GIANT CELL TUMOUR

OSTEOCLASTOMA

GIANT CELL TUMOUR

IT is an aggressive lesion characterised by well vascularised tissue made up of plump spindly or ovoid cells in addition to numerous multinucleated giant cells uniformly dispersed through out the tumour tissue .

This lesion represents about 5% of all primary bone tumours

GIANT CELL TUMOUR

It is distinct neoplasm of undifferentiated cell

Locally aggressive Usually Benign neoplasm Involves the end of the bone At the epiphysio metaphysial area Usually after epiphyseal closure

GIANT CELL TUMOUR

Exact cell of origin not known Can be from marrow monocyte Consists of proliferating mononuclear

cells and multinucleated giant cells

HISTORY

HISTORY JOHN HUNTER &JOHN ABERNETHY-1804 –

first classified about tumour

In 1818 SIR ASTLEY COOPERS and TRAVERS first described about this lesion

They called this fungus medullary exostosis

This tumor was thought to be malignant and often treated with amputation

HISTORY

1853-PAGET called it BROWN or MYLEOID tumour

1912-BLOODGOOD first coined the phrase GIANT CELL TUMOUR OF THE BONE then only the nonmalignant behavior of this lesion was first established

GIANT CELL TUMOUR

INCIDENCE-

Peak incidence 20-40

Can occur before physial closure then it will be in metaphysis

female :male =1.5 :1

In SEA countries incidence is 20% of primary tumour

GIANT CELL TUMOURLOCATION

Distal femur 27 Proximal tibia

20 Distal radius Sacrum

11 Distal tibia 5 Proximal humerus 4 Proximal femur 4

CLINICAL FEATURES

PAIN –near articular cartilage

SWELLING -eccentric

Clinical features

JOINT SYMPTOMS Weakness limitation of motionPain when there is pathological fractureTenderness with EGG SHELL CRACKINGDue to jt invovement disuse atrophy ,jt

effusion,

RADIOLOGY

ECCENTERIC expansible osteolytic lesion

Well demarcated or merges with metaphysis

Trabeculae- SOAP BUBBLE APPEARANCE

No periosteal new bone formation

Pathological fracture Subchondral bone

involvement Closed physis will be seen

CAMPANACCI GRADINGAccording to Radiology

Stage I-Normal bony contour Stage II- Expansile lytic lesion but no break in cortex Stage III-Destructive radiolucent lesion, cortical break

and soft tissue involvement BETTER PROGNOSIS-Outer border-intactInner margin-sharp AGGRESSIVE –Cortical breakSoft tissue involvement

MRI AN CT

It helps in early diagnosis and soft tissue involvement.

FALSE POSITIVE or NEGATIVE

In the spine ,tumors such osteoblastoma, ABC and metastasis may be found in the same location as GCT

They may have overlapping MRI characterstics

PATHOGENESIS

Hypothesis by GESHICKTER and COPELAND-

Spindle shaped neoplastic mononuclear cells stimulate immigration of blood monocyte into the tumour tissue and promote formation of OSTEOCLAST LIKE GIANT CELLS

The giant cells are innocent lookers but the culprit are SPINDLE CELLS

MONONUCLEAR SPINDLE SHAPED CELLS

Chromosome abnormality Neoplastic oncogene-p53

,C-myc ,C-fox, N-myc

CYTOKINE DIFFERENTIATE FACTOR

Macrophage recruitment activation TNF ,IFNע ,M- CSF

Fusion of mononuclear cells

MULTINUCLEATED GIANT CELLS

TYPICAL HISTOLOGY

Multinucleated giant cells

Round mononulear cells

Spindle shaped cells

SPINDLE SHAPEDCELLS

ATYPICAL HISTOLOGY

Giant cells with predominance of spindle cells and this can be mistaken for FIBROSARCOMA

Tumour in blood vessels

MONONUCLEAR CELLS

Phenotypically resembles connective tissue stromal cells

Receptors for parathyroid hormone

Produce collagen Don’t express

macrophage surface antigen

MULTINUCLEATED GIANT CELLS

Multinucleated giant cells (50-150nuclei,10-15 microns) are formed from mononuclear cells

PREDOMINANT TYPE-Large multinucleated cells where individual nuclei are identical to stromal cells

MINORTY-Small size, dark pyknotic nuclei ,bright eosinophilic cytoplasm

MULTINUCLEATED GIANT CELLS

STROMAL CELLS DERIVED FROM

TYPE I-Fibroblast or undifferentiated bone marrow mesenchymal cells

TYPE II-monocyte –macrophage osteoclast lineage

Rarely contain foci of reactive bone so not to confuse with OSTEOSARCOMA

PATHOLOGY

Giant cells are not diagnostic They are also seen inABC,UBCNonossifying fibromaChondroblastomaBrown tumourFibrous dysplasiaOsteogenicsarcomaThese are variant of GCT

EVING and JAFFE GRADINGSTAGE STROMA GIANT CELLS

I CONSPISIOUS PLENTY

II PROMINENT REDUCED NUMBER

III SARCOMATOUS SPARSE

SECONDARY CHANGES IN GCT

TREATMENT AIM

Eradicate the growth completely at the initial surgery

Local ablation without sacrificing joint function

Lowers the risk of reccurence The appropriate treatment has been

controvorsial

CHONDROBLASTOMA(histology)

In nuclei there will be folding or cleft Stromal background Mononuclear cells will be rounded

whereas it will be spindle shaped in GCT.

Preop management and planning Aggressive nature of this lesion so firm

diagnosis should be established ie malignancy should be ruled out by prior biopsy and other investigation.

OPERATIVE PLAN MUST INCLUDE THIS THREE FACTORS

1.type of resection.2.The use of adjuvant therapy3.Type of material to be used to fill the

defect

TREATMENT Intralesional curettage. EN BLOCK exicision Curettage (if the joint surface can be saved) Curettage and bone grafting Curettage with adjuvant chemotherapy and

biphosphonate Curettage and acrylic bone cementation Curettage and cryosurgery Excision and reconstruction Irradiation Embolisation

EN BLOCK EXCISION

Lesions of sacrificial part Lower end of ulna Upper end of fibula Phalanges Metatarsals rays

INTRALESIONAL CURRETAGE

Adequate exposure with large cortical window

High power burr Pulsatile jet lavage

If Curratage only used than recurrence rate is 40%(mayo clinic study)

ADJUVANT TO AUGMENT CURRATEGE

PHENOL-12-50% conc

Disadvantage-

Easily absorbed

Nephrotoxic

High nonunion rate

Soft tissue complication

HYDROGEN PEROXIDE

ADJUVANT S BONE CEMENT Bone cement

+ADRIAMYCIN+METHOTREXATE to reduce recurrences

Cementation with calcium phosphate

CRYOSURGERY WITH LIQUID NITROGEN -196’ ;it create 1-2cm zone of tissue necrosis.

CostLocal complicationNot easily availableStorage difficulties# rate increased

DO THESE ADJUVANT HELP

YES It eliminate the microscopic disease Curettage and cementation causes a 2mm

osteolytic lesion zone surrounding the cement due to thermal injury

REMOVAL of tumour seems to be more important factor

Trieb et al- recurrence rate is same

CEMENTINGADVANTAGE DISADVANTAGE

The monomer is cytotoxic

Thermal effect

Radiographic detection of recurrence is easier

Immediate structural support and early ambulation

Not biological material so strong in compression but weak in shear and torsional forces

Fear of long term degeneration of articular cartilage in subchondral lesion in wt bearing stress

TREATMENT

Chen-chen 2005 -when residual subchondral bone after an extended curretage is <5mm then multilayer reconstruction technique is recommended

REINFORCEMENT PINS

STEINMANN pins has been used to to reinforce bone cement used to fill large subchondral defects

SOME FORM OF INTERNAL FIXATION SHOULD BE THERE

ARGON CAUTERIZATION

BONE GRAFT(if no cryotherapy is used )

ADVANTAGE DRAWBACK

Remodelling along stress lines

Autograft quantity is less

Reconstruction is permanent Donor site morbidity

Allograft is expensive

Recurrence is difficult to spot

EXCISION AND RECONSTRUCTION

TURN O PLASTY Arthrodesis Arthroplasty

WIDE RESECTION AND RECONSTRUCTION

Larger the area of subchondral bone affected worse prognosis

Thus even in benign tumour resection may be the preferred option

When the skeletal integrity is unlikely to be restored after healing leading to compromise in ultimate function

OPTION

MEGA JOINT REPLACEMENT Biological reconstruction like autograft

arthrodesis microvascular fibular reconstruction

ILIZAROV method Osteoarticular allograft

CHEMOTHERAPY

NO effective chemotherapy agent available

RADIOTHERAPY When complete excision or curratage is

not possible Aggressive, multiple recurrent tumor The use of modern megavoltage

radiation may reduce the rate of malignant transformation

EMBOLIZATION

Transcatheter embolization of blood supply

Reembolisation monthly

Certain unresectable tumor like sacral,pelvic

PREOP EMBOLIZATION

Resectable tumor-perop bleed and size

BIPHOSPHONATE

Pamidronate, zoledronate It induces apoptosis in osteoclast like

giant cells Help in limiting tumour progression

AMPUTATION

Malignant tumour Fungation Recurrence after surgery and irradiation Deep seated associated infection Extensive destruction of bone Severe disability

RECCURENCE

Mainly due to incomplete initial removal of tumor

majority occurs with in 2 years

MANAGEMENT- Steyern et al-same as that of primary

DIAGNOSIS OF RECCURENCE

Curretage and cementation causes a 2mm osteolytic zone surrounding the cement due to thermal injury

A thin sclerotic rim forms by 6 months Failed development of sclerotic margin

ay suggest reccurence Akhane et al-total ser acid phosphatase

can be used as tumour marker

METASTASIS

Mean interval is 2-5 years LUNG-commonestGood prognosis unlike other tumour Regional LN, mediastinum Scalp, pelvis It looks like primary Treatment is wide resection like

lobectomy

MALIGNANT GCT Tender mass in the region of

previously treated GCT Skin changes from prior radiation

therapy c/o pain H/O previously GCT average

10yrs backCommonly post irradiation 75%Rarely at the treated surgical site of

GCTPOOR PROGNOSISTREATMENT-Preop chemotherapy+wide surgical

resection or amputation

MULTICENTRIC

Multicentric GCT occurs in <1% of all patients with GCT.

ONLY 43 patients are reported till now

MALIGNANT GCT

X RAY DD

Benign GCT,reccurence GCT

Osteomyleitis

PATHOLOGY-tumour breaks cortex, necrosis,soft tissue extension ,hemmoragic foci,

Histology-nuclear pleomorphism

DIFFERENTIAL DIAGNOSISRADIOLOGICAL

Chondroblastoma

Osteosarcoma

fibrosarcoma

Malignant fibrous histiosarcoma

PATHOLOGICAL

Benign malignant

ABC,chondroblastoma,

GCreparative granuloma

Malignant fibrous histiosarcoma,Malginant GCT,Osteosarcoma containing GCT

IF not treated then it Leads to destruction of cortical bone to soft tissue invasion and finally ulceration of skin

CONCLUSION

GIANT CELL TUMOUR is challenging surgical problem due to its divergent unprediticable and biological behaviour

Modality of treatment is essentially surgical For conservation of limb en block resection with

reconstruction is best

But commonly used is intralesional curettage Irradiation is for nonaccessible lesion Amputation is resort of desperation

FUTURE GENETIC

No recurrent chromosomal structural or numeric aberation of importance has been detected yet…

When confronted with rearrangemnt ,especially concerning 16q22 or 17p3,an associated ABC should be excluded

Cytogenetic morphological

The most frequent anamoly is telomeric association,the most most frequent association 11p,13p,14p,15pand 19,20,21q

FUTURE

Clinical studies on treatment on GCT with CALCITONIN have shown positive results probably due to control of OSTEOCLASTOGENESIS

OSTEOPROTEGRIN influences osteoclastogenesis and may be used for the treatment of GCT