TUMOURS OF BONE

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Bone tumors are very diverse in morphology and biological potential

According to their biological behaviour, they are divided into

benign and malignant lesions

MOST bone tumors are benign lesions

Bone Tumors

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Classification of Bone Tumours

Benign tumor is a localized mass that grows by expansion and, given sufficient time, would cease growing

Benign tumor is a localized mass that grows by expansion and, given sufficient time, would cease growing

Malignant tumor is characterized by uncontrollable growthMalignant tumor is characterized by uncontrollable growth

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Benign neoplasms of bone

Benign neoplasms of bone :

Osteoma

Osteoid Osteoma

Osteoblastoma

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OSTEOMA

A solitary benign neoplasm characterized by a proliferation

of either compact or cancellous bone, usually in an

endosteal or periosteal location

•Essentially restricted to craniofacial skeleton

•Rarely in long bones

A solitary benign neoplasm characterized by a proliferation

of either compact or cancellous bone, usually in an

endosteal or periosteal location

•Essentially restricted to craniofacial skeleton

•Rarely in long bones

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Clinical features Site: Skull (frontal sinus), condyle M>F Presents as slow growing, painless bony mass Paranasal sinus: pain swelling, sinusitis nasal discharge Soft tissue osteoma osteoma mucosae / osteoma cutis Children rarely affected (Gardner’s syndrome)

Gardner’s syndrome:• Multiple osteomas of skull

and mandible• Multiple sebaceous cysts• Desmoid tumors• Skin fibromas• Colonic polyposis

Gardner’s syndrome:• Multiple osteomas of skull

and mandible• Multiple sebaceous cysts• Desmoid tumors• Skin fibromas• Colonic polyposis

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Radiographic findings

Round to ovoid (1-5 cm)

Sharply circumscribed, blastic/ sclerotic mass

Not associated with surrounding bone destruction

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Histology Well circumscribed, non encapsulated Composed of condensed masses of mature lamellar bone Scanty marrow/ prominent fibro fatty marrow Variable quantities of woven bone may be admixed Osteoblastic activity present In any given area- bone appears normal

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Course and treatment

Treatment: excision

Margins of >1 mm are unnecessary

Follow-up: not important

Finding of osteoma in jaw- suspect Gardner’s syndrome

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OSTEOID OSTEOMA

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•A distinctive, benign lesion characterized by a

< 1.5cm mass of abnormal bone (nidus)

•Nidus – richly innervated by nerve fibers,

thereby evoking considerable pain

•A distinctive, benign lesion characterized by a

< 1.5cm mass of abnormal bone (nidus)

•Nidus – richly innervated by nerve fibers,

thereby evoking considerable pain

Clinical features

Incidence: 3% of primary bone tumors

Age: < 20 yrs

Sex: M:F= 3.1

Location:

<80% in long bones,

10% in spine

Rarely involve skull,

jaw bones, clavicle, sacrum

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Clinical features

Pain: -progressive type, associated with tenderness

-intense at night,

-relieved by aspirin

Swelling and redness: -superficially located lesions

-imitates osteomyelitis

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Radiological features:

Typical findings:

Thick, smooth, convex, homogenous periosteal density

The Nidus:

1. Round to ovoid contour

2. Small size: < 2cm in diameter

3. Blastic center: homogenously dense

4. Thin 1-2 mm peripheral radiolucent zone

Exceptions: radiolucent nidus: osteoid phase13

Gross :

Early lesions are cherry red in color

More mature are yellow-white

Nidus may fall out of the bone like a pea

Consistency of nidus: soft and granular to

densly sclerotic

Reactive host bone sclerosis

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Histology

Nidus : variable quantitites of osteoid and woven bone

studded with osteoclasts and numerous dilated vessels

Some regions generally show osteoblastic rimming

Woven bone edges of nidus are sharply circumscibed

from surrounding, thickened or irritated host lamellar

trabecular bone

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Variable histologic findings

Increased cellular activity Osteoclasts Peripheral fibrovascular zone Surrounding bone sclerosis Chronic inflammation

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Special stains

Silver stains reveal non myelinated axons within the lesion

Correlates with high level of pain associated with it

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Disease course and treatment

Completely benign

Malignant transformation absent

Complete excision of nidus- curative

Removal of reactive bone not necessary

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OSTEOBLASTOMA

A rare benign tumour, typically larger 1.5cm,

characterized by osteoid and woven bone production

First delineated by Jaffe and Litchenstein in 1956

A rare benign tumour, typically larger 1.5cm,

characterized by osteoid and woven bone production

First delineated by Jaffe and Litchenstein in 1956

It was also called as giant osteoid osteoma

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Osteoblastoma

Incidence: Rare- 1 % of bone tumors

15%- facial bones(mandible)

36%- skull

30%- long bones

Age: < 30 yrs (median: 18yrs)

M:F= 2:1

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Signs and symptoms

Local bony expansion with mild, dull, persistent pain,

unresponsive to aspirin

Potential for progressive growth- swelling of jaw,

pathologic fractures and loosening of teeth

Temporal bone: facial paralysis, hearing loss,

Neurologic disorders secondary to spinal tumors

Alkaline phosphatase may be increased

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Radiographic features

Well defined, mixed radiolucent- radiopaque mass

Size: avg: 3.55cm

Commonly expands bone in

a fusiform manner often

Surrounded by thin rind of benign host bone sclerosis

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Gross

Reasonably well circumscribed

Tumour tissue is usually red , granular and friable

Some lesions are;

Whitish yellow, gritty and hard

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Histological features

Well circumscribed, nonencapsulated

Irregular trabeculae in loose fibrovascular stroma

Matrix is variably calcified

Bone shows prominent reversal lines

Trabeculae and broad osteoid seams- rimmed by plump

osteoblasts which tend to aggregate

Osteoblasts- small/large vesicular nuclei, abundant cytoplasm

Osteoclasts are usually present

Stroma is loosely fibrous with numerous dilated capillaries 24

Histologic features Conventional osteoblastoma: Osteoid and woven bone production

– Thick osteoid seams cover the surfaces of the woven bone

Prominent osteoblastic rimming Reversal lines Loose intertrabecular stroma Richly vascular Sprinkling of osteoclasts

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Variants of osteoblastoma

Pseudomalignant ( bizzare) osteoblastoma Totally benign entity Bizzare nuclei Lacks mitotic activity Mimicks malignancy

Bizzare nuclear appearance

degenerative change

“pseudomalignant”

Bizzare nuclear appearance

degenerative change

“pseudomalignant”26

Malignant osteoblastoma

Features of conventional osteoblastoma Blue spiculated bone Foci of sheets of plumper osteoblasts Greater nuclear pleomorphism Presence of mitotic activity along with atypical mitoses Age> 70 yrs Local recurrence Absence of metastases

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Course and treatment

Conventional form: Conservative surgical treatment – usually entire lesion is

removed by curretage Response to treatment is nearly always good May recur over a period of 1-10 years Radiation therapy contraindicated Osteoblastoma osteosarcoma

Aggressive forms: En block resection Follow – up is important

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Also referred as osteogenic sarcoma is the 3rd most common cancer in adolescence, occurring less frequently than lymphomas and brain tumors. It is

thought to arise from a primitive mesenchymal bone forming cell and is characterized by production of osteoid

Introduction to Osteosarcoma

Etiopathogenesis

Environmental factors

Chromosomal abnormalities

Genomic alterations

Tumor suppressor gene dysfunction

Etiopathogenesis

General risk factors:Rapid bone growth ( adolescent growth spurt)

In jaws, incidence seen 1 or 2 decades after adolescenceExcludes rapid bone growth as causative agent

Environmental factors

Syndromes associated

Reported in Rothmund-thompson syndromeLi-fraumeni syndromeHereditary retinoblastoma

Genomic alterations

• Loss of heterozygosity of 10q21.1 -- most common osteosarcoma.

• Loss of chromosomes 9, 10, 13, and 17 • Gain Of chromosome 1.

Tumor suppressor gene dysfunction

p53 gene:

Well-known tumour-suppressor genesThe p53 mutated in 22% of osteosarcomasPrototypical condition --Li-fraumeni syndrome -- High-grade conventionalRetinoblastoma (Rb) genes :critical for cell-cycle control Inherited mutation ->retinoblastoma syndrome > multiple malignancies including osteosarcomaLOH – poor prognosis

Classification of osteosarcoma

Based on etiopathogenesis

Osteosarcoma classified in to

2 groups

Classification based on location - Fletcher

Clinical features

Osteosarcoma – clinical features

Extragnathic Affects most rapidly growing parts of

skeleton Metaphyseal growth plates of

Humerus, Femur and Tibia Males > females Bimodal 10-20yrs, > 50yrs

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• Comprises 6.5% • Mean age according to Garrington et.al – 34 – 36yrs• Men : female == 1. 1 : 1• Swelling rather than pain – common• Often succeed tooth extraction• Maxilla and mandible -equally involved.

Osteosarcomas of jaw

Clinical presentation

Other complaints

Paresthesia

Displacement of teeth

Trismus

Hypoesthaesia or paresthaesia in the

case of the mandibular tumours

Lack of healing

swelling at the site of tooth exraction

Epistaxis

Eye problems,

Nasal obstruction

Weight loss

Other complaints

Paresthesia

Displacement of teeth

Trismus

Hypoesthaesia or paresthaesia in the

case of the mandibular tumours

Lack of healing

swelling at the site of tooth exraction

Epistaxis

Eye problems,

Nasal obstruction

Weight loss

• 90% high grade osteosarcoma -- soft tissue extensions

Difference

Gross

Large mass extending into the soft tissuesFish flesh appearanceBoth distal and proximal margins are well definedSoft , fleshy/ gritty - depending on osteoid production

Well circumscribed, lobulated, glistening grayish white

Radiologic and Histologic features

Radiologic appearance

Varied appearance, often mixture of radiolucency with opacityNakayama et al described four radiographic patterns•Osteolytic•Osteolytic dominant•Osteogenic dominant •Osteogenic.

Hypothesis for types of ossificationTumor stage Radiologic features Histologic features

Early -Amorphous

ossification

Intermediate -Mixture of

amorphous and lamellar

ossification

Advanced - Lamellar

ossification

BRAZILIAN JOURNAL OF OTORHINOLARYNGOLOGY 71 (2) PART 1 MARCH/APRIL 2005

Radiologic presentationsIn about 80% - one or more of following type seen

1.Sunray/ Sun burst 2.Codman’s Triangle3.Widening of PDL space

Sunburst appearance

If invades periosteum, thin spicules of new bone formed

Codman’s triangle

Destruction of cortex by tumor

Lifts up periosteum

Reactive new bone formation at junction

CODMANS

TRIANGLE

Widening of PDL

Garrington et al1 mentioned that

•Radiological evidence of a symmetrically

widened periodontal ligament space is a

significant early finding in OSJ

•Absence of lamina dura

Histologic variants

Classification based on location - Fletcher

Osteoblastic variant

Approx, 50% of all conventional type•Osteoid – fine , lace like between tumor cells•Amount of mineralisation – variable•Tumor osteoid surrounded by fibroblast like cells•Less commonly organized into trabeculae•Tumor cells – relatively uniform -- spindle shaped -- bizarre, hyperchromatic nucleus

Chondroblastic variants

prevalence – 25%, most common variant in jaw•Cartilage - in form of lobules•Towards periphery –hypercellular, spindling•Center of lobule/ detween spindle cells – osteoid•Cells within lacunae – marked anaplasia

Fibroblastic variant

• Least common, Approx. 25% • Pure spindle cell growth with only small foci of matrix• Arranged in herring bone pattern ( resembles fibrosarcoma) Plump cells with pink cytoplasm resembling epithelial cell• In approx. 1/4th O.S benign giant cells are scattered

throughout

Small cell osteosarcomaSmall cell osteosarcoma Ewing sarcoma

osteoid/ bony matrix

Small foci of chondroid

Fibrinous deposition amongst tumor

Marked cellularity with little stroma

Tumor cells – uniformly bland and

undifferentiated, small hyperchromatic,

round to oval

Mitotic index - low

Telangiectatic osteosarcoma

• Approx 4% of all O.S, most lethalCriteria used for diagnosis:1. Pure lytic, destructive lesion usually in metaphysis of a long bone of a young pt.1. Gross – cavity separated by septa or a cavity containing

blood clot2. Microscopically – septa separate spaces and simulates the

appearance of an aneurysmal bone cyst.

Lining cells are pleomorphic

Blood soaked sponge

Pic of T.OS and Aneurysmal bone cystTelangiectatic variant Aneurysmal Bone Cyst

Lining cells -- AnaplasticLoosely arranged spindle cells

No tumor osteoid

Lack of atypia

Histology of periosteal variant

• Malignant chondroid

• Anaplastic spindle cells

• Osteoid with or without

calcification

• Mitotic figures

Features Paraosteal periosteal High grade surface

osteosarcoma

Clinical

features

Lobulated nodule attached

to cortex by short stalk

Lobulated nodule Least common, worst

prognosis

Radiograp

h

Radiodense and lobulated

mass attached by a broad

base to underlying bone

No periosteal elevation/

bone formation

Histologic

features

Fibroblastic differentiation

Well developed bony

trabeculae

Malignant chondroid , less

osteoid

Sheets of pleomorphic

spindle cells, osteoid

matrix, lacks cartilage

Staging and grading of osteosarcoma

Universally accepted staging system not commonly used•Stage I – Low – grade lesion•Stage II – High- grade lesion•Stage III – Metastatic diseaseSub Stages:A.Intramedulary lesionB.Local extramedullary spreadSite of primary:I.Distal extremity – Best prognosisII.Distal Femur – Intermediate prognosisIII.Axial Skeleton – Worst prognosis

• Shafer, Hine, Levy. Shafer’s textbook of Oral Pathology 6th

edition

Routine protocol

1. Initial chemotherapy of about 5 inductions2. Surgery (Resection of involved segment of bone)3. Additional 2 – 3 inductions postoperative chemotherapy

Historical Background First described by James Ewing in 1921

Angervall and Enzinger in 1975 described the extra

skeletal form tumor

Termed as Ewing’s sarcoma of Soft tissue

Ewing’s Sarcoma/PNET

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Exact origin of cells questioned ???

Ewing believed cells were derived from marrow

endothelium

Tumor arose from undifferentiated cells of the

reticuloendothelial system

Neuroectodermal in origin and derived from cells

of the neural crest cells

HISTOGENESISES/PNET

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Cytogenetic abnormality i,e t(11;22) found in 80-90% of cases.

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AGE: Peak prevalence- 2nd or 3rd decade 80% affected <20yrs at diagnosis 50% tumor detected during 2nd decade

SEX: Slight male predilection (Neville) Whites mostly affected with blacks almost never developing

this tumor

Clinical featuresES/PNET

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SITE: Long bones, pelvis and ribs

Jaw involvement seen in 1 to 2 % cases (Gnathic or craniofacial bones)

Tumor of jaw present as swelling, pain, loose teeth & paresthesia.

Mandible affected twice as maxilla

ES/PNET

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Anywhere in the body Most common

– Deep soft tissues of extremities mostly upper thigh or buttock

– Upper arm

– Shoulder

– Para vertebral chest wall

Tumor attached to a major nerve shows signs and symptoms of diminished neurologic functions

Sites for Extraskeletal ES/PNET

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Rapidly growing, deeply located mass measuring 5-10 cm

Painful in one-third of cases

Progressive sensory or motor disturbances

Preoperative period is 1 year

Fever, leukocytosis and elevated ESR may be sometimes misleading

Clinical presentation ES/PNET

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Macroscopic findings: Multilobulated, soft and

friable

Rarely > 10 cms

Gray-yellow or gray-tan appearance

Areas of necrosis, cyst formation or hemorrhage

No calcification72

ES/PNET

Marked cellularity with little stroma

Solidly packed, lobular pattern of uniform round cells

Cells have uniform, small, hyperchromatic, round or ovoid nucleus 10-15μm with distinct nuclear membrane

Cytoplasm ill-defined with scanty & pale staining Mitotic index low

Multinucleated giant cells are usually not present Intracytoplasmic glycogen highlighted by PAS stain

Filigree pattern

Histopathology

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ES

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MONOTONOUS PROLIFERATIONS OF ROUND CELLS

ES

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COMPRESSED BLOOD VESSEL

ES

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CELLS WITH CLEARED OUT CYTOPLASM

ES

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FILIGREE PATTERN

ES

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CD 99 POSITIVITY

ES/PNET

Form diffuse sheets, lobules, nests, or alveoli of small round

cells with hyperchromatic round to oval nuclei

Cytoplasm indistinct except in areas where cells are more mature

Elongated hair like cytoplasmic extensions coalese to form

rosettes (Homer-Wright rosette)

Focal lack of cohesiveness may mimic rhabdomyosarcoma (Peudoalveolar pattern)

Dense chromatin clumping and mitoses frequent

PNET

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Distinctive lobular architecture

PNET

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HOMER-WRIGHT ROSETTES

PNET

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Pseudo alveolar pattern

PNET

EWING SARCOMA SHOWS: Densely packed uniform cells with round or oval nuclei Finely dispersed chromatin Narrow rim of cytoplasm & sparse organelles Rare cytoskeletal microfilaments & pools of glycogen

PNET: Some degree of neural differentiation in the form of dense-core

neurosecretory granules, neuritic cell processes, synaptic-like junctions, and microtubules

Ultrastructure

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ES/PNET

ES/PNET currently treated by neoadjuvant chemotherapy with surgical resection followed by adjuvant chemotherapy

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Treatment

References

Shafer, Hine, Levy. Shafer’s textbook of Oral Pathology 6th edition

Neville, Damm, Allen, Bouquot. Oral and maxillofacial pathology, 3rd edition

Joseph M Mirra ‘Bone tumours: Clinical, radiological and pathological correlation’ Volume 1

Marx RE and Stern D ‘Oral and maxillofacial pathology: A rational for diagnosis and treatment’

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K. Krishnan Unni and Carrie Y Inwards ‘ Dahlin’s Bone Tumours’ 6th edition

R A Cawson, E W Odell – Cawson’s essentials of oral pathology and oral medicine – 7th edition

R.A Cawson. Lucas Pathology of tumours of oral tissues 5th edition

Eversole R.Benign Fibro-Osseous Lesions of the Craniofacial Complex - A Review. Head and Neck Pathol.2008; 2 :177–202

References

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Thank you