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.

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Bone tumors

2. 2
Bone tumors
Benign Malignant
Primary Secondary
= metastatic

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• 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.

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Osteolytic metastasis

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Spine, prostate carcinoma metastatic to vertebrae

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Radiodense lesion
Osteoblastic Metastasis

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8. 8
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

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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

10. 10
Age and bone tumors
• Remember these general age ranges:
– Metastatic neuroblastoma*: infants &
toddlers
– Ewing's sarcoma: older children &
adolescents (5-20)
– Osteosarcoma: adolescents and young
adults(10—20).
– 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

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Location in bone

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

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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 **

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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.

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Classification of primary bone tumors
• Primary BT classified in to ten groups
1. Osteogenic (bone forming)
– Benign: osteoma, osteoid osteoma* and
osteoblastoma
– malignant: Osteosarcoma (osteogenic
sarcoma)*
2. Chondrogenic (cartilage forming)
– Benign: osteochondroma*, chondroma*,
chondroblastoma
– malignant: chondrosarcoma*
3. Unknown origin:
– Giant cell tumor* (benign / malignant)
– Ewing’s sarcoma* (malignant)

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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

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BONE-FORMING TUMORS
Benign

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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

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Osteoma

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• 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.
Osteoid osteoma***

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Osteoid osteoma
Radiolucent focus
(nidus)
surrounded by
densely sclerotic bone

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Radiolucent focus (nidus)
surrounded by densely sclerotic bone

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• *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.

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Malignant bone forming tumor

25. 25

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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 (Paget’s
disease of bone etc.)

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• 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.

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• 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
disease

30. 30
Risk factors for osteosarcoma
• Paget’s 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

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Destroyed cortex
Tumor massGrowth plate

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Osteosarcoma

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Codman triangle

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Soft tissue mass
Sunburst
appearance

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

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Osteoid

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Spindle shaped cells Osteoid

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• 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%.

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Benign
Cartilaginous tumors of bone

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• 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).

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Osteochondroma

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• 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.
• Ollier’s disease : multiple enchondromas.
• Maffucci's syndrome : multiple enchondromas
plus hemangiomas of soft tissues.

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Chondroma

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Malignant cartilaginous tumor

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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.

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Chondrosarcoma

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• Gross:
– grayish blue, glistening and semi-
translucent.
• 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

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Tumors of uncertain origin

53. 53

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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).

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• 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.

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Ewings Sarcoma
Tan to red to brown tumor mass

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"small round blue cells"

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

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Onion skin appearance
of reactive new bone

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• 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)

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• 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% 5-
year survival.

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• 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).

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Giant cell tumor

64. 64

65. 65

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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
tibia >Lower end of radius.

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Giant cell tumor

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Giant cell tumor

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"Soap bubble"
lesion.

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Soap bubble
appearance

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Round to oval
Mononuclear cells
Multinucleated giant
cells

72. 72

73. 73
• 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

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Epiphysis
Femur, tibia
radius
20-40 yrsGiant cell tumor
Diaphysis
Pelvis, ribs,
shoulder bones.
40-60Chondrosarcoma
Diaphysis
Femur , pelvis,
tibia
5-20 yrsEwing’s sarcoma
LocationAgeTumor
Metaphysis
Femur, tibia,
humerus
10-20 yrsOsteosarcoma

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Fibrous and fibro-osseous tumor

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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

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Fibrous cortical defects and
Non-ossifying fibromas

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Fibrous cortical defects and
Non-ossifying fibromas
• 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

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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.

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

81. 81Fibrous dysplasia

82. 82
Fibrous dysplasia:Types
– 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
abnormalities

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

84. 84
Shepherd Crook deformity
Café-au-lait spots

85. 85
Additional Images
For Self Study

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