Pathology of bone tumors

Pathology of bone tumors

1. Bone tumors Dr. Subhash Kumar Das Resident Department of Orthopaedics SBH

2. Introduction Bone tumors are diverse in their gross and morphologic features Innocuous to the rapidly fatal. Critical to diagnose these tumors correctly, stage them accurately and treat them appropriately Affected patients should survive and maintain optimal function of the affected body parts. Most bone tumors are classified according to the normal cell or tissue type they arise from.

3. Most frequent benign tumors - Osteochondroma and fibrous cortical defect. Most common malignant tumor – Osteosarcoma followed by chondrosarcoma and Ewing sarcoma (excluding malignant neoplasms of marrow origin such as myeloma, lymphoma and leukemia)

4. Precise incidence of specific bone tumors is not known Relatively infrequent Great diversity Occur at all ages / any part of body Certain tumors target particular age group and sites Diagnosis requires integration of Clinical history Radiographic appearance Histopathology

5. Age and location Most develop during the first several decades of life and have a propensity to originate in the long bones of the extremities. Location of a tumor provides important diagnostic information.

6. Bone Tumours Sites of Occurrence

7. Clinical presentation of Bone tumors Pain Slow-growing mass Sudden pathologic fracture Radiologic imaging studies - Important role in diagnosing these lesions. In addition to Provides exact location Tumor extent Aggressiveness of the tumor

8. Classification of Bone tumors

9. Bone Tumours Sites of Occurrence Giant cell tumour Cho n d r obla s t oma Ewing’s Osteosarcoma

10. BONE-FORMING TUMORS Production of bone by the neoplastic cells. The tumor bone is usually deposited as woven trabeculae and is variably mineralized. Benign – Osteoma, Osteoid Osteoma and Osteoblastoma Malignant - Osteosarcoma

11. Oste o ma Benign, Often craniofacial in location Hamartomatous / reactive & not true tumor. Histologically dense lamellar bone (closely resemble normal bone). Gardner Syndrome: Autosomal Dominant condition associated with multiple, Osteoma, Osteochondroma, GIT po l yps, skin tumors. C o l on Cancer may occur

12. Osteoid Osteoma Osteoid osteoma are less than 2 cm in greatest dimension and usually occur in patients in their teens and twenties. 90% of patients are teens or in their 20’s. Osteoid osteomas can arise in any bone but 50% of cases involve the femur or tibia, affecting mainly the cortical bone (diaphysis or metaphysis) Osteoid osteomas are characteristically painful at night. The pain is caused by excess prostaglandin E2 (due to proliferating osteoblasts) and is relieved by aspirin.

13. Osteoid Osteoma X-Ray: This is the central nidus of an osteoid osteoma. Radiographically, there is a small round central lucent area in the femoral cortex surrounded by sclerotic bone. Micro: the central nidus of an osteoid osteoma is composed of irregular reactive new woven bone dispersed in a highly vascular stroma X-Ray & Microscopy

14. Central nidus – Actual tumor

15. Osteoblastoma Osteoblastoma is larger than 2 cm and involves the spine more frequently The pain is dull, achy, and unresponsive to salicylates Tumor usually does not induce a marked bony reaction.

16. Osteosarco m a Osteosarcoma is a malignant mesenchymal tumor in which the cancerous cells produce bone matrix. Most common primary malignant tumor of bone Occurs in all age groups but has a bimodal age distribution 1 st peak - 75% occur in persons younger than 20 years of age 2 nd peak occurs in the elderly – Predisposing conditions - Pagets disease, bone infarcts and prior irradiation Men are more commonly affected than women

17. Major sites of origin of osteosarcoma Usually arise in the metaphyseal region of the long bones of the extremities, and almost 50% occur about the knee

18. Pathogenesis 70% of osteosarcomas have acquired genetic abnormalities such as ploidy changes and chromosomal aberrations RB, the retinoblastoma gene, a critical cell cycle regulator p53, a gene whose product regulates DNA repair and certain aspects of cellular metabolism. Li-Fraumeni syndrome Abnormalities in INK4a, which encodes p16 (a cell cycle regulator) and p14 (which aids and abets p53 function), also are seen in osteosarcoma

19. Morp h ology Site of origin (intramedullary, intracortical, or surface) Degree of differentiation Multicentricity (synchronous, metachronous) Primary (underlying bone is unremarkable) or secondary to preexisting disorders such as benign tumors, Paget disease, bone infarcts, previous irradiation Histologic features (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, and giant cell).

20. Classification of Osteosarcomas Intramedullary osteosarcomas Conventional osteosarcoma Telangiectatic osteosarcoma Small cell osteosarcoma Osteosarcoma in Paget disease Post-irradiation osteosarcoma Surface osteosarcomas Parosteal osteosarcoma Periosteal osteosarcoma

21. Osteos a rc o ma Typically present as painful and progressively enlarging masses. Sometimes a sudden fracture of the bone is the first symptom. Classic X ray findings: Codman’s triangle (periosteal elevation) Sunburst pattern Bone destruction Clinical & X-ray findings Codman Triangle Sunray appe a ra n ce Sunray appe a ra n ce

22. Gross Big bulky tumors that are gritty, gray-white, and often contain areas of hemorrhage and cystic degeneration. Destroy the surrounding cortices and produce soft- tissue masses. They spread extensively in the medullary canal, infiltrating and replacing the marrow surrounding the preexisting bone trabeculae.

23. Osteosarcoma of the upper end of the tibia. The tan-white tumor fills most of the medullary cavity of the metaphysis and proximal diaphysis. It has infiltrated through the cortex, lifted the periosteum, and formed soft-tissue masses on both sides of the bone.

24. Microscopy Tumor cells vary in size and shape and frequently have large hyperchromatic nuclei. Bizarre tumor giant cells are common along with mitoses. The formation of bone by the tumor cells is characteristic. Neoplastic bone usually has a coarse, lace-like architecture When malignant cartilage is abundant, the tumor is called chondroblastic osteosarcoma. Vascular invasion and necrotic areas are present.

25. Coarse, lacelike pattern of neoplastic bone produced by osteiod deposition . Note the mitotic figures

26. Metastasis, Treatment and Prognosis Highly aggressive neoplasms Hematogenous mode of spread 90% have metastases to the lungs, bones, brain and elsewhere. Treated with a multimodality approach that includes chemotherapy 5-year survival rate – 20%

27. CARTILAGE-FORMING TUMORS Characterized by the formation of hyaline or myxoid cartilage Benign – Osteochondroma , Chondroma , Chondroblastoma, Chondromyxoid fibroma Malignant - Chondrosarcoma

28. Oste o cho n dro m a Also known as an exostosis Benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk. Most common benign bone tumor; about 85% are solitary Multiple hereditary exostosis syndrome , which is an autosomal dominant hereditary disease. Hereditary exostoses are caused by germline loss-of-function mutations in either the EXT1 or EXT2 genes

29. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood, but multiple osteochondromas become apparent during childhood. Men are affected three times more often than women Develop only in bones of endochondral origin and arise from the metaphysis near the growth plate of long tubular bones, especially about the knee Incidental finding or presents as slow growing masses

30. Oste o cho n dr o ma Hereditary (multiple) or sporadic (single) Benign bone growths capped with cartilage affects children/ adolescent males; may be asymptomatic or cause pain, producing deformity hereditary type can undergo malignant transformation (Chondrosarcoma ) E x o s tosis

31. Morph o logy Sessile or mushroom shaped Range in size from 1 to 20 cm. The cap is composed of benign hyaline cartilage varying in thickness and is covered peripherally by perichondrium. The cartilage has the appearance of disorganized growth plate and undergoes enchondral ossification, with the newly made bone forming the inner portion of the head and stalk.

32. Encho n dro m a Benign Single or multiple sites Often involves small bones of hands and feet. Well demarcated, mature cartilage. Hereditary – multiple enchondromatosis. Usually over one side of the body. ( Ollier’s disease ). Maffucci's syndrome - multiple bone chondromas and hemangiomas of soft tissue Increased risk for chondrosarcoma

33. Enchondroma of the phalanx with a pathologic fracture. The radiolucent nodules of hyaline cartilage scallop the endosteal surface.

34. Ch o nd r o s a r c oma Production of neoplastic cartilage Subclassified according to site as central ( intramedullary ) and peripheral ( juxtacortical and surface ). Histologically, they include conventional (hyaline and/or myxoid) , clear cell , dedifferentiated , and mesenchymal variants. Age > 40 years Men 15% of conventional chondrosarcomas arise from a preexisting enchondroma or osteochondroma.

35. Morphology - Gross Large bulky tumors are made up of nodules of gray-white, somewhat translucent glistening tissue

36. Microscopy Tumors vary in degree of cellularity, cytologic atypia, and mitotic activity. Presence of anaplastic chondrocytes – Grade 1, 2 and 3

37. Metastasis and Prognosis Direct correlation between the grade and the biologic behavior of the tumor 5-year survival rates were 90%, 81%, and 43% for grades 1 through 3, respectively Spread preferentially to the lungs and skeleton Treatment of conventional chondrosarcoma is wide surgical excision

38. Miscellaneous tumors of bone GIANT-CELL TUMOR EWING SARCOMA/PRIMITIVE N EUROECTODERMAL TUMOR ANEURYSMAL BONE CYST

39. Giant cell Tumour of Bone Known as osteoclastoma Common tumour – 20% of all benign bone tumors Age - 20 -40 years Slight female preponderence Histogenesis – not known

40. Epiphysis of long bones affected Radiolucent lesion involving end of long bones Almost always solitary Grossly dark brown - due to abundant vascularity Areas of necrosis and cystic change present

41. Giant cell tumor

42. Magnetic resonance image of a giant-cell tumor that replaces most of the femoral condyle and extends to the subchondral bone plate.

43. Morp h ology HPE - 2 major population of cells Multinucleated giant cells - reactive component Neoplastic component – round to spindle shaped mononuclear cells Large number of osteoclast likes giant cells with mononuclear cells.

44. Giant cell tumor

45. Clinical features Local pain – mistaken for arthritis Wide variety of bone disorder may contain multinucleated giant cells Brown tumor Aneurysmal bone cyst Unpredictable behaviour Recurrence common after curettage

46. Ewing’s Sarcoma Most common form of bone tumour in children / adolescent Peak incidence 2 nd decade Highly aggressive tumour Must be differentiated from other small blue cell tumours. Translocation involving the EWS gene on chromosome 22 and a gene encoding an ETS family transcription factor; the most commonly involved ETS gene is FLI1

47. Present as painful enlarging masses Tender, warm, and swollen . Plain radiograms show a destructive lytic tumor that has permeative margins and extension into the surrounding soft tissues. The characteristic periosteal reaction produces layers of reactive bone deposited in an onion-skin fashion.

48. Morp h ology Arise in medullary cavity Soft, expansive mass Site – femur, tibia, pelvis – diaphysis commonly affected Extends beyond medullary cavity

49. HPE Sheets of small round cells Small, fairly uniform nuclei Scant cytoplasm Cytoplasm contain glycogen (PAS stain) Produce reactive bone / not osteoid Presence of Homer-Wright rosettes (tumor cells arranged in a circle about a central fibrillary space) is indicative of neural differentiation

50. Ewings tumour

51. Immunohistochemical study needed to distinguish from Neuroblastoma Rhabdomyosarcoma Lymphoma EWS express neural marker

52. Clinical features Pain and local inflammation Fever is common Biopsy needed for diagnosis Recent advances in treatment improved outlook of patients 5 year survival rate is 75%

53. ANEURYSMAL BONE CYST Benign tumor of bone characterized by multiloculated blood-filled cystic spaces that may present as a rapidly growing expansile tumor First 2 decades of life and has no sex predilection Metaphyses of long bones and the posterior elements of vertebral bodies Most common signs and symptoms are pain and swelling

54. Coronal computed axial tomography scan showing eccentric aneurysmal bone cyst of tibia

55. Aneurysmal bone cyst with blood-filled cystic space surrounded by wall containing proliferating fibroblasts, reactive woven bone, and osteoclast-type giant cells.

56. Metastatic tumors to bone Pathways of spread Direct extension Lymphatic or hematogenous dissemination intraspinal seeding (via the Batson plexus of veins) Adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. In children, metastases to bone originate from neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma.

57. References Robbins and Cotran Pathological basis of disease 8 th edition Campbell Operative Orthopaedics 13 th edition

58. Thank You…