Bone tumour

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1. Bone Tumour Classification ,Investigations, General Management . Moderator : Dr. P. Tahbildar Prof.&HOD, Orthopaedics Presenter : Dr. S. H. Ranna PGT, Orthopaedics 09/12/2015

2. INTRODUCTION Defined by Willis, is "an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change.“ BURNET (1957) defined it as “a primary change in the character of cells, which undergo a series of mutations with an increased growth potential rendering them insusceptible to normal growth control”.

3. CLASSIFICATION All lesions structurally resembling neoplasms, are not true neoplasms. Difficult to classify bone tumors

4. In bone along with the true osteogenic tissues, other elements are present like marrow, fat, nerves etc.

5. Facts before classifying a particular tumor:- To define the cell of origin. To identify the cytology of the tumor cells and its stroma as well as their degree of differentiation. To observe the behavior and growth of the tumors.

6. VARIOUS CLASSIFICATIONS BENIGN AND MALIGNANT PRIMARY and SECONDARY

7. DUTHIE, BELHOBEK & MARK classification:- A. True bone tumors:- arising from cells , whose function is primarily skeletal bone formation. B. Tumors arising from tissues normally present in bone but not participating in bone formation. C. Tumors arising from included tissues. D. Metastatic tumors of bone 

8. A .TRUE BONE TUMOURS 1. Osteoblasts (active ossification) BENIGN Osteoid Osteoma osteoblastoma MALIGNANT Osteosarcoma Primary Parosteal 2. Chondroblasts (active cartilage form. BENIGN Chondroma Benign chondroblastoma Chondro- myxoid Fibroma MALIGNANT Chondrosarcoma

9. 3. Fibroblasts (active collagen form.) BENIGN: Fibroma Solitary bone cyst Non ossifying Fibroma Fibrous dysplasia MALIGNANT Desmoid sarcoma Malignant fibrous histiocytoma 4. Osteoclasts BENIGN Osteoclastoma Aneurysmal bone cyst MALIGNANT Malignant Osteoclastoma

10. B .NON OSTEOGENIC BONE TUMOURS 1. from the fibrous tissue :- Periosteal Fibroma Periosteal fibrosarcoma Malignant fibrous osteocytoma 2. from the blood vessels :- Hemangioma Hemangioblastoma ABC Angiosarcoma

11. 3. from the elements of bone marrow :- Myeloma Reticulum cell sarcoma Hodgkin’s disease of bone Lymphosarcoma Ewing’s sarcoma 5. From nerves Neurilemmoma Neurofibroma 6. Tumors of synovium Synovial cell sarcoma 4. from adipose tissues Lipoma Liposarcoma 7. Striated muscle Rhabdomyosarcoma

12. C. TUMORS ARISING FROM INCLUDED TISSUES Adamantinoma: “ the dermal inclusion tumors ”; origin is unknown. Chordoma : Remnants of notochord. D. METASTATIC TUMORS OF THE BONE : from primary in- Thyroid Breast Lung Kidney Prostate  

13. Tumour like lesions of bone 1. REACTIVE BONE LESIONS STIMULATING TUMORS: Osteoid Osteoma Benign osteoblastoma Non osteogenic Fibroma 2. HAMARTOMAS OF BONE Osteochondroma Enchondroma Fibrous dysplasia 3. CYSTIC LESIONS OF BONE: Solitary bone cyst ABC

14. W.H.O. CLASSIFICATION 1.CARTILAGE TUMOURS 2.OSTEOGENIC TUMOURS Osteochondroma Chondroma Chondroblastoma Chondromyxoid Fibroma Chondrosarcoma Osteoid Osteoma. Osteoblastoma Osteosarcoma

15. 3.FIBROGENIC TUMOURS Desmoplastic Fibroma. Fibrosarcoma. 4.FIBROHISTEOCYTIC TUMOURS Benign fibrous histiocytoma. Malignant fibrous histiocytoma. 5.EWINGS SARCOMA/PNET Ewing’s sarcoma. 6.HAEMATOPOITIC TUMOURS Plasma cell myeloma Malignant lymphoma 7.GIANT CELL TUMOUR Giant cell tumour Malignant giant cell tumour 8.NOTOCHORDAL TUMOUR Chordoma

16. 9.VASCULAR TUMOUR Hemangioma Angiosarcoma 10.SMOOTH MUSCLE TUMOURS Leiomyoma Leiosarcoma 11.LIPOGENIC TUMOURS Lipoma Liposarcoma 12.NEURAL TUMOURS Neurilemmoma 13.MISCELLANEOUS TUMOURS Adamantinoma Metastatic malignancy 15.JOINT LESION: synovial chondromatosis 14.MISCALLANEOUS LESSION Aneurysmal bone cyst Simple cyst Fibrous dysplasia

17. STAGING OF BONE TUMOURS The aims of staging: To help in the overall evaluation of prognosis To facilitate the design of a therapeutic plan to optimize the benefit of different methods of treatment. To provide a standardized methodology to compare results from different institutions. HISTORY OF STAGING 1959 : American Joint Committee for cancer (AJC) suggested a staging system. 1977 : A clinic-pathological staging system for soft tissues sarcoma was published by Russell.  1980 : Enneking, Spanier and Goodman developed their staging system for both bone and soft tissue sarcomas.

18. ENNEKING SYSTEM OF STAGING The system is based on the combination of:- Grade of the tumor (Gₒ,G₁,G₂) Anatomic site of the tumor (T₀,T₁,T₂) Presence or absence of metastasis (M₀,M₁)

19. HISTOLOGICAL GRADE: BRODER’S grading of malignancy is used: GRADE I : well differentiated (<25% of anaplastic cells) GRADE II : moderately differentiated (25- 50% anaplastic cells) GRADE III : moderately differentiated (50 –75% anaplastic cells) GRADE IV : poorly differentiated (>75% anaplastic cells)

20. RADIOGRAPHIC ASSESSMENT LODWICK’S IA well marginated without deformation or expansion. LODWICK’S IB well defined lesion, but irregularly marginated . Septated appearance. Expansion, bulging or deformation . LODWICK’S IC ragged permeative interface with adjacent bone -Cortical destruction,codmans triangle etc

21. LODWICK’S II often have a generous reactive rim of cancellous bone admixed with defects of extra capsular &/or soft tissue extension LODWICK’s III poorly marginated interface with a diffuse permeative border. HIGH GRADE SARCOMA

22. IA IB IC II III

23. ANATOMICAL SITE The anatomic location of a tumor lesion directly influences the prognosis & also the choice of surgical procedures. NATURAL BARRIERS TO TUMOR GROWTH Cortical bone Growth plate Articular cartilage Fascia enclosing a compartment Joint capsule Tendon sheaths Nerve sheaths Ligaments

24. ENNEKING STAGES OF BENIGN MUSCULOSKELETAL TUMOURS:- 1 (LATENT) 2 (ACTIVE) 3 (AGGRESSIVE) GRADE G0 G0 G0 SITE T0 T0 T1-2 METASTASIS M0 M0 M0-1 CLINICAL COURSE Latent, static, self healing. Osteoid Osteoma Active, progressive, expands bone and fascia(ABC) Aggressive, invasive, and breaches bone or fascia.(GCT) Radiologic grading IA IB IC

25. ENNEKING STAGES OF MALIGNANT MUSCULOSKELTAL LESION: IA IB IIA IIB IIIA IIIB Grade G1 G1 G2 G2 G1-2 G1-2 Site T1 T2 T1 T2 T1 T2 Metastasis M0 M0 M0 M0 M1 M1 Radiographic grade II II III III III III

26. UPSTAGING AND DOWNSTAGING OF TUMOR LESIONS: Some benign lesions that are stage 2 active or even stage 3 aggressive during adolescence may undergo involution into stage1 lesion once the growth ceases.i.e. Downstaging eg. Exostosis or Osteochondroma.

27. Upstaging of tumour Radiation may transform GCT, chondroblastoma and some benign lesions into sarcomas. Repeated inadequate surgical interventions. By virtue of either regional or distant metastasis, stage II or stage I malignancy may turn into stage III. Malignant GCT Benign GCT

28. AJCC STAGING SYSTEM T Stages T0 : No evidence of the tumor T1: Tumor is 8 cm (3 inches) or less T2: Tumor is larger than 8 cm T3 : Tumor cells detected at another site(s) on the same bone M Stages M0: No distant metastasis M1: Distant metastasis M1a: Cancer has spread only to the lung M1b: Cancer has spread to other sites N Stages N0: No spread to nearby (regional) lymph nodes N1: Cancer detected in nearby lymph nodes GRADES   G1–G2: Low grade G3–G4: High grade

29. Stage IA T1, N0, M0, G1-G2: Tumor is confined to the bone, less than 8 cm in size, and is low grade. Stage IB T2, N0, M0, G1-G2 Tumor is confined to the bone, larger than 8 cm, and is low grade Stage IIA T1, N0, M0, G3-G4 Tumor is confined to the bone, less than 8 cm, and is high grade Stage IIB T2, N0, M0, G3-G4 Tumor is confined to the bone, larger than 8 cm, and is high grade.

30. Stage III T3, N0, M0, Any G Tumor is confined to the bone& tumor cells are found at other sites on the bone i.e. skip metastasis. Stage IVA Any T, N0, M1a, Any G: Tumor has spread to the lung. Stage IVB Any T, N1, Any M, Any G Tumor has spread to lymph nodes and distant sites, or Any T, Any N, M1b, Any G: Tumor has spread to distant sites other than the lung.

31. INVESTIGATIONS OF BONE TUMOUR PLAIN X-RAYS: What is the age? What type of bone involved and where is the lesion in the bone? What is the lesion doing to the bone and Are the margins of the lesion well or ill defined? What is the bone doing in response and is there any periosteal new bone formation? Is the cortex eroded or destroyed? Does the tumour extent to soft tissue? Is there any calcification of lesion matrix? Is the lesion solitary or multiple?

32. What is the age ?

33. 2.What type of bone involved and where is the lesion? In the transverse plane : Central: Enchondroma. Eccentric : GCT, Osteosarcoma, Chondromyxoid fibroid. Cortical : Osteoid Osteoma, Non Ossifying Fibroma Parosteal: Parosteal Osteosarcoma, Osteochondroma.

34. In the longitudinal plane EPIPHYSEAL METAPHYSEAL DIAPHYSEAL Chondroblastoma Clear cell Chondrosarcoma GCT ABC Geode (subchondral cyst) Infection Eosinophilic granuloma Non ossifying Fibroma -Chondromyxoid Fibroma -GCT, ABC, Solitary bone cyst/Brodies abscess -Osteochondroma. -osteogenic sarcoma, Chondrosarcoma. Non ossifying Fibroma Ewing sarcoma Osteoid Osteoma. Osteoblastoma Metastasis. Reticulum cell sarcoma. Leukemia Lymphoma. Adamantinoma.

35. BONE TUMOURS&COMMONEST SITE BONE TUMOURS COMMONEST SITE ENCHONDROMA Metaphyses of small bone of hands & feet GCT,ABC,Osteosarcoma Lower end femur > upper end tibia OSTEOCHONDROMA Lower end femur>prox. Tibia>prox. humerus CHONDROBLASTOMA,SBC Proximal humerus > prox. femur EWINGS SARCOMA Femur > Fibula > tibia OSTEOID OSTEOMA Femur > tibia OSTEOBLASTOMA Posterior spine Adamantinoma Mandible > tibia Fibrous dysplasia Ribs > Upper Femur > Tibia > Lower Femur. Chordoma Sacrum > anterior vertebral body.

36. 3.What is the lesion doing? margins are well or ill defined? Type 1: Geographic pattern: 1a. well defined lucency with sclerotic margin. 1b. well defined lytic focus without sclerotic rim, Enchondral scalloping may seen. 1c. lytic lesion with ill defined margin.

37. INCREASES AGGRESSIVENESS 1. GEOGRAPHIC PATTERN

38. Type 2 : Moth –eaten appearance: Multiple scattered holes that vary in size and seems to arise separately. Areas of destruction with ragged boarders. Implies more rapid growth probably malignancy. E.g. myeloma metastasis, infection, Osteosarcoma etc.

39. Type 3 : Permeative pattern : Ill defined lesion with “multiple worm holes” spread through marrow space. Implies aggressive malignancy.

40. 4.What is the bone doing in response? 3 type of bone response: Lysis or lucency - bone destruction. Sclerosis -bone reaction. Periosteal reaction - remodeling of bone. Rate of growth determines type of bone response to the lesion. Slow progression sclerosis predominates. Rapid progression destruction predominates.

41. PERIOSTEAL REACTION Two types of periosteal reactions: Benign: solid type. Aggressive: Lamellated or onion peel, Sunburst and Codman’s triangle types.

42. Benign: solid type. Slow-growing tumors provoke focal cortical thickening A continuous layer of new bone that attaches to outer cortical surface OSTEOID OSTEOMA

43. AGGRESSIVE PERIOSTEAL REACTION Unilamellated periosteal reaction. Lamellated or onion peel. Sunburst or hair on end or spiculated. Codman's Triangle periosteal reaction.

44. Unilamellated periosteal reaction Single layer of reactive periosteum. Smooth and continuous. Hypertrophic osteoarthropathy

45. Lamellated or onion peel lesion grows unevenly in fits and starts. Alternating layers of opaque and lucent densities Ewing's sarcoma, infection.

46. Sunburst or hair on end lesion grows rapidly but steadily. Sharpey's fibers become stretched out & ossify. Osteosarcoma

47. Codman's Triangle Too fast growth for periosteum to respond. only the edges of raised periosteum will ossify forming a small angle with the surface of bone.

48. Zone of Transition Most reliable indicator for benign versus malignant osteolytic lesions . “ Narrow” , if it is so well defined that it can be drawn with a fine-point pen. Wide : An aggressive process should be considered, Narrow zone Wide zone

49. two tumor like lesions which may mimic a malignancy and have to be included in the differential diagnosis.

50. 5.Is there any calcification of lesion matrix? Chondroid matrix: Calcifications in chondroid tumors has many descriptions: rings-and-arcs, popcorn, focal stippled or flocculent. stippled flocculent Rings& arc

51. Osteoid matrix mineralization SOLID CLOUD LIKE IVORY LIKE OPACITY

52. CT SCAN/MRI extends the range of x-ray diagnosis. Its greatest value is in the assessment of tumour spread: a) within the bone b)into the nearby joint c) into the soft tissues. Blood vessels and the relationship of the tumour to the perivascular space are well defined.

53. PRINCIPLE OF BONE TUMOUR BIOPSY 1.After evaluation & imaging complete

54. TYPES OF BIOPSY Fine needle aspiration biopsy (FNAB) Core needle biopsy (CNB) Surgical (open) biopsy Incisional biopsy removes only part of the suspicious area, enough to make a diagnosis . Excisional biopsy removes the entire tumor or abnormal area,

55. GENERAL MANAGEMENT OF BONE TUMOUR Multidisciplinary team approach Benign asymptomatic tumors If certain observe If in doubt biopsy Benign symptomatic or enlarging tumors Biopsy Excision/ curettage Suspected malignant tumors If primary admit for work-up Staging Choices; amputation, limb sparing surgery, adjuvant therapy

56. TUMOUR EXCISION Enneking classification of local procedures I-A - Wide excision I-B - Wide excision with larger clearance II-A - Wide excision/amputation II-B - Radical resection or disarticulation III - Palliative treatment Low grade intra compartmental lesions – wide resection and management of metastases

57. LIMB SALVAGE A set of surgical procedures designed to accomplish removal of a malignant tumor and reconstruction of the limb with an acceptable oncologic, functional, and cosmetic result.

58. INDICATION Every patient with tumor of the extremity should be considered for limb salvage if the tumor can be removed with an adequate margin and the resulting limb is worth saving. certain that there are no skip lesions and if a functional limb can be preserved. No justification for limiting the limb salvage process based only on the prognosis.

59. STEPS FOR LIMB SALVAGE wide excision of tumour with preservation of neurovascular structures. The resulting gap is then dealt with several ways: Short diaphyseal segments - bone grafts. Longer gaps may require custom made or modular made implants. Osteo-articular segments can be replaced by large allograft, endoprostheses or allograft-prosthetic composites. In growing children extendible implants used in order to avoid repeated surgery.

60. BARRIERS TO LIMB SALVAGE: Poorly placed biopsy incisional complications. Major Neurovascular involvement which unable to repair. Grossly displaced pathologic fracture. Fungating and infected tumors. Recurrence of malignant tumors Inability to afford chemotherapy

61. Enneking classification of amputations:

62. GOALS OF TREATMENT WITH CHEMOTHERAY: Cure Control – Stop growing & spreading of the tumour. Palliation – In advance stage, aim is to relieve symptoms.

63. Before an operation (neo-adjuvant therapy ) . AIM DISADVANTAGE To shrink the tumour mass ( tumour necrosis) To make surgery less destructive, more effective & less post operative metastasis. To kill micro metastatic. To prevent development of resistant clones. Patients resistant to chemotherapy get delayed for surgery. Complication of chemo may delay the surgery. Post op. Infection & wound complication is common. Neo adjuvant chemo has to be stopped 3-4 week prior to surgery.

64. After an operation (adjuvant therapy). To destroy the micro metastasis after total resection of tumour mass  recurrence decreases. This reduces chances of resistance developing. If total removal of tumour mass failed by surgery, Started 3 wks after surgery so that wound is healed.

65. Chemo irradiation : Palliative chemotherapy : Chemotherapy given same time with radiotherapy. This to potentiate radiation therapy. Given without curative intent relieves symptoms in advanced cases. Decrease tumour load. And increase life expectancy.

66. Chemotherapy used in sarcoma Sarcoma Drugs used Neoadjuvant/adjuvant palliative Ewing's sarcoma Vincristine, ifosfamide/doxorubicin Definite survival benefit Useful with salvage Osteosarcoma cisplatin,doxorubicin,methotrexate,ifosfamide,etoposide. - do- Some benefit with salvage,rarely curative Leiomyosarcoma/ sunovial sarcoma Doxorubicin, ifosfamide, No benefit on survival, improve local control 25% modest benefit

67. Criteria for describing response to chemotherapy Huvos et al Grading Complete response: Complete remission i.e. disappearance of all detectable malignant disease. Partial response: Malignant mass decreased by > 50%. Stable disease : No change in measurable tumour mass. Progressive disease : Increase by at least 25 % of the mass or appearance of new lesions. Gr - I- Necrosis in 0-50 % of field. Gr -II- Necrosis in 50-90 % of field. Gr -III- Necrosis in over 90 % of field. Gr- IV- Necrosis in all fields.

68. Chemo sensitive Chemo resistant 1. Osteosarcoma 1.Chondrosarcoma 2.Ewing’s sarcoma 2.Malignant Fibrous histiocytoma 3. Multiple myeloma & plasmacytoma 3.Malignant GCT 4. Lymphoma 4.Fibro sarcoma 5. Angiosarcoma 5.Adamantinoma 6.Chordoma BONE TUMOUR & CHEMOSENSITIVITY

69. RADIATION THERAPY: Direct Damage  produces double-strand breaks in DNA to kill a cell. Indirect Damage  generates intracellular free radicals  damages cell membranes, proteins and organelles.

70. Common Types of Ionizing Radiation X-rays and Gamma rays are the most commonly used forms of radiation for cancer treatment. X-rays are generated by linear accelerators. Gamma rays are generated from decay of atomic nuclei in radioisotopes such as Cobalt and Radium .

71. Radiosensitive bone tumours small blue cell tumour like multiple myeloma, lymphoma and Ewing’s sarcoma. Carcinomas metastatic to bone with the exception of renal cell carcinoma are radiosensitive. Radiation therapy as such has got no role GCT, in fact it may lead to malignant transformation.

72. THANK YOU ALL