Bone Pathology

Question 1

Osteomyelitis

Answer 1

Definition: inflammatory lesion
Etiology: bacterial infection (septicemia)
Staphylococcus aureus
Young child, pain in a long bone
Metaphysis (adjacent to the epiphyseal plate)
Risk: sickle cell disease, complication of compound fractures

Localized bone pain, swelling
Radiological changes, blood cultures are positive, open biopsy
Treatment antibiotics

Question 2

Pathogenesis of Osteomyelitis

Answer 2

1. Infection > Bacteremia
2. Acute inflammation in metaphysis of long bone
3. Necrosis of bone forming the sequestrum
4. Reactive new bone: the involucrum (woven bone)
5. Untreated > sinuses form, draining pus via cloacae

Question 3

General Steps of Bone Infection

Answer 3

1. Normal bone with capillaries close to epiphyseal plate (most affected area)
2. Infection occurs
3. Bacteria is invading and growing; if goes untreated, then it spreads
4. Reaction of woven bone/ spread and invasion of bacteria

Question 4

Involucrum

Answer 4

Subperiostial shell of viable new bone

Question 5

Cloaca

Answer 5

Hole formed in the bone during the formation of a draining sinus

Question 6

Sequestrum

Answer 6

Any tissue that has been sequestered

Example: a piece of dead bone that has become separated during the process of necrosis from the sound bone

Question 7

Metastasis into the Bone

Answer 7

1. Colonization of tumor in the tissue (primary)
2. Angiogenesis occurs (production of vessels) to feed the tumor
3. Invasion of primary tumor cells into the vessels and usually these metastasize
   Once cells go into vessels and reach the bone, similar process like osteomyelitis where the cells invade the bone; appendicular skeleton is most frequently involved

Question 8

Cancer Activation of Osteoclasts vs. Osteoblasts

Answer 8

Cancer cells activate osteoclasts cause osteolytic metastases
Cancer cells activate osteoblasts cause osteoblastic lesions
Myeloma cells create exclusively osteolytic lesions in bone

Kidney, lung, GI and malignant melanoma = lytic bone lesions

Prostate = Wnt proteins = osteoblastic bone formation

Most metastatic disease are mixed lesions

Question 9

Vicious Cycle of Cancer Cells & Bone Cells

Answer 9

Cancer activates PTHrP to activate osteoblasts then RANKL/RANK to activate osteoclasts to cause demineralization and GFs to increase the cancer cells = cycle continues

OPG is an Ab that interferes with RANK ligand to eliminate activation of osteoclasts and then is prevents or decreases metastatic disease; non specific to tumor cells but can happen in other cases as well

Question 10

Osteoid Osteoma

Answer 10

Small and painful lesion
Osseous tissue (nidus) surrounded by reactive bone formation
5-25 years old
Cortex of diaphysis of tubular bones lower extremity
Spherical, hyperemic, 1 cm diam., easily enucleated
Micro: thin, irregular, trabeculae within a cellular granulation tissue containing osteoblasts and osteoclasts, more mature in the center, often partially calcified
Clinical presentation: pain, nocturnal, exacerbated by the intake of alcohol and relieved by aspirin (prostaglandin)
Treatment: surgical excision

Question 11

Osteochondroma

Answer 11

Osteochondroma with a thickened hyaline cartilage cap which matures via endochondral calcification to bony trabeculae surrounded by fat and hematopoietic marrow

Question 12

Osteosarcoma

Answer 12

Highly malignant
Adolescents 10-20 years old
2:1 male to female
2/3 mutations in the retinoblastoma (Rb) gene; p53.
Tall persons, often arises near the knee, proximal humerus second most common site
75% arise adjacent to the knee or shoulder
Woven bone in periosteum; reactive bone makes a triangle around to prevent invasion of tumor

Question 13

Osteosarcoma Hallmarks

Answer 13

Bone destruction and formation (neoplastic bone)
Codman triangle incomplete rim of reactive bone produced by periosteum
Gross is variable
Malignant cells with osteoblastic differentiation producing woven bone.
+ for alkaline phosphatase and osteonectin
Spreads through the bloodstream to the lungs

Question 14

Osteosarcoma Clinical Features and Tx

Answer 14

Mild or intermittent pain
Swollen and tender
Adjacent joint becomes functionally limited
Serum alkaline phosphatase increased (*)
Treatment amputation or disarticulation + chemotherapy

Question 15

Ewing Sarcoma

Answer 15

Primary small round cell tumor
6-10% of primary malignant bone tumors
Ewing sarcoma / PNET
Youngest age at presentation 10-15 y/o
boys, whites
t(11,22) translocation causes (EWS-FLI1) fusion = dominant oncogene

Question 16

Ewing Sarcoma: Presentation, Morphology, Dx, and Tx

Answer 16

Presentation: diaphyses of long tubular bones, (femur); painful enlarging mass, systemic: fever, ESR elevated, anemia, leukocytosis.

Morphology: medullary cavity, invade the cortex and periostium even soft tissue
Tan- white with hemorrhage and necrosis
Dense sheets of uniform small, round cells with scant cytoplasm rich in glycogen
Homer-Wright rosettes.

Diagnosis:
Plain x rays: destructive lytic tumor with extension into surrounding soft tissue

Treatment: chemotherapy + surgical excision + radiation.

Question 17

Chondrosarcoma

Answer 17

Grade 1: more differentiated and look more closer to cell of origin; morphology is closer to normal
Grade 2: variation in shape and size of nuclei and more aggressive
Grade 3: less differentiated and not close to cells or origin; nuclear hyperchromasia and pleomorphism

Question 18

Skeletal Muscle Tumors

Answer 18

Almost always malignant
Rhabdomyosarcoma, skeletal muscle differentiation
Alveolar (20%), embryonal (60%) and pleomorphic (20%)
Most common soft tissue sarcoma (