiency; not enough mineralized osteoid (normal), just not enough mineralized so soft bone (more protein)
• Dietary deficiency of Vit D, malabsorption, lack of sunlight, renal and liver diseases
• Rickets - improper calcification of bone, more unmineralized bone present so becomes weak, LOTS of protein, NO mineralized protein/bone
• Rickets in kids
• Osteomalacia in adults

Question 9

Fibrous Dysplasia

Answer 9

• BENIGN non-tumorous replacement of marrow by fibrous tissue
• mono- or poly-ostotic
• deformity, swelling, fracture
• may be associated with precocious puberty in girls and pigmented skin (cafe-au-lait) spots = McCune-Albright Syndrome

Question 10

Pyogenic Osteomyelitis

Answer 10

• Most often caused by bacteria that reaches bone via direct inoculation, blood stream, or contiguous spread - stab wound; open fracture
• pyogenic = pus formation
• usually seen in children
• Staph. Aureus - most common 80-90%
• E.coli, pseudomonas, klebsiella in urinary tract infections and drug addicts
• Haemophilus influenzae and group B Strept in newborns

Question 11

Pyogenic Osteomyelitis (cont)

Answer 11

• Salmonella in sickle cell disease
• In ~50% of cultures NO organism identified
• Lytic lesion with surrounding sclerosis (denser bone)
• fever, chills, leukocytosis, pain
• 5-25% become chronic infection (not cured)

Question 12

Chronic Osteomyelitis

Answer 12

Involucrum: periosteal new bone forms around a piece of necrotic bone; living, body produces to try to prevent the spread of infection

Sequestrum: dead or necrotic (ioslated and avascular) piece of bone surrounded by pus; surgical interventaion/removal; can never heal because avascular

Sequestrum - classic area is in tibia fracture; or when bone graph doesn’t take causes too much pressure from bone plates that can choke off healthy bone

Question 13

Bone Tumor factors important to determine exact nature of the lesion

Answer 13

• clinical presentation
• radiographic appearance
• age of patient
• LOCATION of lesion
• microscopic appearance

Question 14

Bone Tumors: epiphyseal lesions

Chondroblastoma

Answer 14

• rare tumor seen in children and adolescents with open growth plates

Question 15

Bone tumors: epiphyseal lesions

Giant Cell Tumor

Answer 15

• Most common tumor of epiphyses in skeletally mature individuals with closed growth plates
• shows metaphyseal extension

Question 16

Bone Tumros: Metaphyseal intramedullary lesions

Answer 16

• Osteosarcoma centered in metaphysis
• chondrosarcoma and fibrosarcoma
• osteoblastoma
• enchondroma
• fibrous dysplasia
• simple bone cyst
• aneursymal bone cyst

Question 17

Bone tumors: Metaphyseal lesions centered in the cortex

Answer 17

• Non-ossifying fibroma (NOF)
• osteoid osteoma

Question 18

Bone tumors: Metaphyseal exostosis

Answer 18

• Osteochondroma

Question 19

Bone tumors: Diaphyseal intramedullary lesions

Answer 19

• Ewing’s sarcoma
• lymphoma
• myeloma
• common for fibrous dysplasia and enchondroma

Question 20

Bone tumors: Diaphyseal lesions centered in the cortex

Answer 20

• Adamantinoma
• Osteoid osteoma

Question 21

Metastatic cancers

Answer 21

• most frequent malignant tumors found in bone
• NOT primary bone tumors = metastatic
• predominant occurence in children first decade of life and adults over 40
• multifocality and predilection for hematopoietic marrow sites in the axial skeleton and proximal long bones
• Distal metastases RARE; small bones of hands and feet RARE

Question 22

Most common malignancies producing skeletal metastases

Answer 22

• ADULTS - carcinomas of the prostate, breat, kidney, lung, thyroid, colon, melanomas
• CHILDREN - neuroblastoma, rhabdomyosarcoma, retinoblastoma

Question 23

Primary bone tumors

Answer 23

• predominant occurence in first 3 decades of life during ages of the greatest skeletal growth activity
• Common sites: distal femur and proximal tibia (bones with highest growth rate)
• Osteosarcoma and multiple myeloma have highest incidence, followed by chondrosarcoma and Ewing’s sarcoma

Question 24

Benign tumors

Answer 24

• Far more common than malignant
• some not true neoplasms - hamartomas
• most common: osteochondroma, non-ossifying fibroma, enchondroma

Question 25

Bone tumors: 2 important features

Answer 25

* ability to de-differentiate = low-grade transforming into a high-grade sarcoma * tendency of high-grade sarcomas to arise in damaged bone, at sites of bone infarcts, radiation osteitis and Paget's disease

Question 26

Tumors of children and young adults

Answer 26

* priamry osteosarcoma and Ewing's sarcoma * occurrence of these in middle-aged patients extremely unusual

Question 27

Skeletal malignancy \>40

Answer 27

* most common: metastatic cancer * multiple myeloma and chondrosarcoma most common * osteosarcomas are secondary, develop at sites of bone damage * Giant cell tumor - locally aggressive lesion, occurs in skeletally mature patients, 20-50, never seen in children or patients older than 60

Question 28

Osteoma

Answer 28

* Benign lesions of bone found in head and neck * project from subperiosteal or endosteal surfaces of cortex * slow growing, no clinical significance unless cause obstruction or cosmetic issues * no malignant potential

Question 29

Gardener's syndrome

Answer 29

* multiple osteoma of the mandible and maxilla, along with frontal, sphenoid and ethmoid sinuses * Rare in long bones or phalanges * cutaneous and soft tissue tumors

Question 30

Osteoid osteoma

Answer 30

* Benign * \< 2 cm * 75% patients \<25 * more in female * 50% in femur or tibia * PAINFUL, NOCTURNAL, RELIEVED BY ASPIRIN * Histologically: well-circumscribed, vascular tissue

Question 31

Osteoblastoma

Answer 31

* larger \> 2 cm * in young people * more often in the spine; SPs * pain is dull, achy * NOT RELIEVED BY ASPIRIN, * NO vascular channels

Question 32

Osteosarcoma

Answer 32

* most common primary malignant tumor of bone * malignant mesenchymal tumor where neoplastic cells produce bone matrix * bimodal age distribution * 60% occur around knee region * genetic mutations in RB gene, p53, p16, Cyclin D1 * neoplastic bone has coarse, lace-like architecture

Question 33

Osteogenic sarcoma

Answer 33

* painful, enlarged mass (may present as sudden fracture) * X-ray shows large desctructive mixed lytic and blastic lesion * bulky, gritty, grey-white hemorrhagic tumor may break thru cortex, lifting periosteum, causing reactive periosteal bone formation * Codman triangle = triangular shadow b/w the cortex and raised ends of periosteum * SEEN MOSTLY IN THE KNEE

Question 34

Exostosis (osteochondroma)

Answer 34

* Benign * cartilage-capped outgrowth attached to underling skeleton by bony stalk * single or multiple (multiple hereditary exostosis - AD * cap is hyaline cartilage, apepars disorganized growth palte; cortex of stalk merges w/ cortex of host bone so medullary cavity of osteochondroma and bone continuous

Question 35

Chondroma

Answer 35

* Benign lesions of mature hyaline cartilage * most common intraosseous cartilage tumors (20-50 yrs) * Enchondromas w/i medullary cavity, solitary and in feet or hands * Juxtacortical or subperiosteal chondromas arise on the bone surface * Asymptomatic, stable, rarely progress to malignancy * Enchondromas common in short long bones

Question 36

Ollier disease (enchondromatosis)

Answer 36

multiple enchondromas; frequently transform into chondrosarcoma

Question 37

Maffuci syndrome

Answer 37

Multiple enchondromas and soft tissue hemagiomas, may have more cellularity and atypia microscopically

Question 38

Chondrosarcoma

Answer 38

* malignant tumor which produces neoplastic cartilage; half as freq as osteosarcoma; Pts usaully \>40 yrs old * subclassified as intramedullary or juxtacortical, and conventional , myxoid, clear cell, dedifferentiated, mesenchymal * commonly in pelvis, shoudler, ribs * RARE in distal extremities * painful, progressively enlarging mass * direct correlation b/w hiostological grade and biological behavior of tumor * \>10 cm are aggressive

Question 39

Fibrous Cortical Defect

Answer 39

* very common, 50% seen in children \> 2 yo; may be developmental defects rather than neoplasms * most in distal femur or proximal tibia * usually 0.5 cm; if grow to 5-6 cm then become nonossifying fibromas (adolescence) * asymptomatic; usually undergo spontaneous resolution and are replaced by normal cortical bone * if progress to NOF, may be present with pathological fracture req biopsy and curettage

Question 40

Nonossyifying Fibroma

Answer 40

* moderately cellular lesion composed of cytologically benign fibroblasts (spindle cells) in a storiform (pinwheel) pattern * has histiocytes which can be multinucleated giant cells or clusters of foamy macrophages

Question 41

Ewing sarcoma

Answer 41

* PNET = primitive neuroectodermal tumor * small round blue cells; neural differentiation * 2nd most common bone tumor in peds * tumor arises in medually cavity, invades cortex and periosteum * tan-white soft tissue mass with areas of hemorrhage and necrosis * painful, enlarging mass, tender, warm, swollen, esp. femur * may have fever, leukocytosis, anemia

Question 42

Giant Cell Tumor (Osteoclastoma)

Answer 42

* consists of multinucleated osteoclast-type giant cells * uncommon, locally aggressive * Pts in 20-40s * majority arise around knee * probably from monocyte-macrophage line (giant cells form from fusion of mononuclear cells) * X-ray: large, lytic lesion eroding into subchondral bone plate; often overlying cortex is destroyed, resulting in soft tissue mass outlined by thin shell of reactive bone * grossly, large, red-brown with cystic degen

Question 43

Osteoarthritis: Degen joint disease

Answer 43

* progressive erosion of articular cartilage; usually aging related (primary) * can be secondary to previous trauma, congential deformity, marked obesity, diabetes, hemochromatosis * aging "wear and tear" and genetics contribute * degeneration of hyaline cartilage - incr water and decr conc of proteoglycans, decr local synth of type II collagen

Question 44

Osteoarthritis (presentation)

Answer 44

* usually Pts have dep, achy pain which worsens with use, morning stiffness, crepitus, limitation of ROM * osteophytes may impinge on nerves, radicular pain and muscle spasm may occur * commonly involved joints: hip, knees, lower lumbar and cervical vertebrae, fingers * Heberden nodes = women, in fingers; are prominent osteophytes at DIP joints

Question 45

Rheumatoid Arthritis

Answer 45

* chronic inflammatory, autoimmune, systemic dx * mostly affects joints but also skin, blood vessels, heart, lungs, muscles * Joints: nonsuppurateive, inflammatory synovitis that leads to articular cartilage destruction and ankylosis of joints * Women more affected than men * Pts have serum RF, and IgM antibody reactive with Fc portions of Pts own IgG * synovial fluid will show nonspecific inflammatory inflitrate with neutophils, high protein, low mucin * thought to be an autoimmune dx triggered by exposure of genetically susceptible Pt to some unknown arthritogenic antigen

Question 46

Infectious Arthritis

Answer 46

* gonococcus etc. * children under 2, H. Influenza is the organism * Late adol and young adults - Gonococcous more prevalent = STDs * older children and adults - Staph. aureus * sickle cell = Salmonella * acutely: joint swollen, red, warm, very painful movement; fever, leukocytosis common * chronic: intermitten swelling, joint contracture, pain, stiffness and draining sinuses common

Question 47

Lyme Arthritis

Answer 47

* spirochete Borrelia burgdorferi * untreated Pts develop joint symptoms w/i few wks to 2 yrs form onset of dx * arthritis is remitting and migratory, affecting large joints esp. knees, shoulders, elbows, ankles * chronic papillary synovitis with synoviocyte hyperplasia, fibrin deposition, lymphocyte infiltration, onionskin thickening * need serology for diagnosis

Question 48

Gout

Answer 48

* form of inflammatory arthritis produced in response to deposition of sodium urate crystals in periarticular tissues; end reslut of hyperuricemia * transient acute attacks of arthritis from crystallization of urates w/i joints - deposition of TOPHI = large aggregates of urate crystals with surrounding inflammatory rxn * most Pts develop urate nephropathy - renal disorder assoc w/ deposition of monosodium urate crystals in renal medually interstitium - may form uric acid stones

Question 49

Hyperuricemia to become Gout

Answer 49

* age, genetic predisposition, heavy alcohol consumption, obesity, certain drugs (thiazides), lead toxicity * Primary Cause: overproduction of uric acid w/ normal excretion * Secondary causes: normal uric acid production w/ under-excretion as seen in chronic renal dx; overproduction of uric acid w/ incr urinary excretion (minority of cases)

Question 50

Classical 4 stages of Gout

Answer 50

1. Asymptomatic hyperuricemia 2. Acute gouty arthritis (excruciating pain with warmth, redness, tenderness esp. big toe) 3. asymptomatic intercritical gout 4. chronic tophaceous

Question 51

Chronic tophaceous arthritis

Answer 51

urates heavily encrust articular surfaces and form visible deposits on synovium. Synovium becomes hyperplastic, fibrotic, thickened by inflammatory cells and forms a pannus that destroys cartilage leading to bone erosions

Question 52

Tophi deposits of gout

Answer 52

pathognomonic, large aggregates of urate crystals surrounded by intense inflammatory rxn of macrophages, lymphocytes, and giant cells