Martin: Bone Tumors and Tumor-Like Lesions Flashcards
How does osteoid osteoma differ from osteoblastoma in terms of size and bone predilection?
- Osteoid osteoma: <2cm in diameter; predilection for appendicular skeleton (50% involve femur or tibia) arising in cortex
- Osteoblastoma: are >2cm and involve posterior spine (laminae and pedicles)
How does the pain and responsiveness to aspirin/NSAIDs differ between osteoid osteoma and osteoblastoma?
- Both are painful, and the pain is typically worse at night
- Osteoid osteoma DOES respond to aspirin/NSAIDs
- Osteoblastoma DOES NOT respond!
What is a radiographic clue for osteoid osteoma?
- Thick rind of reactive cortical bone; surrounding a nidus
- Osteoid osteomas elicit formaion of a tremendous amount of reactive bone
Describe the characteristic morphology of osteoid osteoma and osteoblastoma?
Haphazardly interconnecting trabeculae of woven bone that are rimmed by prominent osteoblasts
What is the bimodal age of distribution seen with osteosarcoma; which sex is most affected?
- 75% occur in pt’s <20 y/o
- 2nd peak in older adults (>65 y/o), frequently in assoc. w/ Paget disease, bone infarcts, and prior radiation
- Men more commonly affected
Which part of bones do osteosarcomas arise in and which bones are most often affected?
- Arise in metaphyseal region of long bones of extremities
- Almost 50% occur about the knee (i.e., distal femur or prox. tibia)
How do osteosarcomas typically present?
- Painful, progressively enlarging mass
- Sometimes sudden fracture is the 1st sx
What are the characteristic X-ray findings with osteosarcoma?
- Large destructive, mixed lytic and blastic mass w/ infiltrative margins
- Frequently breaks thru periosteum, resulting in reactive periosteal bone formation –> Codman triangle = elevated periosteum
Germline mutation in what gene are associated with a 1000-fold increased risk for osteosarcoma; occurence in sporadic tumors?
- Germline mutation in RB = 1000-fold ↑ risk
- This mutation is present in up to 70% of sporadic tumors
Li-Fraumeni syndrome is associated with what germline mutation; have an increased risk for what MSK pathology?
- Germline TP53 mutations
- Greatly ↑ risk of osteosarcoma
Which morphological feature of osteosarcomas is diagnostic; what is seen?
- Formation of bone by the tumor cells = diagnostic
- Neoplastic bone usually has fine, lace-like architecture but also may be deposited in broad sheets of primitive trabeculae
Osteosarcomas frequently metastasize via which route and to where?
Hematogenously to the lungs, bone, and brain
What is the most common benign bone tumor?
Osteochondroma (aka exostosis)
Majority (85%) of osteochondroma arise how and the remainder are associated with what herediatry disease?
- 85% are solitary; arise in early adulthood w/ men 3x > women
- Remainder assoc. w/ multiple hereditary exostosis syndrome, an autosomal dominant hereditary disease
Where in bone do osteochondromas arise and which bones most often affected?
- Only bones of endochondral origin and arise from the metaphysis near the growth plate
- Long tubular bones, especially near knee
- Occasionally seen in bones of pelvis, scapula,andribs
Hereditary osteochondroma (exostoses) and some sporadic types are assoc. w/ what mutations?
- Hereditary = germline loss-of-function EXT1 or EXT2
- Sporadic = ↓ expression of EXT1 or EXT2
- These genes encode enzymes that synthesize heparin sulfate gylcosaminoglycans
What is the characteristic morphology and growth pattern of osteochondromas?
- Are sessile or pedunculated w/ cap composed of benign hyaline cartilage varying in thickness
- Cortex of newly formed stalk merges w/ cortex of the host bone, so that medullary cavity of the osteochondroma and bone from which it arises are in continuity
What is a complication of osteochondroma that is more often seen in those assoc. w/ multiple hereditary exostosis?
Progression to chondrosarcoma
What are chondromas and what are they known as if they arise in the medullary cavity vs. surface of bone?
- Benign tumors of hyaline cartilage
- In medullary cavity = enchondromas
- Surface of bone = juxtacortical or subperiosteal chondromas
Which 2 non-hereditary disorders are characterized by multiple enchondromas; characteristics of each?
- Ollier syndrome = multiple enchondromas
- Mafucci syndrome = multiple enchondromas + angiomas –> ↑ risk of chondrosarcoma and other malignancies
What is the size and characteristic morphology of enchondromas; how does this differ in the non-hereditary disorders Ollier and Maffucci syndrome?
- Usually <3cm and are gray-blue and translucent
- Well-circumscribed nodules of hyaline cartilage containing benign chondrocytes
- Periphery may ossify and center can calcify and infarct
- Ollier and Maffucci: ↑ cellularity and atypia
Which age group is Chondrosarcoma most often seen in and it commonly arises in which bones?
- Usually 40 y/o + with Men 2x > female
- Axial skeleton: pelvis, shoulder, and ribs
Sporadic chondrosarcomas may have what mutations?
- IDH1 and IDH2 mutations
- Silencing of the CDKN2A tumor suppressor gene by DNA methylation
What is characteristically seen on radiographic imaging of chondrosarcoma?
Calcified matrix appears as foci of flocculent densities
What is the gross morphology of chondrosarcomas?
Large bulky tumors made up of nodules of glistening gray-white, translucent cartilage but matrix is often gelatinous or myxoid
How are chondrosarcomas graded and what is unique about this grading?
- Assigned a grade from 1 to 3
- Direct correlation between grade and behavior
What is the behavior of chondrosarcomas and how may they metastasize and to where?
- Invade locally, painful enlarging mass.
- 70% of grade 3 spread hematogenously, especially to lungs
Ewing Sarcoma is a malignant bone tumor characterized by what?
Primitive round cells without obvious differentiation
Ewing sarcoma is most often seen in which age group and has a predilection for which ethnicity?
- 80% arise in pt’s <20 y/o with slightly more males affected
- Striking predilection for whites, while blacks/asians rarely affected
Where in bones does Ewing Sarcoma arise and which bones are most often affected?
- Arise in the diaphysis of long tubular bones; in the medullary cavity
- Especially the femur and flat bones of the pelvis
How does Ewing Sarcoma typically present?
- Painful enlargin mass; frequently tender, warm, and swollen
- Some have systemic findings that mimic infection –> including fever, ↑ ESR, anemia, and leukocytosis!
Plain radiographs of Ewing Sarcoma will show what; what is characteristic of the periosteal rxn of these tumors?
- Destructive lytic tumor w/ permeative margins that extends into surrounding soft tissues
- Produces layers of reactive bone deposited in an onion-skin like fashion
Which translocation and fusion gene product is characteristic of Ewing Sarcoma?
t(11;22) –> EWS-FL11 gene
What does the presence of Homer-Wright rosettes in Ewing Sarcomas indicate?
A greater degree of neuroectodermal differentiation
What is an important prognostic finding associated with tx of Ewing Sarcoma?
Amount of chemotherapy-induced necrosis
Which bone tumor composed of multinucleated osteoclast-type giant cells is benign, but locally aggressive?
Giant Cell Tumor
Where do Giant Cell Tumors most often arise?
- Epiphyses, may extend into metaphysis
- Majority around knee (distal femur and prox. tibia)
Why are giant cell tumors so highly destructive?
↑ RANKL from neoplastic cells with loss of feedback btw osteoblasts and osteoclasts that normally regulates process of bone remodeling
What is fibrous dysplasia and what has it been likened to?
- Benign tumor likened to localized developmental arrest
- ALL components of normal bone present, but they do not differentiate into mature structures
Fibrous dysplasia is due to mutations in what; what other pathology is this gene mutated in?
- Somatic gain-of-function mutation during development in GNAS1
- Leads to constitutively active GS-protein
- This gene is also mutated in pituitary adenomas
Characteristic morphology of fibrous dysplasia includes what?
Curvilinear shapes of the trabeculae of woven bone mimic Chinese characters and bone lacks prominent osteoblastic rimming
Monostotic fibrous dysplasia is seen on radiographic imaging as what?
Ground glass appearance and well-defined margins
