Sarcomatoid Carcinomas

Sarcomatoid CarcinomasSarcomatoid Carcinomas

Dr. Serpil Dizbay SakDr. Serpil Dizbay Sak

A group of poorly differantiated non-A group of poorly differantiated non-small cell lung carcinomassmall cell lung carcinomas

Common denominatorCommon denominator SarcomaSarcoma or or sarcoma likesarcoma like

differentiationdifferentiation

Morphologic components in Morphologic components in lung carcinomaslung carcinomas

EpithelialEpithelial Squamous cellsSquamous cells GlandsGlands Indiffferentiated Indiffferentiated

epithelial cellsepithelial cells Small Small

neuroendocrine neuroendocrine cellscells

Non-epithelialNon-epithelial Spindle cellsSpindle cells Giant cellsGiant cells Sarcoma Sarcoma

component component MuscleMuscle BoneBone CartilageCartilage

Non-epithelial components in Non-epithelial components in lung carcinomalung carcinoma

Described by Kika (1908)Described by Kika (1908) Barbarkos (1985): 49 casesBarbarkos (1985): 49 cases

TerminologyTerminology

sarcomatoid carcinomasarcomatoid carcinoma pleomorphic carcinomapleomorphic carcinoma giant cell carcinomagiant cell carcinoma spindle cell carcinomaspindle cell carcinoma biphasick lung tumorbiphasick lung tumor pseudosarcomatous carcinomapseudosarcomatous carcinoma carcinosarcomacarcinosarcoma pseudosarcomapseudosarcoma ..............................

WHO (1981)WHO (1981)

I. I. Epithelial tumorsEpithelial tumorsA.A. BenignBenignB.B. Displasia-carcinoma Displasia-carcinoma

in situ in situ C. MalignantC. Malignant 1.Squamous cell ca.1.Squamous cell ca. -spindle cell -spindle cell

carcinomacarcinoma4. Large cell ca.4. Large cell ca.

--giant cell carcinomagiant cell carcinoma

II.Tumors of the soft II.Tumors of the soft tissuetissue

III.III.Mesothelial tumorsMesothelial tumors

IV. MiscelleneousIV. Miscelleneous tumorstumors1.carcinosarcoma1.carcinosarcoma

2.pulmonary 2.pulmonary blastomablastoma

3...........3...........

Pleomorphic sarcomatoid ve Pleomorphic sarcomatoid ve sarcomatous elemanlar içeren sarcomatous elemanlar içeren

carcinomascarcinomas ( (WHO 99)WHO 99)

a. Carcinomas witha. Carcinomas withspindle and/or giant cells spindle and/or giant cells 1.pleomorphic carcinoma1.pleomorphic carcinoma 2.spindle cell carcinoma2.spindle cell carcinoma 3.giant cell carcinoma3.giant cell carcinoma

b.carcinosarcomab.carcinosarcomac.pulmonary blastomac.pulmonary blastoma

sarcomatoid carcinoma sarcomatoid carcinoma (WHO 2004)(WHO 2004)

pleomorphic carcinomapleomorphic carcinoma spindle cell carcinomaspindle cell carcinoma giant cell carcinomagiant cell carcinoma carcinosarcomacarcinosarcoma pulmonary blastomapulmonary blastoma

Epidemiological and Epidemiological and Ethiological FeaturesEthiological Features

General featuresGeneral features Age:60Age:60 M/F:4/1 M/F:4/1

Pulmonary Pulmonary blastoma:blastoma: M/F:1/1M/F:1/1 Fourth decadeFourth decade

SmokingSmoking Asbestosis Asbestosis

sarcomatoid carcinomas: sarcomatoid carcinomas: rare tumorsrare tumors

Within all lung carcinomasWithin all lung carcinomas 0.3- 1.3 % 0.3- 1.3 %

A spindle cell tumor in lung A spindle cell tumor in lung Most likely a sarcomatoid Most likely a sarcomatoid

carcinomacarcinoma


pleomorphic carcinomapleomorphic carcinoma spindle cell carcinomaspindle cell carcinoma giant cell carcinomagiant cell carcinoma carcinosarcomacarcinosarcoma pulmonary blastomaapulmonary blastomaa

Ankara University School of Ankara University School of Medicine 2000-2006 MarchMedicine 2000-2006 March

26 cases26 cases 23M; 3F23M; 3F

Age: 43-78Age: 43-78 61.161.1

26 cases26 cases

Epithelial Epithelial componentcomponent adenocarcinoadenocarcino

ma: 12 ma: 12 squamous: 8 squamous: 8 large cell: 2 large cell: 2

sarcomatoid sarcomatoid componentcomponent giant cell:15giant cell:15 spindle:18spindle:18

26 Cases26 Cases

1: single component (giant cell)1: single component (giant cell) 19: two components19: two components 5: three components5: three components 1: four componets1: four componets

Typical cells of sarcomatoid Typical cells of sarcomatoid carcinomacarcinoma

spindle cellsspindle cells giant cellsgiant cells

These cells should be malignant!!These cells should be malignant!!

CD68Keratin CD68



pleomorphic carcinomapleomorphic carcinoma

Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell neuroendocrine neuroendocrine


spindle cell spindle cell carcinomacarcinoma

giant cell giant cell carcinomacarcinoma

10 % minimum

WHO

WHO

WHO


Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell




Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell



pleomorphic carcinomapleomorphic carcinoma Non-small cell Non-small cell

carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell





spindle cell carcinomaspindle cell carcinoma A lung carcinoma with A lung carcinoma with onlyonly spindle spindle

cellscells MalignantMalignant spindle cells forming: spindle cells forming:

Cohesive islandsCohesive islands FasciclesFascicles Storiform organizationStoriform organization

A prominent lymphoplasmacytic A prominent lymphoplasmacytic infiltrationinfiltration (Inflammotory sarcomatoid carcinoma (Inflammotory sarcomatoid carcinoma

Wick, 1995)Wick, 1995)

spindle cell carcinomaspindle cell carcinoma

Epithelial Epithelial differentiationdifferentiation Absent by HEAbsent by HE Can be Can be

demonstrated bydemonstrated by İmmunohistochemistİmmunohistochemist

ryry EMEM

Inflammatory sarcomatoid Inflammatory sarcomatoid carcinomacarcinoma

Moderate Moderate pleomorphismpleomorphism

Spindle cellsSpindle cells OrganizationOrganization

FascicularFascicular StoriphormStoriphorm

Can have mixoid Can have mixoid areasareas

Keratin



giant cell carcinomagiant cell carcinoma

pleomorphic mono/multinuclear giant pleomorphic mono/multinuclear giant cellscells large, multilobulated, discohesive cellslarge, multilobulated, discohesive cells

No additional componentNo additional component

WHO

giant cell carcinomagiant cell carcinoma

İnflammation with İnflammation with prominant prominant neutrophile neutrophile leucocytesleucocytes

Within the tumor Within the tumor cells cells Phagocytosis?Phagocytosis? Emperipolesis?Emperipolesis?

TTF1


pleomorphic carcinomapleomorphic carcinoma spindle cell carcinomaspindle cell carcinoma giant cell carcinomagiant cell carcinoma carcinosarcomacarcinosarcoma pulmonary blastomaapulmonary blastomaa

carcinosarcomacarcinosarcoma

carcinoma (non-carcinoma (non-small cell)small cell) squamous cell 70 %squamous cell 70 % adeno 20-30 %adeno 20-30 % large cell %10large cell %10

Differantiated Differantiated sarcomasarcoma Malignant cartilageMalignant cartilage Malignant boneMalignant bone Malignant muscleMalignant muscle

&

WHO

WHO


Sarcomatous component is more Sarcomatous component is more prominent in most cases:prominent in most cases: carcinoma component must be searched carcinoma component must be searched

Sarcoma may consist of Sarcoma may consist of indifferantiated ‘spindle’ cells in most indifferantiated ‘spindle’ cells in most areas:areas: Differantiated sarcoma component Differantiated sarcoma component

must be searchedmust be searched


In metastasesIn metastases Both componentsBoth components OrOr

carcinoma onlycarcinoma only Sarcoma only Sarcoma only



blastomablastoma

pulmonary pulmonary blastomablastoma

Pleuropulmonary Pleuropulmonary blastomablastoma

Monofazik pulmonary blastoma: Fetal adenocarcinoma: İyi diferansiye fetal adenocarcinoma

Force&Patterson, 2003

pulmonary blastomaapulmonary blastomaa

Barret ve Barnard Barret ve Barnard 19451945

Spencer Spencer 1961 1961 Anologous of other “blastomas”?Anologous of other “blastomas”?

A tumor of adulthoodA tumor of adulthood General features do not fit in a General features do not fit in a

“blastoma” profile “blastoma” profile A peripheral paranchimal sarcomatoid A peripheral paranchimal sarcomatoid

carcinoma carcinoma (Souza, Stackhouse, Millard)(Souza, Stackhouse, Millard)

pulmonary blastomapulmonary blastoma

Epithelial Epithelial componentcomponent Well differantiated Well differantiated

fetal fetal adenocarcinomaadenocarcinoma

Primitive Primitive mesenchymal mesenchymal stromastroma

In some casesIn some cases OsteosarcomaOsteosarcoma ChondrosarcomaChondrosarcoma RhabdomyosarcomRhabdomyosarcom

a a


Tubules rich in Tubules rich in glycogenglycogen

Primitive stromaPrimitive stromafetal lung

10-16 gestationel week

pulmonary blastomaapulmonary blastomaa

GlandsGlands pseudostratifiedpseudostratified non-ciliatednon-ciliated columnarycolumnary

CytoplasmCytoplasm Clear- light Clear- light

eosinophiliceosinophilic NucleiNuclei

UniphormUniphorm


intracytoplasmic intracytoplasmic vacuoles vacuoles “endometrioid” “endometrioid” SubnuclearSubnuclear SupranuclearSupranuclear PAS pozitivePAS pozitive

MorulesMorules Neuroendocrine Neuroendocrine


Makishi,2006

Keratin SYN


Stromal cellsStromal cells Blastema likeBlastema like ovale-spindle cells ovale-spindle cells

on a mixoide on a mixoide backgroundbackground

Condansation Condansation around glandsaround glands

WHO


SarcomaSarcoma spindle cellsspindle cells rhabdomyosarcomarhabdomyosarcoma chondrosarcomachondrosarcoma OsteosarcomaOsteosarcoma

WHO

pleomorphic pleomorphic carcinoma carcinoma sarcomatoid sarcomatoid componentcomponent TTF-1: 43.1 %TTF-1: 43.1 % CK7: 62.7 %CK7: 62.7 % SP-A: 5.9 %SP-A: 5.9 %

spindle and giant spindle and giant cell carcinomacell carcinoma TTF-1: 55 %TTF-1: 55 % CK7: 70 %CK7: 70 % SP-A :0 %SP-A :0 %

Keratin

TTF-1

TTF1

sarcomatoid carcinoma: sarcomatoid carcinoma: differential diagnosisdifferential diagnosis

localized fibrous tumorlocalized fibrous tumor sarcomatoid mesotheliomasarcomatoid mesothelioma inflammatory pseudotumorinflammatory pseudotumor primary and metastatic sarcomasprimary and metastatic sarcomas

Localized fibrous tumorLocalized fibrous tumor

Presentation ( a pleural tumor)Presentation ( a pleural tumor) Keratin (-)Keratin (-) CD34 (+)CD34 (+)

mesotheliomamesothelioma

PseudomesotheliomatousPseudomesotheliomatous sarcomatoid sarcomatoid carcinomacarcinoma Similar clinical presentationSimilar clinical presentation Biphasic tumor Biphasic tumor

Immunohistochemisty is of limited valueImmunohistochemisty is of limited value Keratin & vimentin coexpression in both Keratin & vimentin coexpression in both

tumorstumors Mesothelial markers (calretinin) may helpMesothelial markers (calretinin) may help TTF-1 is negative in mesotheliomaTTF-1 is negative in mesothelioma

sarcomatoid carcinomasarcomatoid carcinoma- inflammatory myofibroblastic inflammatory myofibroblastic

tumortumor

Usually in a childUsually in a child Benign looking cellsBenign looking cells InflammationInflammation Epithelial markers are negativeEpithelial markers are negative

Can be a problemCan be a problem

HistogenesisHistogenesis

1.1. Sarcomatoid component is reactiveSarcomatoid component is reactive

2.2. Multiclonal hyphotesis:Multiclonal hyphotesis:Collusion of two tumors originating from two Collusion of two tumors originating from two

different cellsdifferent cells

3.3. Monoclonal hyphotesis:Monoclonal hyphotesis:one stem cell, divergent differentiationone stem cell, divergent differentiation

• Morphological spectrumMorphological spectrum• Keratin expression in sarcomatoid componentKeratin expression in sarcomatoid component• Similar mutations in both componentsSimilar mutations in both components

Stem cell

Sarcoma

Carcinoma

Stem cell CarcinomaCarcinoma

Sarcoma

Nakajima, 1999

Nakajima,1999

Rossi,2003

Median:10.5 m.

Median: 9 m.

Median: 31 months

Sarcoma like tumor in lung:Sarcoma like tumor in lung:

“ “sarcomatoid” carcinomas are mor sarcomatoid” carcinomas are mor frequent in lung than in true frequent in lung than in true sarcomassarcomas

Generous sampling may helpGenerous sampling may help 1 sample for every cm.1 sample for every cm.

To find carcinomaTo find carcinoma To find differantiated sarcomaTo find differantiated sarcoma

Sarcoma like tumor in lung:Sarcoma like tumor in lung:

Try different epithelial markers and Try different epithelial markers and increase the number of stained increase the number of stained blocks when neededblocks when needed

KeratinKeratin TTF1TTF1 p63p63

Don’t push itDon’t push it Maybe it is really a SARCOMAMaybe it is really a SARCOMA

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Sarcomatoid Carcinomas