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Immunohistochemistry of soft tissue tumor

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Immunohistochemistry

Major advances :

antigen retrieval techniques (HIER)

sensitive detection systems

numerous antibodies of good quality

Standardization :

automated immunostainers

quality assurance programs

Impressive amount of new information :

12 000 papers/year

internet (Pubmed, Immunoquery,)

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Future of IHC is promising

Tissue microarray cDNA microarray

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Immunohistochemistryof soft tissue tumors

STT: several lines of differentiation

Numerous pseudosarcomatous benignlesions

Non-mesenchymal malignant tumors

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Soft tissue tumors

ImmunohistochemistryConditions of use

Complementary to H and E

Quality of technique Panel of markers

Quality of interpretation

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Basic panel of antibodies for soft

tissue tumors

Cytokeratin EMA

S100 protein

Desmin

Smooth muscle actin

CD34

Sarcomatoid carcinomaSynovial sarcoma,...

Nervous and melanocytic

Muscle tumorsMyofibroblastic lesions

Numerous tumors

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Basic panel

AE1/AE3

EMA

S100 protein

SMA

Desmin

CD34

CD99

CD31

HMB45/Melan A

CD20/CD3/CD30

Chromogranin A

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New antibodies

Myogenin

H-caldesmon

CD117 (c-kit)

HHV8

MDM2/CDK4

CD163

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Unuseful antibodies

Vimentin

BCL2

Antichymotrypsin

Myoglobin

NSE

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Soft tissue tumors

ImmunohistochemistryInterpretation

Quality of technique Type of positivity

Expected positivities Unexpected positivities

S ft ti t

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Soft tissue tumors


PNET CD99Type of positivity

ERMS - myogenin

SFT- CD99

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Poorly specific markers

CD34

CD99

EMA

S100 protein

SMA

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Soft tissue tumors which are CD34 positive

Vascular tumors

DFSP

Solitary fibrous tumor

GIST

Spindle cell/pleomorphic lipomas

Some nervous tumors

Epithelioid sarcoma

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Soft tissue tumors which are CD99 positive

PNET

Synovial sarcoma

Solitary fibrous tumor

Mesenchymal chondrosarcoma

Neuroendocrine carcinoma

Lymphoblastic lymphoma

Alveolar rhabdomyosarcoma

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Markers with unexpected positivities

Cytokeratin Desmin

CD31

CD117

Fli-1.

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Unexpected positivity for cytokeratin

Leiomyosarcoma

Rhabdomyosarcoma

PNET

Epithelioid vascular tumors

Melanoma

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PNET and cytokeratin

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Tenosynovial tumor and desmin

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Histiocytes and CD31

CD68

CD31

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Soft tissue tumors

ImmunohistochemistryPractical interests

Identification of a benign lesion

Nature of an undifferentiated malignanttumor

Classification of a sarcoma

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Soft tissue tumors

ImmunohistochemistryBenign vs malignant

Major and frequent problem

Solution : - clinical context- H and E

Usefulness of IHC

Soft tissue tumors

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Soft tissue tumors


Rare/atypical benign lesions

Nerve sheath tumors

Histiocytic lesions

Rare tumors : ( paraganglioma,glomus T, SFT, angiomyolipoma,myoepithelioma)

Myofibroblastic lesions

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Atypical/rare benign nerve

sheath tumors -S100 protein

Ancient schwannoma Cellular shwannoma

Myxoid neurofibroma

Neurofibroma with nuclear atypia

Diffuse neurofibroma Granular cell tumor

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Cellular schwannoma

S1

B i hi ti t fib

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Benign histiocytofibroma

CD34

DFSP

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DFSP

CD34

R b i t

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Rare benign tumors

Paraganglioma :

chromogranin A, S100+ Glomus T :

SMA, caldesmon

SFT : CD 34 +

Myoepithelioma : AE1/AE3, PS100+

Perineurioma :

EMA+

Glomus T - SMA

Rare benign tumors

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Rare benign tumors

Paraganglioma :

S100 and

Chromogranin A +

S100

Chromogranin A

S ft ti t

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Soft tissue tumors



Nature of an undifferentiated malignanttumor


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Non-mesenchymal malignant tumors

Carcinoma

Melanoma

Lymphomas

Be careful if :

Previous history of cancer Some localisations

Non-specific pattern

Non mesenchymal malignant

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Non-mesenchymal malignant

tumorsLocalisations at risk

Skin and mucosae

Lymph node areas In the vicinity of some viscera

(lung, kidney, thyroid, breast)

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Non mesenchymal malignant

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Non-mesenchymal malignant

tumorsSolutions

If previous history: compare bothtumors

Correct sampling

IHC : AE1/AE3, S100, CD20,.

55 year-old male

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Sarcomatoid carcinoma

Polypoid tumor of the tongue

Cyt

Soft tissue tumors

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Soft tissue tumors



Nature of an undifferentiated malignant

tumor


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Immunohistochemistry usefulness

Sarcomas with specific IHC

Sarcomas with useful markers Sarcomas with no specific markers


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Rhabdomyosarcoma Vascular sarcomas

GIST

Dedifferentiated liposarcoma

Epithelioid sarcoma

Clear cell sarcoma Intra-abdominal desmoplastic tumor

Myogenic transcription factors

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Myogenic transcription factors

Myogenin and MyoD1

Immature skeletal muscle

Specific marker :

myogenin > myoD1

nuclear positivity

regenerative muscle

Sensitivity and histologic types

Alveolar rhabdomyosarcoma

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y

m o e

Embryonal rhabdomyosarcoma

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Embryonal rhabdomyosarcoma

m o e

Pleomorphic rhabdomyosarcoma

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m o e

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Vascular sarcomas

Spindle cell angiosarcoma

Epithelioid angiosarcoma

Kaposi sarcoma

Epithelioid hemangioendothelioma

Vascular sarcomas

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Vascular sarcomas

Useful markers

CD 31 + CD 34 +

Factor 8 +

FLI1 +

HHV8 +/-

cytokeratin +/- EMA +/-

C-Kit +/-

Vascular sarcomas

U f l k

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Useful markers

Epithelioid

angiosarcoma:

CD31,CD34 +

Vascular sarcomas

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Vascular sarcomas

Useful markers

Kaposi sarcoma: CD34, CD31 and HHV8+

CD34

HHV8

Human Herpes Virus 8 (HHV8)

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Kaposi sarcoma

Effusion lymphoma Castleman disease

Nuclear positivity

Kaposi sarcoma

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p

HHV8

CD117 (c kit)

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CD117 (c-kit)

C-kit tyrosine kinase receptor

(mast cells, melanocytes, germ cells,

interstitial cells of Cajal)

GIST : mutation of c-kit permanent TK activity

CD117 positive in 95 % of GIST

CD117 positivity is required for imatinib treatment

CD117 - c-kit

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CD117 positivity

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CD117 positivity

Angiosarcoma

PNET

Chondrosarcoma

Synovial sarcoma

Carcinomas

GIST

Mast cell disease

Seminoma

Melanoma

CML

Immunohistochemistry of GIST

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Immunohistochemistry of GIST

CD117 95%

CD34 60-70%

H-caldesmon 80%

SMA 15-60%

S100 protein 5-10%

MDM2/CDK4

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MDM2: Inhibitor of P53 protein

MDM2/CDK4 amplification in well

diff/dediff liposarcomas

IHC with IF2 antibody for MDM2

Diagnosis of dediff. liposarcoma

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m

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mdm2

Epithelioid sarcoma

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Epithelioid sarcoma

Useful markers : ,CytoK, EMA, CD34+

and CD31-

CytoK

Clear cell sarcoma/Soft tissue

melanoma

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melanoma

Useful markers: S100,

HMB45, MELAN A,

MART1 +

S100

HMB


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Immunohistochemistry usefulness


Sarcomas with useful markers Sarcomas with no specific markers

Sarcomas with useful markers

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Synovial sarcoma

Leiomyosarcoma

PNET

DFSP

MPNST

Extra-skeletal myxoid chondrosarcoma

Synovial sarcoma

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y

Useful markers

AE1/AE3 + (65%)

EMA + (95%)

CD34 - (+ 5%)

S100 + (30%)

CD99 + (>50%)

Spindle cell synovial sarcoma

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EMA

AE1/AE3

Useful markers:

EMA,

AE1-AE3, CD34

Leiomyosarcoma

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y

Useful markers

H-caldesmon (40-70%)

SMA (70%) Desmin (50%)

H-caldesmon

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Regulator of smooth muscle contraction Positivity in: - smooth muscle tumors

- glomus tumor

- GIST

- angiomyolipomas

Negative in: - myofibroblastic proliferations

- skeletal muscle tumors

Pleomorphic leiomyosarcoma

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SMA des

caldesm

Muscular markers

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Desmin : smooth muscle and skeletal muscle

Smooth muscle actin : smooth muscle and

myofibroblasts

Myogenin : immature skeletal muscle

H-caldesmon : smooth muscle

Sarcomas with useful markers

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Synovial sarcoma

Leiomyosarcoma

PNET

DFSP

MPNST

Extra-skeletal myxoid chondrosarcoma

Tumors with no specific marker

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Fibrosarcoma

Myxofibrosarcoma Low-grade fibromyxoid tumor

Osteosarcoma

Myxoid/round cell liposarcoma

Pleomorphic liposarcoma

Pleomorphic MFH

Immunohistochemistryof soft tissue tumors

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Conclusions

Major tool for soft tissue tumors

Quality of technique

Panel of markers depending on H and E

Global interpretation

ihc sa bey05

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