MODERATOR-DR. S. S. THAKUR

BONE TUMOR

• A bone tumor, is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign or malignant.

• Bones are classified according to their shape-• Long bone• Flat bone• Short bone.

Long bone anatomy• Diaphysis: long shaft of bone• Epiphysis: ends of bone• Epiphyseal plate: growth plate• Metaphysis: b/w epiphysis and diaphysis• Articular cartilage: covers epiphysis• Periosteum: bone covering (pain sensitive)• Sharpey’s fibers: periosteum attaches to underlying

bone• Medullary cavity: Hollow chamber in bone

- red marrow produces blood cells- yellow marrow is adipose.

• Endosteum: thin layer lining the medullary cavity

Diaphysis

Epiphysis

Metaphysis

• Histology of bone tissueCells are surrounded by matrix.

- 25% water- 25% protein- 50% mineral salts

4 cell types make up osseous tissueOsteoprogenitor cellsOsteoblastsOsteocytesOsteoclasts

• Osteoprogenitor cells:- derived from mesenchyme- unspecialized stem cells- undergo mitosis and develop into osteoblasts- found on inner surface of periosteum and endosteum.

Osteoblasts:

- bone forming cells- found on surface of bone- no ability to mitotically divide - collagen secretors

          Osteocytes: 

- mature bone cells- derived form osteoblasts- do not secrete matrix material- cellular duties include exchange of nutrients and waste with blood

• Osteoclasts- bone resorbing cells- bone surface- growth, maintenance and bone repair

Abundant inorganic mineral salts:- Tricalcium phosphate in crystalline form called

hydroxyapatite Ca3(PO4)2(OH)2

- Calcium Carbonate: CaCO3

- Magnesium Hydroxide: Mg(OH)2

- Fluoride and Sulfate

Osteoprogeniter cells &Osteoblast

Osteoclast 

Precursors of malignancy in bone

• High Risk• Ollier disease (Enchondromatosis)• and Maffucci syndrome• Familial retinoblastoma syndrome• Rothmund-Thomson syndrome (RTS)• Moderate Risk• Multiple osteochondromas• Polyostotic Paget disease• Radiation osteitis

• Low Risk• Fibrous dysplasia• Bone infarct• Chronic osteomyelitis• Metallic and polyethylene implants• Osteogenesis imperfecta• Giant cell tumour• Osteoblastoma and chondroblastoma

Classification of primary tumour involving bones

Histological type

Benign Malignant

Hematopoietic Myeloma

Malignant lymphoma

Chondrogenic Osteochodroma chondrosarcoma

Chondroma

Chondroblastoma

Chondromyxoid fibroma

Histological type

Benign Malignant

Osteogenic Osteoma Osteosarcoma

Osteoid osteoma

osteoblastoma

Unknown origin Giant cell tumour

Ewing tumour

Giant cell tumour

admantinoma

Histological type

Benign Malignant

Histiocytic origin

Fibrous histiocytoma

MFH

Fibrogenic Metaphyseal fibrous defect

Dysplastic fibroma

Fibrosarcoma

Notochordal Chordoma

Vascular Hemangioma Hemangioendothelioma

Hemangiopericytoma

Lipogenic Lipoma Liposarcoma

Neurogenic Neurilemmoma

Distribution of bone tumors in long bones 

• Epiphyseal lesions: • Chondroblastoma • Giant cell tumor

• Metaphyseal intramedullary lesions: • Osteosarcoma • Chondrosarcoma • Aneurysmal bone cyst

• Metaphyseal lesions centered in the cortex: • Nonossifying fibroma (NOF) • Osteoid osteoma

• Metaphyseal exostosis: • Osteochondroma

• Diaphyseal intramedullary lesions: • Ewing’s sarcoma • Lymphoma • Myeloma • Fibrous dysplasia • Enchondroma • Diaphyseal lesions centered in the cortex: • Adamantinoma • Osteoid osteoma

Sites of Tumors

Important Facts• 0.001% of all cancers• MC benign tumor--- Osteochondroma; Osteoid

Osteoma• MC Skeletal malignancy– Metastasis.• MC Bone tumor in Pediatric age group & adults-

Osteosarcoma• MC in < 10 y--- Ewing’s sarcoma• MC Primary bone tumor – Multiple Myeloma

PRESENTING SYMPTOMS Patient may present with• An abnormal radiographic finding detected during evaluation of unrelated problem• PAIN:- is most frequent symptom • MASS:- rate of enlargement is important• -Fluctuating mass can be cyst,ganglion or hemangioma• -Family H/O masses near the joint may be indicator of Ollier’s disease or Maffucci

Syndrome• NEUROLOGICAL SYMPTOM:- found in few patients such as sacral tumors & with tumors

located near the nerve causing compression of nerve,especially common in sciatic notch ,inguinal canal & popliteal fossa

• UNEXPLAINED SWELLING OF THE LOWER EXTREMITY:- found in pelvic• tumors which are painless & without a palpable mass & cause swelling due to

compression of iliac vein.

PHYSICAL EXAMINATION• Evaluation of patient’s general health• TUMOR MASS should be measured & its location,shape,

consistency,mobility,tenderness,local temp & change with position should be noted.

• SKIN & SUBCUTANEOUS TISSUE :• Small dialated superficial veins overlying the mass are produced

by large tumors• Café-au-lait spots & subcutaneous neurofibromas indicate Von

Recklinghausen’s disease• A venous malformation Maffucci Syndrome• REGIONAL LYMPH NODES: sign of metastatic disease• Atrophy of surrounding musculature should be recorded,also

neurological deficits & adequacy of circulation.

HISTORY OF THE PATIENT• AGE:- most imp information,bcoz of their presentaion in sp age

group.• 1st decade- usually ABC ,SBC• 2nd decade-Chondroblastoma,osteosarcoma,Ewings• 3rd decade- GCT• 4th decade- chondrosarcoma• 5th decade- Multiple myeloma• SEX:- less imp than age• RACE:- little imp, Ewings rare in african descent• H/O any exposure to radiation Tt or Carcinogens- bone seeking

radionucleotide can cause sarcoma.• Various chemical carcinogens- zinc beryllium silicate, beryllium oxide.• Currently the most worrisome & controversial is Nickel which is used

in many orthopedic devices.

LABORATORY TEST• Alkaline phosphatase – Higher .

• PTH test: Lower.

• Serum phosphorus: Higher

• Ionized calcium and serum calcium: Higher .

INVESTIGATIONS• X-RAY• CT SCAN• MRI• TECHNETIUM BONE SCAN-This type of scan uses a

very low radioactive material (diphosphonate) to see whether or not the cancer has spread to other bones and the damage suffered by the bone.

• PET- uses radioactive glucose to locate cancer. This glucose contains a radioactive atom that is absorbed by the cancerous cells and then detected by a special camera.

BIOPSY• The biopsy is the most conclusive test because it confirms if

the tumor is malignant or benign, the bone cancer type (primary or secondary bone cancer), and stage.

• According to the tumor size and type (malignant or benign) and the biopsy's purpose (to remove the entire tumor or only a small tissue sample), there are two types of biopsies used in bone cancer diagnosis. These are: needle biopsy and incisional biopsy.

• 1. Needle biopsy: During this procedure, a small hole is made in the affected bone and a tissue sample from the tumor is removed.

• There are two types of needle biopsies:• Fine needle aspiration: During this procedure, the tissue

sample is removed with a thin needle attached to a syringe. • Core needle aspiration: During this procedure, the surgeon

removes a small cylinder of tissue sample from the tumor with a rotating knife like device.

• 2. Incisional biopsy: During this procedure, the surgeon cuts into the tumor and removes a tissue sample.

BONE FORMING TUMOURS

• Benign: Osteoma, Osteoid Osteoma,

• Benign Aggressive: Osteoblastoma

• Malignant: Osteogenic Sarcoma

Osteoma

• Benign, asymptomatic, slow-growing osteogenic lesion.

• Age/Sex: 40-50 yr, M:F = 2:1.• Bones involved: flat bones of the skull and

face; may protrude in the paranasal sinus.• Parosteal location.• Gardner’s syndrome.

Ivory like bony mass

Figure 2: The lesion consists of dense and lamellar cortical bone with a focal area of active bone modeling.

Figure 3: Photomicrograph of the more solid area of the lesion to demonstrate the cellular woven character of the bone.

Osteoid osteoma• Signs/Symptoms:

• Pain, characteristically more intense at night, relieved by NSAID and eliminated by excision

• Scoliosis

• Age:• 10-30 years

• Sex:• M > F (2:1)

• Anatomic Distribution:• Nearly every location, most frequent in femur, tibia,( Over 50%) humerus,

bones of hands and feet, vertebrae and fibula• Metaphysis / Diaphysis (cortical) of long bones• Vertebral lesions may be associated with scoliosis.

Small central osteolytic nidus surrounded by dense bone

The small, reddish central nidus is surrounded by a thick layer of sclerotic bone

Wedge shaped nidus which is surrounded by dense sclerotic bone.

New osteoid and bone formation by plump osteoblasts. The stroma is cellular and well vascularized

Osteoid osteoma with anastomosing trabeculae of woven bone

Osteoblastoma • Also called as Giant osteoid osteoma.

• Osteoblastoma is similar to osteoid osteoma with more aggressive behavior.

• D/D from osteoid osteoma- *Pain

*Absence of reactive bone * Large size

• Location : – In spine or major bones of lower extremity

Well differentiated radiopaque/radiolucent lesion

Osteoblastoma.-The histologic appearance is identical

to that of osteoid osteoma.

Recurrent osteoblastoma.-The appearance is similar to that of osteoid osteoma

Osteosarcoma

• Most frequent primary malignant bone tumour.• Age/Sex :10-25 yrs & >40 , M:F = 3:2• Predisposing conditions: Paget’s disease Radiation exposure Chemotherapy Benign bone lesion Foreign bodies Trauma

Codman’s triangle:   “Sunray “ appearance

Tumor is located at the typical metaphyseal site. The tumor shown in A is largely restricted to bone, whereas that illustrated in B is accompanied by massive soft tissue extension.

‘skip metastasis’ located in the upper half of the femur. The primary tumor was located in the lower metaphysis of the same bone

The malignant bone is more basophilic and has more irregular borders than the preexisting bone trabeculae.

Osteosarcoma showing characteristic basophilic thin trabeculae of neoplastic bone with an appearance that is reminiscent of

fungal hyphae

Lace-like osteoid deposition is very characteristic of this neoplasm.

Osteoblastic osteosarcoma with finely ramifying matrix between tumor cells

Microscopic variants

Telangiectatic :

• Blood filled cystic space and thus radiologically appears as pure lytic lesion.

• Pathological fractures.• Grossly the lesion simulate aneurysmal bone

cyst.• Detection of malignant stroma in the septa

that separate the bloody cysts.

Telangiectatic osteosarcoma.

Telangiectatic osteosarcoma. A The low-power architecture closely simulates the appearance of an aneurysmal bone cyst

B Malignant osteoid is present in the septa

Telangiectatic osteosarcoma. Spaces containing blood are separated by septa. The cells appear malignant even at this level

of magnification

Fibrohistiocytic

Small cell variant:

• Uniform small size tumour cells.• Diffuse pattern of growth.• Simulate Ewing’s sarcoma and malignant

lymphoma.

Anaplastic

Well differentiated intramedullary

.This tumor is microscopically so bland looking as to be often underdiagnosed as a benign lesion.

In contrast to fibrous dysplasia

1- this tumor shows radiographic evidence of cortical destruction.

2-Microscopically, atypia is minimal but still present.3-The invasive growth pattern.

Variants defined on the basis of topographic, clinical and radiographic features:

Juxtacortical (parosteal)• Slightly older age group• Juxtacortical position in the metaphysis of

long bones.

Juxtacortical osteosarcoma of upper femur. There is only minimal involvement of the cortex

Juxtacortical osteosarcoma  large extracortical component

Juxtacortical osteosarcoma--Moderately atypical spindle tumor cells grow between irregularly shaped bone trabeculae

Parosteal osteosarcoma-The spindle cells demonstrate minimal atypia, and the bone appears to arise directly from the spindle

cells.

Periosteal osteosaocoma• Grows on surface of long bones.• Upper tibial shaft or femur.

Periosteal osteosarcoma. The white shining appearance is due to the high content of cartilage

periosteal chondrosarcoma. There is a predominance of myxochondroid areas

Bone formation in the center of a cartilaginous lobule in periosteal osteosarcoma

Osteosarcoma of jaw:• Patients affected are slightly older (average age, 34 years),• And most lesions show a prominent chondroblastic

component.• The most common sites of involvement are the body of the mandible and the alveolar ridge of the maxilla.

Osteosarcoma in Paget’s disease.• Osteosarcoma are of the polyostotic type• Pelvis, humerus, femur tibia & skull.• Large number of osteoclasts alternating with atypical

osteoblast.

Histochemistry, IHC & molecular genetics

• Strong alkaline phosphatase activity.• Vimentin, S-100, keratin & EMA.• Osteonectin, osteocalcin, osteopontin.

Prognostic factors• Paget’s disease• Irradiation• Specific bone involvement• Multifocality• Various types• Microscopic variants• Serum elevation of alkaline phosphatase• Aneuploidy• Post chemotherapy tumour necrosis• RB gene• HER2/neu expression• P-glycoprotein.

CARTILAGE FORMING TUMOURS• Benign: Enchondroma,

Peri-osteal Chondroma, Osteochondroma.

• Benign Aggressive: Chondromyxoid Fibroma, Chondroblastoma.

• Malignant: Chondrosarcoma.

Chondroma• Benign tumor of mature hyaline cartilage• Age – 20-50 yrs• Usually solitary,30% are multiple.• Bones involved: small bones of hand & feet.• Asymptomatic, pain & swelling.Enchondroma is the most common tumor of

the bones of the hand

Enchondromas

• Begin in spongiosa of diaphysis, from which they expand and thin cortex

• Unusual in ribs and long bones

Juxtacortical Chondroma

• Much less common than enchondroma• Involve parosteal region of long bone or small bone of hand

or foot

2 syndromes characterized by multiple chondromas:

• Ollier’s disease

• Maffucci’s syndrome

• Both disorders have 25% risk of malignant transformation to chondrosarcoma

Maffucci syndrome-Innumerable chondromas are seen concentrated in the distal aspect of the extremity

Juxta-cortical - The tumor produces a semispherical expansion of the involved bone.

Enchondroma-The tumor has a typical lobulated appearance

Osteochondroma

• Also known as exostosis.• Most frequent benign cartilaginous tumour.• Age/sex - <20yr, M:F=3:1• Bones involved: lower femur, upper tibia,

upper humerus and pelvis.• Location: Metaphysis

• Probably not a true neoplasm.

• Inactivation of both copies of the EXT gene in the growth plate chondrocytes.

• Presents as slow growing mass, painful.

• <1% cases show malignant transformation.

     A- Large osteochondroma of femur with a bilobed appearance. B Cut surface of osteochondroma of ribthick cartilaginous cup

Projection with cortex continuous with underlying bone; may be pedunculated; cartilaginous cap with frequent

calcification

Microscopic-Mature bone is covered by a well-differentiated cartilaginous cap.

Microscopic

Chondroblastoma

• Rare benign cartilage producing tumour.• Age/Sex : 2nd decade M:F=2:1.• Bones involved: Distal femur ,proximal

humerus and tibia.• Location: Epiphysis• Pain is constant .

Typical sharply delineated lytic appearance of chondroblastoma of humeral head

Gross appearance of chondroblastoma of upper end of the humerus, associated with aneurysmal bone cyst-like changes

Chondroblastoma. A- Small tumor cells of round shape are accompanied by scattered osteoclasts.

 B-Immunoreactivity for S-100 protein in the neoplastic component.

Chondroblast: Prominent Indented NucleusEosinophilic Cytoplasm Thick Cell Membrane

Uniform Appearance of Cells

Chondroblastoma with eosinophilic chondroid matrix, giant cells, and mononuclear cells

Imagine the cells present without the nuclei: The thickened cell membranes would give a chicken wire fence appearance

Chondromyxoid Fibroma

• Benign tumour of cartilaginous origin.• Age/Sex: 20-30 yr/ M:F=2:1• Bones involved: Long bones>flat bones

>vertebrae.• Location: Metaphysis.• Localised pain with or without tenderness

Sharply delimited chondromyxoid fibroma of lower femoral metaphysis in a young boy.

A-Chondromyxoid fibroma of proximal femur extending into soft tissue B-The tumor has a lobulated appearance, in which myxochondroid islands alternate with more cellular foci.

Chondromyxoid fibroma- (A) An irregularly shaped hypocellular center is surrounded by a cellular spindle

cell stroma. (B) The lobules contain tumor cells with small nuclei

and eosinophilic cytoplasmic extensions within a myxoid background

Chondrosarcoma

• Second most common malignant tumour of bones. • Arise de novo or from pre-existing benign

cartilagenous tumour.• Divided into two major categories:

*Conventional chondrosarcoma *Chondrosarcoma variants

Conventional chondrosarcoma

• 30 – 60 yr of age.• M>F• Divided according to location: *Central *Peripheral *Juxtacortical

-Typical chondrosarcoma of femurI-ill defined margins; fusiform thickening of shaft; perforation of cortex

Typical chondrosarcoma

Peripheral Variant:• Tumour is present on the surface of bone.• May arise de-novo or from cartilaginous cap

of preexisting osteochondroma.

Peripheral chondrosarcoma of femur resulting in a huge exophytic mass

Juxtacortical(periosteal) variant:• Location:

– shaft of long bone (most often femur)• Cartilaginous lobular pattern with areas of:

– spotty calcification – endochondral ossification

• Closely related to periosteal osteosarcoma.

Microscopic

• Wide range of differentiation and graded into: – well differentiated – moderately differentiated – poorly differentiated

Well-differentiated chondrosarcoma. The tumor has a distinctly lobulated quality

Well differentiated- High-power appearance of grade 1 chondrosarcoma. A few doubly nucleated cells and

moderate atypia .

Moderately differentiated - High-power appearance of grade 2 chondrosarcoma with necrosis . The nuclei are crowded and

hyperchromatic

Poorly differentiated

Grading system• Grade I : lesions contain hyaline cartilage manifested by

sparse cellularity. The cells typically contain dark, pyknotic nuclei. <20% of cells contain large nuclei and fine nuclear chromatin. Mitosis is absent.

• Grade II: A) lesion are slightly more cellular and >20% nuclei are larger than nucleus of mature lymphocyte. Binucleate cells are easily found. Mitosis is absent.

B) cellular lesions with numerous binucleated cells and nuclear atypia. Mitosis is present but not more than

1/ 10hpf.• Grade III: Mitosis atleast >=2 / 10 hpf

• The main differential is of low grade (Grade 1) chondrosarcoma and enchondroma.

• Features consistent with chondrosarcoma are:*Pain attributable to lesion *Age greater than 50*Cortical destruction and a soft tissue mass*Periosteal reaction and thickening*Endosteal erosion>2/3 cortical thickness on a CT scan*Size greater than 5 cm

Chondrosarcoma variants

Dedifferentiated chondrosarcoma:• Worst prognosis.• Age/sex: sixth decade/ M:F =1:1.• Bones involved: pelvis, femur.• Poorly differentiated sarcomatous component

at periphery of otherwise typical low-grade chondrosarcoma – usually central type – can be peripheral

Gross appearance of dedifferentiated chondrosarcoma of pelvic bone -

Microscopic

• Dedifferentiation: – may be in initial lesion – more often in specimens from recurrent tumor:

• microscopic appearance of this component may be: – rhabdomyosarcoma – fibrosarcoma – osteosarcoma – pleomorphic sarcoma with MFH-like features

The edge of an island of well-differentiated cartilage (upper left) is surrounded by highly pleomorphic sarcoma containing tumor giant cells

Chondrosarcoma is juxtaposed with high-grade malignant fibrous histiocytoma

Clear cell variant:• Behaves as low-grade malignancy • Can undergo dedifferentiation• Age/Sex : 30-40 yrs/M:F= 2.5:1• Location: proximal end of femur and humerus.

Clear cell chondrosarcoma with faint lobulation, woven bone, and clear cells

Mesenchymal variant:

• Usually second or third decade of life • Great variability in clinical course.• Location:

– most commonly: • jaw • pelvis • femur • ribs • spine

Shows an island of well-differentiated cartilage in the center

Cellular, hemangiopericytoma-like component

TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING

OSTEOMA FACIAL BONE

40-50/2:1 MINERALIZED COMPACT BONE

OSTEOID OSTEOMA

CORTEX OF LB

10-30/2:1 “NIDUS” OF IMMATURE BONE SURROUNDED BY SCLEROTIC BONE.

OSTEOBLASTOMA

VERTEBRAE,CORTEX OF LB

10-30/2:1 IDENTICAL TO OSTEOID OSTEOMA BUT LARGER AND OFTEN NO SCLEROSIS

OSTEOSARCOMAA-CONVENTIONAL .B-LOW GRADE CENTRAL

METAPHYSIS OF LB

10-25/3:2

A-OSTEOID FORMED DIRECTLY BY MALIGNAT CELLS

-B- MILDLY ATYPICAL FIBROBLASTIC PROLIFERATION+THICK BONE TRABECULAE

TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING

C-TELANGIECTATIC

METAPHYSIS

BLOOD FILLED SPACE+FIBROUS SEPTAE+HIGHLY MALIGNANT OSTEOID

D-PAROSTEAL

CORTEX OUTSIDE PERIOSTEUM

30-60 YRS MILDLY ATYPICAL FIBROBLASTIC PROLIFERATION+THICK BONE TRABECULAE

E-PERIOSTEAL

CORTEX INSIDE PERIOSTEUM

ABUNDAND CARTILAGE MATRIX +VARIABLE MALIGNANT OSTEOID

TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING

CHONDROMA

HANDS ,FEET,RIBS ,FEMUR

10-40/1:1 VARIABLY CELLULAR HYLINE CARTILAGE

OSTEOCHONDROMA

METAPHYSISOF LBS

10-30/1:1 CARTILAGE CAPPED BONY PROTRUSION

CHONDROBLASTOMA

EPIPHYSISOF LBS

10-20/2:1 CHONDROID LIKE MATRIX, S-100 POSITIVE CELLS WITH GROOVED NUCLEI

CHONDROMYXOID FIBROMA

METAPHYSIS OF LBS

10-30/1:1 HYPOCELLULAR CHONDROMYXOID LOBULES SURROUNDED BY MORE CELLULAR SPINDLE CELL AREAS

TUMOUR LOCATION AGE/M/F SALIENT PATHOLOGIC FINDING

CHONDROSARCOMA

PELIVIS. RIBS ,FEMUR

/3:1

A- CONVENTIONAL

METAPHYSIS 20-80 VARIABLY CELLULAR HYLINE CARTILAGE WITH PERMEATING BONE

B-DEDIFFERENTIATED

METAPHYSIS >30 CONVENTIONAL CHONDROSARCOMA+HIGH GRADE SPINDLE CELL SARCOMA

C- MESENCHYMAL

METAPHYSIS 20-50 UNDIFFERENTIATED SMALL TUMOUR CELLS

WITH +HYLINE CARTILAGE

E- CLEAR CELL EPIPHYSIS 20-70 CONVENTIONAL CHONDROSARCOMA +ABUNDANT LARGE CLEAR CELLS

THANKYOU

PRESENTED BY – DR NARMADA PRASAD TIWARI