Bone tumors Flashcards
What is the usual clinical presentation of a bone tumor?
usually nonspecific, may present;
- pain (e.g. osteoid osteoma= severe pain, worse at night, relieved by aspirin)
- mass (e.g. parosteal osteosarcoma= painless, hard growing mass in popliteal fossa)
- pathologic fracture
- asymptomatic
What are the most common bone tumors in children? young adults? elderly?
- children, adolescents= osteosarcoma, Ewing’s sarcoma
- young adults= giant cell tumor
- elderly= chondrosarcoma
What can the radiological pattern of a bone tumor tell you?
- margins= growth rate
- sclerotic margin is generally an indication of benign, slowly growing neoplasm (there is time for bone growth to happen around the lesion)
- ill-defined margin is generally an indication of malignant, rapidly growing neoplasm
- solid, ivory-like pattern is generally seen in malignant bone matrix forming tumors
- “rings and arcs” are generally seen in chondroid matrix forming tumors
Describe an osteoid osteoma
- long bones (femur, tibia)
- < 2 cm
- night pain
- responds to aspirin
- radiolucent lesions within sclerotic cortex (clear ring around lesion -> slow growing)
Describe an osteoblastoma
- vertebrae or long bone metaphysis
- > 2 cm
- painful but NOT responsive to aspirin
- expansile radiolucency with mottling (less defined borders -> faster growing)
- Look like osteoid osteoma (Circumscribed benign lesion within bone) **Area of immature bone being formed by osteoblasts
What is the prevalence of bone forming (osteogenic) tumors?
- relatively rare group of tumors (compared to carcinomas and hematopoietic tumors)
- malignant bone tumors comprise ~0.2% of all types of cancer
- they represent and important percentage of potentially curable cancers following multimodal therapy
What is the prevalence of osteosarcoma?
-
most common sarcoma of bone (35%)
- ~2000 new cases per year in the US
- 26% chondrosarcoma, 16% Ewing, 8% chordoma, 6% MFH
- bimodal age distribution, M>F
- mean age= 15 yo (60% of cases 10-20)
- 2nd peak in ages 55-80
Where are osteosarcomas commonly found?
- malignant mesenchymal tumor in which cells produce osteoid or bone
- most common in the metaphysis of long bones
- esp. femur, tibia, humerus
- seen in flat bones/spine in older patients
- hematogenous spread to lungs is common and happens early in the cancer progression
What is the pathogenesis of osteosarcoma?
Several factors increase osteosarcoma risk;
- inherited mutant allele of RB (retinoblastoma) gene
-
mutation of p53 suppressor gene causing Li-Fraumeni
- increased risk of bone/soft tissue sarcomas, early onset breast cancer, brain tumors, leukemia
- overexpression fo MDM2 (5-10%), INK4 and p16
- sites of bone growth/disease (i.e. Paget disease)
- prior irradiation
What are the clinical/radiological findings of an osteosarcoma? How do you treat it?
- infiltrative tumor, extending into soft tissue
- malignant cells producing osteoid
**treat with neo-adjucant chemotherapy and surgical resection (poor prognosis before the development of chemotherapy, now 60-65% 3-5 yr survivial for patients without metastasis)
Describe an osteochondroma
- most common benign tumor of bone
- common in metaphysis of long bones
- malignant transformation is rare (<1%) but increased risk (~40%) in hereditary multiple exostoses (multiple osteochondromas)
- autosomal dominant, most commonly secondary to mutations in EXT-1 (8q24)
Descibe an enchondroma
- benign hyaline cartilage lesion (intramedullary chondroma)
- usually asymptomatic, incidental finding
- appendicular skelton (esp small bones of hands and feet)
- X-rays; lytic, lobulated, corical thinning
- Micro; lobules of hyaline carilage, minimal atypia
- Treatment; none unless lesions shows changes (onset of pain= evidence of malignancy)
Describe two types of multiple chondromatoses
**both common point mutations in IDH1 or IDH2
-
Ollier disease
- multiple enchondromata
- tend to have regional distribution
- may or may not have severe skeletal malformation
-
Maffucci syndrome
- multiple enchondromata + angiomata
- severe skeletal malformation
- higher incidence of malignant transformation
Describe the prevalence of chondrosarcomas
- second (after osteosarcomas) most common bone sarcoma (26%)
- wide range of ages, mainly older adults (above 40-50 yo)
- peak during 6th/7th decades
Where are chondrosarcomas often located?
- central skeleton; pelvis and ribs (45%)
- humerus/femur (metaphysis or diaphysis)
What are the common characteristics of chondrosarcomas grossly/on imaging?
- medullary location, cortical erosion or destruction
- frequently contain calcifications, “popcorn like”
- occasional soft tissue extension (not as aggressive as osteosarcoma)
- generally more cellular and nuclei more pleomorphic than enchondromas
- binucleation is frequent, but doesn’t suffice for malignant diagnosis
Describe the grading system for chondrosarcomas
- grade 1= more matrix than cells (though a little more than normal)
- grade 2= more atypia, focal areas of increased dense cellularity
- grade 3= even more atypia and mitotic figures (more aggressive but less common)
What is the prognosis for chondrosarcomas? What are some observed variants?
- 5 year survival
- grades 1,2= 80-90%
- grade 3= 29% (pulmonary metastasis)
- Variants;
- de-differentiated (look like embryonic tissue)
- myxoid
- clear cell
- mesenchymal
- juxtacortical
Describe a non-ossifying fibroma
- common developmental benign cortical defect
- 1 in every 4 individuals
- multifocal in 25% of cases
- tibia, femur (metaphysis) 1st-3rd decades
- incidental finding or pathological fracture
- eccentric, lytic, peripheral sclerosis (slow growing)
Describe fibrous dysplasia
- developmental arrest of bone
- monostotic (one site)
- most common, seen in adolescents
- ribs, mandible, femur
- polyostotic (multiple sites)
- infancy/childhood
- crippling deformities, craniofacial involvement common
- e.g. McCune-Albright syndrome
Describe McCune-Albright syndrome
- polyostotic fibrous dysplasia with endocrinopathies and cafe au lait spots
- sexual precocity, acromegaly, Cushing syndrome
- rare form; F>M
- activating germline mutations of GNAS (GTP binding protein) result in excess cAMP leading to endocrine gland hyperfunction
Describe the pathology and treatment of fibrous dysplasia
Pathology;
- haphazard, curvilinear, randomly oriented woven bone trabeculae (“Chinese characters”), surrounded by fibroblastic stroma
- no significant osteoblastic rimming
**Treat conservatively, except the polyostotic form
Describe Ewing Sarcoma
**PNET (primitive neuroectodermal tumor)
- second most common malignant bone tumoe in childhood
- adolescents, young adults, M>F
- present as painful, often enlarging masses
- found in diaphysis of long tubular bones (ribs, pelvis)
Describe the appearance of Ewing Sarcoma grossly/on imaging
- destructive moth-eaten, permeative medullary lesion with large soft tissue mass
- “onion skin” pattern of periosteal reaction in response to rapid growth
- hemorrhage and necrosis common
Describe the appearance of Ewing Sarcoma on histology
- sheets of primitive small round blue cells with primitive neural phenotype (“rosettes”)
- membranous CD99
- contain abundant glycogen
What is the pathogenesis and treatment of Ewing sarcoma?
Pathogenesis:
- EWS protein involved in >95% of ES/PNET
- t(11,22) present in 85% of tumors
- EWS gene on 22q fused with FLI-1 transcription factor on 11q
**Treat with chemo/surgery, radiation may be added (stage 1= 5 year survival 70% with chemo/RT)
Describe the prevalence and common location of giant cell tumors
- young adults (20-40 yo), older adolescents (skeletally mature), F>M
- epiphyseal location (knee, proximal humerus, radius)
- most are benign, locally aggressive (may destroy cortex of bone and extend into soft tissue)
Describe metastatic bone tumors
- most common malinant bone tumor, especially in adults (20x more frequent than primary bone tumors)
- mostly multiple; solitary lesions may mimic a primary bone tumor and precede discovery of its source
- 70% go to axial skeleton (skull, ribs, vertebrae, sacrum)
- mostly lytic
- may be blastic (bone forming); breast, prostate
- 80% come from “BLT-KP”
- breast, lung, thyroid, prostate, and kidney
