Chapter 26: 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); no bony reaction
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 for osteoid osteomas
- 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?
Haphazardly interconnecting trabeculae of woven bone that are rimmed by prominent osteoblasts
Which histologic features of osteoid osteomas and osteoblastomas help to distinguish them from osteosarcomas?
Relatively small size, well-defined margins, and benign cytologic features of the neoplastic osteoblasts
How is osteoid osteoma vs. osteoblastoma treated?
- Osteoid osteoma is frequently treated w/ radiofrequency ablation
- Osteoblastoma is usually curetted or excised en bloc
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 mutations in what gene are associated with a 1000-fold increased risk for osteosarcoma; occurrence 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
Besides RB and tP53, what is another gene associated with increased risk of osteosarcoma?
What is the function of this gene?
CDKN2A (inactivated in many osteosarcomas)
-encodes two tumor suppressors, p16 and p14
Why do osteosarcomas peak in incidence around the time of the adolescent growth spurt and how does this relate to their location?
- Occur most frequently in the region of the growth plate in bones with the fastest growth
- The ↑ proliferation at these sites may predispose to mutations
What is the gross appearance of osteosarcomas?
bulky, gritty, gray-white tumors containing hemorrhage and cystic degeneration
-destroys cortex, spreads to soft tissue → ST mass, spreads through medullary canal & replaces marrow
Which morphological feature of osteosarcomas is diagnostic; what is the appearance of the neoplastic bone?
- 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
What is the histologic appearance (micro) of osteosarcoma?
pleomorphic, large hyperchromatic nuclei, bizarre giant tumor cells, abundant mitoses (including abnormal tripolar forms)
When malignant cartilage is abundant in osteosarcomas they are referred to as what?
Chondroblastic osteosarcoma
Osteosarcomas frequently metastasize via which route and to where?
Hematogenously to the lungs, bone, and brain
What is the multi-modality approach to tx of osteosarcomas?
- Neoadjuvant chemotherapy, which is given under the assumption that all pt’s have occult metastases at time of dx
- Followed by surgery & postop adjuvant chemotherapy
What is the most common benign bone tumor?
Osteochondroma (aka exostosis)
What is another name for osteochondroma?
exostosis
Majority (85%) of osteochondroma arise how and the remainder are associated with what hereditary 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, and ribs (but less common)
Hereditary osteochondroma (exostoses) and some sporadic types are assoc. w/ what mutations?
What do these genes encode?
- 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; bluish-white cartilaginous cap overlies the bony cortex
- 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 age group are enchondromas most often seen in and which bones most often affected?
- 20-50 y/o
- Appear as solitary metaphyseal lesions of tubular bones of the hands and feet
Which 2 non-hereditary disorders are characterized by multiple enchondromas; characteristics of each?
- Ollier syndrome = multiple enchondromas (not hereditary)
- Mafucci syndrome = multiple enchondromas + angiomas –> ↑ risk of chondrosarcoma and other malignancies
Which mutations have been identified in the chondrocytes of syndromic and solitary enchondromas?
Heterozygous mutations in the IDH1 and IDH2 genes
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 malignancies are those with Mafucci Syndrome at increased risk of developing?
Chondrosarcoma + ovarian carcinomas and brain gliomas
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
A majority of chondrosarcomas arise de novo, but some arise from which 2 pre-existing tumors?
Osteochondroma or enchondromas
Chondrosarcomas arising in associated with syndromes such as multiple osteochondroma syndrome or those that are chondromatosis-related have which mutations?
- Multiple osteochondroma syndrome: mutations in EXT genes
- Chondromatosis-related: IDH1 and IDH2
Sporadic chondrosarcomas may have what mutations?
- IDH1 and IDH2 mutations
Which variant of chondrosarcoma is characterized as being composed of islands of well-differentiated hyaline cartilage surrounded by sheets of small round cells, which can mimic Ewing Sarcoma?
Mesenchymal chondrosarcoma
Which variant of chondrosarcoma has nodules of glistening gray-white, translucent cartilage; matrix is often gelatinous or myxoid and can ooze from cut surface; spotty calcifications and central necrosis may create cystic spaces?
conventional
Which variant of chondrosarcoma is considered low-grade with a high-grade component; no cartilage?
dedifferentiated
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
What is the 5-year survival for grade 1 vs. grade 3 chondrosarcomas and how are they tx?
- Grade 1 have 5-year of 80-90%; drops to 43% for grade 3
- Tx is by wide surgical excision
Ewing Sarcoma is a malignant bone tumor characterized by what? Aka what is the histology of ewing sarcoma
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 the treatment and 5-year survival with Ewing Sarcomas?
- Tx w/ neoadjuvant chemotherapy followed by surgical excision with or without radiation
- 5-year survival of 75% and long-term cure in 50%
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
The neoplastic cells of Giant Cell Tumors express high levels of what?
RANKL –> promoting proliferation and differentiation of osteoclasts
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 the treatment, recurrence rate and prognosis for Giant Cell Tumors?
- Tx with curettage —> 40-60% will recur locally
- 4% will metastasize to lung, may regress and seldom fatal
Aneurysmal bone cyst (ABC) frequenlty arises in which bones?
- Metaphysis of long bones
- Posterior elements of vertebral bodies
Signs and sx’s of Aneurysmal bone cyst (ABC)?
- Most common = pain + swelling
- If involves vertebrae, can compress nerves –> neurologic sx’s
How do aneurysmal bone cyst (ABC) appear radiographically?
- Eccentric, expansile lesion w/ well-defined margins
- Most being completely lytic, often w/ thin shell of reactive bone at the periphery
CT and MRI of aneurysmal bone cyst (ABC) may demonstrate what?
Internal septa and characteristic air-fluid levels
The spindle cells of aneurysmal bone cyst (ABC) frequently demonstrate which mutations?
Chr 17p13 rearrangement —> USP6 overexpression
Unusually dense calcified matrix called “blue bone” is seen in some cases of what bone tumor?
Aneurysmal bone cyst (ABC)
Morphology of aneurysmal bone cyst (ABC)?
- Multiple blood-filled cystic spaces separatd by thin, tan-white septa
- Septa are composed of plump, uniform fibroblasts, multinucleated osteolcast-like giant cells, and reactive woven bone
What are fibrous cortical defects (aka metaphyseal fibrous defects); where and in whom do they arise; defining characteristics?
- Extemely common arising in 30-50% of children >2 y/o
- Arise eccentrically in metaphysis of distal femur and prox. tibia
- Almost 1/2 are bilateral** or **multiple
How does fibrous cortical defect differ from nonossifying fibroma?
- Fibrous cortical defects: typically small, about 0.5cm in diameter
- Nonossifying fibroma: larger, up to 5-6cm in size; usually not detected until adolescence or adulthood
What is the characteristic morphology of the fibroblasts and macrophages seen in both fibrous cortical defect and nonossifying fibroma; what other finding is commonly present?
- Cytologically bland fibroblasts arranged in storiform (pin-wheel) pattern***
- Macrophages may take form of clustered cells w/ foamy cytoplasm or multinucleated giant cells
- Hemosiderin is commonly present
What are the characteristic findings on radiograph of fibrous cortical defects and nonossifying fibromas?
Eccentric lobulated radiolucency surrounded by thin rim of sclerosis
What is the typical behavior and prognosis of fibrous cortical defects?
- Most have limited growth potential and undergo spontaneous resolution within several years
- Few progressively enlarge –> nonossifying fibroma may present w/ pathologic fracture or require biopsy and curettage to exclude other tumor types
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
Which 2 syndromes are associated with fibrous dysplasia and what is seen in each?
- Mazabraund syndrome: fibrous dysplasia (usually polyostotic) + soft tissue myxomas
- McCune-Albright disease: unilateral bone lesions w/ café-au-lait skin pigmentations + endocrine abnormalities; esp. precocious puberty
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 most often occur when and affects which bone; presenting sx’s?
- Early adolescence and equally in boys and girls; typically asymptomatic
- The femur, tibia, ribs, jawbones, calvarium, and humerus = most commonly affected
fibrous dysplasia is seen on radiographic imaging as what?
Ground glass appearance and well-defined margins
Polyostotic fibrous dysplasia appears when, affects which bones, and produces what problems?
- Slightly earlier than the monostotic form
- Femur > skull > tibia > humerus > ribs > fibula > radius > ulna > mandible > vertebrae
- Propensity to involve shoudler and pelvic girdles –> severe, progressive disease w/ crippling deformities and fractures
What is a rare complication of polyostotic fibrous dysplasia?
Malignant transformation —> sarcoma
Which cancers in adult most frequently metastasize to the bone?
Prostate + breast + kidney + lung
Which cancers in children most frequently metastasize to the bone?
Neuroblastoma + Wilms tumor + Osteosarcoma + Ewing sarcoma + Rhabdomyosarcoma
Skeletal metastases are typically multifocal, but carcinomas from which 2 sites may present with solitary lesions?
Kidney and thyroid carcinomas
Metastases from which site produces a blastic (bone forming) pattern?
Prostatic adenocarcinoma
