Bone Tumors Pavel Douša

The essential prerequisite for effective diagnosis and treatment of patients with bone tumors is an interdisciplinary cooperation. On the treatment of these patients taka part pediatricians, general practitioners, orthopedic surgeons, pathologists, oncologists, radiologists and rehabilitation specialists.

Examination Medical history Clinical examination X-ray Laboratory exams CT, MRI, angiography Biopsy

Painful tumors - clinical features associated with bone tumors include pain, deformity and impairment of function; - pain is feature common to almost all malignant tumors of bone, but may or may not be present in benign lesions; - malignant bone tumors are usually associated with deep, aching pain, which, although not sharp and sometimes not severe, is quite distressing to the patient because of its constancy; - pain that persists at night & is not relieved by rest is suggestive of malignancy; however, certain benign tumors, such as osteoid osteoma, are characterized by nocturnal pain;osteoid osteoma - mild, dull, aching back pain that suddenly becomes excruciating w/ such insignificant trauma as sitting down a bit hard suggests Pathologic compression frx in vertebra involved by metastatic cancer; Pathologicmetastatic cancer

Pathologic fractures - many tumors gradually erode bone and weaken it to the extent that it cannot withstand the strain of ordinary use; -in such situations, minimal trauma may precipitate pathologic frx; -if there were no symptoms prior to time of frx, chances are that tumor is benign; -solitary bone cyst, fibrous dysplasia, nonossifying fibroma, and enchondromas are benign lesions that frequently are first noted because of fracture; -on other hand, if frx has been preceded by dull, aching pain, possibility of malignant primary bone tumor or metastasis is likely;

Benign Bone Tumors - benign bone tumors generally do not extend beyond the cortex of bone; - often these tumors are surrounded by a radiodense margin of bone; - where as metaphyseal tumors are common, diaphyseal tumors are uncommon; - diff dx of benign diaphyseal tumors includes EOG and fibrous dysplasiaEOGfibrous dysplasia

Radiographic Features of Bone Tumors - note whether the bone formed in tumor is being produced by actual tumor cells or by normal osteoblasts reacting to tumor - while several benign tumors may form bone, only osteogenic sarcoma is a malignant bone forming tumor - host bone often responds to a tumor by combination of resorption and bone formation - reactive bone that forms the thin sclerotic border of slowly growing tumor may be mature lamellar bone - some tumors, such as typical osteochondroma, are so characteristic that x-rays alone can establish the diagnosisosteochondroma

Malignant lesions -are suggested if the boundaries of the tumor are ill- defined, if there are no sharp borders, if the lesion has a mottled appearance, and if it has broken out of the confines of the bone and destroyed cortex, malignancy is to be suspected -malignant tumor cells that extend through the cortex may elevate periosteum and stimulate it to produce a small triangle of reactive bone (Codman's triangle) where periosteum is lifted from the shaft; -formation of new osseous tissue outside involved bone is suggestive of malignancy but can also be found in cases of infection and in myositis ossificans;myositis ossificans -subperiosteal new bone formation, which has laminated or onionskin appearance, is seen in Ewing's sarcoma, but it may also be found in other conditions, such as infection;Ewing's sarcomainfection

Biopsy of MSK tumors May accomplished with a large needle or by open surgical methods; - needle bx - fine needle biopsy: - relies on cytologal interpretation - its accuracy ranges between 65 to 95% - core needle biopsy: - uses trocar cannula system, - allows for immuno-histochemical analysis; - accuracy ranges between 75 to 95%; - incisional open bx: - where several areas of a tumor must be evaluated

Surgical Staging System for Musculoskeletal Tumors Stage determined by three different sub-categories -Grade: Histology with aid of radiographic findings and clinical correlation G 0: benign grade, uniform cell type without atypia, no mitoses G 1: Low grade, uniform cell type without atypia, few mitoses G 2: High grade, atypical nuclei, mitoses pronounced -Site: T 1: Intracompartmental (Confined within limits of periosteum) T 2: Extracompartmental (Breach in an adjacent joint cartilage, bone cortex (or periosteum), fascia lata, quadriceps, and joint capsule) -Metastasis: M 0: No identifiable skip lesions or distant metastases. M 1: Any skip lesions, regional lymph nodes, or distant metastases.

Surgical Staging System Benign: 1 Latent G 0 T 0 M 0 2 Active G 0 T 0 M 0 3 Aggressive G 0 T 1-2 M 0-1

Enneking's Staging System of Malignant Bone Tumors Ia G 1 T 1 M 0 Ib G 1 T 2 M 0 IIa G 2 T 1 M 0 IIb G 2 T 2 M 0 IIIa G 1-2 T 1 M 1 IIIb G 1-2 T 2 M 1 Treatment of any potentially malignant bone tumor always begins with staging. Chest CT scan to evaluate for pulmonary metastasis, bone scan or skeletal survey for distant metastases or skip lesions.

Division of Bone Tumors Osseous Osteoid osteoma Classic osteosarcoma Osteoblastoma Osteochondroma Cartilaginous Enchondroma Chondrosarcoma Chondroblastoma Osteochondroma Fibrous Fibrous Dysplasia Malignant fibrous histiocytoma Ossifying fibroma

Division of Bone Tumors Reticuloendothelial Eosinophilic granuloma Ewing's sarcoma Vascular Aneurysmal bone cyst Angiosarcoma Hemangioma Unknown origin Simple bone cyst Giant cell sarcoma Giant Cell Tumor Chordoma Misc Multiple Myeloma

Treatment Surgical treatment Radiotherapy Chemotherapy

Osteochondroma / Osteocartilaginous Exostosis - a developmental dysplasia of peripheral growth plate which forms a cartilage capped projection of bone found near metaphyses of long bones - peripheral chondroblast grows outward from the metaphysis, acting as an ectopic growth plate - it is the most common benign bone tumor - usually occurs in long bones, but may occur any bone that is preformed in cartilage

Treatment - surgical resection is indicated for persistant irritation (from bursitis) or for neurovascular comprimise; - surgical resection is also indicated for continued osteochondroma growth after skeletal maturity (in which case malignancy is suspected); - definitive treatment includes marginal excision of an active exostosis, - prognosis for a solitary exostosis is excellent (< 5% recurrence following marginal excision);

Osteoid Osteoma - benign osseous tumor usually less than 1.5 cm in diameter, comprising 11% of all benign bone tumors, no cases of malignant transformation has been reported - occurs primarily in adolescents and less often in children; - presenting symptom is well localized pain which may be more severe at night & is relieved by aspirin or other prostaglandin inhibitors - location: - most common site is proximal femur & diaphysis of long bones; less often: foot (talus, navicular, or calcaneus) & in posterior spine

Osteoid Osteoma Radiographs: - intense bony rxn to small nidus is hallmark of osteoid osteoma, however, may be difficult to see on x-rays; CT Scan: - nidus is best localized w/ CT - tell radiologist of diff dx:

Treatment: - osteoid osteoma may resolve spontaneously w/ time (especially when located in the hand), however, most patients prefer not to wait 2 to 4 years for resolution; - when nidus is located in a low stress area such as metaphysis, treatment should consist of en bloc excision w/ surrounding small block of reactive bone;

Osteosarcoma - malignant tumor of bone in which neoplastic osteoid is produced by a proliferating spindle cell stroma; - most common primary malignant bone tumor of mesenchymal derivation; - arises in adolescents & affects males slightly more often than females.

Osteosarcoma affected sites: - occurs in region of knee (distal femur or proximal tibia) in 50% of pts; - other sites include proximal humerus, proximal femur, & pelvis; - most osteosarcomas occur in the metaphysis; - infrequently occurs in the spine

Osteosarcoma Classification: - classic - telangiectatic - parosteal - periosteal ________________________________________ Clinical Presentation: - initial symtom is a painful bony mass; - significant number of osteosarcomas in adults occur in assoc w/ Pagets disease;

Treatment of Classic Osteosarcoma - surgery alone as a treatment yields only a 20% survival rate - non metastatic disease treated with chemotherapy and surgery, expected survival is 60-80% - chemotherapy (neoadjuvant, adjuvant): - with adjuvant chemotherapy, the 5 year survival rate is > 50%; - some surgeons insist on preoperative chemotherapy in the management of osteosarcoma; - good response to chemotherapy is indicated by 90% tumor necrosis on biopsy; chemotherapy

Enchondroma benign and asymptomatic cartilaginous tumor of bone which most often occurs in adolescents or young adults; - it is an intramedullary cartilage lesion located in central metaphysis; - most often affects small tubular bones of hands or feet (40-65%); - may also affect proximal humerus and femoral shaft;proximal humerus

Treatment - asymptomatic solitary enchondromas may be followed non operatively w/ serial radiographs; - prognosis for benign enchondroma is excellent. - if solitary or multiple enchondromas become symptomatic or begin to enlarge, they may require biopsy to r/o malignancy;

Ewing's Sarcoma - prevalence: - it represents approx 7% of all primary bone malignancies; - Ewing's sarcoma is more common in males - source: - uncertain origin; - may arise from primitive reticulum cells of marrow; - age: - it is a tumor of children & young adults, w/ most cases occurring between ages of 10 and 20 years; - 3% occurs in children less than 3 years of age; - 64% of Ewing's sarcoma occur in the second decade

Clinical Presentation - may mimic osteomyelitis w/ fever, elevated WBC, & sed rate, wt loss, anemia;osteomyelitis - sites: - femoral diaphysis > pelvis, tibia, humerus, fibula & ribs; - develops in axial skeleton in large proportion of pts (about 40 %); - tumors in pelvis are typically detected later & are therefore larger, with a poorer prognosipelvisfibularibspelvis - distant metastases are noted at diagnosis in about 20% of cases;

Prognosis - potentially the most lethal of all the bone tumors; - most important adverse prognostic factor was metastatic disease detectable at the time of diagnosis; - it almost always presents as a stage IIb lesion; - before routine use of adjuvant chemo, pts w/ Ewing's were treated w/ XRT alone, & 5 year survival rate was no more than 15%; - w/ use of adjuvant chemo, 5 year survival rate to more than 60%;stage

Treatment treatment consists of chemotherapy, surgical resection & possible XRT; - radiotherapy: - approx % of primary ewing's tumors are sensitive - obviously XRT is not desirable in children because of its effect on the growing limb and because of the possibility for causing secondary tumors (can be up to 20%); -chemotherapy: - addition of chemotherapy with surgery increases survival to greater than 70% at 5 years;chemotherapy: -wide surgical excision: - limb salvage w/ insertion of long stem tibial component:

Malignant Fibrous Histiocytoma Osseous Sarcoma: - occur less often in bone than in soft tissue; - occurs in older patient population & may arise out of Pagets Dz or from a bone infarct - it usually presents as an aggressive stage IIb sarcoma; - pathologic frx may be the presenting feature; - has a high rate of metastasis, especially to regional lymph nodes.Pagets Dzstage IIbpathologic Clinical Presentation: - presents in adults; - may present as large mass involving deep soft tissues of proximal limbs; - may present as a small, superficial, low grade tumor in the distal limbs;

Treatment - attention is directed to ruling out metastases to the regional lymph nodes; - low grade stage I tumors usually develop in more peripheral & superfical locations than do high grade tumors. - treatment w/ wide surgical excision is usually adequate, w/ amputation reserved for multiple recurrances. - stage II tumors require excision w/ wide margins or amputation; - preop XRT or postoperative chemo, or both, may be indicated;stage

Simple Bone Cyst -a membrane lined cavity containing a clear yellow fluid. -occurrs most often in children 4-10 years of age. -lesions remain asymptomatic unless complicated by fracture. -they enlarge during skeletal growth and become inactive, or latent, after skeletal maturity. -lesion appears to arise from the growth plate & in early stages, lesion is lies adjacent to growth plate. -predilection for the metaphysis of long bones;

Treatment - goal of treatment is prevention of pathologic fracture;pathologic -simple cysts are treated with curettage and bone grafting; -recurrence is high for active cysts (50%) & low for latent cysts (10%); -alternative treatments: - steroids mg of methylprednisolone infused into cavity; - autologous bone marrow injection: - multiple drill holesmethylprednisolone

Multiple Myeloma -myeloma is malignant tumor of plasma cells arising from a single clone; -multiple myeloma accounts for > 40% of primary malignant tumors of bone. -it is most common malignant primary tumor of bone -may arise as single intraosseous tumor but more often it develops as multiple painful lesions throughout skeleton (multiple myeloma); -pts present in their middle fifties or older (60-70 yr) -constitutional symptoms, anemia, thrombocytopenia, and renal failure;

Treatment - XRT: - myeloma is sensitive to XRT, & reossification of tumor defects may ocurr within several months. - XRT is recommended for intractable bone pain, esp if pain is localized; - it can be dramatically effective in relieving symptoms; - Chemo: - when dz is disseminated, chemo is indicated - 5 year survival remains under 30%; - Surgical Fixation: