Bone Tumors B&B

Question 1

what are the classic causes of osteoclastic vs osteoblastic lesions, respectively?

Answer 1

multiple myeloma —> osteoclastic lesions: bone breakdown by metastasis

prostate cancer —> osteoblastic lesions: deposition of new bone

Question 2

which patients do primary bone tumors most often affect?

Answer 2

children/young adults (growing), males (longer bones = more growth)

often involve lone bones, especially at knees

Question 3

where are the 2 most frequent sites of pathologic fractures?

Answer 3

fracture in bone weakened by underlying abnormality, often from minor trauma

1. proximal femur
2. humerus

Question 4

how do osteoid osteoma present?

Answer 4

small benign bone tumors of osteoblasts, occur mostly in young men (teens/20s) in appendicular skeleton - mostly at knee (tibia/fibula)

present with bone pain at night, responsive to aspirin

Question 5

benign bone tumors of osteoblasts which may cause bone pain at night, but are responsive to aspirin

Answer 5

osteoid osteoma: occur on surface of cortex/diaphysis

osteoid core (radiolucent) surrounded by rim of woven bone

Question 6

osteoid osteoma vs osteoblastoma

Answer 6

osteoid osteoma: small (<2cm) benign tumors of osteoblasts, cause bone pain at night but responsive to aspirin

osteoblastoma: larger tumor (>2cm) that often involves spine, pain not responsive to aspirin

Question 7

what type of bone disorder may precede colon symptoms in Gardner’s Syndrome?

Answer 7

Gardner’s syndrome: variant of FAP (familial adenomatous polyposis), mutation in APC gene —> chronic polyp disorder

may present with osteomas (benign bone growths) in skull or mandible which may precede colon symptoms

Question 8

how does the most common primary bone tumor present?

Answer 8

osteosarcoma: malignant tumor of osteoblasts, more common in males with bimodal age distribution (75% young adults, 25% older adults with bone disease)

—> painful/enlarging bone mass or pathologic fractures occurring in metaphysis of long bones

Question 9

what does biopsy of osteosarcoma show?

Answer 9

malignant tumor of osteoblasts

histology —> pleomorphic cells (varying shapes) + irregular osteoid formation (appears pink due to protein)

Question 10

what are 2 classic x-ray findings of osteosarcoma?

Answer 10

malignant tumor of osteoblasts

1. Codman triangle: tumor breaks through cortex and lifts periosteum (looks like triangle on surface of bone on x-ray)
2. sunburst/sunray sign: tiny bone fibers form in periosteum (looks like sunburst around metaphysis on x-ray)

Question 11

what is development of osteosarcoma associated with? (3)

Answer 11

malignant tumor of osteoblasts

1. prior radiation - following childhood cancer
2. Paget’s disease
3. familial cancer syndromes/germline mutations (familial retinoblastoma/Rb mutation, Li Fraumeni syndrome/p53 mutation)

Question 12

how is osteosarcoma treated?

Answer 12

[malignant tumor of osteoblasts]

treat with ”en bloc” resection (removal of entire tumor in 1 piece + layer of healthy tissue) or amputation

all patients presumed to have metastasis - always treat with chemotherapy! either before (“neoadjuvant”) or after surgery

Question 13

Pt is a 21yo M presenting with a painful and enlarging bone mass that was detected following a fracture of their femur metaphysis. X-ray shows the growth of tiny bone fibers around the periosteum in the shape of a sunburst. FMH is significant for familial retinoblastoma. How will the patient be treated?

Answer 13

osteosarcoma - histology shows Codman triangle (tumor breaks through cortex, lifts periosteum) and/or sunburst sign (around metaphysis)

tx: “en bloc” resection (remove entire tumor in 1 piece) or amputation + CHEMOTHERAPY (always presume metastasis!)

[associated with prior chemo, Paget’s disease, inherited genetic conditions

Question 14

from which cells are Ewing sarcoma derived, and where do they occur?

Answer 14

malignant bone tumor of undifferentiated neuroectoderm cells

occur in diaphysis of long bones - usually femur, also tibia/fibula/humerus/pelvis

Question 15

which bone tumors present at the youngest age?

Answer 15

Ewing sarcoma: malignant tumor of undifferentiated neuroectoderm cells, 80% <20 years old (M>F)

aggressive w/ early metastasis

Question 16

aggressive malignant tumors occurring in the diaphysis of long bones, often with early metastasis

Answer 16

Ewing sarcoma: malignant tumor of undifferentiated neuroectoderm cells, 80% <20 years old (M>F)

Question 17

how do patients with Ewing Sarcoma present?

Answer 17

Ewing sarcoma: malignant bone tumor of undifferentiated neuroectoderm cells, 80% <20 years old (M>F)

painful, growing mass that is warm/swollen, may have fever/leukocytosis

[appears similar to osteomyelitis, but blood cultures are neg. for bacteria]

Question 18

how can Ewing Sarcoma be differentiated from osteomyelitis?

Answer 18

both present with warm/swollen mass, fever/leukocytosis

Ewing sarcoma: malignant bone tumor of undifferentiated neuroectoderm cells —> sterile blood cultures/ tumor aspiration

osteomyelitis: bone infection —> blood cultures pos. for bacteria

Question 19

what is the classic x-ray and histology finding of Ewing sarcoma?

Answer 19

Ewing sarcoma: malignant bone tumor of undifferentiated neuroectoderm cells

x-ray - onion skin appearance due to layering near periosteum, caused by splitting of the cortex

histology - sheets of small, round cells (primitive cells)

Question 20

what genetic defect is associated with most cases (85%) of Ewing sarcoma?

Answer 20

Ewing sarcoma: malignant bone tumor of undifferentiated neuroectoderm cells

associated with genetic translocation of chromosomes 11 and 22 —> fusion of EWSR1 (22) and FLI1 (11) genes, detected with FISH

Question 21

Pt is a 17yo M presenting with a painful, growing mass over the diaphysis of the femur which is warm and swollen, as well as fever and leukocytosis. Tumor aspiration was found to be sterile. X-ray shows “onion skin” appearance of the bone. Genetic testing reveals a fusion of genes found on chromosome 22 and 11, respectively. What is the diagnosis?

Answer 21

Ewing sarcoma: malignant bone tumor of undifferentiated neuroectoderm cells, presents at young age and is aggressive w/ early metastasis

85% associated with genetic translocation of EWSR1 (ch22) and FL1 (ch11)

Question 22

from which cells are giant cell tumors of the bone derived, and where do they usually occur?

Answer 22

aka osteoclastoma - benign tumor of osteoclasts, but locally aggressive (resorb lots of bone)

occur in epiphysis, most commonly in femur/tibia (at knee)

Question 23

what drives giant cell tumors of the bone to grow?

Answer 23

aka osteoclastoma - benign tumor of osteoclasts, but locally aggressive (resorb lots of bone), occur in epiphysis

stromal tumor cells express high levels of RANK-L

Question 24

tumor growing in the epiphysis of a long bone =

Answer 24

giant cell tumor, aka osteoclastoma: aka benign tumor of osteoclasts, but locally aggressive (resorb lots of bone)

Question 25

where do osteochondromas occur?

Answer 25

benign cartilage-forming tumor due to lateral projection of growth plate at the metaphysis

Question 26

if an osteochondroma becomes malignant, how does this occur?

Answer 26

benign cartilage-forming tumor due to lateral projection of growth plate at the metaphysis

rare to become chondrosarcoma, but if so due to malignant transformation of the cartilage cap

Question 27

X-ray of a 15yo M reveals a cartilage-capped bone spur (“exostosis”) arising from lateral projection of the growth plate. What is the diagnosis, and how will this be treated?

Answer 27

osteochondroma: benign cartilage-forming tumor due to lateral projection of growth plate at the metaphysis

stopping growing once growth plate closes, treated with simple excision

[exostosis = new bone growth on surface of bone]

Question 28

what causes fibrous dysplasia of the bone, and where does this occur?

Answer 28

benign tumor of woven bone surrounded by fibroblasts

occur in early adolescence, grow until growth plate closes

occur in medulla/diaphysis

Question 29

what are the classic histology and x-ray findings of fibrous dysplasia?

Answer 29

benign tumor of woven bone surrounded by fibroblasts in the diaphysis/medulla

histology - wavy lines trabeculae of woven bone

x-ray - lytic lesions in diaphysis

Question 30

where along bones do simple bone cysts (unicameral bone cysts) occur?

Answer 30

metaphysis of bone, most commonly proximal humerus or femur

Question 31

where do chondromas occur?

Answer 31

benign cartilage tumor, either in medullary cavity (endochondroma) or surface of bone (juxtacortical chondroma)

occur in small bones of hands and feet

Question 32

where do chondromas vs chondrosarcomas occur?

Answer 32

chondroma = benign cartilage tumor, occur in small bones of hands and feet

chondrosarcoma = malignant cartilage tumor, occur centrally (pelvis, shoulder, ribs)

Question 33

patient presenting with bone pain/ fractures with LOW calcium and HIGH PTH = problem due to …

Answer 33

low vitamin D - either lack in diet/sunlight, malabsorption, renal failure (problem activating vitamin D)

Question 34

which of the following would NOT occur in the diaphysis?
a. Ewing sarcoma
b. Giant cell tumor
c. Osteoid osteoma
d. Fibrous dysplasia
e. metastasis from another site

Answer 34

b. giant cell tumor - occurs in epiphysis

all others occur in diaphysis of long bone

Question 35

what is the most common type of long bone tumor to occur in the metaphysis?

Answer 35

osteosarcoma - most common type of primary bone tumor

Question 36

how does the bone variant of Langerhans cell histiocytosis present?

Answer 36

malignant proliferation of Langerhans cells, bone variant causes eosinophilic granuloma —> bone mass in skull of children

differentiate from bone tumor by Langerhans cells and eosinophils in biopsy

[Langerhans = dendritic cells of myeloid origin, but similar to histiocytes, aka tissue macrophages]

Question 37

bone mass in skull of child with eosinophils in biopsy =

Answer 37

Langerhans cell histiocytosis: growth of Langerhans cells, bone variant causes eosinophilic granuloma —> bone mass in skull of children

Question 38

how can Langerhans cell histiocytosis be differentiated from bone tumors?

Answer 38

malignant proliferation of Langerhans cells, bone variant causes eosinophilic granuloma —> bone mass in skull of children

biopsy shows Langerhans cells and eosinophils (not found in bone tumors)