Tumor

Resection

-Radical – entire muscle

-Wide – outside reactive zone (MRI)

-Marginal – through reactive zone (MRI)

-Intralesional

Staging

-Osteosarcomas present most often in stage IIB

-I – low grade

-II – high grade (B is extra-compartmental)

-III – mets

-AJCC Staging System

  • Histo grade (high or low)
  • Most important determinant for prognosis
  • Size (big or small)
  • Depth (deeper is worse)

-Fibrous dysplasia is sclerotic in femoral neck

Periacetabular lesions – often chondrosarcoma

Lodwick classification – radiology

-I – geographic w/ sclerotic rim, II – distinct border, III – indistinct border

Big 5 (can look like anything)

-Metastatic CA

-Cartilage lesions

-Fibrous dysplasia

-Infection

-EG

Common agents for Osteosarcoma

-MTX

-Doxorubicin – cardiotoxicity

-Bleomycin – lung prob

Chemotx

-Cells most sensitive in G1-S phase

-Bone sarcomas – Chemo, Radiation, Chemo

-Soft tissue sarcomas –Radiation

Radiation

-Dose measured in grays

  • 1 rad = 1 centigray

-typically 180-200 cGy/day, 5 days a week

-if prior exposure less than 45 Gy, wound will heal

-45-55 Gy, probably will heal

-over 65 Gy, will not heal

-radiation for round cell lesion – ewing’s, LA, Myeloma, and mets

-risk of post-radiation sarcoma 13%

  • high grade lesions – poor prognosis

Molecular biology

-Chromosomal translocations – up to 95% of sarcomas

-Ewings 11, 22

-Alveolar Rhabdo 2, 13

-Synovial Sarcoma X, 18

-Myxoid Liposarcoma 12, 16

-Chondrosarcoma 9, 22

-CCSA 12, 22

-Tumor suppressor genes

  • Rb – recessive suppressor
  • Basis for all retinoblastomas
  • 15% get other neoplasms
  • 35% of osteosarcomas have Rb mutations
  • p53
  • mutated in 50% of all tumors
  • dominant suppressor
  • arrests cell cycle when DNA damage is noted
  • G1 phase
  • occurs in osteosarcoma

-Oncogenes

  • Genes involved in growth of the cells

Less than 1 in 10,000 cells capable of metastasis

Bone Producing Lesions

-Osteoid Osteoma

  • Young pt
  • 50% long bones of LE
  • PAIN from PG
  • Inc w/ time
  • Night pain
  • Relieved by NSAIDs
  • Nidus w/ reactive bone
  • Can produce growth disturbances
  • Nidus < 1.5 cm
  • Always HOT on bone scan
  • May spontaneously resolve in 5-7 yrs
  • Need CT imaging in spine to identify
  • MRI w/ extensive edema – like marrow-placing neoplasm
  • Histo
  • Sharp demarcation b/w nidus and reactive bone
  • Variable degree of mineralization in nidus
  • Woven bone and Osteoblastic rimming
  • Tx: radiofrequency ablation
  • 2nd tx – remove nidus
  • if failed – then open curettage

-Osteoblastoma

  • Rare, in young pt
  • Pain, but not relieved w/ ASA
  • Mixed lytic/blastic lesion
  • Blastic in extremities
  • Lytic in spine (40% occur in spine) (posterior elements)
  • calcified lesion in post elements
  • Larger than 2.0 cm
  • HOT on bone scan
  • Looks like osteoid osteoma
  • Tx: marginal resection vs. extended intralesional curettage w/ adjuvant agent (5% phenol, liquid nitrogen, argon beam laser, cement)
  • Recurrence 10-20%
  • Histo: immature osteoid, mineralized matrix, fibrovascular stroma

-Osteosarcoma

  • MC primary sarcoma of bone
  • Adolescents and young adults
  • Associated w/ Paget’s
  • High grade intramedullary
  • MC form
  • 85%
  • most present as IIB lesions
  • 10-20% present w/ mets
  • lung mets 90%
  • bone mets 20%
  • 50% occur around knee
  • mixed lytic/blastic lesion
  • skip lesions – need to look for
  • poor prognosis (same as if w/ met)
  • mandatory bone scan and chest CT evaluation
  • on bone scan, hot around and photopenic in center, either is
  • lesion w/ necrosis in center
  • or cyst
  • pain MC symptom
  • Histo
  • Lacy osteoid and stromal cells malignant looking
  • May be giant cells, small cells
  • Tx
  • Multiagent chemo, surgery, chemo
  • Necrosis of > 98% good prognostic sign
  • Local recurrence is poor prognosis
  • In pathologic fracture – amputation vs. limb salvage is equal survival advantage
  • Expression of multidrug resistance gene – poor prognosis
  • 25% primary lesions, 50% in metastatic lesions
  • Telangectatic
  • IM lesion
  • Looks similar to ABC
  • Lytic, destructive, expansile lesion
  • Histo
  • Lakes of blood
  • Malignant cells
  • Ulnar-based distal radius lesion is usu telangectactic OS (not ABC)
  • Parosteal Osteosarcoma
  • Female predominance
  • Low grade surface lesion on metaphysis of long bones
  • Distal femur 80%
  • Formation of painless mass, firm/fixed
  • Heavily ossified XX appearance, stuck-on, lobulated appearance
  • Histo
  • Look like fibrous dysplasia
  • Bone trabeculae
  • Bland spindle cells around bone

-Myositis Ossificans

  • Juxtaposed to bone (not stuck on bone)
  • Mineralized appearance on XX
  • Mineralizes from periphery in (osteosarcoma mineralizes from in to periphery)

-Osteochondral Exostosis

  • Shares the cortex (not stuck-on)

-Periosteal Osteosarcoma

  • Female > male
  • Diaphysis of tibia or femur
  • XX w/ sunburst lesion resting in saucerized cortical depression
  • Histo w/ chondroblastic appearance, intermediate to high grade
  • Need chemo, resection , chemo
  • Prognosis worse then parosteal, better than standard OSA

-Enchondromas

  • Benign in medullary cavity, metaphysic
  • Rarely symptomatic
  • 60% hands and feet, 20% femur, 10% prox humerus
  • pathologic hand fx common
  • XX: stippled calcification, rings/arcs, popcorn calcification
  • Rarely purely lytic
  • If calcified lesion w/ lytic focus, then could be malignant degeneration
  • Histo: small chondroid cells in lacunar spaces, myxoid, blue balls of cartilage
  • Infarct is in differential – but more “smoke up the chimney”
  • Observation w/ serial radiographs
  • If changing, must biopsy and remove entire lesion
  • Ollier’s disease – multiple lesions
  • Risk of sarcomatous degeneration 30%
  • Often unilateral
  • Maffucci sx – multiple lesions and soft tissue angiomas
  • High risk of malignancy (visceral malignancy)
  • High risk of CHSA
  • Histo: blue balls of cartilage
  • Warm on bone scan

-Periosteal chondromas

  • Rare, develops on surface of bone under periosteum
  • 50% of lesions on proximal humerus
  • pain common (tendon insertions irritated)
  • histo similar to enchondromas
  • looks like low-grade CHSA
  • treatment: marginal excision

-Osteochondromas

  • MC tumorlike lesion
  • Arise secondary to aberrant cartilage on bone surface
  • Painless mass
  • May have mechanical sx
  • XX: shares the cortex, IM contents flow into lesion
  • 35% around knee, points away from joint
  • bright on MRI T1: gad, fat, proteinaceous fluid, melanin, methemoglobin
  • bright on T1 and T2
  • Histo: cartilage cap 2-3 mm thick
  • Looks like nl physis; primary trabeculae & active chondrocytes
  • If growing in adult – then low grade OSA
  • Beware cartilage cap > 2 cm (malign degeneration)
  • Tx: observation
  • Multiple hereditary osteochondromas – higher rate of malignant degeneration (into CHSA)

-Chondroblastomas

  • Epiphyseal lesion of young pt (can cross physis)
  • 50% in skeletally immature pt
  • painful lesion
  • 30% around knee, also prox humerus, prox femur
  • Xx thin sclerotic rim, possible mineralization
  • Histo: chicken wire calcification, cobblestone appearance
  • Tx: meticulous curettage and bone grafting
  • Recurrence 30% in some series
  • Local adjuvant tx: phenol, cryotherapy
  • 2-5% lesions metastasize to lung

-Chondromyxoid fibroma

  • Rare chondroid lesion, 2nd, 3rd decade of life, males > females
  • 30% knee, followed by feet, pelvis
  • cortical thinning but no periosteal rx
  • Pain common sx – swelling
  • XX: lytic, eccentric, demarcated from bone
  • Histo: stellate appearing cells, fibrous spindle cells
  • Tx: curettage and grafting
  • Recurrence up to 25% in some series

-Chondrosarcoma

  • 2nd MC primary bone sarcoma
  • pelvis 25%, ribs, femur, prox humerus
  • pt older than 50
  • Pain presenting sx
  • Soft tissue component can mineralize
  • XX: destructive, reactive cortical changes, mineralization
  • MRI T2 – high signal, gad – high signal
  • Histo: increased cellularity, multinucleated cells, enlarged cartilage cells
  • Most lesions low to intermediate grade
  • Lesions of axial and proximal skeleton more aggressive
  • Tx: wide surgical excision
  • Mostly chemo/radiation resistant
  • Histo grade correlates w/ presence of mets
  • Most important determinant of survival
  • Dedifferentiated type
  • 80% metastatic rate
  • XX: superimposed widely destructive region
  • 50% w/ pathologic fx
  • pain is presenting feature
  • Histo: chondroid and spindle areas (high-grade spindle component)
  • 30% femur, 20% pelvis
  • Tx: chemo, resection, chemo
  • 13% survival @ 5 yrs
  • MDR gene identified in nl and neoplastic cartilage
  • Resistance to chemo
  • P-glycoprotein on cell membrane

-NOF

  • Found in up to 30% of skeletally immature pt
  • most resolve spontaneously
  • distal femur, prox tibia, dist tibia
  • well-demarcated, eccentric, lobular
  • bright on T2
  • not hot on bone scan
  • histo: spindle cells in whorled bundles, giant cells, hemosiderin
  • Tx: observation if ASx, curettage/BG if Sx
  • Jaffe-Campanacci Sx: multiple NOF w/ café au lait, retinal prob

-Desmoplastic fibroma

  • Painful rare neoplasm in young
  • Bony counterpart to desmoid
  • Femur, tibia, humerus
  • XX: lytic, expansile, well-defined margin
  • Histo: spindle cells, swirling fibrous cells
  • Low grade malignant
  • Tx: aggressive curettage

-Fibrosarcoma of Bone

  • Pt over 50
  • 50% around knee, pelvis, prox humerus
  • XX: lytic lesion w/ destructive features
  • Histo: spindle cells, herringbone pattern
  • Tx: wide surgical resection
  • High grade chemo, but difficult in elderly
  • High grade lesions prognosis 30% at 5 yrs
  • Tx: like OSA

-Benign Fibrous Histiocytoma

  • Rare
  • Ilium, ribs MC, but also in tibia, femur
  • XX: lytic lesion w/ sclerotic border
  • More centrally located than NOF
  • Pain is presenting Sx (unlike NOF)
  • Histo: foamy macrophages, spindle cells, storiform pattern
  • Tx: curettage and BG

-MFH

  • Pt over 50
  • 30% around knee, pelvis, too
  • 30% felt to arise from chronic condition (infx, implant)
  • w/ soft tissue component
  • XX: lytic, destructive
  • Histo: large, pleomorphic nuclei, storiform pattern
  • Tx: chemo, resection, chemo
  • Prognosis similar to OSA, 60% at 5 yrs

-Chordoma

  • Malignant lesion from notochordal tissue
  • Occurs at ends of spine
  • 85% spheno-occipital and sacrum
  • insidious onset of pain
  • need to do rectal exam
  • soft tissue mass
  • CT/MRI mandatory to delineate lesion
  • Histo: lobules of myxoid tissue, physaliferous cells (pink, bubbly, abundant cytoplasm w/ nuclei)
  • Need to save S1, 2, 3 unilaterally or S1, 2 bilateral for nl bladder/bowel function
  • Tx: wide resection, radiation
  • Recurrence very common
  • Metastatic dz in 30-50%
  • 5 yr survival 60%

-Hemangioma

  • 20% in spine
  • often asx, may have pain
  • multifocal lesions poss
  • XX: lytic lesion, mild cortical expansion, trabecular striations
  • Jail-bar vertebra
  • Tumor destroys cross-trabeculae only
  • Honeycomb appearance
  • Warm to hot on bone scan
  • Histo: dilated thin-walled blood vessels
  • Tx: observe if asx, curettage and BG if symptomatic
  • Low-dose radiation for inaccessible lesions

-Hemangioendothelioma/Angiosarcoma of Bone

  • Malignant, rare
  • Multifocal
  • Pt present w/ pain
  • “crawling up the bone” – consider vascular lesion
  • Histo: varies
  • Tx: wide resection, radiation

-Lymphoma

  • Non-hodgkin’s LA
  • Metastatic focus to bone
  • 50% in pt over 40
  • pelvis, femur, humerus, vert bodies
  • pain
  • soft tissue mass frequently present
  • round blue cell lesion
  • XX: mottled appearance, reactive bone, cortical destruction, may be blastic
  • Involves bone diffusely (esp in pelvis)
  • LCA positive (binds to CD45)
  • Very hot on bone scan
  • Histo: mixed round cell infiltrate
  • Tx: radiation and chemo (surg rarely required)
  • Stain for leukocyte common antigen, or B or T cell markers
  • Fx after Bx / XRT

-Myeloma

  • Plasma cell malignancy over 50 yo
  • Most frequent neoplasm presenting as skeletal lesions
  • Axial and proximal appendicular skeleton
  • Pain, anemia, infx, renal failure
  • 50% w/ elevated creatinine
  • 30% w/ hypercalcemia
  • 15% w/ amyloidosis
  • XX: punched out lesions in bone, expansile appearance
  • 1/3 ‘cold’ on bone scan
  • M spike of serum electropherogram
  • IgG 50%, IgA 25%
  • More than 10% plasma cells on marrow aspirate
  • Urine show Bence Jones protein
  • Tx: chemo, radiation (surg for stabilization of bones)
  • Surgery
  • Conservative route (choose ORIF vs. hemi)
  • Prog poor

-Solitary plasmacytoma

  • 25% have + M-protein
  • No diffuse involvement
  • May go on to develop MM
  • Tx: w/ radiation
  • Osteosclerotic form
  • Ass w/ polyneuropathy
  • Lytic/sclerotic lesion
  • POEMS sx: polyneuropathy, organomegaly, endocrinopathy, M protein, Skin changes
  • Tx: radiation: neuro changes don’t improve

-Giant Cell Tumor

  • Aggressive benign lesions age 20-40
  • Young pt get metaphyseal, older epiphyseal
  • 60% around knee, distal radius, sacrum (neuro def common)
  • r/o hyperPTH (may be multicentric)
  • XX: lytic, eccentric, subchondral lesion
  • Histo: giant cells, mononuclear cells, reactive bone
  • Bone scan – can be doughnut (bone in middle)
  • Hot on bone scan
  • Tx: aggressive exteriorization, extended curettage/burring
  • Adjuvant tx may prevent recurrence
  • PMMA reduced recurrence to 3% w/ cementation
  • May metastasize to lungs – 2%
  • No correlation b/w histo and clinical aggressiveness
  • Radiation for inoperable lesions

-Epiphyseal lesion of bone (differential)

  • GCT
  • Chondroblastoma
  • Clear cell chondrosarcoma

-Ewing’s sarcoma

  • Pt 5-25 yo
  • Under age 5, consider leukemia, metastatic NB
  • Over age 30, met or LA
  • 3rd MC primary sarcoma of bone
  • pelvis, femur most
  • in ribs, called Askin’s tumor
  • XX: moth-eaten, permeative of diaphysis, metaphysic, onion-skin, sunburst appearance
  • Hot on bone scan
  • Soft tissue mass
  • Diffuse, extension up IM canal
  • 90% w/ t(11:22)
  • pain, fever, leukocytosis, anemia, elevated ESR
  • Histo: monotonous, smudge blue cells, pseudo-rosettes (true rosettes in NB)
  • circles of round cells surrounding pink ground subst
  • stains for intracell glycogen are +
  • Mets to lung MC
  • Pelvic lesions w/ poor prog, extremity lesions better
  • Tx: chemo, resection, chemo (may be radiation)
  • Prognosis: 60% survival
  • 40% in pelvic lesions
  • 15% if present w/ mets
  • workup
  • MRI, CT chest, bone scan, Bone marrow biopsy

-Adamantinoma

  • Rare lesion of tibia
  • 50% cases synchronously involve tibia and fibula
  • pain, bowing deformity of tibia
  • XX: demarcated mixed lytic/sclerotic lesion, bowing of anterior cortex
  • Histo: epitheliod cells in stroma, fibrous tissue
  • can also be columnar cells in palisading fashion
  • May be continuum of osteofibrous dysplasia (Campanacci dz)
  • Soft tissue mass
  • Tx: wide surgical resection
  • Lesion is low grade malignancy
  • Lung mets in 25% cases

-ABC

  • Under 20 yo
  • Can arise in preexisting GCT, CBMA, CMF, Fib Dys
  • Vertebra, long bones
  • XX: lytic, eccentric, expansile lesion
  • MRI: gad around outside (rim enhancement), dark on T1, bright T2, see fluid-fluid lines
  • Hot on bone scan
  • Histo: lakes of blood w/o endothelial lining
  • Tx: aggressive curettage and BG
  • Recurrence about 25%
  • Adjuvant tx

-SBC

  • Pt 3-14, cystic lesion of metaphysis
  • 80% in prox humerus, prox femur in young pt
  • older pt in ilium, talus, calcaneus
  • 50% present with fracture
  • caused by physeal disturbance, resorptive erosion from pressure
  • Xx: central lucency, thinning of cortex
  • Thinner bone than in ABC
  • Active cyst abuts physis, latent cyst nl intervening bone
  • Histo: thin fibrous lining, giant cells, hemosiderin
  • Tx: obs/aspiration, injx/curettage and grafting
  • Fallen leaf sign
  • Histo: bone, fibrous lining, fluid
  • 2% invade across physis
  • injection w/ methylprednisolone, marrow, or bone substitute

-Histiocytosis X

  • Hand-Schuller-Christian Dz
  • Bone, visceral involvement
  • Classic triad < 25% pt: diabetes, exopthalmus, lytic bone skull lesions
  • Leterer-Siwe dz fatal in young children

-EG

  • Single, or multiple bones
  • Pain, swelling MC presentation
  • XX: well-demarcated, lytic lesion, destroy cortex, “punched-out”
  • Hot on bone scan
  • Vertebra plana
  • Vertebra will reconstitute with time (not nl appearing)
  • Histo: Langerhans cell (histiocyte w/ grooved nucleus), “coffee-bean nuclei”, eosinophils, mitotic figures
  • Tx: variable, self-limiting, low dose radiation or curettage, BG
  • EM: racquet shaped Birbeck granules

-Fibrous Dysplasia

  • Polyostotic form: LE and homolateral pelvis
  • 20% multifocal
  • Endocrine abn common
  • Albright’s precocious puberty, café au lait
  • Hyperthyroidism, Cushing’s associated
  • Vert level is rare
  • Xx: ground glass, lytic, well-defined sclerotic rim, expansile, angular in appearance
  • Histo: no osteoblastic rimming, fibroblasts w/ dense collagen matrix, Chinese characters, woven bone
  • osteob rimming is reactive, while no rimming is tumor
  • Tx: w/ cortical bone (if cancellous bone, then fibrous dysplasia heals w/ fibrous dysplasia)
  • Observation in most pt
  • Graft w/ cortical allograft to prevent resorption
  • Can look like anything
  • MRI: bright on T2 (if cystic), bright on gad
  • Not hot on bone scan

-Osteofibrous dysplasia

  • Rare lesion of tibia in young pt
  • Tibial bowing/prominence
  • XX: anterior cortex, multiloculated
  • MRI: T1 “crawling lesion”
  • Histo: rimming osteoblasts, fibroblast-like spindle cells
  • Tx: observation until maturity

-Paget’s

  • 5th decade (3-4% population)
  • often asx
  • onset insidious
  • 4 hallmarks
  • coarse, purposeful trabeculae
  • thickening of cortex
  • enlargement of bone
  • mixed lytic / blastic pattern
  • early stage – lytic bone, late is blastic
  • etiology: paramyxovirus (inclusion body in osteoclast)
  • scribbled bone
  • Histo: marrow fibrosis, prominent vascularity, mosaic pattern
  • Pre-treat to decrease bleeding problems
  • Tx: bisphosphonates, calcitonin
  • Paget’s sarcoma 1-15% transformation rate
  • < 20% 5 yr survival
  • tx like bone sarcoma

-Metastatic Bone Dz

  • over age 40
  • path fx in 8-30% pt w/ mets
  • breast, lung, prostate, kidney, thyroid
  • lung – cookie bite out of cortex
  • mets distal to elbow/knee usu lung or renal
  • Histo: glandular pattern
  • Renal is more destructive than lung
  • They bleed (also myeloma and thyroid)
  • Thyroid and renal cell may be cold on bone scan
  • Tx: to maintain skeletal integrity
  • In hip fx, go aggressive (choose hemi vs. ORIF)
  • Use bisphosphonates, PMMA, radiation as adjuncts
  • Batson’s plexus
  • Valveless system
  • Retrograde embolism from breast, prostate, lung, kidney, thyroid
  • stain positive for cytokeratins

-Osteomyelitis

  • Minimal osteolysis w/ surrounding sclerosis
  • Sequestrum – dead bone
  • Involucrum – reactive bone around it
  • Histo: granulation tissue, mixed cell pop of inflam cells, poly, lymphocytes
  • Chronic infx may present w/ SCC
  • Fungal osteomyelitis – Langhans cell (multinucleated cell ass w/ spores)
  • Ass w/ squamous cell CA (chronic osteomyelitis)

Sarcomas

-radiation carries 20% risk of major wound compl

-Calcifying aponeurotic fibroma

  • Young children
  • Benign
  • Hands and feet
  • Tx: local excision (recurrence common)

-Fibromatosis

  • Firm nodules fibroblasts
  • Nodules are painful early, contractures late (Dupuytren’s)
  • Lederhosen’s in feet
  • Peyronies in penis

-Extra-abdominal Desmoid Tumor

  • Most locally invasive of all soft tissue tumors
  • Cold on bone scan
  • Recurrence common
  • XRT effective adjuvant tx
  • high rate of recurrence
  • Prognosis good
  • Histo: dense fibrous tissue, spindle cells, looks like scar

-MFH

  • Pt 30-80 in age
  • Enlarging, painless mass
  • Large enough > 10 cm, then sx
  • MRI: inhomogeneous mass
  • Histo: storiform spindle cells
  • Fibrosarcoma – herringbone pattern
  • Tx: wide resection, radiation (pre and post)
  • Prognosis poor
  • Survival 5 yr 50%
  • Mets present in 30%

-Dermatofibrosarcoma protuberans

  • Nodular cutaneous tumor – early adult life
  • Intermediate grade
  • Grows slowly but progressively
  • 40% upper or lower ext
  • Histo: uniform fibroblasts, storiform pattern
  • Tx: wide resection
  • Margin > 3 cm w/ lower recurrence
  • Adjuvant XRT consider

-Lipomas

  • Slowly growing, painless
  • MRI shows fat
  • Tx: observation, resection if symptomatic
  • atypical lipoma
  • lobules of fat on MRI
  • different b/c in liposarcoma, lobules not fatty
  • 10% risk of transformation to liposarcoma

-Lipoblastomas

  • In kids
  • Immature fat – does not follow fat MRI signal

-Liposarcomas

  • Range from low grade to high
  • Imaging shows ‘stranding’ through mass
  • Higher grade lesions metastasize to retroperitoneum
  • Histo: more fibrous stromal background, has some fat in it, large/clear cytoplasm
  • Not fat density or fat signal
  • Tx: wide excision, radiation
  • Prognosis – 5 yr survival rates

-Neurilemoma/Schwannoma

  • Benign nerve sheath lesion of adults 20-50
  • Asx x for presence of mass on flexor surfaces
  • Lesion may wax and wane in size
  • MRI eccentric mass to nerve
  • On gad – mixed signal
  • Histo: antoni A – compact spindle cells, nuclear palisading, verocay body
  • Antoni B – haphazard matrix w/ delicate collagen, irr vessels
  • Tx: removal of mass, leave nerve intact
  • Prognosis excellent

-Neurofibroma