Bone tumors

Bone tumors

Benign
Primary

Malignant
Secondary = metastatic

Metastasis is the MC malignancy of bone. Breast cancer is the MC primary site. Others include: Prostate ,Lung ,Kidney and thyroid Nature of metastasis Osteolytic: Destructive Most mets (breast**, lung, kidney etc) Osteoblastic: Reactive new bone formation Carcinoma prostate**, breast Ca.
3

Osteolytic metastasis

Spine, prostate carcinoma metastatic to vertebrae

Osteoblastic Metastasis

Radiodense lesion

Primary Bone tumors: Clinical presentation

Benign tumors: Usually asymptomatic Present as painless mass *Osteoid osteomas are painful, *Enchondromas may cause a stress #. Usually detected incidentally. Malignant tumors: Present with : Pain Swelling or a Pathological fracture

Important parameters for diagnosis of bone tumors

1. Age of patient 2. Bone involved 3. Specific area within the bone (epiphysis, metaphysis, diaphysis) 4. Radiographic appearance 5. Gross and microscopic features

Remember these general age ranges: Metastatic neuroblastoma*: infants & toddlers Ewing's sarcoma: older children & adolescents (5-20) Osteosarcoma: adolescents and young adults(1020). Giant cell tumors: young adults & middle age (20-40) Chondrosarcoma: middle age (40-60) Multiple myeloma : middle to old age (>40) Metastatic cancer: middle and old age
10

Age and bone tumors

Location in bone

11

Location in bone
Diaphysis: Ewing's sarcoma**, chondrosarcoma , enchondroma. Epiphysis: Giant cell tumor** (osteoclastoma) Metaphysis: Osteogenic sarcoma**

12

Risk factors for bone sarcoma

Include some familial syndromes (e.g Li Fraumeni) radiation therapy. However, most cases are unrelated to any of these. In the previously irradiated patient, the commonest primary bone cancer: osteosarcoma **

13

Treatment
Benign tumors may be treated by curettage and packing with bone chips from elsewhere. Malignant tumors require resection, radiation, and/or chemotherapy. Osteosarcoma and Ewing's sarcoma often respond well to chemotherapy.
14

Classification of primary bone tumors

1. Primary BT classified in to ten groups Osteogenic (bone forming) Benign: osteoma, osteoid osteoma* and osteoblastoma malignant: Osteosarcoma (osteogenic sarcoma)* Chondrogenic (cartilage forming) Benign: osteochondroma*, chondroma*, chondroblastoma malignant: chondrosarcoma* Unknown origin: Giant cell tumor* (benign / malignant) Ewings sarcoma* (malignant)

2.

3.

15

4. Fibrogenic (from fibroblasts) Benign: Fibrous cortical defect / nonossifying fibroma *, Fibrous dysplasia* Malignant: fibrosarcoma 5. Hematopoietic (from hematopoietc elements) multiple myeloma 6. Histiocytic origin (from histiocytes) 7. Notochordal 8. Vascular 9. Lipogenic 10.Neurogenic
16

BONE-FORMING TUMORS
Benign

17

Osteoma
A benign bone forming tumor. Occurs in middle aged adults (40-50yrs) Sites: usually occurs in the skull (sinuses most common) ,facial bones and jaw. Usually harmless, they may impinge on the brain, obstruct sinus drainage, or look ugly. Histologically resemble normal bone If multiple, suspect Gardener's syndrome
18

Osteoma

19

Osteoid osteoma***
A benign painful* tumor of osteoblasts. Occurs in individuals 5-25 yrs old. Sites: Metaphysis/diaphysis of femur and tibia cortex of bone (size: <2cm*) Clinical: well-localized pain (Nocturnal). pain is relieved by aspirin Micro: Central nidus of osteoid surronded by dense sclerotic rim of bone X ray reveals: a small radiolucent focus (nidus) surrounded by densely sclerotic bone. 20

Radiolucent focus (nidus) surrounded by densely sclerotic bone

Osteoid osteoma
21

Radiolucent focus (nidus) surrounded by densely sclerotic bone

22

*Osteoblastoma ("giant osteoid osteoma"): Similar to osteoid osteoma But is larger (>2cm) and Arises in the vertebral bodies Pain not worse at night and not relived by aspirin.
23

Malignant bone forming tumor

24

25

Osteosarcoma (= osteogenic sarcoma) Cancer of the osteoblasts The malignant tumor cells make osteoid. The 2nd MC primary malignant tumor of bone (1st is multiple myeloma). Age: (bimodal) 10-20 years old Arises de novo. >40 years old Usually secondary to risk factors (Pagets disease of bone etc.)
26

 Location: Most in the metaphyseal region of long bones. Lower end of femur (most common) Upper end of tibia Upper end of humerus Less commonly in flat bones jaw.
27

28

Osteosarcoma: TYPES: Primary Osteosarcoma Arise in absence of associated bone disease. In patients < 20 years From metaphyseal region of long bones. Genetic association: 2/3rd show inactivation of Rb gene** Common in Li-Fraumeni syndrome** (p53 gene inactivation) Secondary Osteosarcoma Occurs in older people Both in flat and long bones In a background of preexisting bone 29 disease

Risk factors for osteosarcoma

Pagets disease of bone Osteosarcoma of the pelvic bones Irradiation (radium watch dial workers) Bone infarct Osteomyelitis Clinical features: Local pain, tenderness , swelling and pathological fracture

30

Destroyed cortex Tumor mass Growth plate

31

Osteosarcoma

32

Codman triangle

33

Soft tissue mass

Sunburst appearance

34

Gross: Gray white mass with areas of hemorrhage and necrosis Destroys cortex and invades adjacent soft tissue Elevates the Periosteum , producing Codmans triangle on X ray. Sunburst appearance : due to calcified osteoid extending into the adjacent soft tissue.
35

Osteoid

36

Spindle shaped cells

Osteoid

37

Microscopy: Tumor cells produce osteoid. Tumor cells may be spindle, oval or round. Spread: Metastasize through blood stream lung the most common site. Treatment: Surgery (limb sparing) with Preoperative and postoperative Chemotherapy. Prognosis five-year survival 50-60%.
38

Cartilaginous tumors of bone

Benign

39

40

Exostosis ("osteochondroma): Most common** benign bone tumor. Tumor: Mushroom shaped Composed of outgrowth of bone (exostoses) capped by benign proliferating cartilage. Age: 10-30 Location: Usually located in the metaphysis of long bone. Can be: solitary or multiple If Multiple then k/a osteochondromatosis: Hereditary multiple exostoses Increased risk of transformation into chondrosarcoma (if multiple). 41

Osteochondroma

42

Chondromas: benign tumor composed of hyaline cartilage If located within shaft of bone then k/a enchondroma. Site: small bones of hand and feet (proximal phalanges). Can be Solitary Multiple (called enchondromatosis) Chondrosarcoma risk with multiple tumors. Olliers disease : multiple enchondromas. Maffucci's syndrome : multiple enchondromas 43 plus hemangiomas of soft tissues.

Chondroma

44

45

Malignant cartilaginous tumor

46

47

Chondrosarcoma
A malignant tumor of chondroblasts. MC primary malignant cartilaginous tumors. Age: 40-60 years Location: Central skeleton: ribs, shoulder and Pelvic bones and Upper end of femur and humerus Can arise de novo or secondary to osteochondromatosis or enchondromatosis.
48

Chondrosarcoma
49

50

 Gross: grayish blue, glistening and semitranslucent. Micro: composed of atypical chondrocytes and chondroblasts often with multiple nuclei in a lacuna. Biologic behavior and Prognosis depends on the grade of tumor. Metastasis Hematogenously to lungs
51

Tumors of uncertain origin

52

53

Ewing's Sarcoma
An extremely malignant tumor composed of small round blue cells. Arises within the marrow cavity. Histogenesis uncertain: Current evidence: Probably of neuroectodermal origin. Reasons: Specific translocation : t(11;22) Same translocation also present in similar tumor of soft tissue known as PNET (primitive neuro-ectodermal tumor).
54

Age: Most occur in teenagers 5-20 yrs Genetics: classic translocation t(11;22) which produces the EWS-FLI1 fusion gene. Gross: Arises in medullary cavity in the diaphysis of long bones. Most common sites are the femur, pelvis and the tibia. Penetrates the cortex to produce : White tan mass with necrosis and hemorrhage. 55

Ewings Sarcoma Tan to red to brown tumor mass

56

"small round blue cells"

57

Glycogen, seen as reddish granular material in cytoplasm by PAS stain.

58

Onion skin appearance of reactive new bone

59

Microscopy: Tumor composed of Sheets of "small round blue cells" with little cytoplasm. Cells are loaded with glycogen. Glycogen can be seen by PAS stain. Homer Wright rosettes (tumor cells arranged in circle about a central fibrillary space)

60

X ray: Concentric onion skin layering of new periosteal bone. Clinical features: It presents as an infection with fever, Painful enlarging mass often tender Heat over the tumor. Therefore simulates osteomyelitis. Prognosis: Radiation + Chemotherapy+ surgery 75% 5year survival.
61

Differential diagnosis: Other small round blue cell tumors metastatic neuroblastoma metastatic malignant lymphoma acute lymphoblastic leukemia Rhabdomysarcoma IHC will help differentiate ES from these small round blue cell tumors (SRBCT).
62

Giant cell tumor

63

64

65

Giant cell tumor ("osteoclastoma")

A locally aggressive potentially malignant tumor composed of : multinucleated giant cells (nonneoplastic) admixed with mononuclear cells (neoplastic). More common in females than males. Seen in patients 20-40 years of age Arises in the epiphysis and extends into metaphysis Favored locations: Classical : epiphysis of long bone. Sites most commonly affected: Lower end of femur> Upper end of 66 tibia >Lower end of radius.

Giant cell tumor

67

Giant cell tumor

68

"Soap bubble" lesion.

69

Soap bubble appearance

70

Multinucleated giant cells

Round to oval Mononuclear cells

71

72

 Gross: Cut section of the tumor: Solid red brown mass with hemorrhage and cystic degeneration Microscopy: Two components Osteoclast like giant cells: Large with 20-30 nuclei. Are Not neoplastic. Formed due to fusion of monocytes. Mononuclear stromal cells. Are the neoplastic cells and determine the behavior. X-ray:A lytic expansile lesion in the epiphysis. May have a soap bubble appearance. Clinical behavior: Unpredictable 73

Tumor
Ewings sarcoma

Age
5-20 yrs

Location
Diaphysis Femur , pelvis, tibia Metaphysis Femur, tibia, humerus Epiphysis Femur, tibia radius Diaphysis Pelvis, ribs, shoulder bones.
74

Osteosarcoma

10-20 yrs

Giant cell tumor Chondrosarcoma

20-40 yrs

40-60

Fibrous and fibro-osseous tumor

75

Fibrous cortical defects and Non-ossifying fibromas

Essentially the same disease except for a difference in size. Fibrous cortical defects : 1-4 cm Non-ossifying fibromas : 5-10 cm. Both are benign tumor like lesions

76

Fibrous cortical defects and Non-ossifying fibromas

77

 Clinical: Extremely common: (1/3rd of normal children) Asymptomatic / fracture Occur in the long leg bones of children (cortical aspect of metaphysis). Femur>tibia>fibula Made of fibroblasts,and lipid-laden macrophages X ray: irregular, sharply demarcated radiolucent defect in the metaphyseal cortex. Treatment: often resolves spontaneously 78

Fibrous cortical defects and Non-ossifying fibromas

Fibrous dysplasia
Benign non-neoplastic process of bones. Characterized by 1. replacement of marrow by fibrous tissue. 2. presence of poorly formed woven bone arranged in Chinese letter pattern. Primarily targets ribs, femur, or cranial bones of children and young adults.

79

Fibrous tissue

Wavy spicules of woven bone ("chinese characters");80

Fibrous dysplasia

81

 Monostotic fibrous dysplasia Involvement of single bone Usually asymptomatic Polystotic fibrous dysplasia Involvement of Multiple bones. Often symptomatic deformities and fractures of craniofacial bones Shepherd Crook deformity of proximal femur. McCune-Albright syndrome Polystotic disease with endocrine 82 abnormalities

Fibrous dysplasia:Types

Fibrous dysplasia McCune-Albright syndrome : features include Polystotic disease precocious sexual development irregular skin pigmentation (caf-au-lait spots) (akin to coast of Maine) Fibrous dysplasia: Clinical course Secondary sarcoma may develop after irradiation (rarely).
83

Shepherd Crook deformity Caf-au-lait spots

84

Additional Images
For Self Study

85

86

87

88

89

90

91

92