Oncology - Orthobullets

• Breast
• Lung
• Thyroid
• Renal
• Prostate

• Spine #1: most common thoracic
• Proximal femur #2
• Humerus #3

Proximal femur

Tumor induced activation of osteoclasts: Through RANKL pathway

Hydration: volume expansion

Loop Diuretics

Bisphosphonates

calcitonin: inhibit osteoclast and increase renal excretion of calcium

There is vascular spread through Batson's vertebral plexus: Valveless venous plexus of the spine that provide a route for mets from organs to axial structures

Activation of WNT pathway: for example prostate cancer secretes endothelin 1

• COnfusion
• Muscle weakness
• Poluuria/polydipsia
• Nausea/vomiting
• dehydration

Thyroid and myeloma: evaluate with skeletal survey

Small cell lung cancer

• Lung cancer
• Lung or renal

• Thyroid
• Kidney: RCC

• Female > male
• 30-50
• Distal femur > proximal tibia > distal radius > sacral ala
• Lung: usually benign

Hand lesions

GCT

Bisphosphonates: osteoclast inhibitors...may decrease size of defect

Denosumab: Rankl inhibitor > shows sclerosis and reconstitution of cortical bone

HIgh grade sarcoma: poor prognosis

Anterior elements

Teleangectatic osteosarcoma

• GCT
• CHondroblastoma
• Aneurysmal bone cyst
• Osteoblastoma
• Chondromyxoid fibroma

Treatments is extended intralesional curetage and bone grafting

• Osteochondroma: <1% risk
• Multiple hereditary exostosis: 1-10% transformation
• Enchondromas: 1%
• Ollier's disease: 25-40 risk malignant transformation
• Maffucci's: 100% risk malignant transformation

RT-PCR showing increased telomerase activity

Clear cell chondrosarcoma: can look like low grade chondroblastoma

Mesenchymal chondrosarcoma: needs neoadjuvant chemo followed by wide resection

• Intra-lesional curettage
• WIde excision: no chemo or radiotherapy
• Chemotherapy + wide excision

Focal fibrocartilagenous dysplasia: classic consists of a lucency in the medial cortical border of the metaphysis

Observation: varus will correct with growth

Bone infarct: also looks like smoke up chimney

• Poor: very aggresive
• Wide excision: does not respond to chemo or radtx
• CD31/CD34

Neuroblastoma

• CLose to adrenals or spinal cord: from sympathetic neural tissue
• Children < 2
• Neoadjuvant chemo, stem cell transplant and surgical excision

• WIlms
• Rhabdomyosarcoma
• Neuroblastoma
• Non hodgkin lymphoma
• Ewing sarcoma

Plantar fibromatosis similar to dupuytrens

Spindle cells in cartwheel pattern

Wide local resection and adjuvant radiation: if tumor >5cm add radiation

• ABC
• Regular osteosarcoma
• Neoadjuvant chemo and limb salvage resection: chemo is doxy/cisplatin/methotraxate/fosamide
• 98% necrosis in biopsy: good prognosis

• Depth: most important..if <0.7 mm 96%..if >4mm 47% (breslow classification)
• Male sex
• lesion on neck or scalp
• Positive lymph nodes or mets
• ulcerations

Neural crest cells

• Local resection with 1 cm margin
• Local resection with 1-2 cm margin and sentinel node biopsy
• Amputation

• CHondroblastoma
• Infection
• GCT
• Clear cell chondrosarcoma

• GCT
• ABC
• Ewings
• CHordoma
• Osteosarcoma

• Chondrosarcoma
• Paraosteal osteosarcoma: low grade only
• Chordoma
• Adamantinoma

Melorheostosis

• Dripping candle wax
• Benign
• Symptomatic: treat if severe contractures,limited mobility, pain

Smooth muscle lining blood vessels

Early wide resection +/- chemo

Multiple intramuscular myxomas associated with fibrous dysplasia

Benign soft tissue mass confined to skeletal muscle: intramuscular

Liposarcomas are intermuscular

Marginal excision: if symptomatic

SCC resulting from chronic draining wounds or burn scars

Rate of transformation is 1%

Subungual region

• Paroxysmal pain
• Exquisite tenderness to touch
• Cold intolerance

• Small bluish nodule: difficult to see if subungual
• Love test: pressure with pinhead leads to exquisite tenderness
• Hildreth test: Tourniquet inflation reduces pain and tenderness caused by love test

Marginal excision is curative

• Soft tissue hemangioma
• Angiosarcoma: use MRI

• Non-op: NSAID's stockings, activity modification
• Sclerotherapy or embolization
• Surgical excision

Metabolic dysfunction of phosphate regulation: leads to periaricular calcinosis in extracapsular soft tissues

Renal failure

Treat like HO: Remove once mature

Neurofibroma: from non-myelating schwann cells as well as fibroblast (predominant)

Schwannoma: Schwann cells alone

• ON MRI
• Schwanoma: eccentric to nerve
• Neurofibroma: Central to nerve fibers

Neurofibromatosis

• 2 or more neurofibromas or one plexiform neurofibroma
• Axillary/groin freckling
• 6 or more cafe au lait spots: 5mm if prepubertal or 15mm in postpubertal
• Sphenoid wing displasia or CPT
• 2 or more lisch nodules
• Optic glioma
• 1st degree relative with NF1

• MPNST
• 5% of patients with NF

• Neurofibromas
• Wide surgical resection +radiation
• S100

• Most common in posterior elements spine
• >2cm osteoid osteoma: has a nidus
• Secondary ABC
• Does not respond to NSAID's

• Surgery: does not respond to non op
• Curetage or marginal excision with bone grafting

• Delayed wound healing
• Infection
• Desquamation

• Stiffnes
• Secondary sarcoma
• Fractures

• Radiation dose >59 Gy
• Weight bearing bones: femur
• Female
• Anterior femoral compartment excision
• Periosteal stripping
• Osteoporosis

Chordoma

• Sacrum and coccyx in midline
• Lung: 30-50%
• Palpable on rectal
• Wide resection including nerve roots: radiation if negative margin not achieved

• Bilateral S2 nerve roots
• Unilateral S2-4 nerve roots

• Undifferentiated pleomorphic sarcoma
• Similar to osteosarcoma: but lacks osteoid formation
• Most common metaphysis of long bones
• 25% arise from bone infarcts, pagets, radiation
• P53
• >90% necrosis to neoadjuvant chemo

Neoadjuvant chemo + wide resection + post op chemo +/- radiation(if questionable margins)

• Long bone metaphyseal eccentric: lytic
• Chromosome 6 (q13)
• Children + lobulated tumor with abundant myxoid material
• Extended intralesional curetage and bone grafting

• Non hodgkin b cell lymphoma
• Pelvis, spine, ribs
• Better than secondary lymphoma of bone
• Large ill defined diffuse lytic lesion with mottled appearance
• Small round blue cells
• Multiagent chemo +/- radiation (in persistant disease)

Hemangioma

• Curetage and bone grafting
• Low dose radiation: 25-40Gy)>>if lesion is not accesible

• Shorter operative time
• Decreased morbidity
• Quicker recovery

• Metastasis
• Skip lesions
• Histologic grade
• Tumor size

• Latent: NOF, enchondroma
• Active: ABC, UBC, Chondromyxoid fibroma, chondroblastoma
• Aggresive: GCT

• Grade: low or high
• SIte: Intracompartmental (within bone cortex) or extracompartmental (outside bone cortex)
• Mets: yes or no

• Flexor surface of extremities and head and neck
• NF-2
• String sign
• Verocay bodies
• Excision if symptomatic

• Metaplasia: synovial transformation to chondroid tissue
• Knee
• Multiple intra articular loose bodies
• Symptomatic
• Cartilage nodules only visible on MRI initially

Rhabdomyosarcoma

Embryonal: infants

Alveolar: Adolescents

Botryoid: infants..in vagina

Pleomorphic: older patients

• Embryonal has best survival
• Botryoid is fatal

• t2:13 translocation
• Small round blue cells

In young: Wide excision and chemo

In Old:Wide excision and radiotherapy

Synovial sarcoma

• Gardner and familial adenomatous polyposis
• Shoulder>chest wall/back>thigh
• Beta catenin
• No risk
• Low dose chemo or tamoxifen: since it has 100% estrogen receptor
• Wide excision with radiotherapy

• Longitudinal incision in line with extensile approach
• Avoid neurovascular structures
• Maintain hemostasis
• Through one compartment only
• Drain in line with incision

Epithelioid sarcoma

• Adolescent and young adults
• Painless growing mass

Wid excision +adjuvant radiotherapy + sentinel LN biopsu

• Proximal femur
• Neuroblastoma
• Chordoma
• Rhabdomyosarcoma
• Epithelioid sarcoma
• Synovial sarcoma
• Osteochondroma

• A low grade malignant tumor
• Mid tibia: anterior cortex
• Yong adults: 20-40
• Can go to lung: 25%
• Soap bubble appearance: multiple sharply circumscribed lucent lesions with interspersed sclerotic bone in the mid tibia
• Wide surgical excision:often requires intercallart resection

• EG: single self limiting lesion in younger patients
• Hand Schuller Chirstian: Disseminated LCH with bone and visceral involvement
• Letterer-siwe disease: fatal...occurs in young children

Type of langerhans cell histiocytosis

• Lytic skull lesions
• Diabetes insipidus
• exophthalmos

Chemotherapy and referal to pediatrics for assessment of systemic disease

Coffee bean idented nuclei

COnservative: usually a self limiting entity

• Metaphysis of long bones: most common posterior distal femur
• 95% long term survival if local control achieved
• Heavily ossified lobulated mass arising from cortex: appears stuck on cortex

Wide local excision: no need for chemo unless high grade component on histology

• Anterior tibia cortex
• Anterior or anterolateral bowing of tibia
• Anterior eccentric lytic lesion in tibia
• Pseudoarthrosis: 10-30%

• Direct trauma/intramuscular hematoma
• Quads/brachialis
• Mass begins to decrease after one year
• Rest and activity modification: avoid passive stretching

• Osteosarcoma
• Dedifferentiated chondromsarcoma
• Malignant fibrous histiocytoma
• Ewing sarcoma

• Cardiotoxicity: leads to CHF
• Pulmonary fibrosis
• Myelosupression

Heavy chains (IgG and light chain (kappa or lambda)

Multiple myeloma

• CHromosome 13 deletion or translocation
• CIrculating plasma cells
• increased beta 2 microglobulin
• Decreased serum albumin
• INcreased marrow microvessels

CRAB

• Hypercalcemia
• renal insufficiency
• Anemia
• BOne lesions

• SPEP/UPER
• CALCIUM
• HEMOGLOBIN
• CREAtinine

• Chemotherapy
• Stem cell transplant
• Bisphophonates: reduce skeletal events

• Plasma cell
• Light chains
• Solitary plasmocytoma

• Between muscle and joint capsule: hip>knee>elbow>shoulder
• Brain trauma

• HIgh ISS
• TBI: in spastic limb
• SCI: compete >incomplete
• Prolonged coma
• Decubitus ulcers
• DISH/ank spond
• Femoral nail: worse if piriformis entry
• Surgical approach: iliofemoral > kocher langenbech > ilioinhuinal
• THA approach: Anterior > lateral > posterior
• TKA if notching or periosteal stripping

Triphasic bone scan

• ALP: increased > removes inhibitors of mineraization
• CRP: Elevated >>once normalized may be sign of maturity
• ESR: elevated 12 weeks  after THA is predictor for HO
• CK: correlates with muscle involvement

INdomethacin 75mg/day for 10 days to 6 weeks: literature seems to show no great benefit

Radiotherapy: single dose of 700cGy within 72 hrs of surgery

Osteochondroma

• Derived from aberrant cartilage from the perichondral ring
• 10-20 years old
• Autosomal Dominant
• EXT gene: loss of regulation of indian hedgehog
• Low grade chondrosarcoma

• SH fracture
• Radiation
• Surgery

• Autosomal dominant
• EXT1-3
• EXT 1
• 5-10%: proximal lesions more likely than distal lesions

Cortex of lesion in continuity with cortex of native bone...medullary cavity also in continuity with native bone

Osteochondromas lead to

• Subluxation radiocapitellar joint
• LLD
• Valgus deformity knee
• Ulnar deviation of wrist

Intramedullary osteosarcoma

• PAgets disease
• Distal femur/proximal tibia
• Lung
• Mytation in Rb gene

• Advanced stage
• Response to chemo: tumor necrosis from sample
• Tumor size
• High serum alk phos
• High LDH
• +ve margins

• Sunburst periosteal reaction
• Codman triangle
• Blastic destructive lesion

Multi agent chemotherapy and wide resection

• Pre op chemo: 8-12 weeks
• Post op chemo: 6-12 months

Tumor necrosis >98%: good prognosis

• 5-25 years
• 50% in diaphysis of long bonesTranslocation T11:22
• EWS-FLI1
• Small round blue cells

• Tumor size >  8cm or 100cm3 
• Spine and axial worse than proximal extremity worse than distal extremities
• Age >14
• Male
• Elevated LDH
• p53 mutation
• Metastases: MOST IMPOSTANT PROGNOSTIC FACTOR
• Chemo responce: <90% necrosis

• onion skinning
• sunburst priosteal reaction

Neoadjuvant chemo + wide resection + adjuvant chemo +/- adjuvant radiation

Radiation of: positive margins, metastasis, poor chemo response

• Bone sarcoma: secondary to radiotherapy ...risk 10-20% at 20 years
• Treatment related acute myeloid leukemia/myelodysplasia
• Metastases

t12:16

• Low grade (well differentiated(: < 1%
• Myxoid (intermediate grade): 10-30%
• High grade: >50%

MDM2/CDk14

Low grade (ALT): wide resection>>>low risk of mets/dedifferentiation

Intermediate or high grade

Wide surgical excision and adjuvant radiotherapy

• Fertility consult
• Echocardiogram
• CBC
• 24hr urine

Lng

• High grade
• size >5cm
• Tumor deep to the fascia

Radiation and wide surgical excision

50-60 Gy

• 30% wound complication
• Greater radiation induced morbidity and chance of radiation induced sarcoma: need bigger fields

• 50-60 Gy
• 30 Gy
• 6 Gy
• 30-35 Gy in 15 fractions or 50Gy in 25 fractions

Renal, thyroid, lung

Tokahashi score: >8 means  >6 months to live

palliative: pain control and radiotherapy

SUrgery: decompression stabilization and post op radiation

• 80% age <25
• Epiphyseal: distal femur and proximal tibia most common
• CHondroid on histology
• To lung but are benign: similar to GCT
• Well circumscribed epiphyseal lytic lesion with rim of sclerotic done: can have cortical expansion, punctate calcification not always present
• Cobblestone or chickenwire pattern
• Extended intralesional curetage and bone grafting

• Abnormal bone remodelling: excessive bne resorption and abnormal bone formation
• Paramyxovirus or RSV
• Mostly spontaneus: if inherited its autosomal dominant
• Hiho output cardiac failure

Osteosarcoma, fibrosarcoma and chondrosarcoma

• Bone pain
• Long bone bowing
• Fractures: tend to be transverse
• Large joint arthritis
• Secondary sarcoma

Pagets disease

• Elevated
• Normal

Aim for osteoclast inhibition

• Bisphosphonates
• Calcitonin: decrease size and resorptive capacity of osteoclasts

Teriparatide is contraindicated bc of risk of secondary sarcoma

• diaphysis of long bones
• p53
• 98% tumor necrosus
• Expression of MDR gene: pumps chemo out of cell
• Periostal sunburst or hair on end reaction
• Osteoid and chondrobalstic matrix

Neoadjuvant chemo >restage > wide resection > post op chemo

• Proliferation of synovial villi and nodules: hemosiderin stained multinucleated giant cells
• Intra articular: Knee > hip > ankle
• Giant cell tumor of nerve sheeth
• 5q33: increased CSF1 expression
• Csystic erosion with sclerotic margins on both sides of joint
• Blooming artifact: becasue of iron in hemosiderin deposits
• Brownish/red inflammaed synovium

COmbined open/arthroscopic synovectomy: marginal excison

In giant cell tumor of nerve sheeth: marginal excison is ok but recurrence is high

External beam radiotherapy: reduces rate of recurrence to 10-20%

• Temporary failure of medullary bone formation near physis<20
• Metaphysis adjacent to physis: proximal humerus most common
• UBC decrease in size and may heal

Latent: if normal bone separates UBC from physis

Active: Cyst adjacent to physis

• Central, lytic, well demarcated metaphyseal lesion
• Cystic expansion with symmetric thinning or cortices: not wider than physis
• Fallen leaf sign: path fracture with fragment at the base of empty cyst

Immobilization after path fracture: 15% heal after farcture

Aspiration and methylprednisone injection: for active cysts...may require multiple injections

Curetagge, bone grafting and internal fixation: avoid in active UBC bc communication with physis may lead to growth arrest

• <20
• Posterior elements
• Bubbly appearance: expansile, eccentric lytic lesion with bony septae
• FLuid/fluid levels

• GCT
• CHondroblastoma
• Fibrous dysplasia
• Chondromyxoid fibroma
• NOF

Teleangectatic osteosarcoma

Non op until fracture heals

Agressive curetage and bone grafting +/- adjuvants

• Phenol
• Argon beam
• Liquid nutrogen

• Arises near joints but rarely within joint: most common sarcoma of the foot
• Translocation t(x:18): forms SYT-SSX1/2
• Common (30%-60%): goes to lung
• SYT:SSX2: better prognosis
• Wide resection and adjuvant radiotherapy: chemo may be beneficial

• Synovial
• Epithelioid
• Angiosarcoma
• Rhabdomyosarcoma
• Clear cell

• Proximal femur > tibial diaphysis
• Posterior elements: Thoracic and lumbar > cervical in concavity of scoliosis
• Scaphoid and proximal phalanx
• Talar neck

• Nidus containing osteobalsts surrounded by sclerotic zone (reactive zone)
• pain worse at night and relieved by NSAID's
• Makes symptoms worse
• <2cm
• Early resection within 18 months in kids <11

NSAID's until it resolvea

RFA: 90% succesfully treated with 1-2 sessions of rfa

Surgical resection and curetage: digital lesions (RFA would burn skin) or lesions close to nerves/vessels (in spine)

NOF

• 30% of children with open physis have NOF
• Metaphysis of long bones
• Jaffe-campanacci syndrome: multiple NOF, cafe au lait, mental retardation, heart eyes and gonads involved

Metaphyseal eccenttic buccly lesion surrounded by sclerotic rim: as child grows lesion migrates towards diaphysis

Observation and follow up: curetage and bone grafting in the case of pathologic lesion

• Hyaline cartilage
• Hand (60%) > feet
• Chondroblasts escape from the physis into medullary canal and begin proliferating there
• Well defined central lucent medullary lesions that calcify over time (pop corn)

Serial x rays for n patients and long term follow up in mafucci or olliers disease

ENchondroma

Ollier's disease: Multiple enchondromatosis >>risk malignant tranformation < 30%

Maffucci syndrome: Multiple enchondromas and sost tissue angiomas.....enchondromas expand cortices and angiomas seen as phleboliths >>>malignant tranformation 50-100%..can also have visceral malignancies

• None
• None

• ENchondroma erosion cortex <50% thickness
• Chondrosarc erosion cortex >50% thickness (scalloping)
• Chondrosarc leads to cortical thickenning and expansion...enchondroma lead to cortical thinning and expansion
• Chondrosarc are larger: >5cm

• Failure of normal production of lamellar bone
• Proximal femur
• GS alpha protein:increased cAMP production

• McCune albright: cafe au lait, endocrinopathy, unilateral polyostotic FD
• Mazabraud syndrome: polyostotic FD and soft tissue intramuscular fibromas

Osteofribrous dysplasia: Location anterior tibial diaphysis > bowing

MFH, fbrosarcoma, osteosarcoma: 1%

• Central lytic lesions in medullary canal: may have cortical thinning and be expansile
• Ground glass appearance
• Sheppard crook deformity

Observation if asymptomatic

Bisphosphonates: in symptomatic polyostotic FD >>decreases pain and bone turnover

ORIF with bone grafting, never use autograft, best choice is cortical allograft...Use nail if possible