CARTILAGE FORMING TUMOURS

CARTILAGE FORMING TUMORS

• 1) OSTEOCHONDROMA

• 2) CHONDROMA

• 3) CHONDROBLASTOMA

• 4) CHONDROMYXOID FIBROMA

• 5) CHONDROSARCOMA

CHONDROSARCOMA

• Comprises a group of trs with the common feature being the production of neoplastic cartilage.

CHONDROSARCOMA(CS)• 3rd most common malignant bone tumor

(myeloma & OS).• Age 40 yr or older (adults with mature

skeletons). M: F ratio is 2:1.• Arise in central portions of skeleton including

pelvis, shoulder, and ribs/proximal parts of tubular bones of the limbs.

• Painful, progressive enlarging masses.• Rarely involves the distal extremities in contrast

to enchondromas.

SUBTYPES OF CS• ACCORDING TO SITE: Intramedullary (Central) Juxtacortical ( Surface) Extraskeletal Soft Tissue Chondrosarcoma

(Mesencymal type).• ACCORDING TO HISTOLOGY: Conventional (or myxoid/hyaline CS) Clear cell CS Dedifferentiated CS Mesenchymal CS . PRIMARY (DE-NOVO) .SECONDARY (EXOSTOSIS or OLLIERS DISEASE). .

• A) CONVENTIONAL CS: GROSS

- Composed of malignant hyaline & myxoid cartilage.

- Tends to involve the large flat bones (pelvic-periacetabular region and shoulder girdle) of adults.

- Metaphysis or proximal diaphysis of long tubular bones. Distal parts are not involved.

- Can also involve the nasal & laryngeal bones.- Not seen in the small bones of the hands & feet).

RADIOLOGICAL FEATURES

• Metaphysis or diaphysis of long bones.• Large LYTIC lesions with radiodense

stippling, curlicues, rings due to matrix calcifications (spotchy calcification & ossification).

• Triad 1) Bone expansion (fusiform) 2) Cortical thickening. 3) Cortical erosion with permeation

into surrounding soft tissue.

GROSS: - Large bulky trs made up of nodules of gray-

white, translucent somewhat glistening tissue.- Foci of calcification, myxoid change, cyst

formation.- ***Malignant cartilage infiltrates the marrow

spaces & surrounds pre-existing bony trabeculae,

- Adjacent cortex is eroded or thickened & tr infiltrates into the surrounding tissues,

MICROSCOPIC PICTURE CONVENTIONAL CS

• Vary in degree of cellularity, cytologic atypia, mitotic activity

• Three grades: 1-3• Low grade or grade 1 CS : Mild

hypercellularity, scattered chondrocytes with plump vesicular nuclei, small nucleoli, few binucleate cells, low mitosis.

• Grade 3 : marked hypercellularity, extreme pleomorphism, bizarre tumor giant cells, frequent mitosis & necrosis.

• B) DEDIFFERENTIATED CS:(1O%).

- comprises of a “mixture” of low grade chondrosarcoma adjacent to a poorly differentiated high grade sarcoma such as MFH, fibrosarcoma , or osteosarcoma.

D/D: Chondroblastic OS

• C) CLEAR CELL SC:

- Large malignant chondrocytes cells with abundant clear cytoplasm, well defined cell outlines, centrally placed nucleus with a prominent nucleolus.

- Cells arranged in lobules.

- Osteoclast like giant cells (edge of lobule) & woven bone trabeculae (centre of lobule).

D/D :

• D) MESENCHYMAL CS:

- 1/3 cases are seen in soft tissues.- Young adults.- Jaw bones & ribs.- Islands of W.D hyaline cartilage surrounded by

sheets of round blue cells having hemangiopericytoma like b.v.

- Biphasic tumour- D/D:

CHONDROSARCOMA of Rt FEMUR

CS of hip bone.

LOW GRADE CS

CHONDROSARCOMA

CHONDROSARCOMA

MYXOID CS

High grade CS

DEDIFFERENTIATED CS

CLEAR CELL CS

CLEAR CELL CS

CLEAR CELL CS

MESENCHYMAL CS

http://1.bp.blogspot.com/-AUjP-Tuq5Ak/TgwMklHljdI/AAAAAAAABU8/DJBpWz0K39g/s1600/Chondrosarcoma+02.jpg

PROGNOSIS OF CS.

• 5 yr survival is 90%, 81%, and 43% for grade 1-3 respectively

• Size :>10cm poor prognosis

• Metastasis

CLINICAL FEATURES

• Painful progressive enlarging trs.

• Spread occurs to lungs & skeleton.

2. OSTEOCHONDROMA (EXOSTOSIS)

• Benign cartilage-capped outgrowth attached to underlying bone by stalk

• Usually single

• Multiple in hereditary exostosis

• Solitary: in late adolescence & early adulthood

• Multiple : in childhood

• Male : Female ratio is 3:1

• Site : arises from metaphysis of long bones esp. about knee.

MORPHOLOGY

• Mushroom shaped outgrowth from surface of a bone,

• Size : 1-20cm

• Cap of benign hyaline cartilage of variable thickness with inner bony head & stalk

CLINICAL PRESENTATION

• Asymptomatic slow growing tumors

• Can be painful when impinge on nerve or stalk is fractured

• Epiphyseal growth disturbances in multiple exostosis

• Rarely development of chondrosarcoma

exostosis

3) CHONDROMA: Benign tumour composed of benign hyaline

cartilage.

• ENCHONDROMA: within medullary cavity

• SUBPERIOSTEAL OR JUXTACORTICAL CHONDROMA: Present on surface of bone (humerus 50%)

• SOFT TISSUE CHONDROMAS.

ENCHONDROMA• The most common intraosseous cartilage tumor.• Age: 20-50 yr• Solitary lesions• Site : metaphyseal region of short tubular bones

of hands & feet• OLLIER DISEASE: multiple enchondromas.• 25% of pat with Ollier Disease dev Chondrosarcoma• MAFFUCCI SYNDROME: enchondromas with soft

tissue hemangiomas• Risk of malignant trs is more in Maffucci synd.

MORPHOLOGY

• Size: less than 3 cm• Gross: nodular grey blue translucent mass• Microscopically:- - Well circumscribed lesions. - Hyaline matrix. - Benign chondrocytes within lacunae. - Ossification & calcification are frequent. - chondromas of small bones of hands &

feet tend to hypercellular (resembling grade 1 CS)

ENCHONDROMA

PERIOSTEAL CHONDROMA (saucerized,well demarcated,cortical lucency) appearance

CLINICAL FEATURES

• Symptomatic,

• Painful mass,

• Pathologic fracture,

• X-RAYS: O-ring sign (well demarcated radiolucent lesions ).

• MAFFUCCI SYNDROME: risk of developing other malignancies

chondroma

MULTIPLE CHONDROMAS IN OLLIER DISEASE

Multiple enchondromas in OLLIER DISEASE

4) CHONDROBLASTOMA

• Rare tumor.• Seen in young adults.• Epiphysis(50%) or apophyseal (iliac

crest/greater trochanter of femur:15%).• Morphology : sheets of polyhedral chondroblasts

with well defined borders , pink cytoplasm, nuclear grooves, coffee bean appearance (D/D:LCH )hyaline matrix with chicken-wire, FINE calcification, osteoclast type giant cells.

• RADIOLOGY:

-Extremely well demarcated lesion almost always in epiphysis or may extend into metaphysis (with an open epiphyseal plate).

- Surrounded by dense sclerotic border.

Chondroblastoma.

Chondroblastoma showing delicate fine chicken-wire calcification outlining the degenerative tumour cells

Chondroblastoma with chicken wire calcification

Chondroblastoma with a sclerotic rim

5) CHONDROMYXOID FIBROMA

• Rare tumor

• Age: teens & twenties

• Site : long tubular bones

• Morphology: well circumscribed, glistening tan grey tr tissue,

• Microscopically: nodules of hyaline cartilage with intervening myxoid tissue & osteoclast giant cells

EWING SARCOMA/PNET

EWING SARCOMA/PNET.

• ES and PNET are “Round blue cell tumors of bone & soft tissue”.

• Other Round Blue Cell Trs are :- Lymphoma, rhabdomyosarcoma, neuroblastoma, oat cell carcinoma, retinoblastoma, medulloblastoma.

• Have a neural phenotype.• Both differ only in their degree of neural

differentiation.• Tumors that demonstrate neural differentiation by

light microsopy, immunohistochemistry ,or E/M are labelled PNETs.

• Those that are undifferentiated are diagnosed as ES.

• ES & PNETs : comprise 6-10% of primary bone tumors.

• 2nd most common malignant bone tumor in children after OS.

• Age: 10-15 yr.• Boys more frequently affected.• More in whites.• Site: arises in medullary cavity of Diaphyses or

Metaphysis of long bones esp. femur • 85% have : t(11; 22)translocation.• 5-10% have : t(21; 21) translocation.• Less than have: t(7; 22) translocation.• Those that affect the chest wall are called

“ASKIN TUMOUR”.

MORPHOLOGY• GROSS: Arises in medullary cavity Tan white tr tissue Vast areas of hemorrhage & necrosis• MICROSCOPICALLY: - Composed of sheets of small, round cells. - High N/C ratio. - Round nuclei having salt & pepper chromatin /frequent

mitosis. - Scant cytoplasm. - Clear cytoplasm( glycogen): positive for PAS. - Homer-Wright rosettes (tr cells are arranged in a circle

about a central fibrillary space indicative of neural differentiation).

• Pattern: tumor is divided by fibrous septa into irregular lobules of closely packed round blue tumor cells.

• Tumor cells are arranged around capillaries.

• Areas of necrosis & acute inflammation present .

X-RAYS

• Lytic,destructive tumor with permeative margins with patchy subperiosteal, successive reactive bone formation producing “onion-skin” radiographic appearance.

• Invade cortex & periosteum producing soft tissue mass.

• SUN-BURST (hair on end appearance) when new bone is laid down perpendicular to cortex.

• CODMAN TRIANGLE :formed b/w elevated periostium & destroyed cortex.

• IHC:

1) CD 99+(MIC 2+)

CLINICAL PRESENTATION

• Painful enlarging masses• Frequently tender, warm & swollen• Fever, leucocytosis, anemia & elevated

ESR,• Soft tissue ES• Treatment: chemotherapy Surgical excision Radiations• Prognosis: 75% 5-year survival

EWING SARCOMA

EWING SARCOMA

EWING SARCOMA

EWING SARCOMA

IHC ; CD99+(MIC 2+)

IHC (CD99; MIC-2)

GIANT CELL TUMOUR (OSTEOCLASTOMA)

GIANT CELL TUMOR (OSTEOCLASTOMA)

• Uncertain histogenesis• Age: 20-40 yr with no sex predilection• Believed to have monocyte-macrophage

lineage• Site : EPIPHYSES of long bones , majority

around knee joint• Most are solitary• Multiple or multicentric in distal extremities

MORPHOLOGY

• GROSS: Large red brown masses Areas of cystic degeneration• MICROSCOPICALLY: 1) Uniform oval mononuclear cells with

indistinct cell borders which appear to grow in syncytium (neoplastic component)

2) Osteoclast type giant cells (100 or more nuclei): is the non-neoplastic component, scattered REGULARLY throughout the tumor.

• D/D:

1) brown tumour of hyperparathyroidism,

2) giant cell reparative granuloma,

3) chondroblastoma &

4) pigmented villonodular synovitis

Biologic behaviour

• Aggressive lesions

• About 40-60% recur after curretage

• Approx. 4% result in distant metastases

• Grading of giant cell tumor : not satisfactory

• Malignant transformation following radiotherapy

X-RAYS

• Large , purely lytic , & eccentric lesion at the end of expanded long bone

• Overlying cortex is destroyed producing soft tissue mass delineated by thin shell of reactive bone

• Characteristic “ SOAP BUBBLE” appearance

GCT

GCT (BONE)

Giant Cell Tr

Giant cell tr

Giant cell tumour

GCT

ANEURSYMAL BONE CYST (ABC)

ABC

• Benign bone tr. • Formation of of multiloculated blood filled

cystic spaces.• Rapidly growing, EXPANSILE LESION.• Recurring, rapidly destructive lesion.• Less than 20yrs.• Not a true cyst but rather a collection of

blood filled cytic spaces NOT LINED BY ENDOTHELIUM.

LOCATION:

• Metaphyseal region of long bone or

• Vertebra (dorsal elements).

• Eccentric

CYTIGENETICS:

• Upregulation of USP-6 fusion gene(chr17).

Radiology: X-ray:-

1. Lytic, expansile, destructive,

2. Eccentric bone lesion (BLOW –OUT) appearance.

3. Well defined margins

4. Metaphyseal location.

CT/MRI: Peculiar fluid filled levels & internal septa

L/M:

1. Lesion has vascular spaces ranging from small cap sized to large sinusoids separated by fibrous septae (spindle shaped fibroblasts, scattered m/n giant cells, osteoblasts associated with reactive immature woven bone (fibre osteoid).

2. Cartilage type matrix (BLUE BONE):1/3 cases.

• ABC like areas can be seen :

1. GCT.

2. CHONDROBLASTOMA.

3. Fibrous dysplasia.

• SOLID VARIANT of ABC.

METASTATIC TUMOURS

METASTATIC TUMORS

• Most common form of skeletal malignancy• 75% in adults come from prostate, breast,

kidney & lung malignancies.• In children, neuroblastoma, Wilms tumor &

rhabdomyosarcoma send their metastatic secondary deposits to bone.

• Typically multifocal deposits but can be solitary • Site: axial skeletal , femur ,& humerus• Radiographically: Purely lytic Purely blastic Mixed lytic & blastic

• Lytic lesions in cases of Ca kidney, lung, GIT, malignant melanoma

• Blastic lesions in prostate adenocarcinoma

• Mixed lytic & blastic in majority of metastases

• 85 SLIDES

FIBROUS & FIBRO-OSSEOUS TUMOURS

FIBROUS & FIBRO-OSSEOUS TUMORS

• 1) Fibrous cortical defect (FCD ,MFD)

• 2) Non-ossifying fibroma (NOF)

• 3) Fibrous dysplasia

• 4) Fibrosarcoma

• 5) Malignant fibrous histiocytoma

1) FIBROUS DYSPLASIA

• Benign tumor likened to development arrest

• Three clinical presentations:

1. Monostotic

2. Polyostotic

3. Polyostotic with café au lait skin pigmentations & endocrine abnormalities

1) MONOSTOTIC FIBROUS DYSPLASIA

• 70% of all cases

• Equally seen in boys & girls

• Early adolescence

• Asymptomatic or cause enlargement & distortion of bone

2) POLYOSTOTIC FIBROUS DYSPLASIA

• 27% of cases

• Younger age

• Involvement of shoulder & pelvic girdles resulting in crippling deformities like shepherd crook deformity & spontaneous fractures

3) McCUNE-ALBRIGHT SYNDROME

• Polyostotic firous dysplasia with café au lait skin pigmentation and endocrinopathies

• Sexual precocity, hyperthyroidism, pituitary adenomas, & adrenal hyperplasia

MORPHOLOGY of FIBROUS DYSPLASIA

• Well circumscribed lesions• Tan white & gritty• Composed of curvilinear trabeculae of

woven bone resembling chinese letters & shapes.

• Surrounded by moderately cellular fibroblastic proliferation

• Bone trabeculae lack osteoblastic rimming

X-RAYS

• Typical ground glass appearance & well-defined margins

FIBROUS DYSPLASIA

DEVELOPMENTAL & ACQUIRED ABNORMALITIES

• Complex, variable

• Frequently genetically based

• Manifest during early age

• Collectively termed skeletal dysplasias

SYSTEMIC DISORDERS:

• 1) Achondroplasia

• 2) Osteogenesis imperfecta

• 3) Osteopetrosis

• 4) Foetal rickets

1) ACHONDROPLASIA

• Major cause of dwarfism

• Defect in paracrine system resulting in reduction in proliferation of chondrocytes in growth plates

• Enlarged head with bulging forehead, shortened proximal extremities depression of root of nose

• Normal intelligence, reproductive status

2) OSTEOGENESIS IMPERFECTA(BRITTLE BONE DISEASE)

• Type I collagen defect disease

• Skeletal manifestations & changes in structure of tissue rich in type I collagen like joints, eyes, ears, skin, & teeth

• Morphologically : Too little bone

Osteoporosis with cortical

thinning

LOCAL DEFECTS:

• Failure of development of bone (congenital absence of phalanx, rib or clavicle)

• Formation of extra bones( supernumerary ribs or digits)

• Fusion of two adjacent digits (syndactyly)

• Development of long ,spider like digits

Four major subtypes

• OI TYPE I :Postnatal fractures

blue sclerae

• OI TYPE II: Perinatal lethal

• OI TYPE III :Progressive deforming

• OI TYPE IV: Postnatal fractures

Normal sclerae

3) OSTEOPETROSIS(MARBLE BONE DISEASE)

• Rare genetic disease characterized by reduced osteoclast bone resorption

• Diffuse skeletal sclerosis• Stone like quality of bones (too much bone)• Four types• Bones lack medullary cavity & ends of long

bones are bulbous• Neural foramina are small

METABOLIC & ENDOCRINE BONE DISEASES

• Osteoporosis

• Osteomalacia & rickets

• Scurvy

• Hyperparathyroidism

• Thyroid dysfunctions

• Renal osteodystrophy

• Skeletal fluorosis

OSTEOPOROSIS(OSTEOPENIA)

OSTEOPOROSIS(OSTEOPENIA)

• Reduced bone mass & increase fractures

• May be localized or generalized

• LOCALIZED: Disuse osteoporosis of limb

• GENERALIZED:

1) PRIMARY: Postmenopausal

Senile

Idiopathic

Cont.

2) SECONDARY:

a) ENDOCRINE: Hyperparathyroidism

Hypo-hyperthyroidism

Hypogonadism

Pituitary tumors

Diabetes, type I

Addison disease

b) DRUGS : Anticoagulants

Chemotherapy

Corticosteroids

Anticonvulsants

Alcohol

c) NEOPLASIA: Multiple Myeloma

Carcinomatosis

d) GASTROINTESTINAL: Malnutrition Malabsorption Hepatic insufficiency Vit.C , D deficienciese) MISCELLANEOUS: Osteogenesis imperfecta Immobilization Pulmonary disease Homocystinuria Anemia

PATHOGENESIS

• Peak bone mass is achieved in early adulthood after cessation of modelling

• Depends on 1):Hereditary factors like type of vit. D receptor inherited, gene for collagen 1A1, estrogen receptors, insulin –like growth factor

2): Physical activity 3): Muscle strength 4): Diet 5): Hormonal state 6): Sex: more in females

Cont.

• In 4th decade, amount of bone resorbed by BMU exceeds that what is been formed resulting in steady decrease in skeletal mass.

• Average 0.7% bone loss per year• Rapid bone loss in women following

menopause• More in whites

MORPHOLOGY

• Entire skeletal is involved but certain regions are more severely involved

• More in those bones that have increase surface areas such as vertebral bodies

• Trabeculae are thinned , lose their connections leading to microfractures & collapse

• Clinical features: Loss of height Lumbar lordosis & kyphoscoliosis Fractures• Prevention: Exercise Calcium & Vit. D intake Pharmacologic agents

PAGET DISEASE( OSTEITIS DEFORMANS)

• Collage of matrix madness• Three phases: 1): initial osteolytic stage 2): mixed osteoclastic- osteoblastic stage 3): osteosclerotic stage• Age: mid- adulthood• More in whites• Common in Europe, America, Australia• Rare in native populations of Scandavia, China,

Japan, & Africa

PATHOGENESIS

• First described by Sir James Paget

• Thought to be inflammatory

• Followed by many hypotheses

• Finally again considered as infective process

• Slow virus infection by paramyxovirus

• Hyperresponsive to vit. D & RANKL

• Familial predisposition

MORPHOLOGY

• Bone resorption with many osteoclasts• Mixed stage resulting in MOSAIC pattern of

cement lines• Quiscent osteosclerotic stage: After many

years, excessive bone formation results so bone becomes compact producing osteosclerosis

• Cotton-wool appearance on X-rays

HYPERPARATHYROIDISM

• Primary or secondary• Entire skeleton is affected• Increased osteoclastic activity• Thin cortex• Osteoclasts tunnel into & dissect centrally along length of

trabeculae (RAIL-ROAD) producing dissecting osteitis• Predisposes to microfractures & hemorrhages with

multinucleated giant cells creating BROWN TUMOR• Generalized osteitis fibrosa cystica ( von Recklinghausen

disease): Severe hyperparathyroidism. Combination of increased bone activity, peritrabecular fibrosis, & cystic brown tumors

RENAL OSTEODYSTROPHY

• Seen in ch. renal disease• Involves two events: hyperphosphataemia &

hypocalcemia• HYPERPHOSPHATAEMIA: In CRF, impaired

PO4 excretion leads to its retention. Cause secondary hyperparathyroidism

• HYPOCALCEMIA: Occurs due to decrease conversation of vit. D metabolite to its active form

• METABOLIC ACIDOSIS: