Carcinosarcoma

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Abstract

Carcinosarcoma is a very rare, aggressive tumour composed of epithelial and stromal components which both fulfill criteria of malignancy.This presentation is based on a case of carcinosarcoma which was located in the left side buccal mucosa of a 70 year old male patient who was presented to DHP and then treated with surgical resection of the lesion and neck dissection.

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INTRODUCTION

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CARCINOSARCOMA

malignant neoplasm that contains elements of carcinoma

and sarcoma, extensively intermixed as to indicate

neoplasia of epithelial and mesenchymal tissue.

Source: National Institute of Health-USA4

EPITHELIAL COMPONENTUndifferentiated SCCSquamous cell carcinomaPoorly differentiated adenocarcinoma

It may also include ,Adenoid cystic carcinomaEpithelial myoepithelial carcinomaSalivary duct carcinoma.

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NON-EPITHELIAL COMPONENT.Undifferentiated spindle cell sarcoma

Other reported sarcomatous elements include, FibrosarcomaOsteosarcomaLeiomyosarcomaLiposarcomaFollicular dendritic cell sarcomaUndifferentiated sarcomaMyxoid sarcomasRhabdomyosarcomaChondrosarcoma 6

Incidence inside the oral cavityExtremely rareFew cases had been reported

TongueGingivaeFloor of the mouthBuccal mucosa

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Aggressive nature of the tumor

Undergo Rapid growth Difficulty of complete surgical removal

due to, Lack of demarcati0n between normal and pathological tissues

Invasion.

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TREATMENT

• Due to the aggressive nature and high rate of recurrence carcinosarcomas are treated with,

• Surgical excision Together with

• Chemotherapy• Radiotherapy

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Case report

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A 70 year old male presented with a swelling on left side cheek for 3months duration.

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Complain of : Patient was referred from ++++++

Hospital due to a growth on left side cheek.History of presenting complaint :

Patient noticed a small lump on the L/S cheek 3 months back. It grew rapidly. Patient visited to +++++++ hospital ,from there he was referred to DHP.

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Past Medical History : No abnormality detected

Past Dental History : No Significant past dental history

Social History :MarriedFather of a 2 childrenSupervisor at a tea estate

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Habits : Chewing betel for 20-30 years4-5 quids per day with all ingredients

Family History : No relevant family history

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ExaminationGeneral Patient was distressed

Extra oral examinationInspection : No significant findingsPalpation : Firm swelling on L/S cheek

Intra oral examination : 2 lesions

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Major lesion Site : Left side cheekSize : 3×2×1.5cmShape : More or less oval in shapeColour: Brownish to Gray in colourConsistency : FirmNon tenderPedunculated mass

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Anterior cheek lesionSite : extend to Lt side commissural regionSize : 1×1.5cm in sizeMargins : elevated margins with irregular

surface Ulcerated Indurated

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Provisional Diagnosis

Squamous cell carcinoma

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Special investigations

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Ultra sound scan of NeckMultiple reactive lymph nodes in Lt side level

I & II No evidence of metastasis

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BiopsyMultiple incisional biopsies from major

lesion,base of the major lesion & anterior cheek lesion were taken under GA & sent for histopathological investigations.

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Histopathological Findings

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Histopathological findingsMain specimen

o Ulcerated, unencapsulated tumour.o Composed of spindle cells with

increased mitosis.o Few duct like structures lined by

dysplastic epithelium within the tumour

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Specimen from anterior cheek lesion & base of the major lesion - islands of squamous cell carcinoma invading in to superficial corium

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Squamous cell Ca.

Spindle cell Sarcoma

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Squamous cell Ca.

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Immunohistochemistry• Spindle cell component: smooth muscle actin & vimentin positive

• Ductal component: cytokeretin positive, S100 negative

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Actin Positive Spindle cell component

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Cytokeratin Positive

These histopathological and immunohistochemical features are consistent with

those of

Carcinosarcoma

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ManagementLt. cheek resection & reconstructed with

forehead flapPartial alveolectomy of Lt side jawSupraomohyoid block dissection

Specimens were sent for histopathological investigatigations.

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Postoperative periodOn the 12th post operative day patient had

developed a salivary fistula.On 18th post operative day Falp revision was

done under LA.Patient has been discharged.

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CarcinosarcomaDiscussion

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Carcinosarcoma Definition

A malignant neoplasm that contains elements of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat) so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue.

Source: National Institute of Health-USA

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Synonyms

Carcinosarcoma(Minkler et.al. 1970)Spindle-cell carcinoma or Pleomorphic

Carcinoma(Ellis & Corio 1980,Zarbo et.al. 1986,Ellis et.al. 1987)

Spindle-cell SCCPseudosarcoma(Lane 1957)True malignant mixed tumourSarcomatoid carcinoma

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Classification

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Squamous cell carcinoma (SCC) is an epithelial malignancy with morphologic features of squamous cell differentiation without additional features suggestive of

other differentiated tissues.

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Oral SCC

Verrucous Ca. Exophytic or papillary Ca. Basaloid Ca. Adenosquamou

s Ca.Adenoid cystic

Ca.Carcinomaa cuniculatum

Spindle cell/Sarcomatoid

Ca

Variants of squamous cell carcinoma (SCC) frequently arise within the mucosa of the upper aero digestive tract, accounting for up to15% of SCCs in these areas.

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Each of these variants has a unique histomorphologic appearance, which raises a

number of different differential diagnostic considerations.

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Epidemiology

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Extremely RARE.

Head-and-neck sites ; in descending Frequency

LarynxOral cavityHypopharynx and pyriform sinusSinonasal tractOropharynx

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Carcinosarcoma (CS) is sometimes found in other parts of the body.

Incidence is more common in the upper body, particularly the lungs

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In oral cavity carcinosarcoma can arise from either salivary glands or oral

mucosa.

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Features Salivary glands Oral mucosa

1. Number of cases reported

70(Gnepp et.al in 1993)

6(T.Takata et.al.1991)

2. Sites Parotid 66% (commonest)SM 19%Palate 14%

Lower lip (commonest), Tongue, Floor of the mouth, Lower gingivae ,Buccal mucosa

3. Sex No significant sex predilection

Male > Female

4. Age Mean age 58yrs Mean age 72yrs

5. Presence of primary lesion

Most cases arise de novo. But occasionally may have a history of Pleomorphic adenoma.

De novo or from a preexisting SCC, Verrucous carcinoma, Leukoplakia

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Aetiology

IdiopathicRadiation /trauma has been emphasized by

some authors (Green & Bernier 1959)Accumulation of genetic mutations could be a

factor.

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Clinical Features

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Symptoms are often present for a short duration

Nearly all cases are described or received as;- Polypoid masses .- Mean size of about 2.0cm- Frequently ulcerated. - With a covering of fibrinoid necrosis.- Firm and fibrous cut surface. (Similar to conventional SCC, most tumours are T1 lesions at presentation.)

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These carcinosarcomas occur most frequently on the lower lip,tongue and alvelolar ridge in either polypoid,exophytic or endophytic configurations.

Surface ulceration is common with these tumors. As with any ulcerated lesion, these are likely to be infected and therefore may exude pus or contain abscess formation.

Cervical lymphadenopathy is infrequent,distant metastasis may/not present.

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Investigations

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•MRI•CT•Scintigraphy•Histopathological investigations;

- Incisional biopsy- Excisional biopsy- Immunohistopathological investigations.

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Ultra sound scanning to detect lymph node involvement.

Chest X-ray & Gastroendoscopy to detect distant metastases.

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HISTOLOGY

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• Carcinosarcoma composed of heterologous malignant epithelial & stromal components which both fulfill histological criteria of malignancy.

• Usually Sarcomatous component is predominent.

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Biphasic presentationUlceratedCarcinomatous component is either blended

or in transition with sarcomatous component.HypercellularityVariable patterns of spindle-cell growth in

sarcomatous componentPleomorphismIncreased mitotic figures

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Carcinomatous component is usually

Undifferentiated SCCSquamous cell carcinomaPoorly differentiated adenocarcinoma

It may also include Adenoid cystic carcinomaEpithelial myoepithelial carcinomaSalivary duct carcinoma.

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The sarcomatous component is usually,

Undifferentiated spindle cell sarcoma

Other reported sarcomatous elements include Fibrosarcoma Osteosarcoma Leiomyosarcoma Liposarcoma Follicular dendritic cell sarcoma Undifferentiated sarcoma Myxoid sarcomas Rhabdomyosarcoma Chondrosarcoma

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Areas of squamous differentiation are most consistently identified at the base of the polypoid lesion, at the advancing margins, or within invaginations at the surface where the epithelium is not ulcerated or denuded.(Condition is same in our patient)

CS will often present with little invasion into the underlying stroma, as it is polypoid.

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Extensive infiltration and tissue destruction are common, as is perineural invasion and angioinvasion. Lymphatic spread is less common.

Metastases to other sites or lymph nodes may show the carcinomatous or the sarcomatous components alone, or they may be mixed.

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Compare with our patient; Component In salivary

gland carcinosarcoma commenest

In oral mucosal carcinosarcoma

commenest

In our patient

Carcinomatous

Adenocarcinoma

Squamous cell carcinoma

Squamous cell carcinoma

Sarcomatous Chrondosarcoma

Undiferentiated Spindle cell sarcoma

Leiyomyosarcoma

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So its extremely difficult in making the correct diagnosis of this tumor from a small biopsy specimen.

It is well illustrated by varies diagnoses

based on biopsy specimens.

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Immunohistochemistry

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Immunohistochemical markers are used in aid of diagnosis.

Eg; -Cytokeratin - Vimentin - S-100 - Actin

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Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue.there fore carcinomatous componentwhich is derived from epithelial tissue is strongly positive for cytokeratin

Vimentin is a member of the intermediate filament family of proteins that is especially found in connective tissue. This filament is used as a marker for mesodermally derived tissues, and as such can be used as an immunohistochemical marker for sarcomas.

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Immunohistochemistry for smooth muscle actin & vimentin reveals positivity in spindle cell component while the squamous cell component shows cytokeratin positivity.

S-100 is negative.

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Our patient’s immunohistochemical profile

Immunohistochemical marker

Carcinomatous component

Sarcomatous component

Cytokeratin + -

Smooth muscle actin - +

Vimentin - +

S-100 - -

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HISTOPATHOGENISIS

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Two antithetical hypotheses have been advanced to explain the histogenesis of carcinosarcomas:

1. Multiclonal origin/ convergence hypothesis-arising from two or more stem cells

2. Monoclonal origin/ Divergence hypothesis-from a single totipotential stem cell that differentiates in separate epithelial and mesenchymal directions.

Recent immunohistochemical and chromosomal analyses appear to have settled this argument in favour of the monoclonal hypothesis.

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But some of the cases showed a sharp demarcation between the carcinomatous & sarcomatous elements without transition zone & different immunohistochemical staining pattern of the two components for epithelial & mesenchymal markers which suggests a different cell origin for each tumor cell types.

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However possibility remains that the demarcation may not signify a different origin, since carcinoma components are demarcated in some sarcomatoid carcinomas in which the sarcomatous component derives from metaplasia of the epithelial cells.

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Treatment modalities for sarcomatoid carcinoma.

• The primary treatment modality for sarcomatoid carcinoma should be the same as for squamous cell carcinoma which consists of;

1. SURGICAL EXCISION of the lesion with an adequate margin.2. ADJUVANT IRRADIATION may be

beneficial in patients who have positive surgical margin or who have nodal metastasis.

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The role of the chemotherapy has not been established, but it may decrease the incidence of recurrence or metastasis of primarily sarcomatous tissue.

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Prognosis Mean survival time of those dead of the

disease is 2 years.

No clinical or histomorphological characteristic other than distant metastasis was found to be a reliable prognostic indicator.

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SummeryA 70 years old male presented with a

rapidly growing swelling on left side cheek for 3months duration,and treated by surgical excision,was diagnosed as Carcinosarcoma.

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