Bone pathology

Question 1

Bone Intercellular Signals

Answer 1

Receptor Activator of NF-KappaB Ligand (RANKL)

• Expressed on Osteoblasts
• Upregulated by PTH, vitamin D3, some malignancies
• Binds to RANK (TNF family) on Osteoclasts and precursors to activate them
• Function inhibited by Osteoprotegrin (OPG); TNF family: binds to RANKL acting as a decoy preventing RANK-RANKL interaction.
  
  • osteoporosis -> decr in OPG production

Question 2

Answer 2

Osteoporosis: Metabolic Bone Disease -> Abnormal bone modeling/remodeling

• *Gross:**
• widened Haversian canals in cortex
• compression fracture: Horizontal bone thinned out (red);
• Vertical bone thickened
• *Structural**
• distal radius -> Colle’s fractures
• femur and hip
• *Microscopic:**
• nl bone (left)
• osteoprosis (right)
• disappearance of trabecular bone aka spongy bone

EtioPathogenesis: Primary Osteoporosis

• 1. Postmenopausal, 2, Aging, 3, Physical activity decr
• decr serum estrogen -> incr. IL-1, IL-6, and TNF -> incr RANK expression -> incr osteoclast activity and decr activity of osteoblasts

Etiopath of Secondary Osteoporosis

• Endocrine
  
  • Hyperparathyroidism
  • Hyperthyroidism, Diabetes Type I, Addison’s disease, Pituitary tumors, vit D allele variation
• Neoplasia: Carcinomatosis, multiple myeloma, paraneoplastic disease
• Gastrointestinal: Malnutrition, hepatic insufficiency, vitamin D or C deficiency, malabsorption
• Drugs: Chemotherapy, corticosteroids (nl serum Ca2+ levels), alcohol
• Immobilization

Dx: XRay & DEXA scan

Question 3

Answer 3

HyperPTH leading to 2o osteoporosis

• incr PTH -> osteoblast stim -> incr RANKL -> osteoclast activity
• Osteoclastic tunneling
• 2 types

Osteitis fibrosa cystica: Brown tumour (Gross image)

• microfractures -> neovascularisation, hemorrhages, giant cell-like tumours
• hemosiderin deposits
• ribs, diaphyses of long bones, fingers
• *Osteitis dissectans (microscopic image)**
• Osteoclastic tunneling
• splitting like railroid tracks

Etiology

Increased PTH resulting in increased osteoclast activity.
1° - adenoma – high Ca, low PO43-
2° - renal failure – low Ca, high PO43- (opposite levels vs 1o)
3° - initially secondary cause that turned primary due to cellular adaptive change

Sx: Stones, Bones, Moans

• Renal stones due to nephrocalcinosis
• Bone density decreased
• Psychiatric sx
• Groans: abdominal problems such as anorexia, constipation, and ulcers
• *C&C:**
• metastatic calcifications: kidney, lungs, and stomch

Question 4

Renal Osteodystrophy

Answer 4

• Chronic renal failure → hyperphosphatemia →
• Hypocalcemia → Secondary incr PTH
• Reason for Hypocalcemia
  
  • Decreased vitamin D metabolism in kidney (inhibition of conversion of vitamin D to active metabolites by phosphate)
  • Diminished intestinal absorption of vitamin D
• Iron and aluminum accumulation in bone (from dialysate) prevents further bone deposition
• incr PTH → incr Osteoclastic activity → incr Bone resorption
• decr Matrix mineralization (osteomalacia)
• Osteoporosis
• Growth retardation

Question 5

Answer 5

Vitamin D Deficiency: Osteomalacia & Rickets

• Defective mineralization of osteoid
• Malnutrition, malabsorption, receptor abnormalities, lack of sun exposure
• Under-mineralized matrix
  
  • – Persistent hyaline cartilage
  • – Fractures, skeletal deformity
• *Microscopic:** Abnormal mineralization
• mineralized osteiod (black)
• un-mineralized osteiod (pink)
• *Etiopath:**
• Vit D deficiency leading to diminished bone density
• Vit D deficiency in Adults from malnutrition, decr sun exposure, renal and liver disease

Sx Children: bowed legs, pigeon breast, frontal bossing, rachitic rosary

Sx Adults: weak bone, easily fractured

• *Dx:**
• low serum Ca2+ and phosphates
• High PTH and Alkaline phosphatase (due to activation of osteoblasts to calcify in basic env)

Question 6

Scurvy

Answer 6

Metabolic Bone Disease -> Abnormal matrix production

Etiopath: Vitamin C deficiency

Sx:

• Failed cross-linking of collagen
• Fragile capillaries and venules – Subperiosteal hemorrhages
• Defective osteoid synthesis – Microfractures
• Bony deformities

Question 7

Answer 7

Paget’s Disease: Metabolic Bone Disease -> Abnormal bone modeling/remodeling

X-Ray

• Remodelling is focal -> enlarges bone
• lytic and sclerotic areas; too much osteoclastic or osteoblastic activity (haywire)

Gross:

• affects flat and long bones
• weaker so easily fractured
• red due to hypervascularity

Microscopic:

• haphazard cement lines -> mosaic pattern

Etiology

• More common in Caucasians
• Virally induced [Paramyxovirus (measles, RSV) - nucleocapsid antigens identified in osteoclasts) (Paramyxovirus- slow virus disease)
• Genetic predisposition: p62 mutation
• Enlarges in any bone -> larger hats

Pathogenesis

• localized (does not involve entire skeleton)
• defect in signalling bw osteoblasts and osteoclasts
• Virus stimulates IL-6
• IL-6 & M-CSF -> Activate osteoclasts
• Osteoclasts hyperresponsive to RANKL & vit. D
• p62 incr RANK/RANKL SIGNALLING incr Osteoclasts
• 3 Disease of stages -> sclerotic bone
  
  • Osteolytic Stage: Osteoclastic activity- patchy, florid
  • Mixed Lytic and Blastic Stage: Predominently Osteoblastic
  • Osteosclerotic (burnt-out) Stage: End stage: incr bone mass; mosaic pattern

Sx: often Asx and incidental finding

• increasing hat size
• lion-like face

Diagnosis:

• X-ray: May be monostotic or polyostotic (multiple bones)
• ↑Serum Alkaline Phosphatase
• ↑ Urinary Hydroxyproline
• nl serum Ca2+ and phosphate

C&C:

• Deformities – Pain (compressed nerves)
• Fracture/Microfractures -> Pain
• Degenerative Joint Disease -> Pain
• hearing difficulties if ossicles affected
• Rarely:
  
  • High-Output cardiac failure (osteoblastic phase) due to AV malformations from bone remodeling leading to shunting
  • 2o osteosarcoma

Question 8

Achondroplasia

Answer 8

Achondroplasia aka disportionate dwarfism

• bow leg
• Shortened limbs and ribs
• Normal head, IQ, reproductive system and life expectancy
• *Etiopath:**
• AD FGFR3 mutation leading to constituitively active FGFR3 signaling lead to decr endocondral ossification (cartilage development)
• sporadic mutation commonly
• Disordered proliferation of chondrocytes in cartilage anlage and growth plate
  
  • – decr Proliferation
  • – decr hypertrophy
  • – Incomplete endochondral ossification
• *Dx**
• clinical presentation
• prenatal US measurements

C&C: gibbus deformity

Question 9

Answer 9

Osteogenesis Imperfecta

X-ray: every bone has fractures (hyperdense areas showing callous formations)

Etiopath:

• deficiencies in type I collagen synthesis due to AD COL1A1 and COL1A2 mutations
• Most commonly recognized congenital disease affecting collagen production
• Multiple clinicopathological subtypes

Sx:

• Involves bone matrix and other connective tissues with type 1 collagen: joints, eyes (blue sclera), skin, ears, teeth
• blue sclera due defective collagen in eyes -> shows the choroidal vv

Question 10

Ehler-Danlos Syndrome

Answer 10

• Hetrogenous group of CT disorders, recently classified in diff types
• lysyl hydroxylase def. or collagen synthesis dysfunction

Sx:

• Hyperextensibility of skin, easy bruising, hypermobile joints,
• Aortic dissection;
• blue sclerae may be present
• Bone is osteopenic, kyphoscoliosis, spondolisthesis

Question 11

Marfan’s Syndrome

Answer 11

Heterogeneous group of inherited (AD) CT disorder affecting bones, heart, aorta and eyes

Etiopath: Mutation in locus of fibrillin gene on chromosome 15

Sx:

• Usually tall with exceptionally long extremities, and long tapering fingers and toes
• Hyperflexible joints, kyphosis, scoliosis, pectus excavatum
• Eyes: subluxation of lens – ectopia lentis
• CVS: Mitral valve prolapse, Aortic dilatation due to cystic medial necrosis – AR; Aortic dissection, dissection also common in kidney and coronary aa

Question 12

Acute osteomyelitis

Answer 12

Xray: mix lytic and sclerotic areas in bone

• *Microscopic:**
• pus and necrotic debris
• enlarged Haversian canals

Acute osteomyeltis features

• Usually Bacterial but No organism isolated in 50%.
• S. aureus (80-90%) – receptors for bone matrix components e.g. collagen
• Gram -ve rods (E. coli, Klebsiella, Pseudomonas) – Genitourinary (GU infection), IV drug abuse
• Mixed bacterial (direct inoculation)
• H. influenza (neonates)
• GBS (neonates)
• Salmonella (sickle cell disease)

Epidemiology

• Young, growing children
• Adults (> 50 years)
• Gender M:F = 2:1
• Typical presentation: young boy presenting w hot, swollen leg
• Acute Osteomyelitis is worse in infants and young children
• Location
• Long tubular bones (femur, tibia, humerus)
• Vertebral bodies
• Predisposing factors: catheter, trauma, infection, underlying disease, IV drug abuse

Pathogenesis

• Acute inflammation
• Bone necrosis
• Subperiosteal abscess
• Progressive ischemia leads to segmental bone necrosis (sequestrum) surrounded by viable new bone (involucrum) formation
• Draining sinus tracts
• Extension into joint space

Sx:

• bone pain w fever and leukoctyosis
• lytic focus surrounded by sclerosis on XRay

Dx: Blood culture

Rx

• Treat early
• IV antibiotics 4-6 weeks
  
  • Exception: Children with hematogenous spread
    
    • Oral therapy if organism is susceptible
    • Good compliance
    • Rapid response
• Consider surgical debridement

Question 13

Answer 13

Osteopetrosis (stone-like bones) aka marble bone disease

X-rays: Bones lack medullary canal

• Increased bone density (hyperdense on Xray)
• Bulbous misshapen (distorted) ends of long bones -> ERLENMEYER’S FLASK DEFORMITY
• Diffuse symmetrical skeletal sclerosis

Microscopic: Medullary cavity abnormally filled with 
primary spongiosa and no hematopoietic elements

Etiopath:

• defective osteoclast-mediated bone resorption.
• Several variants with the most common
• AD adult form with mild clinical manifestations,
• AR infantile, with a severe/lethal phenotype
• Can arise due to:
  
  • Brittle bone disease
  • Dysfunction of 1. Carbonic Anhydrase (CA II), 2. Proton pump, 3. Chloride channel
    
    • Inability of osteoclasts to degrade pre-existing cartilage and bone.
    • Persistence of cartilage anlage (primary spongiosum) in medullary cavity.
  • Progressive deposition of bone on pre- existing matrix without osteoclastic activity (or without osteoclasts)

Sx:

• Bones are abnormally brittle and fracture
• Structural changes in spine -> more bone to disc material.
• Thickening of skull -> narrowing of foramina
• Hepatosplenomegaly from extramedullary hematopoiesis (EMH) & pancytopenia
• vision and hearing impairments
• hydrocephalus
• Renal Tubular Acidosis (RTA) due to CA deficiency

C&C

• Cranial n. palsies due to nerve compression (carpal tunnel and cranial nerve deficits ex. Bell’s palsy, hearing and vision loss)
• Pancytopenia due spongiosa taking over medulla and decreasing hematopoietic cells.
• Recurrent infections due to reduced marrow size.

Question 14

Chronic Osteomyelitis

Answer 14

5-25% of Acute Osteomyelitis do not resolve -> Chronic Osteomyelitis

• – Delay in diagnosis
• – Inappropriate treatment:
  
  • Inappropriate antibiotics
  • Therapy is too short
• – Inadequate surgical debridement – extensive necrosis
• – Underlying medical condition (eg. diabetes)

Pathogenesis:

• – Chronic inflammation
• – Resorption of dead bone
• – Deposition of woven bone

C&C

• Brodie abscess: Intracortical abscess
• Sclerosing OM of Garré: Jaw - extensive new bone obscuring the underlying bone
• Recurrent acute exacerbations
• Pathologic fracture
• Secondary amyloidosis
• Endocarditis
• Sepsis
• Septic Arthritis
• Rarely, malignant complications
  
  • – Squamous cell carcinoma of fistula tract
  • – Sarcoma of infected bone

Question 15

Answer 15

Tb osteomyelitis (Pott’s fracture)

Morphology:

• caseous granulomatous inflammation instead of abscess (other bacterial)
• destruction of vertebrae and IV
• can also affect hips and knees

Etiopath:

• 1-3% of patients with pulmonary TB
• Immunocompetent or compromised
• Location: Spine (Pott’s spine) > knees > hips
• Burrowing abscesses with caseating granulomas and calcification

Skeletal Tb

• Very Destructive
• Spreads through medullary cavity causing extensive caseous necrosis
• Extends thru IV discs involving multiple bones
• Difficult to control

C&C:

• kyphosis -> Gibbus deformity
• spinal cord compression

Question 16

Answer 16

Osteoarthritis: non-inflammatory arthritis

Morphology

Xray:

• Changes in Wt. bearing cartilage & bones
• Arrows indicate osteophytes; Repair response: Fibrocartilage grows over articular cartilage from periphery → Osteophytes
• Radio-lucent = subchondral sclerosis
• Radio-dense area = subchondral cysts (synovial fluid forced into subchondral microfractures in a ball-valve manner)

Microscopic: Fibrillation & Vertical Cracking indicating joint degeneration

• Eburnation & erosion
  
  • cartilage thinning
  • exposure of subchondral bone and remodelling
  • ivory appearance of bone
• Arrows 1: eburnation
• Arrows 2: subencondral cysts
• Arrows 3: nl/what it should look like

Primary

– Aging phenomenon; Most common form of arthritis

– Oligoarticular: hands, hips, knees, metatarsophalangeal joints

– 80-95% of people over 65 years

• Risk factors
  
  • Female sex
  • Obesity
  • Hereditary

Secondary

– Younger patients

– Predisposition

• Diabetes
• Hemachromatosis
• Ochronosis: alkaptonuria due to Homogentisate oxidase def.; exam q
• Obesity
• Congenital deformity

– Polyarticular

– Severe

• Risk factors
  
  • – Trauma
  • – Neuromuscular dysfunction
  • – Metabolic disorders

Etiology

• Changes in components of articular cartilage
  
  • – Altered proteoglycans
  • – Diminished pliability of collagen
• Changes in chondrocytes
  
  • – IL-1 and TNF-a break down matrix
  • – Inhibit type II collagen synthesis
• Other changes: Non-inflammatory with some signs of signalling from:
  
  • – Proinflammatory cytokines
  • – Inflammatory cells

Pathogenesis

• Degenerative disease of cartilage (chondrocytes and matrix) but NO JOINT FUSION; Central destruction
  
  • – Direct injury
  • – decr Synthesis
  • – incr Enzymatic breakdown:
    
    • MMP breakdown Proteoglycans (PG) (stromelysins) & collagen (collagenases)
    • Metalloproteinases are regulated by cytokines (IL-1 and TNF)
    • Genetic predisposition (cartilage abnormalities) -?collagen genes mutations
• Injury & repair of the subchondral bone and/or synovium (secondary to cartilage degeneration) leading to:
  
  • Chondrocyte proliferation- “cloning”
  • incr water related to decr proteoglycan content (chondromalacia- softening)
  • Type II collagen: decr synthesis and incr breakdown

Sx:

• 1st Carpometacarpal joint – most commonly affected joint in hand (subluxation, ”squaring”)
  • Haberden’s nodes - DIP
  • Bouchards’s nodes – PIP
• Unilateral (typically) but can be bilateral

C&C:

• spinal stenosis
• cervical spondylsis

Question 17

Answer 17

Rheumatoid Arthritis

Morphology:

Clinical and Xray

• Joint space - narrowed with pannus (fibrosing ankylosis)
• Eventually ossifies (bony ankylosis)
• Inflammation of adjacent tendons, ligaments, and muscle

Microscopic

• Papillary Synovial Hyperplasia
• Bulbous fronds
• ​synovium filled with inflammatory cells (lymphocytes, macrophages) and rice bodies made of fibrin and neutrophils (slide 15 not shown)
• Pannus formation: overgrowth of synovium (below); pannus fibrosis -> bone metastasis -> fusion of joints -> ankylosis

Xray: showing ankylosis

Etiology

• polyarthritis: pain, inflammation, swelling, autoimmune destruction (auto-Ab RF, ACPA)
• Prevalence estimated at ~0.5 - 1%
• Female:male ratio = 2.5:1
• Genetic predisposition assoc HLA-DR4 locus
• Environmental triggers: smoking, infections (EBV, E. coli), stress

Pathogenesis

• Subarticular Osteoporosis; Peripheral destruction
• Incr Osteoclastic activity (due to incr RANKL produced by activated T cells and synovial fibroblasts) -> Subchondral cysts, Osteoporosis (localized and systemic)

1. Activation of macrophages & B-cells
2. Antibodies against self-antigens in the joint (Autoantibodies = Rheumatoid Factor)

IgM directed against IgG (IgG bind the Fc portions of IgG)

3. Inflammation, cytokines, TNF, antibodies –> destruction of joint

Sx

• Symmetrical arthritis, typically of the hands and feet, also often involving ankles, knees, wrists, elbows and shoulders
  
  • MCP & PIP but NOT DIP
  • knees involved but NOT hip
  • Z-deformity of thumb
  • ulnar deviation of digits due to myofibroblasts contraction (part of pannus)
  • thenar atrophy from CTS
  • Swan-neck deformity
  • Boutonniere deformity
• Joint destruction occurs early and is a marker for disease progression
• Rheumatoid nodules (25% of Pt) characterized by central area of necrosis w epithelioid histiocytes
• Skin subject to pressure - ulnar aspect of forearm, occiput, lumbosacral area
• Non-tender firm nodule in subcutaneous fat
• Also develop in Joints, Tendons, Soft Tissue, Lung, Heart (peri-, myo-, endocardium), Aorta, Spleen, Viscera
• fever, malaise, weight loss, and myalgias

Assoc disorders

• Soft tissue- Rheumatoid nodules
• Lung involvement
• Vasculitis
• Uveitis: Usually in juvenile RA
• incr risk of lymphoma

Dx

• X-ray
• anti-CCP Ab
• anti-RF Ab

C&C​

• RA is a systemic disease w a course of symmetric arthritis and Chronic papillary synovitis
• End-stage lung disease
• Vasculitis & its complications
• – Myocardial infarction, cerebrovascular disease, renal failure, pleural effusions, mesenteric and intestinal infarction, gangrene
• Systemic amyloidosis
• Anemia of chronic disease
• Baker cysts behind knee
• Iatrogenic effects of Tx- Immunosuppression
• Life Expectancy decr by 3-7 yrs

Question 18

Differences: OA vs RA

Answer 18

• Morning stiffness: morning stiffness longer for RA
• Activity: RA better with activity
• Joint distribution
  
  • OA: weight bearing joints and PIP & DIP
  • RA: wrist /MCP/PIP
• RA is systemic disease - fever, weight loss
• OA has reparative activity and new bone formation – osteophytes, subchondral sclerosis
• RA - No reparative bone formation - periarticular osteopenia

Question 19

Gout

Answer 19

Etiopath

• Peak in 5th decade
• Linked to duration of hyperuricemia (20-30 years)
• Hyperuricemia
  • 1o: genetic predisposition
  • 2o: increased nucleic acid turnover
    
    • poor renal fx is most common
    • leukemia and myeloproliferative disorders, Lesch-Nyhan syndrom, alcohol, obesity, drugs, purine rich diet

Chronic destructive process of multiple joints

• Incite inflammatory response
• Bone and joint destruction
• May ulcerate skin

Question 20

Seronegative Spondyloarthropathies

Answer 20

• Heterogeneous group of diseases
• Arthritis one of several manifestations
• In part, immune mediated
• Similar, but milder disease than rheumatoid arthritis
• axial skeleton involvement
• **HLA-B27 associated **

​Pathogenesis

• Chronic synovitis
• Destruction of articular cartilage and subchondral bone
• Fibrosis and narrowing of joint space (fibrosing ankylosis)*
• Ossification of fibrous tissue (bony ankylosis)*
• Enthesis affecting joint motility
• *Most common is ankylosing spondylitis affecting sacroiliac joints and spine

C&C (Pathoma):

• uveitis
• Aortitis and Aortic regurg

Question 21

Infectious Arthritis

Answer 21

• Extension from osteomyelitis
• Hematogenous seeding
• Bacteria commonly: Rapid joint destruction
  
  • N. Gonnococcus (adults):
    
    • Presentation: sexual active Pt w hot, swollen joint
  • S. Aureus (children and adults)
  • Mycobacteria
  • Borrelia (Lyme disease)
• Viral: Parvovirus B19

Sx

• involves a single joint usually knee
• warm, erythematous joint w limited range of motion
• fever, increased WBC

Question 22

Bone tumours: General principles

Answer 22

• Most common malignant tumor is a METASTASIS from another site:

Common Primary sites:

• B (breast)
• L (lung)
• T (thyroid)
• – and
• Kosher(kidney)
• Pickle (prostate): produce osteoblastic lesions whereas the rest produce osteolytic lesions

Question 23

Bone Tumours by location

Answer 23

Diaphysis:

• Ewing’s Sarcoma
• Adamantinoma

Metaphysis

• Osteosarcoma
• Chondrosarcoma
• Osteochondroma
• Aneurysmal Bone Cyst Enchondroma

Epiphysis

• Chondroblastoma
• Giant Cell Tumor

Question 24

Osteoid Osteoma

Answer 24

• Benign Bone Forming Tumor of osteoblast affecting young adults
• Male predilection
• Presentation (typical):
• Predilection for appendicular skeleton/cortex of long bone diaphysis
• Classic clinical presentation: young male w Nocturnal bone pain alleviated by aspirin
• **Dx: **bony mass w radiolucent (osteoid) core

Question 25

Osteoma (Bone Island)

Answer 25

Benign – Mature bone: cortical bone where it should not be – **Predilection for craniofacial bones** – **Gardner’s Syndrome: assoc w FAP **

Question 26

Answer 26

Osteosarcoma **Xray (below):** sunburst appearance **Gross image (below):** * Codman’s triangle * white spots: osteoid tissue replacing marrow **Microscopic:** * immature un-mineralized bone surrounded by neoplastic cells * large pleiomorphic cells **Epidemiology** Most common bone sarcoma (20%) – Bimodal age distribution * Elderly (Paget’s, radiation) * Children, young adults – Location * **Metaphyseal (long bones**) in youth; typically around knee where most of the proliferative growth plates occur * Flat bones in elderly: more in pelvis **Etiopath** * Anatomic location * – Intramedullary (usually low grade) – Intracortical (high grade) * – Juxtacortical (low or high grade) * Grade * – Grade 1: mild cytologic atypia * – Grade 2: intermediate cytologic atypia * – Grade 3: high grade, pleomorphic cytological atypia * Osteoblastic, chondroblastic, fibroblastic histology * Hereditary tumours: * germline p53 mutations (Li-Fraumeni) * hereditary Rb * Sporadic * – P53 mutations * – MDM2 (inactivates apoptotic capacity of p53) * – Rb mutations are rare

Question 27

Cartilage tumours: General features

Answer 27

Most are benign -\> chondroma occur in medulla of small bones of hands and feet Types of cartilage: – Hyaline (found in tumors and normal) – Myxoid (found only in tumors) – Fibrocartilage (rare in tumors) – Elastic (extremely rare in tumors) Malignant tumours -\> chondrosarcoma -\> occur in pelvis and central skeleton

Question 28

Answer 28

Enchondroma **XRay:** * circumscribed lesion with punctate ?lytic areas * radio-lucent in medulla: un-mineralized bone; characteristic of disease * Sign: O-sign **Etiopath** * Benign: Hyaline and myxoid cartilage * Metaphyseal and diaphyseal * Medullary cavity * May erode (but not invade) cortex * Present with pathologic fracture * Solitary or syndromic (Ollier’s or Mafucci’s disease) * May give rise to chondrosarcoma; **Malignant Transformation!** **​Sx:** * Nodules on distal extremities, non-invasive nodules of cartilage (unmineralized). * May be surrounded by erythema and hemangiomas. **Assoc conditions** * Multiple Enchondromatosis * Ollier’s Disease * – Disfiguring * – 20% develop chondrosarcoma * Mafucci’s Disease * – Enchondromas and soft tissue vascular tumors such as hamangioma * – 20% develop chondrosarcoma * – 100% develop another extraskeletal malignancy: ovarian carcinoma, brain glioma, lung carcinoma

Question 29

Osteochondroma

Answer 29

* Benign cartilage tumor of metaphysis -\> lateral projection as a cap typically around knee, hands, and feet -\> contiguous w marrow space * Young adults * Occur only in bones with endochondral ossification **Etiopath** * Etiology unclear * Assumed to arise from displaced fragments of growth plate * New evidence suggests clonal proliferation (neoplasm) **EXT gene family mutations ** **C&C: **transformation into osteosarcoma

Question 30

Answer 30

Chondrosarcoma **Gross:** arrow points at mass at metaphysis **Microscopic:** glassy blue matrix w chondrocytes -\> cartilage disease (too cellular) **Etiopath:** * Typically occurs in older adults * Pelvis, humerus, proximal femur (rare in hands and feet) * **May arise in enchondroma (low grade)** * Low grade (1/3) do not metastasize, but may recur and dedifferentiate * High grade metastasize * Hematogenous spread: lung & liver

Question 31

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Answer 31

Giant Cell Tumor of Bone **Xray:** well circumscribed radiolucent area showing expanding lytic lesion (sometimes soapy bubble) **Microscopic:** stromal cell (w RANKL) recruiting osteoclastic giant cells (w RANK) **Etiopath:** * Benign locally aggressive tumor * 4-5% of all primary bone tumors * Age 20-40 yrs * **Epiphysis** * End of long bones **Sx**: pain in distal femur or proximal tibia C&C: spread to lungs (2%)

Question 32

Ewing’s Sarcoma & Primitive Neuroectodermal Tumor (PNET)

Answer 32

* Family of small blue cell tumors with a characteristic **t(11;22) and t(21;22)** * arises from **neuroectoderm** * 6-10% of all primary malignant bone tm. * Age: youngest among malignant bone tm * **Diaphysis of long bones** * **​grows from medullary cavity** * **onion-skin appearance** * Prognosis: dismal, improves by chemo

Question 33

Aneurysmal bone cyst

Answer 33

* Non-neoplastic locally aggressive lesion of the bone and seen in first 2 decades of life and show a slight female preponderance. * It involves the metaphyses of the long bones. X-ray shows characteristic purely lytic lesion involving the metaphyses of a long bone with an eccentric, blow out appearance and extension into the soft tissue, which is limited by a thin shell of new bone. Grossly, it shows cavities separated by septa. The spaces contain blood or serum. * Microscopically, there are cysts of various sizes separated by septa. The septa are composed of loosely arranged spindle cells and benign giant cells. The spaces are lined by cuboidal cells. The septa show capillary proliferation. Areas may show relatively solid proliferation of cells. * treated by simple curettage but they can recur.