Cancer Osteoma

Epidemiology - Usually solitary - Usually found in middle-age adults - Associated with Gardner syndrome (if multiple)

Pathogenesis - Slow growing - Frequently arise/found inside skull or facial bones

Lab/Gross - Composed of woven/lamellar bone - Bosselated, round to oval sessile tumors - Deposited in a cortical pattern w/ haversian-like systems - By definition less than 2 cm in greatest dimension - Round to oval masses of hemorrhagic gritty tan tissue - Well circumscribed and composed of a morass of randomly interconnecting trabeculae of woven bone; rimmed by osteoblasts - Greater than or equal to 2 cm in size - Round to oval masses of hemorrhagic gritty tan tissue - Well circumscribed and composed of a morass of randomly interconnecting trabeculae of woven bone; rimmed by osteoblasts - Does not induce a marked bony reaction

Clinical Features - Of little significance unless they cause obstruction/imping e on structures (brain/eye), interfere w/ fx of oral cavity or cause cosmetic problems - Painful due to excess PGE2 release from osteoblasts (severe nocturnal pain relieved by aspirin) - Dramatically relieved by ASA

Prognosis/Tx - Do NOT transform to osteosarcoma

Osteoid Osteoma

- Patients usually in teens/twenties - Men > women (2:1)

- Predilection for appendicular skeleton (femur/tibia most common) - Commonly arise in bone cortex Nidus=radiographically a small round lucency that may be centrally mineralized

- Readily treated by conservative surgery - Malignant transformation is remote (except when treated with radiation; which promotes malignant trans.) -radioablation

Osteoblastoma

- More frequently involves the spine - Commonly arise in bone cortex

- Dull, achy pain - Not responsive to salicylates

- Distal femur, proximal

- Readily treated by conservative surgery - Malignant transformation is remote (except when treated with radiation; which promotes malignant trans.) -curetted or excised en bloc in a conservative fashion - Multimodality:

Osteosarcoma

- bimodal: 75% in ages < 20, elderly with predisposing traits (flat and long bones) - More common in men than women -in metaphysical region of long bones of extremities; 50% knee -Occur @ sites of bone growth - Aka: exostosis - Multiple: Multiple Heredity Exostosis (AD; inactivation of both EXT genes); childhood - Solitary: late adolescence, early adulthood - Men>women (3:1)

tibia; metaphysic plates - Most common in head, shoulder, hip and knee* - Genetic mutations are fundamental - RB, p53, INK4A, CDK4, p16, CYCLIN D1, MDM2 - Cell cycle regulator genes - Subtypes grouped according to anatomic portion, degree of diff, multicentricity, primary/secondary -cancerous cells produce bone matrix - Develops in bones of endochondral origin; arise from metaphysic near the growth plate of long tubular bones (especially knee) - Occasionally found in pelvis, scapula and ribs - Rarely involve short tubular bones of hands/feet

- Hemorrhagic & cystic - Infiltrate marrow - Bulky tumors; gritty, gray-white - Formation of bone is characteristic; cartilage/fibrous tissue may be present - Pleomorphic cells w/ large hyperchromatic nuclei; bizarre giant cells - Cartilage capped outgrowth attached to underlying skeleton by bony stalk (protruding mushroom) - Range from 1-20 cm - Composed of hyaline cartilage covered peripherally by perichondrium - Appearance of disorganized growth plate - Usually < 3cm - Blue, gray-blue translucent color with a nodular configuration - Nodules of cartilage and are wellcircumscribed w/ hyaline matrix - The cartilage @ the

Osteochondro ma exostosis

- Painful, progressively enlarging masses - Sudden fractures - Codmans triangle: triangular shadow between the cortex & raised ends of periosteum -sudden fracture= first symptom -spread hematogenously , pulmonary metastases, - Slow growing - Can be painful if impinge on nerve - Frequently detected incidentally - In hereditary form: underlying bones may be bowed or shortened - Usually stop growing @ time of growth plate closure

Standard: chemotherapy and limb salvage - @ time of dx: 1020% have pulmonary mets - 90% who die have metastases to the lung, bone, brain and elsewhere - Long term survival 60-70%

- Rarely give rise to chondrosarcoma or other sarcoma - Risk of malignant transformation is higher in hereditary syndrome

Chondroma

Endochondroma are usually found in pts age 20-40s & are solitary

- Benign tumor of hyaline cartilage - Enchondroma (in medullary cavity) most common - or subperiosteal/juxtacortical (on bone surface) - Endochondromas are primarily found in short tubular bones (hand/feet) - Ollier disease = multiple

- Most are asymptomatic - Detected incidentally - Occasionally are painful & cause pathologic

- Solitary chondromas rarely undergo malignant transformation Enchondromatoses are more associated with malignant

enchondromas Maffucci syndrome = enchondromatosis + soft tissue hemangiomas - Develop from the remains of growth plate cartilage in bones that undergo enchondral ossification

periphery undergoes enchondral ossification and the center frequently calcifies & dies - On x-ray: O ring sign is present - Highly cellular, hyperlobulated nuclei w/ longitudinal grooves - Sheets of compact polyhedral chondroblasts w/ well-defined borders - Mitotic activity & necrosis frequently found - Chicken-wire pattern - Non-neoplastic osteoclast giant cells are scattered throughout - X-ray: well-defined lucency w/ spotty calc. - Well-circumscribed, solid, glistening tangray tumor - Nodules of hyaline cartilage and myxoid tissue w/ fibrous septae - Greatest cellularity @ periphery - In cartilaginous regions: tumor cells are in lacunae; in myxoid areas: cells are stellate

fractures

transformation - Maffucci syndrome patients are at risk for other malignancies (ovarian CA, brain glioma)

Chondroblasto ma

- Rare - Young patients in teens - Male: female = 2:1

- Benign tumor - Most commonly found in knee less commonly found in the pelvis/ribs and in older pts - Predilection for epiphyses and apophyses

- Usually painful (due to location near joint) - Recurrences not uncommon

- Distant metastases to the lung are rare (usually after fracture/curettage)

Chondromyxoi d Fibroma

- Teens and twenties - Male predominance - Rarest cartilage tumor

- Most frequently in metaphysic of long tubular bones

- Localized, dull achy pain

- Simple curettage - Do not pose a threat for malignant transformation

Chondrosarco ma

- Patients are usually 40+ - Men are 2x more likely to be affected than women - No race predilection - Clear cell & mesenchymal variants in younger patients (teens/twenties)

-produce neoplastic cartilage - Broad spectrum of findings - Subclassifications: Site: intramedullary or juxtacortical Histo: conventional, clear cell, dedifferentiated or mesenchymal - Significant number arise in association w/ pre-existing enchondroma - Arise in central portions of skeleton (pelvis, shoulder, ribs) - Clear cell variant originates in epiphyses of long tubular bones - Rarely involves distal extremities

- Varying degrees of cytologic atypia w/ hyperchromatic nuclei - X-ray: eccentric geographic lucency that is well delineated from bone by rim of sclerosis - Composed of malignant hyaline & myxoid cartilage - Myxoid: viscous, ooze when cut; spotty calcifications & central necrosis; adjacent cortex is thickened/eroded - Dediff: Low-grade w/ second highgrade component - Clear cell: sheets of large, malignant cells w/ abundant clear cytoplasm, osteoclast-type GC and intralesional reaction bone formation - Mesenchymal: Islands of well-diff hyaline cartilage surrounded by small round cells - X-ray: Prominent endosteal scalloping; more radiolucent = high grade

- Painful, progressively enlarging masses

- Low grade: causes reactive thickening of the cortex - High grade: destroys the cortex and forms soft tissue mass - Correlation between grade & biological behavior - None of grade 1 metastasized - Size is another prognostic feature (> 10 cm behave more aggressively) - Metastasize preferentially to the lungs/skeleton - Tx = wide surgical excision - Mesenchymal & dediff additionally treated w/ chemo

Fibrous Cortical

- FCD: Found in 30%-50% of

- FCD: Developmental defect; found in distal femur/prox tibia

- FCD: asymptomatic; incidentally found; limited growth

- FCD: for those that enlarge; require biopsy to

Defects & Nonossifying Fibroma

children >2

- Those that grow frequently develop into NF; one half are bilateral/multiple

Fibrous Dysplasia

- Monoostotic: boys=girls, most common in early adolescence - Polyostotic: manifests slightly earlier than monoostotic - Polyostotic disease: somatic mutations in Gprotein leads to excess cAMP; girls more frequently affected than boys

- Benign tumor; likened to localized developmental arrest - Components of normal bone are present, but do not differentiate - Monoostotic (70%): most common; ribs, femur, tibia, jawbones, calvaria and humerus; dont evolve - Polyostotic (27% -without endocrine dysfxn): femur, skull, tibia; craniofacial involvement present in half; all forms have propensity to involve shoulder/pelvic girdle - Polyostotic Disease: multiple bones + endocrinopathies; McCuneAlbright syndrome (3%): sexual precocity, hyperthyroidism, adrenal hyperplasia; bone & cafau-lait spots frequently unilateral somatic gain of fxn mutation in GNAS gene-hyperactive guanyl nucleotide binding protein-drive abnormal growth

- Well-circumscribed, intramedullary lesions; vary greatly in size - Moderately cellular - Trabeculae mimic Chinese characters - Nodules of hyaline cartilage w/ disorganized growth plate appearance - Cystic degeneration, hemorrhage and foamy macs are common findings - Xray: ground glass appearance w/ welldefined margins

potential and most undergo spontaneous resolution; few progressively enlarge & can cause path. fracture Variable Monostoticminimal symptoms Polystoticprogressive disease

r/o other type of tumor

- Rare to have sarcomatous transformation (polyostotic involvement required) - Use of radiation increases risk of malignant transformation -bisphosphonates

- Large, hemorrhagic, tan-

Fibrosarcoma & Malignant Fibrous Histiocytoma

- Middle aged & elderly - Fibrosarcoma: male=female - MFH: men more frequently affected

- Fibroblastic collagenproducing sarcomas of bone - Usually arise de novo; some secondary tumors - Usually in metaphyses of long bones & pelvic flat bones

Ewing Sarcoma & PNET

- Average= 1015 years old - Boys more freq. than girls - More common in whites - t(11;22) most common; also t(21;21) or t(7;22) - Fusion of EWS gene to a member of ETS family transcription factor (mainly FLT1) - EWS-FLI1 forms dominant oncogene; constitutively

- Primary malignant small round cell tumors - Usually arises in diaphyses of long tubular bones (femur, flat bones of pelvis)

white masses - Destroy underlying bone - Frequently extend into soft tissue - Fibrosarcoma: malignant fibroblasts arranged in a herringbone pattern; most lowintermediate grade - MFH: Background of spindle fibroblasts arranged in storiform pattern; large, ovoid, bizarre multinuc tumor GC intermixed; generally high-grade - Xray: permeative/lytic - Arise in medullary cavity - Usually invade cortex & periosteum producing soft tissue mass - Composed of sheets of uniform, small round cells that are slightly larger than lymphocytes - Tan-white tumor that contains areas of hemorrhage & necrosis - Scant cytoplasm, rich in glycogen - Homer-Wright rosettes is indicative of neural diff

- Enlarging painful masses - Pathologic fracture is a frequent complication

- Prognosis depends on grade; high-grade have poor prognosis

- Present as painful, enlarging masses - Affected site is tender, warm and swollen - Some patients have systemic findings: fever, elevated SED rate, anemia, leukocytoses

- Treatment includes chemotherapy and surgical excision w/ or w/o radiation - At least 50% of cases are long term cures; 75% 5 year survival

active transcription factor stimulating cell proliferation

Giant Cell Tumor

- Patients twenties to forties

- Believed to have monocyte macrophage lineage - Uncommon benign tumor; but locally aggressive - Involve both epiphyses and metaphyses in adults; confined to growth plate in adolescents - Most commonly arise in knee - Most are solitary -RANK/RANKL signaling pathway

Aneurysmal Bone Cyst

-in first two decades of life

-bening tumor of bone characterized by multiloculated blood-filled cystic spaces -rapidly growing expansile tumor 17p13 translocation-

- Contains fibrous septae but generally little stroma - Xray: destructive lytic tumor w/ permeative margins and extension into soft tissue -destructive lytic tumor that has permeative margins and extension into soft tissue; periosteal reaction produces layers of reactive bone deposited in onion-skin fashion. - Large and redbrown - Uniform oval mononuclear cells that have indistinct cell membrane and appear to grow in a syncytium - Mitoses are frequent - Necrosis, hemorrhage, hemosiderin deposition and reactive bone formation are common secondary features -blood filled cystic spaces separated by thin, tan-white septa walls have fibroblasts

- Location leads to complaints of arthritis-type symptoms - Occasionally present as pathologic fracture

- Conservative surgery (40-60% recurrence rate) - Up to 4% metastasize to the lung - Sarcomatous transformation is rare

Affects metaphysis of long bones and posterior elements of vertebral bodies -causes pain and swelling -eccentric ,

Surgical: curettage or en bloc resection

upregulation of USP6, a deubiquitinating enzyme

expansile lesion with welldefined margins