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

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.
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

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.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

21. determine its growth rate.
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
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

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
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

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 .
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

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.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

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.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

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

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.g prox 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. 
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. .

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.

51. 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.

52. Example of poorly performed biopsy
Transverse incisions should not be used

54. 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

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

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

57. 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

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

59. 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

60. 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

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

62. Osteoid Osteoma

63. Bone Island

64. CARTILAGE LESIONS Chondroma Enchondroma Olliers disease
Maffuci synrome

65. CARTILAGE LESIONS
Osteochondroma

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

67. Cystic lesions
Unicameral bone cyst
Aneurysmal bone cyst

68. Aggressive benign tumors
Chondroblastoma
Giant cell tumor

69. Aggressive benign tumors
Chondromyxoid fibroma

70. 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

71. Osteosarcoma

73. Chondrosarcoma

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

76. Adamantinoma
Bubble-like appearance
85% occur in tibia

77. The end
Thank you