Primary bone tumors presenter: ondari n.j FACILITATOr: prof. gakuu 28-10-2013

Outline Introduction Classification Epidemiology Evaluation Staging Principles of management Selected tumors Therapeautic advances

Introduction Forms 0.2% of human tumor burden Primary malig bone tumors make 1% of all malignant tumors Carcinoma commonly metastasize to LN except BCC Sarcomas commonly metastasize hematogenously Most have male predominance excep GCT, ABC

Classification Based on tissue of origin Bone Cartilage Fibrous tissue Bone marrow Blood vessels Mixed Uncertain origin

Evaluation History Physical examination Investigations; labs, imaging Biopsy

Analytic approach to evaluation of the bone neoplasm

Evaluation; history Age Symptomatology Pain Swelling History of trauma Neurological sympts Pathological fracture

Evaluation; physical examination Lump/swelling 5S MTC Effusion Deformities Regional nodes

Evaluation; imaging Plain radiograph CT scan MRI Radionuclide scanning PET

Radiography Information yielded by radiography includes : Site of the Lesion Borders of the lesion/zone of transition Type of bone destruction Periosteal reaction Matrix of the lesion Nature and extent of soft tissue involvement

Radiographic features of bone tumors

Site of the Lesion Determined by the laws of field behavior and developmental anatomy of the affected bone, a concept first popularized by Johnson. Parosteal osteosarcoma -posterior aspect of the distal femur Chondroblastoma -epiphysis of long bones before skeletal maturity Adamantinoma and osteofibrous dysplasia have a specific predilection for the tibia A lesion's location can also exclude certain entities from the differential diagnosis. E.g Giant cell tumor -articular end of bone. Location in relation to the central axis of the bone esp in long tubular bone, such as humerus, radius, femur, or tibia. For example, simple bone cyst, enchondroma, or a focus of fibrous dysplasia -always centrally located Eccentric location is Xteristically observed in aneurysmal bone cyst, chondromyxoid fibroma, and nonossifying fibroma

Predilection of Tumors for Specific Sites in the Skeleton

Site of the lesion. Parosteal osteosarcoma Adamantinoma Chondroblastoma

Site of the lesion. Distribution of various lesions in a long tubular bone in a growing skeleton Distribution of various lesions in a long tubular bone after skeletal maturity

Site of the lesion. Location of epicenter of lesion usually determines site of its origin (medullary, cortical, periosteal, soft tissue, or in the joint)

Distribution of various lesions in a vertebra. Malignant lesions are seen predominantly in its anterior part (body) Benign lesions predominate in its posterior elements.

Borders/margins of the Lesion Margins determined by GRate hence benign or malignant Three types of lesion margins are encountered: Sharp demarcation by sclerosis (IA margin), sharp demarcation without sclerosis (IB margin) Ill-defined margin (IC margin) Slow-growing lesions -sharp sclerotic borders; usually indicates that a tumor is benign E.g nonossifying fibroma, simple bone cyst Indistinct borders- typical of malignant or aggressive lesions Post- Radio- or chemo of malignant bone tumors Can exhibit sclerosis and a narrow zone of transition The borders/margins -crucial in determining the growth rate hence whether benign or malignant Three types of lesion margins are encountered: Sharp demarcation by sclerosis (IA margin), sharp demarcation without sclerosis around the periphery of the lesion (IB margin), and Ill-defined margin region (entire circumference or a portion of it) -(IC margin) Slow-growing lesions are marked by sharply outlined, sclerotic borders; usually indicates that a tumor is benign E.g nonossifying fibroma, simple bone cyst, and chondromyxoid fibroma Indistinct borders (a wide zone of transition), are typical of malignant or aggressive lesions Post- Radio- or chemo of malignant bone tumors Can exhibit sclerosis and a narrow zone of transition

determine its growth rate. Borders of the lesion determine its growth rate. sharp sclerotic sharp lytic ill-defined.

Borders of the lesion. A: Sclerotic border typifies a benign lesion e.g nonossifying fibroma in the distal femur. B: A wide zone of transition typifies an aggressive or malignant lesion e.g plasmacytoma involving the pubic bone and supraacetabular portion of the right ilium A: Sclerotic border or narrow zone of transition from normal to abnormal bone typifies a benign lesion e.g nonossifying fibroma in the distal femur. B: A wide zone of transition typifies an aggressive or malignant lesion e.g plasmacytoma involving the pubic bone and supraacetabular portion of the right ilium

Type of Bone Destruction Mechanisms of bone destruction Direct effect of tumor cells Incr osteoclastic activity Cortical bone is destroyed less rapidly than trabecular bone. Loss of cortical bone appears earlier on radiography trabecular bone must be destroyed (about 70% loss of mineral content) before the loss becomes radiographically evident Bone destruction can be described as geographic (type I) - benign lesions moth-eaten (type II) and permeative (type III) - rapidly growing infiltrating tumors Mechanisms of bone destruction Direct effect of tumor cells Complex mechanism in which normal osteoclasts of the host bone respond to pressure generated by the enlarging mass and by active hyperemia associated with the tumor Cortical bone is destroyed less rapidly than trabecular bone. However, loss of cortical bone appears earlier on radiography because its density is highly homogeneous compared with that of trabecular bone. In the latter, greater amounts of bone must be destroyed (about 70% loss of mineral content) before the loss becomes radiographically evident (134). Like the borders of a lesion, the type of bone destruction caused by a tumor indicates its growth rate. Bone destruction can be described as geographic (type I), moth-eaten (type II), and permeative (type III) (105,107) (Fig. 1-12). Although none of these features are pathognomonic for any specific neoplasm, the type of destruction may suggest a benign or a malignant process. Geographic bone destruction is characterized by a uniformly destroyed area usually within sharply defined borders. It typifies slow-growing, benign lesions, such as simple bone cyst, enchondroma, chondromyxoid fibroma, or giant cell tumor. On the other hand, moth-eaten (i.e., characterized by multiple, small often clustered lytic areas) and permeative (i.e., characterized by ill-defined, very small oval radiolucencies or lucent streaks) types of bone destruction mark rapidly growing, infiltrating tumors, such as myeloma, lymphoma, fibrosarcoma, or Ewing sarcoma. However, some nonneoplastic lesions may demonstrate this aggressive pattern. For example, osteomyelitis can exhibit both type II (moth-eaten) and type III (permeative) patterns of destruction (133). Similarly, hyperparathyroidism can cause a permeative pattern (113). The distinction between a moth-eaten and a permeative pattern of destruction may be subtle; often the two patterns coexist in the same lesion

Patterns of bone destruction. permeative type characteristic of round cell tumors geographic a uniformly affected area within sharply defined borders moth-eaten rapidly growing infiltrating lesions giant cell tumor. myeloma Ewing sarcoma

Periosteal Response the pattern of periosteal reaction is an indicator of the biologic activity of a lesion . periosteal reactionsthat can be categorized as; uninterrupted (continuous) or I nterrupted (discontinuous). Any widening and irregularity of bone contour may represent periosteal activity. An uninterrupted periosteal reaction indicates a long-standing (slow- growing), usually indolent, benign process. There are several types of solid periosteal reaction: a solid buttress e.g aneurysmal bone cyst and chondromyxoid fibroma; a solid smooth or elliptical layer e.gosteoid osteoma and osteoblastoma; a single lamellar reaction, such as accompanies Langerhans cell histiocytosis Sunburst (“hair-on-end”) or onion-skin (lamellated) pattern . Codman triangle the pattern of periosteal reaction is an indicator of the biologic activity of a lesion . Bone neoplasms elicit periosteal reactions that can be categorized as uninterrupted (continuous) or interrupted (discontinuous). Any widening and irregularity of bone contour may represent periosteal activity. The solid periosteal reaction represents a single solid layer or multiple closely apposed and fused layers of new bone attached to the outer surface of the cortex. The resulting pattern is often referred to as cortical thickening. Although no single periosteal response is unique for a given lesion, an uninterrupted periosteal reaction indicates a long-standing (slow-growing), usually indolent, benign process. There are several types of solid periosteal reaction: a solid buttress, such as is frequently seen accompanying aneurysmal bone cyst and chondromyxoid fibroma; a solid smooth or elliptical layer, such as is seen in osteoid osteoma and osteoblastoma; an undulating type, most frequently seen in long-standing varicosities, pulmonary osteoarthropathy, chronic lymphedema, periostitis, and, rarely, with neoplasms; and a single lamellar reaction, such as accompanies osteomyelitis, Langerhans cell histiocytosis, and stress fracture. An interrupted periosteal response, on the other hand, is commonly seen in malignant primary tumors and less commonly in some metastatic lesions and highly aggressive nonmalignant processes. In these tumors, the periosteal reaction may appear in a sunburst (“hair-on-end”) or onion-skin (lamellated) pattern . When the tumor breaks through the cortex and destroys the newly formed lamellated bone, the remnants of the latter on both ends of the break-through area may remain as a triangular structure known as a Codman triangle

Types of periosteal reaction. An uninterrupted periosteal reaction usually indicates a benign process, whereas an interrupted reaction indicates a malignant or aggressive nonmalignant process

Examples of Nonneoplastic and Neoplastic Processes Categorized by Type of Periosteal Reaction

Interrupted type of periosteal reaction Ewing sarcoma -lamellated type lamellated or onion-skin type in ewing sarcoma sunburst pattern -osteosarcoma Codman triangle (arrow)

Type of Matrix The matrix represents the intercellular material produced by mesenchymal cells E.g osteoid, bone, chondroid, myxoid, and collagen material . Type of matrix allows differentiation of some similar-appearing E.g differentiating osteoblastic from chondroblastic processes. Calcifications in the tumor matrix, point to a chondroblastic process. Calcifications typically appear as punctate (stippled), irregularly shaped (flocculent), or curvilinear (annular or comma-shaped, rings and arcs). Differential diagnosis of stippled, flocculent, or ring-and-arc calcifications includes enchondroma, chondroblastoma, and chondrosarcoma. A completely radiolucent lesion may be either fibrous or cartilaginous in origin tumor-like lesions, such as simple bone cysts or intraosseous ganglion

Types of matrix: osteoblastic The matrix of a typical osteoblastic lesion is characterized by the presence of the following features A. fluffy, cotton-like densities within the medullary cavity, e.g in this case of osteosarcoma of the distal femur B. presence of the wisps of tumor-bone formation, like in this case of osteosarcoma of the sacrum C. by the presence of a solid sclerotic mass, such as in parosteal osteosarcoma

Types of matrix: chondroid matrix A: Schematic representation of various appearances of chondroid matrix calcifications. B: Enchondroma displays a typical chondroid matrix C: Chondrosarcoma with characteristic chondroid matrix

Soft Tissue Mass A bone lesion associated with a soft tissue mass should prompt the question of which came first. Is the soft tissue lesion an extension of a primary bone tumor, or is it a primary soft tissue tumor invading bone?

Radiographic features differentiating primary soft tissue tumor invading bone from primary bone tumor invading soft tissues.

Benign Versus Malignant Nature clusters of features that can be gathered from radiographs can help in favoring one designation over the other . Benign lesions usually have well-defined sclerotic borders exhibit a geographic type of bone destruction the periosteal reaction is solid and uninterrupted, and there is no soft tissue mass. Malignant tumors often exhibit poorly defined borders with a wide zone of transition; bone destruction appears in a moth-eaten or permeative pattern, and the periosteum shows an interrupted, sunburst, or onion-skin reaction with an adjacent soft tissue mass. NB-benign lesions may also exhibit aggressive features

Radiographic features that may help differentiate benign from malignant lesions

Grading of bone sarcomas Criteria for grading Cellularity Nuclear features Mitotic figures necrosis Correlates with prognosis in some tumors E.g chondrosarcoma, malig vascular tumors Some not amenable to histological grading e.g monomorphic tumors Ewing, MM, lymphoma Some always high grade Sometimes not useful in predicting prognosis Adamantinoma, chordoma

Staging of bone tumors Benign tumors (Enneking staging of benign tumors) Stage 1 - latent Stage 2 - active Stage 3 - aggressive Malignant tumors TNM staging AJCC staging system Musculoskeletal tumor society staging system(enneking) Surgical staging Note Benign tumors - classified using Arabic numerals(1,2,3) Malignant tumors - classified using roman numerals(I,II,III)

William F. Enneking M.D

Enneking classification systems Enneking classification of benign tumors Latent, active, aggressive Enneking surgical staging of malignant tumors Enneking classification of local procedures Intracapsular, marginal, extended, radical Enneking classification of amputations

Enneking classification of local procedures

Enneking classification of amputations

Enneking staging of benign tumors Stage 1; Latent Well defined margin Grows slowly and then stops Heals spontaneously eg osteoid osteoma Neglible recurrence after intracapsular resection Stage 2; Active Progressive growth limited by natural barriers Well defined margin but may expand thinning cortex e.g ABC Negligible recurrence after marginal excision Rx marginal resection Stage 3; aggressive Growth not limited by natural barriers e.g GCT Mets present in 5% of these pts Have high recurrence after intracapsular or marginal resection Extended resection preferred

Enneking surgical Staging of malignant tumors Incorporates degree of differentiation Low grade(stage I) or High grade(stage II) Local extent of tumor Intracompartmental - A Extracompartmental - B distant spread metastasis

Enneking surgical Staging of malignant tumors

AJCC staging for bone sarcomas Based on Tumor grade Low grade(I) High grade(II) Tumor size <8cm -A >8cm -B Presence and location of mets Skip mets -III Pulm mets -IVA Non-pulm mets -IVB

Bone biopsy Options Needle biopsy 90% accuracy at determining malignancy Accuracy at determining specific tumor much lower Absence of malignant cells less re-assuring than incisional biopsy Core biopsy Provides accurate diagnosis in 90% of cases incisional biopsy Primary resection instead of biopsy can be done in; Small(<3cm) subc mass- marginally resected if likely malignant Characteristic radiographic appearance of benign lesion Painful lesion in an expendable bone e.g prox fibula, distal ulna

Tumour Biopsy Principles 1 1.Biopsy done only after evaluation & imaging is complete. determine xteristics and local extent of the tumor and mets Staging helps determine the exact anatomic approach to tumor Biopsy superimposes radiologic changes at the biopsy site, and there4 can alter the interpretation of the imaging studies. 2. Place small incisions whenever possible- skin & capsule 3. The biopsy track be considered contaminated with tumor cells. Track excised en bloc with the tumor subsequently. 4. The surgeon should be familiar with incisions for limb salvage surgery, and also with standard and nonstandard amputation flaps.  1.Biopsy should be done only after clinical, laboratory, and roentgenographic examinations are complete. This will help in planning the placement of the biopsy incision. It will also help to make an accurate diagnosis 2. Place small incisions whenever possible, also use small capsular incisions over the tumour thus reducing bleeding 3. The biopsy track should be considered contaminated with tumor cells. Placement of the biopsy incision therefore is important because the biopsy track should also be excised en bloc with the tumor subsequently. 4. The surgeon should be familiar with incisions for limb salvage surgery, and also with standard and nonstandard amputation flaps.  5. If a tourniquet is used, the limb is elevated before inflation but should not be exsanguinated by compression because the latter may cause tumour spread. 6. Care should be taken to contaminate as little tissue as possible. Transverse incisions should be avoided since they are extremely difficult or impossible to excise with the specimen. The deep incision should go through a single muscle compartment (muscle belly) rather than through an intermuscular plane. Major neurovascular structures should be avoided. Care should be taken not to contaminate flaps. Minimal retraction should be utilized to limit soft tissue contamination. .

Examples of poorly performed biopsies Needle biopsy track contaminated patellar tendon Multiple needle tracks contaminate quadriceps tendon Needle track placed posteriorly, location that would be extremely difficult to resect en bloc with tumor if it had proved to be sarcoma.

Tumour Biopsy Principles 2 5. If a tourniquet is used; The limb is elevated before inflation Avoid exsanguination by compression. 6. contaminate as little tissue as possible. Avoid transverse incisions The deep incision should go thru single muscle compartment (muscle belly) rather than through an intermuscular plane. Major neurovascular structures should be avoided. Care should be taken not to contaminate flaps. Minimal retraction should be utilized to limit soft tissue contamination.

Example of poorly performed biopsy Transverse incisions should not be used

Tumour Biopsy Principles 3 7. If possible soft tissue extension of a bone lesion should be sampled  8. If a hole must be made in the bone, it should be round or longitudinally oval to minimize stress concentration and prevent a subsequent fracture. A fracture may preclude a subsequent limb salvage surgery. PMMA is plugged into the hole to contain a hematoma - minimal.   9. Biopsy should be taken from the periphery of the lesion, which contains the most viable tissue. Biopsy material may be sent for M/C/S if in doubt regarding infection

If hole must be made in bone during biopsy, defect should be round to minimize stress concentration, which could lead to pathological fracture

Examples of poorly performed biopsies Biopsy resulted in irregular defect in bone, which led to pathological fracture

Tumour Biopsy Principles 4 10. A frozen section should be sent intraop to ensure that diagnostic tissue has been obtained. If a tourniquet has been used it should be deflated and meticulous haemostasis ensured before closure. 11. Drains should not be used routinely. If a drain is used, it should exit in line with the incision. The wound should be closed tightly in layers. 12. operating surgeon should accompany specimen to pathologist if feasible Discuss with the pathologist about clinical findings, imaging, intraop findings and the specimen

Example of poorly performed biopsy Drain site was not placed in line with incision

Principles of management Multidisciplinary team approach Benign asymptomatic tumors If certain observe If in doubt biopsy Benign symptomatic or enlarging tumors Biopsy Excision/ curretage Suspected malignant tumors If primary admit for work-up Staging Choices; amputation, limb sparing surgery, adjuvant therapy

Benign tumors - not aggressive Bone-forming tumors   Osteoid osteoma Bone island Cartilage lesions    Chondroma Osteochondroma Fibrous lesions Nonossifying fibroma Cortical desmoid Benign fibrous histiocytoma Fibrous dysplasia Osteofibrous dysplasia Desmoplastic fibroma    Cystic lesions Unicameral bone cyst Aneurysmal bone cyst Intraosseous ganglion cyst Epidermoid cyst Fatty tumors Lipoma Vascular tumors Hemangioma Other nonneoplastic lesions Paget disease Brown tumor-hyperparathyroidism Bone infarct Osteomyelitis

Aggressive benign tumors Giant cell tumor Chondroblastoma Chondromyxoid fibroma Osteoblastoma  Langerhans cell histiocytosis

Osteoid Osteoma

Bone Island

CARTILAGE LESIONS Chondroma Enchondroma Olliers disease Maffuci synrome

CARTILAGE LESIONS Osteochondroma

Fibrous lesions Fibrous dysplasia Nonossifying fibroma Polyostotic Fibrous dyspalsia Shepherd’s crook appearance

Cystic lesions Unicameral bone cyst Aneurysmal bone cyst

Aggressive benign tumors Chondroblastoma Giant cell tumor

Aggressive benign tumors Chondromyxoid fibroma

Malignant Tumors of Bone Osteosarcoma Chondrosarcoma Ewing sarcoma Chordoma Adamantinoma Malignant vascular tumors Malignant fibrous histiocytoma and fibrosarcoma Multiple myeloma and plasmacytoma Lymphoma Metastatic carcinoma

Osteosarcoma

Chondrosarcoma

Ewing Sarcoma may be confused with osteomyelitis Commonly affects diaphysis with onion skin appearance

Adamantinoma Bubble-like appearance 85% occur in tibia

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