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
sarcomatoid carcinoma sarcomatoid carcinoma (WHO 2004)(WHO 2004)
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
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
pleomorphic carcinomapleomorphic carcinoma
Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell neuroendocrine neuroendocrine
differentiationdifferentiation
spindle cell spindle cell carcinomacarcinoma
giant cell giant cell carcinomacarcinoma
10 % minimum
WHO
WHO
WHO
pleomorphic carcinomapleomorphic carcinoma
Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell
spindle cell spindle cell carcinomacarcinoma
giant cell giant cell carcinomacarcinoma
pleomorphic carcinomapleomorphic carcinoma
Non-small cell Non-small cell carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell
spindle cell spindle cell carcinomacarcinoma
giant cell giant cell carcinomacarcinoma
pleomorphic carcinomapleomorphic carcinoma Non-small cell Non-small cell
carcinomacarcinoma squamous cell squamous cell adenoadeno large cell large cell
spindle cell spindle cell carcinomacarcinoma
giant cell giant cell carcinomacarcinoma
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
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
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
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
sarcomatoid carcinoma sarcomatoid carcinoma (WHO 2004)(WHO 2004)
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
carcinosarcomacarcinosarcoma
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
carcinosarcomacarcinosarcoma
In metastasesIn metastases Both componentsBoth components OrOr
carcinoma onlycarcinoma only Sarcoma only Sarcoma only
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
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
pulmonary blastomapulmonary blastoma
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
pulmonary blastomapulmonary blastoma
intracytoplasmic intracytoplasmic vacuoles vacuoles “endometrioid” “endometrioid” SubnuclearSubnuclear SupranuclearSupranuclear PAS pozitivePAS pozitive
MorulesMorules Neuroendocrine Neuroendocrine
differentiationdifferentiation
Makishi,2006
Keratin SYN
pulmonary blastomapulmonary blastoma
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
pulmonary blastomapulmonary blastoma
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 carcinoma- sarcomatoid 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