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Musculoskeletal/Rheum > Bone and Cartilage Tumors > Flashcards

Bone and Cartilage Tumors Flashcards

1
Q

What are the 4 pieces of information needed to diagnose a mass in a bone?

A

[1] the age of the patient
[2] the sex of the patient
[3] the location of the lesion
[4] the radiographic appearance of the lesion

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2
Q

Malignant tumors occurring in the diaphysis are?

A

Ewing’s sarcoma and chondrosarcoma

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3
Q

Benign tumors occurring in the diaphysis are?

A

enchondroma

fibrous dysplasia

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4
Q

Metaphyseal lesions that are malignant are?

A

osteosarcoma and juxtacortical osteosarcomas

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5
Q

Metaphyseal lesions that are benign are?

A 
osteoblastoma, osteochondroma
 non-ossifying fibroma
osteoid osteoma
chondromyxoid fibroma
giant cell tumors
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6
Q

What is more common, primary malignant or benign lesions?

A

Primary benign lesions are more common (malignant primary bone neoplasms account for fever than 1% of all malignant tumors)

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7
Q

How big are osteoid osteomas? How big are osteoblastomas?

A

OO: < 2cm
OB: >2cm

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8
Q

Where do osteoid osteomas most likely form? Where do osteoblastomas usually form?

A

OO: femur or tibia
OB: posterior spine (laminae and pedicles)

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9
Q

What are the symptoms of osteoid osteoma v. osteoblastoma?

A

OO: nocturnal pain that is relieved with aspirin
OB: less frequently assoicated with pain (but pain is not relieved with aspirin)

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10
Q

Which produces a marked bony reaction: osteoid osteoma or osteoblastoma?

A

osteoid osteoma (forms a tremendous amount of reactive bone that encircles the lesion)

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11
Q

How do you differ a benign primary osteogenic bone tumor from osteosarcoma?

A

small size, well-defined margins, and benign cytologic features of the neoplastic osteoblasts

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12
Q

How do you treat osteoid osteoma v. osteoblastoma?

A

Osteoid osteoma is frequently treated by radiofrequency ablation, whereas osteoblastoma is usually curetted or excised en bloc.

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13
Q

True or false: the neoplastic cells in giant cell tumors do not actually cause the destruction.

A

TRUE! The bulk of the tumor consists of non-neoplastic osteoclasts and their precursors (stimulated by RANKL expressed by neoplastic cells) that have abnormal communication with osteoblasts–so localized but highly destructive resorption of bone matrix occurs

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14
Q

Where do giant cell tumors occur?

A

arise in the epiphysis but may extend into the metaphysis: usually near joints (knee and wrist)

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15
Q

What is the name of the RANKL inhibitor that has shown promise in the adjuvant treatment of giant cell tumors?

A

denosumab

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16
Q

True or false: Benign cartilage tumors are much more common than malignant ones.

A

TRUE

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17
Q

What is a benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk?

A

osteochondroma

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18
Q

What is multiple hereditary exostosis syndrome?

A

autosomal dominant hereditary disease with germline loss-of-function mutations in either the EXT1 gene or EXT2 gene (enzymes that synthesize heparan sulfate glycosaminoglycans)

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19
Q

Why is loss of heparin sulfate glycosaminoglycans pathologic in osteochondroma?

A

reduced or abnormal glycosaminoglycans may prevent normal diffusion of the factor Indian hedgehog (Ihh), a local regulator of cartilage growth, thereby disrupting chondrocyte differentiation and local skeletal development

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20
Q

Where are osteochondromas most likely found?

A

bones of endochondral origin and arise from the metaphysis near the growth plate of long tubular bones, especially near the knee

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21
Q

What is the name of a a nonhereditary syndrome of multiple enchondromas or enchondromatosis?

A

Ollier disease

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22
Q

What are benign tumors of hyaline cartilage?

A

chondromas

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23
Q

Where do enchondromas arise?

A

medullary bone, typically in tubular bones of the hand or feet

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24
Q

Where do Juxtacortical chondromas arise?

A

surface of bones

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25
Q

What is a nonhereditary syndrome combining multiple enchondromas with multiple soft tissue hemangiomas?

A

Maffucci syndrome

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26
Q

What is the underlying cause of most enchondromas?

A

Heterozygous mutations in the IDH1 and IDH2 genes

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27
Q

What is the result of heterozygous mutations in the IDH1 and IDH2 genes?

A

acquisition of new enzymatic activity in two isoforms of the enzyme isocitrate dehydrogenase to be able to synthesize 2-hydroxyglutarate. (interferes with regulation of DNA methylation)

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28
Q

How do enchondromas cause transformation by association?

A

2-hydroxyglutarate can diffuse into neighboring cells with normal IDH genes, causing oncogenic epigenetic changes in genetically normal neighbors

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29
Q

Do most enchondromas undergo sarcomatous transformation?

A

NOT sporadic ones–mainly just those associated with syndromes

30
Q

What additional complications do individuals with Maffucci syndrome have?

A

also at risk of developing other types of malignancies, including ovarian carcinomas and brain gliomas

31
Q

What is the name of the malignant tumor in which the cancerous cells produce osteoid matrix or mineralized bone?

A

osteosarcoma

32
Q

Where is the most common site of osteosarcomas?

A

tumors usually arise in the metaphyseal region of the long bones of the extremities, and almost 50% occur around the knee in distal femur or proximal tibia.

33
Q

What is the triangular shadow located between the bone cortex and raised ends of the periosteum (due to osteosarcoma breaking through the cortex and lifting the periosteum, called?

A

Codman triangle

34
Q

What are the well-known mutations of osteosarcomas?

A

RB, TP53, INK4a, and MDM2/CDK4

35
Q

When do osteosarcomas peak in incidence?

A

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

36
Q

What is the most common subtype of osteosarcoma?

A

arises in the metaphysis of long bones and is primary, intramedullary, osteoblastic, and high grade

37
Q

What is the DIAGNOSTIC microscopic finding of osteosarcoma?

A

formation of bone by the tumor cells

38
Q

What is the most common site of metastasis in osteosarcomas?

A

lungs

39
Q

What are malignant tumors that produce cartilage?

A

chondrosarcomas

40
Q

What are the 4 classification of chrondrosarcomas?

A

1) conventional (hyaline cartilage producing)
2) clear cell
3) dedifferentiated
4) mesenchymal variants

41
Q

What are the subdivisions of convential chondrosarcomas?

A

central (intramedullary) and peripheral (juxtacortical)

42
Q

What is the most common type of chondrosarcoma?

A

Conventional central tumors

43
Q

Where do chondrosarcomas commonly arise?

A

axial skeleton, especially the pelvis, shoulder, and ribs.

44
Q

What is a common genetic finding seen in sporadic chondrocarcinomas?

A

Silencing of the CDKN2A tumor suppressor gene by DNA methylation

May also have IDH1 and IDH2 mutations.

45
Q

What is the genetic finding seen in multiple osteochondroma syndrome?

A

exhibit mutations in the EXT genes

may have IDH1 and IDH2 mutations.

46
Q

What is the matrix like in conventional chondrosarcomas?

A

matrix is often gelatinous or myxoid and can ooze from the cut surface.

47
Q

Can conventional chondrosarcomas spread?

A

YES: spreads through the cortex into surrounding muscle or fat

48
Q

What is dedifferentiated chondrosarcoma?

A

low-grade chondrosarcoma with a second, high-grade component that does not produce cartilage

49
Q

What are characteristics of clear cell chondrosarcoma?

A

contains sheets of large, malignant chondrocytes that have abundant clear cytoplasm, numerous osteoclast-type giant cells, and intralesional reactive bone formation

50
Q

What is clear cell chondrosarcoma often confused with?

A

osteosarcoma

51
Q

What are the characteristics of mesenchymal chondrosarcoma?

A

composed of islands of well-differentiated hyaline cartilage surrounded by sheets of small round cells

52
Q

What is mesenchymal chondrosarcoma commonly confused with?

A

Ewing Sarcoma

53
Q

What determines the prognosis of chondrosarcomas?

A

tumor grade

54
Q

How do you treat chondrosarcoma?

A

wide surgical excision and chemotherapy (in mesenchymal and dedifferentiated tumors)

55
Q

What are Ewing sarcoma family tumors (ESFT)?

A

Ewing sarcoma and primitive neuro-ectodermal tumor (PNET)

56
Q

What is Ewing sarcoma?

A

malignant bone tumor composed of primitive small round blue cells without obvious differentiation.

57
Q

Where are ESFTs most commonly found?

A

medulla of the diaphysis of long tubular bones, especially the femur, or in the flat bones of the pelvis

58
Q

The characteristic periosteal reaction produces layers of reactive bone deposited in what fashion?

A

onion skin

59
Q

What mutation is found in most ESFTs?

A

(11;22) (q24;q12) translocation generating in-frame fusion of the EWS gene on chromosome 22 to the FLI1 gene

60
Q

What does the presence of Homer-Wright rosettes (round groupings of cells with a central fibrillary core) indicate ?

A

greater degree of neuroectodermal differentiation

61
Q

True or flase: Malignant bone tumors are much commonly metastatic than primary.

A

TRUE

62
Q

Where are the most popular origins for bone metastasis in adults?

A

prostate, breast, lung and kidney

63
Q

Where are the most popular origins for bone metastasis in children?

A

neuroblastoma, Wilms’ tumor, osteosarcoma, Ewing sarcoma (extraosseous) and rhabdomyosarcoma

64
Q

List the pathways of spread of metastases into bone?

A

(1) direct extension
(2) lymphatic drainage
(3) hematogenous dissemination
(4) intraspinal seeding (via the Batson plexus of veins).

65
Q

True or false: skeletal mets are usually single.

A

FALSE: typically multifocal unless carcinomas of the kidney and thyroid (may present with solitary lesions)

66
Q

Most skeletal metastasis involve what bones?

A

axial skeleton (vertebral column, pelvis, ribs, skull, and sternum)

67
Q

Why is the axial skeleton a popular site of metastasis?

A

red marrow in these areas, with its rich capillary network and slow blood flow, facilitates implantation and growth of the tumor cells

68
Q

What types of cancers metastasize to small bones of hands and feet (very rare occurrence)?

A

lung, kidney, colon

69
Q

What is the pathogenesis behind bone mets?

A

Cross-talk between metastatic cancer cells (prostaglandins, cytokines and PTHrP, which upregulate RANKL on osteoblasts and stromal cells thereby stimulating osteoclast activity) and native bone cells leads to changes in the bone matrix.

70
Q

Sclerotic metastases may be produced by tumor cells secreting what proteins?

A

WNT proteins that stimulate osteoblastic bone formation

71
Q

What type of metastasis is typically “blastic”–forms bone?

A

prostate adenocarcinoma

72
Q

Carcinomas of the kidney, lung, and gastrointestinal tract and malignant melanoma produce what types of lesions?

A

Lytic (bone destroying)

Musculoskeletal/Rheum (12 decks)

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