Primary bone tumors presenter: ondari n.j FACILITATOr : prof . gakuu

1. Primary bone tumorspresenter: ondarin.jFACILITATOr: prof. gakuu 28-10-2013

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

3. 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

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

6. Evaluation • History • Physical examination • Investigations; labs, imaging • Biopsy

7. Analytic approach to evaluation of the bone neoplasm

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

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

11. Evaluation; imaging • Plain radiograph • CT scan • MRI • Radionuclide scanning • PET

12. 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

13. Radiographic features of bone tumors

14. Site of the Lesion • Determined by the laws of field behavior and developmental anatomy of the affected bone, a concept first popularized by Johnson. • Parostealosteosarcoma -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, chondromyxoidfibroma, and nonossifyingfibroma

15. Predilection of Tumors for Specific Sites in the Skeleton

16. Site of the lesion. Parosteal osteosarcoma Adamantinoma Chondroblastoma

17. 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

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

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

20. 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.gnonossifyingfibroma, 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

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

22. 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

23. 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

24. 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

25. Periosteal Response • the pattern of periosteal reaction is an indicator of the biologic activity of a lesion . • periostealreactionsthat 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.ganeurysmal bone cyst and chondromyxoidfibroma; • a solid smooth or elliptical layer e.gosteoidosteoma and osteoblastoma; • a single lamellar reaction, such as accompanies Langerhans cell histiocytosis • Sunburst (“hair-on-end”) or onion-skin (lamellated) pattern . • Codman triangle

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

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

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

29. Type of Matrix • The matrix represents the intercellular material produced by mesenchymal cells • E.gosteoid, 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

30. 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

31. 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

32. 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?

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

34. 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

35. Radiographic features that may help differentiate benign from malignant lesions

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

37. 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)

38. William F. Enneking M.D

39. 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 • Intracapsular, marginal, extended, radical

41. Enneking classification of local procedures

42. Enneking classification of amputations

43. 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

44. 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

45. Enneking surgical Staging of malignant tumors

46. 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

48. 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.gprox fibula, distal ulna

49. 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. 

50. 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.