4/11 Bone Tumors - Corbett Flashcards
key rule of bone tumors
adults v kids
why bone?
radiographic manifestations
METASTATIC tumors are most common malignant tumors involving bone
adults: prostate, breast, kidney, lung make up over 75%
kids: neuroblastoma, Wilm’s tumor, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma
skeletal metastases typically multifocal (axial skeleton, prox femur, humerus)
- why? rich cap network and slow blood flow in red marrow → facilitates implantation and growth of tumor cells
manifestations
- lytic lesions: metastatic cells secrete substances that stimulate osteoclastic bone resorption (kidney, lung, GI tract, malig melanoma)
- sclerotic lesions: stimulate osteoblastic bone formation
- most induce mixed lytic/blastic lesion
prostate cancer and bone lesiosn
prostate cx metastases to bone are osteoBLASTIC
- osteoblastic metastases on bone scan → virtually diagnostic of prostate cancer
tumors
locations
age
morphology
osteoma
- round/oval sessile tumors
- exophytic masses on membranous bone (on or in skull/facial bones)
- solitary, slow growing tumors of little clinical significance
- exceptions: obstruction of sinus, impingement on brain/eye
osteroid osteoma
osteoblastoma
osteoid osteomas (< 2cm)
- teens, 20s
- men: women, 2:1
- cortex of shafts of long bone (femur, tibia, humerus)
- PAIN is principal symptom
- continuous, deep, aching, intense w varying quality/severity; usually localized to site of lesion
- worse at night
- responsive to oral salicylates
- pathologically: WOVEN BONE
- interconnecting trabeculae of woven bone rimmed by osteoblasts producing PGE2 → pain
osteoblastomas (> 2cm)
- frequently involve spine
- pain unresponsive to salicylates
- tumor usually doesnt induce marked bony rxn
osteroid osteoma
osteoid osteomas (< 2cm)
- teens, 20s
- men: women, 2:1
- cortex of shafts of long bone (femur, tibia, humerus)
- PAIN is principal symptom
- continuous, deep, aching, intense w varying quality/severity; usually localized to site of lesion
- worse at night
- responsive to oral salicylates
pathological fts: WOVEN BONE
- interconnecting trabeculae of woven bone rimmed by osteoblasts producing PGE2 → pain
radiological fts
- lucent nidus surrounded by halo of radiodense cortical bone
- maybe a central calcification; cortical thickening and diffuse medullary sclerosis
osteosarcoma
cell of origin
histo hallmark
who gets it?
- risk factors
- genetic predisp
most common primary malignant bone tumor
cell of origin: primitive mesenchymal cells
histo hallmark: malignant osteoid (lacy, disorganized, spiculated)
- 75% of pt younger than 20
- second peak in elderly assoc with conds known to be risk factors:
- Paget’s disease
- bone infarct
- prior irradiation
risk factors:
- rapid bone growth (incr incidence during adolecent spurt, typically in metaphyseal area adj to growth plate)
- environmental factors (radiation)
genetic predisp
- assoc with bone dysplasias (Paget disease, fibrous dysplasia, enchondromatosis, hereditary multiple exostoses)
-
germline mutations
- RB germline mutation (1000x risk)
- Li-Fraumeni syndrome (gemrline p53 mut)
osteosarcoma
location
can occur in any bone
most common in long bones near growth plate
- femur - more distal
- tibia - more proximal
- humerus - more proximal
most common subtype of osteosarcoma
osteosarcoma summary graphic
cartilage forming tumors
majority of primary bone tumors (form hyaline or myxoid cartilage)
benign > malignant
osteochondroma
(exostosis)
most common benign bone tumor
cartilage capped tumor attached by bony stalk to underlying skeleton
- majority solitary 85
- multiple hereditary exostosis syndrome 15 (AD, devp in childhood)
- disturbed epiphyseal growth
- incr risk of CHONDROSARCOMA********
- only in bones of endochondral origin
- arise at metaphysis near growth plate of long tubular bones, esp near knee (femur, tibia, humerus)
- stop growing once normal growth of skeleton complete
tx: surgical excision
multiple hereditary osteochondroma
cause: germline LOF mutations in EXT1 or EXT2 genes → encode proteins fxing in biosynth of heparin sulfate proteoglycans
- can affect Ihh diffusion
disrupts cartilage growth
disrupts chondrocyte differentiation
→→→ allows abnl growth
**INCREASED RISK OF CHONDROSARCOMA (5-20%)**
enchondroma
benign neoplasms of hyaline cartilage
- likely ectopic cartilage rest arising from foci of cartilage displaced or remodeled from growth plate
- in medullary cavity of long bones
- usually centrally located
50% metaphyseal lesions of short tubular bones of hands/feet
multiple and solitary lesions assoc with sporadic mutations in ISOCITRATE DEHYDROGENASE
see nodules of hyaline cartilage rimmed by narrow band of reactive bone
chrondrosarcoma
second most common primary malignant tumor of bone - produces exclusively cartilage
- low grade tumors / low metastatic potential vs high grade aggressive tuors / early metastasis
if tumor exhibits bone-forming elements? NOT A CHONDROSARCOMA!
primary (85) vs secondary (15)
- de novo vs pre-existing lesion
genetics (EXT, IDH1 and 2)
endochondroma
vs
chondrosarcoma
Ewing sarcoma
primitive neuroectodermal tumors
primary malignant small round cell tumors of bone/soft tissue
- share identical chromosome translocation t(11;22)
- EWS(22):FLI1(11) → forms abberant transcriptional complex w RNA helicase A
- show AGGRESSIVE MALIGNANCY
- there are two variants of the same tumor that differ only in degree of neural differentiation
second most common bone malignancy in children/adults
- 80% affected are under 20
- whites >>>> blacks
tend to occure in SHAFT OF LONG TUBULAR BONES (distinct from primary bone tumors)
HomerWright rosettes (tumor cells in circle around central fibrillary space)
ES clinical course and imaging
giant cell tumor
osteoclastoma
- neoplastic cells = osteoblasts making lots of RANKL → stimulates osteoclast precursor prolif and differentiation
localized destructive resorption of bone matrix
most arise in knee at epiphysis (lytic lesion with “soap bubble appearance”)
sx: arthritis, pathologic fracture
fibrous and fibroosseous tumors
- fibrous cortical defects
* loosly arranged whorls of elongated spindled fibroblast-like cells - nonossifying fibromas
- fibrous dysplasia
- arise during skeletal growth/devpt in three patterns
- single bone (monostotic)
- multiple bones (polyostotic)
- McCune Albright syndrome: polyostotic disease w cafe au lait skin pigmentation and endcrine abnl ESP PRECOCIOUS PUBERTY
- intramedullary trabeculae of woven bone (lack osteoblastic rimming, surrounded by cellular fibroblastic prolif)
McCune Albright syndrome
