Immunohistochemistry

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CK7+, CK20+

Pancreaticobiliary, Stomach, Rectum
Bladder
Ovary - mucionous carcinoma

CK7+, CK20-

Endometrium, Ovary (non-mucinous)
Breast
Salivary gland, Thyroid, Lung
Mesothelioma, Kidney - papillary RCC
(BLOK MEST)

CK7-, CK20+

Colon
Merckel cell carcinoma

CK7-, CK20-

Liver (HCC), Kidney (clear cell RCC)
Prostate
Adrenal cortex

CK+, EMA-

HCC, Embryonal carcinoma, Yolk sac carcinoma
Adrenocortical neoplasms, Neuroendocrine neoplasms
Thyroid
(HEY, ANT)

CK-, EMA+

Meningioma, Perineurioma
Plasma cell neoplasms, Anaplastic large cell lymphoma, Lymphocyte predominant cells
RCC

CEA+

Stomach, Colorectum, Pancreaticobiliary
HCC (canalicular)
Lung adenocarcinoma

CEA-

Mesothelioma
Kidney, Adrenal, Prostate
Ovary, Endometrium
(POEMKA)

Vimentin (+) carcinomas

Endometrium
Thyroid, Salivary gland, Sweat gland
Spindle cell carcinoma, Mesothelioma, RCC, clear cell
(SSSR MET)

Vimentin (-) carcinomas

RCC, chromophobe, Prostate
Endocervix (adenocarcinoma), Ovary
Lung carcinoma, Breast
Colorectum, HCC
(REP BLOCH)

Skeletal muscle

Positive (+) Desmin, MyoD
Negative (-) SMA

Smooth muscle

Positive (+) Desmin, SMA, Calponin, Caldesmon
Negative (-) MyoD

Myoepithelial cells

Positive (+) Desmin, SMA, Calponin, Caldesmon
Negative (-) MyoD

Myofibroblast

Positive (+) Desmin, SMA,
Negative (-) MyoD, Calponin, Caldesmon

Neuroendocrine differentiation

Synaptophysin, Chromogranin
NSE
CD56

Melan-A

Positive (+)
Epitheloid melanoma, normal melanocytes, nevi
Adrenocortical neoplasms, Sex-cord stromal tumors
Pecomas (angiomyolipoma, sugar tumor, )
Pigmented tumors

Negative (-)
Spindle cell melanoma, Desmoplastic melanoma

HMB45

Positive (+)
Epitheloid melanoma
Pecomas (angiomyolipoma, sugar tumor, )

Negative (-)
Spindle cell melanoma, Desmoplastic melanoma, normal melanocytes
Adrenocortical neoplasms, Sex-cord stromal tumors
Mature nevus cells (matures toward the base)

S100

Positive (+)
Melanomas, normal melanocytes
Myoepithelial, Nerve sheath ,Granular cell tumors, glioma
Chordoma ,Lipomatous tumors, Cartilage
Langerhans cell histiocytosis

Gliomas

Positive (+) GFAP , S100
Negative (-) CK8, CK18, MNF-116

Vascular differentiation

CD31
CD34
Factor VIII

CD34 (+)

Vascular
Solitary fibrous tumor, DFSP
GIST, Epitheliod sarcoma
Nerve sheath tumor
Granulocytic sarcoma

Prostate cancer (Basal cells vs Acinar)

Basal cells - CK903 (-), p63 (+)
Malignant acinar cells - Racemase (+)

Breast (myoepithelial cells)

Positive (+) SMA, Calponin, p63, S100, CD10

Panel for undifferentiated malignant neoplasms

CK
EMA
S100
CD45

Prostate

PSA
PSAP
P501S

Lung

TTF-1

Thyroid (papillary, follicular)

TTF-1
Thyroglobulin
PAX8

Thyroid (medullary)

TTF-1
Calcitonin

Liver

HepPar-1
Canalicular CD10

Kidney

PAX2
PAX8
RCC
CD10

Adrenal

Inhibin
Melan-A

GYN tract

PAX8
ER/PR (Endomerioid - 100%, serous 50%)
WT1 (serous carcinoma)

Pituitary

Prolactin
GH
ACTH
TSH
LH/FSH

Parathyroid

PTH

Pancreatic islet

Insulin
Glucagon
Somatostatin

Bladder

p63
Thrombomodulin
Uroplakin
GATA3

Intestine

CDX2
Villin

SCC (cervix, anus, tonsil)

HPV
p16

TTF-1

Lung (non-squamous), Small cell lung
Thyroid
Small cell extrapulmonary
Subset ot GYN

CDX2

Large and small bowel
Carcinomas of GI phenotype (adenoca of bladder, mucinous BAC) - variable

PAX2

Pan-renal

PAX8

Pan-renal
Pan-Mullerian (uterus, ovary)
Thyroid

HepPar1

Hepatocellular differentiation
HCC
Hepatoid carcinomas

Panel for small round blue cell tumors

CK EMA
CD45
CD99
SYN, CHR,
TTF1
WT1
Desmin

Lymphoblastic lymphoma

CD45
CD99
TdT
CD34
CD3

Rhabdomyosarcoma, solid alveolar

Desmin
Myo D

Wilms tumor blastema predominant

CK
EMA
WT1
Desmin (blastema)

PNET/Ewing

CD99
NSE
SYN
PAS

Neuroblastoma

SYN (+)
CD99 (-)

Medulloblastoma

SYN (+)
GFAP variable

Small cell carcinoma

CK, EMA (dotlike, perinuclear)
SYN, CHR, NSE, CD56
TTF1

Merckel cell carcinoma

CK, EMA (dotlike, perinuclear)
SYN, CHR, NSE, CD56
CD20+

Desmoplastic small round cell tumor

CK, EMA
NSE
WT1
Desmin

Mesenchymal chondrosarcoma

CD99
S100

Panel for spindle cell tumors

CK, EMA
S100
SMA
Desmin
CD34

Leyomyoma

Desmin
SMA

Leyomyosarcoma

Desmin
SMA
CD99 variable

Rhabdomyosarcoma

Desmin
MyoD

Neurofibroma

S100 (focal)
CD34

Schwannoma

S100 (diffuse)
CD34

MPNST

S100 (focal)
CD34
CK, EMA (focal)

Vascular

CD34
CD31

Fibromatosis

SMA
B catenin

Nodular fasciitis

SMA
CD68

Inflammatory myofibroblastic tumor

SMA, Desmin - (+/-)

Dermatofibroma

CD34 (-)
Factor XIII (+)

Dermatofibrosarcoma protuberans

CD34 (+)
Factor XIII (-)

GIST

c-kit
CD34
DOG1
Bcl-2

Solitary fibrous tumor

CD34
Bcl-2

Hemangiopericytoma

CD34
Bcl-2

Synovial sarcoma

CK, EMA (focal)
Calponin
Bcl-2
CD56

CD34 (-) always

Spindle cell carcinoma

CK, EMA

Spindle cell melanoma

S100 (diffuse)

Estrogen/Progesteron receptor Expression Breast

>1% - Positive
<1% - Negative

HER2 receptor Expression (Breast)

Only membrane
<30% - 0 - Negative
>30% partial membrane staining - 1+ - Negative
>30% complete membrane staining (weak to moderate) - 2+ - Weakly positive
>30% complete membrane staining (moderate to strong) - 3+ - Strongly positive

Breast carinoma, general

Positive (+) CK7+, ER/PR, Her2
Negative (-) CK20-

Metaplastic breast carcinoma

Positive (+) CK903, p63

Phyllodes tumor (stromal)

Positive (+) CD34, ER +/-, B-cathenin +/-
Negative (-) CK903, SMA

Breast fibromatosis

Positive (+) SMA, B-cathenin,
Negative (-) CK903, CD34, ER

Undifferentiated tumors panel

Pan-keratin
CD 45 (CLA)
S-100
Vimentin

Carcinoma panel

Pan-keratin
CK5/6
MNF-116
CK8, CK18
CK903

Sarcoma panel

Pan-keratin
Vimentin
S-100
Desmin
CD45
SMA
Myoglobin
Factor VIII antigen
CD34
CD31
CD99

Lung panel

CK7
CK20
TTF-1

Gastrointestinal panel

CEA
CDX-2
CK7
CK20

Mesothelioma

Positive (+) Calretinin, WT1, CK 5/6, Thrombomodulin, EMA (membranous), MNF (perinuclear), Vimentin
Negative (-) CEA, CD15

Melanoma panel

S-100
HMB-45
Melan A
Vimentin
Pan-keratin

CNS/neural panel

GFAP
S-100
NSE
Vimentin
Pan-keratin
Synaptophysin

Neuroendocrine panel

NSE
Chromogranin
Synaptophysin
Nonsquamous keratin
CD57

Urothelial panel

p63
Uroplakin

Lung squamous cell carcinoma

CK7 -
CK20 -
TTF-1 - (90%)

Lung adenocarcinoma

Positive (+) CK7, 8, 18, 19, CEA, TTF-1
Negative (- ) CK20 (-)

Lung neuroendocrine carcinomas

Positive (+) CK7, TTF-1
Negative (- ) CK20

Pulmonary blastoma

Positive (+) Cytokeratin , TTF-1, CEA, EMA, AFP

Solitary fibrous tumor

Positive (+) CD34, Bcl-2, Vimentin
Negative (- ) Cytokeratins, S-100, Actin, Desmin

Epithelioid mesothelioma

Positive (+) Calretinin, WT1, keratin 5/6
Negative (- ) CEA, TTF-1

Thymoma

Positive (+) CK19, EMA, CEA, CD57. In lymphocyte-rich - CD1, TdT
Negative (- ) CK20

Paraganglioma

Positive (+) Chromogranin, synaptophysin,NSE. S-100- sustentacular cells

Neuroblastoma

Positive (+) NSE, chromogranin, synaptophysin
Negative (- ) CD99

PNET

Positive (+) CD99, NSE, CD57, synaptophysin, chromogranin

Breast acinar epithelial cells

Positive (+) CK18, CK19, EMA

Breast myoepithelial cells

Positive (+) calponin, p63, SMA, CD10,

Hepatocellular carcinoma

Positive (+) HepPar-1, AFP, Canalicular: CD10, CEA
Negative (- ) CK7, CK20, Chromogranin

Hepatoblastoma

Positive (+) HepPar-1, AFP

Cholangiocarcinoma

Positive (+) CK7, CK20 (+/-), Cytoplasmic: CEA.
Negative (- ) HepPar-1, AFP

Hemangioendothelioma

Positive (+) CD31, CD34, Factor VIII
Negative (- ) CEA

Angiosarcoma

Positive (+) CD31, CD34, Factor VIII

Hepatocytes

Positive (+) CK8, CK18, HepPar-1
Negative (- ) Vimentin, EMA, CK7, CK 20, CK19

Bile canaliculi

Positive (+) pCEA, CD10

Mallory hyalins

Positive (+) CK18 Occasionally CK7 , CK19
Negative (- )

Hepatic sinusoidal endothelial cells

Positive (+) in chronic diseases and HCC CD31, CD34, Factor VIII
Negative (- ) Normally CD31, CD34, Factor VIII

Bile ducts

Positive (+) CK7, CK19, CK8, CK18

Bile duct lesions panel

PAS diastase - basement membrane: bile duct injury, PBS
Trichrome - Collagen I - identification of bile ducts
CK 7, 8, 18, 19, EMA - bile duct epithelium - ductopenia
CEA - differentiation HCC from cholangiocarcinoma

Mycosis fungoides

Positive (+) CD4, CD3,
Negative (- ) CD8

MNF-116

Positive (+) All carcinomas
Negative (- ) HCC, adrenocortcal neoplasms,
(+/-) RCC (EMA+), NE (CK8,18+)

DD Paget vs SCC in situ

Paget CK8,18 +,CK903 -
SCC in situ CK8,18 -,CK903 +

DD prostate carcinoma vs urothelial carcinoma

Prostate carcinoma CK903 -
Urothelial carcinoma CK903 +

CK and EMA positive non carcinomas

Synovial sarcoma, epitheloid sarcoma, epitheloid angiosarcoma,
Yolk sac tumor, Embryonal carcinoma, trophoblastic tumors,
Mesothelioma, thymoma, chordoma
High grade MPNST, melanoma, leiomyosarcoma
Gliomas, reactive astrocytes (EMA negative)

DD RCC vs adrenocortical neoplasms

RCC - EMA +
Adrenocortical neoplasms EMA -

DD normal urothelium vs urothelial carcinoma in situ

Normal urothelium p53 -, CK20 (umbrella cells only), E-cadherin (all layers),
Urothelial carcinoma in situ p53 + CK20 (all llayers), E-cadherin (-),

DD bladder muscularis mucosa vs muscularis propria

Muscularis mucosa or desmoplastic myofibroblasts Vimentin +
Muscularis propria Vimentin -

DD primary bladder adenocarcinoma vs metastatic colorectal

Primary bladder adenocarcinoma B-cathenin +, CDX2 (+/-), CK7, (+/-), CK20 (+/-), Thrombomodulin (+/-),
Metastatic colorectal B-cathenin (+/-), CDX2 (+), CK7, (-), CK20 (+), Thrombomodulin (-),

DD urothelial carcinoma vs high grade prostatic

Urothelial carcinoma CK903 (+), Thrombomodulin (+), CK7 (+), CK20 (+), PSA (-), PSAP (-)
High grade prostatic CK903 (-), Thrombomodulin (-), CK7 (-), CK20 (-), PSA (+), PSAP (+)

Paget's disease

Positive (+) EMA, CEA, CK8, CK18, Her-2
Negative (- ) S100 (50%)

GIST

Positive (+) CD117, vimentin, CD34
Negative (- ) SMA, desmin, S-100, GFAP, NSE, CK (usually)

MALT lymphoma

Positive (+) CD20, Bcl-2
Negative (- ) CD5, CD10, CD23, Cyclin D1, Bcl-6

Follicular lymphoma

Positive (+) CD20, CD10, CD23, Bcl-2, Bcl-6
Negative (- ) CD5, CD43, Cyclin D1

Mantle cell lymphoma

Positive (+) CD20, CD5, CD43, Cyclin D1, Bcl-2
Negative (- ) CD10, CD23, Bcl-6

Burkitt's Lymphoma

Positive (+) CD20, CD10, Ki67
Negative (- )

RCC clear cell

Positive (+) PAX8, EMA, CD10, Vimentin
Negative (- ) CK7, CK20, c-kit

RCC papillary

Positive (+) PAX8, CK7, Racemase, Vimentin, CD10 (+/-)
Negative (- ) c-kit,

RCC chromophobe

Positive (+) PAX8, Hale colloidal iron, c-kit, CK7, CD10 (+/-)
Negative (- )

Angiomyolipoma

Positive (+) HMB45, Melan-A, S100 (30%), SMA, desmin, c-kit
Negative (- ) CK, EMA

Mixed epithelial stromal tumor

Positive (+) ER/PR, Desmin, CD10
Negative (- )

Wilms tumor

Epithelial - WT1, CK, EMA
Blastemal - desmin

Clear cell sarcoma kidney

Positive (+) Vimentin
Negative (- ) All other

Adrenocortical neoplasm

Positive (+) Melan-A, Inhibin, MNF, CK8, CK18,
Negative (- ) S100, HMB45, EMA

Pheochromocytoma

Positive (+) Chr, Syn, NSE, CD56, S100 (sustentacular)
Negative (- ) CK

Neuroblastoma

Positive (+) Chr, Syn, NSE, CD56, S100 (septae)
Negative (- ) CD99

Renal oncocytoma

Positive (+) PAX8, c-kit (+/-)
Negative (- ) CD10, RCC, vimentin, colloidal iron (apical)

DD Renal tumors with tubulo-pappilar architecture

Papillary RCC - CK7, racemase
Metanephric adenoma - WT1, CD57
Wilms tumor - WT1

DD renal clear cell tumors

RCC clear cell - CD10, vimentin
Papillary RCC with clear cells - CK7, Racemase, CD10 (+/-)
Clear cell papillary RCC - CK7
Chromophobe RCC - CK7, colloidal iron, c-kit
Xp11 translocation RCC - CD10, Racemase
Angiomyolipoma - HMB45, MelanA, Actin

DD RCC vs Adrenocortical neoplasm

RCC - PAX8, CD10, RCC, EMA
Adrenocortical neoplasm - MelanA, Inhibin, SYN

Seminoma and ITGCN

Positive (+) OCT4, PLAP, PAS, c-kit
Negative (- ) MNF, EMA

Spermatocytic seminoma

Negative (- ) OCT4, PLAP, PAS, MNF, EMA

Embryonal carcinoma, testis

Positive (+) MNF, OCT4, PLAP, CD30
Negative (- ) EMA

Yolk sac tumor , testis

Positive (+) MNF, PLAP, CD30, AFP
Negative (- ) OCT4, EMA,

Choriocarcinoma , testis

Positive (+) MNF, B-HCG, Inhibin, EMA (+/-), PLAP (+/-)
Negative (- ) OCT4

Teratoma, testis

Positive (+) MNF, EMA
Negative (- ) OCT4, PLAP

Sertoli, Leidig, testis

Positive (+) Inhibin, MelanA, CD10, CD99, Calretinin
Negative (- ) EMA, OCT4, PLAP

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