Breast - ductal carcinoma CK7 ER PR GATA3 Mammaglobin (50-70%) GCDFP-15 (50-70%) E-cadherin HMWCK CK20 PAX2 ER/PR/HER2 on all newly diagnosed cases
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1 Adrenal cortical carcinoma Inhibin Synap Melan-A Calretinin Vimentin Chromogr CK7 CK20 Breast - ductal carcinoma CK7 ER PR GATA3 Mammaglobin (50-70%) GCDFP-15 (50-70%) E-cadherin HMWCK CK20 PAX2 ER/PR/HER2 on all newly diagnosed cases Breast - lobular carcinoma CK7 ER PR GCDFP-15 GATA3 Mammaglobin (50-70%) E-cadherin CK20 Breast - myoepithelial markers p63 Calponin SMMHC Cervix - squamous cell ca p63 p16 Cervix - adenocarcinoma CK7* p16 (>90%)* CEA ER P63* CK20 CDX2 TTF-1 Cholangiocarcinoma CK7 CK19 N-cadherin HMWCK CK20 CDX2 Colon - adenocarcinoma CK20 CDX2 CEA CK7 MSI-colon IHC on all newly diagnosed cases of pt3 or pt4 w/o prior chemo/xrt Endometrioid carcinoma CK7* ER* Vimentin* CA125 CK20 CDX2 CEA* *p16 can be positive by non-hpv mechanisms in poorly differentiated endometrial carcinomas (especially squamous morules) Esophagus - adenocarcinoma CK7 CDX2 Hepatocellular carcinoma Glypican Hepatocyte AFP CEA CD10 CK7 CK20 PAX2 Dysplastic nodules also glypican positive, hepatic adenomas and normal hepatocytes are negative Lung - adenocarcinoma CK7 TTF1 CEA CD15 Napsin HMWCK CK5/6 Calretinin WT-1 HBME D2-40 CDX-2 Lung - squamous cell carcinoma p63 HMWCK Napsin (20%) TTF-1 Lung - small cell carcinoma CKCKT Synaptophysin Chromograniin TTF-1 NSE CD56 CK20 Napsin Nasopharyngeal carcinoma EBER (ISH) CKCKT p63 Ovary - mucinous carcinoma CK7 CK20 CDX2 (90%) ER supports if positive Ovary - serous carcinoma WT1* CK7* ER* p53 CA125 PAX 2 (67%) CK20 CDX2 Paget's disease CK7* CAM5.2 EMA CEA Her2 S100* Pancreas - ductal carcinoma CK7 HMWCK CK20 N-cadherin (30%) CDX2 (often + in duodenal/ampullary lesions) Prostate carcinoma PSA PSAP p504 racemase Androgen Receptor Erg (40%) CK7 HMWCK CK20 p63 PAX2 GATA3 PIN4 cocktail includes p63 (nuclear, myoepithelial cells, brown), CK5/14 (nuclear, myoepithelial cells, brown), and racemase (cytoplasmic, most adenocarcinoma, red) Renal - clear cell carcinoma RCC CD10 (membranous) Vimentin PAX2 CK7 CD117 CK20 Renal - papillary carcinoma RCC CD10 (membranous) CK7 PAX2 Vimentin p504s AMACR napsin CK7 CK20 CD117 Renal - chromophobe carcinoma Hale's Colloidal Iron CD117 CK7 PAX2 RCC CD10 Vimentin Salivary - Ductal Androgen Receptor GCDFP-15 Her2 SOX10 SOX10 positive salivary gland tumors: acinic, adenoid cystic, epithelial myoepithelial, myoepithelial carcinomas, pleomorphic adenomas SOX10 negative salivary gland tumors: salivary duct, mucoepidermoid, oncocytic carcinoma, oncocytomas, Warthin's Stomach: Intestinal type CK7 CDX2 CK20 Diffuse/signet ring type CK7 CK20 E-cadherin CDX2 HER2 IHC on newly diagnosed cases Thyroid - papillary & follic. carc. TTF1 Thyroglobulin CK7 HMWCK Vimentin HBME-1 Napsin Thyroid - medullary carcinoma TTF1 Calcitonin CK7 Thymic carcinoma CD117 CK5/6 CD5 P63 Urachal carcinoma CK20 CDX2 CK7 Urothelial carcinoma p63 CK7 CK5/6 HMWCK (34betaE12) GATA3 CK20 PAX2
2 Desmoplastic small round cell CKCKT Vimentin Desmin WT-1 NSE CD99 Myogenin FISH for EWS translocation Ewing's / PNET CD99 S100 (20%) SOX10 FISH for EWS translocation Lymphoblastic lymphoma CD45 TdT CD10 CD79a PAX5 CD3 Merkel cell carcinoma CKCKT CK20 (dot-like) Synapto Chromogr PAX5 (93%) TTF1 Neuroblastoma NF CD56 Synapto Chromogr CD99 FISH for N-MYC amplification Rhabdomyosarcoma - embryonal Myogenin Desmin MSA Rhabdomyosarcoma - alveolar Myogenin (diffuse) Desmin MSA FISH for FKHR translocation; t(2:13) or t(1;13) [FKHR also known as FOXO1] Small cell carcinoma CKCKT Synap Chromogr TTF-1 PAX5 (73%) CK20 Wilms tumor WT1 Vimentin PAX2 CKCKT EMA
3 Alveolar soft part sarcoma TFE-3 (at Phenopath) PAS/D positive crystals MSA SMA CD99 t(x;17) TFE3-ASPL fusion (no FISH available) Angiomyolipoma HMB45 Melan-A Angiosarcoma CD31 CD34 Factor VIII ERG CKCKT Atypical fibroxanthoma (Skin tumor) CD68 CD10 CD99 CKCKT CD34 S100 P63 CD31 desmin Chordoma CKCKT EMA S100 Clear cell sarcoma SOX10 S100 HMB45 Melan A SMA CD99 FISH for EWS translocation (>75%) Dermatofibroma Factor 13a CD34 Dermatofibrosarcoma protuberans CD34 Factor 13a FISH for t(17;22) PDGFB-COL1A1 fusion Endometrial stromal sarcoma CD10 Inhibin b-catenin (nuclear; 40%) Desmin t(7;17) JAZF1-JJAZ1 fusion (no FISH available) Epithelioid sarcoma CKCKT EMA, CD34 (60%) INI1 (loss) Vimentin ERG (38%) Extraskeletal myxoid chondrosarcoma S100 (~20%) SOX10 INI loss (50%) FISH for EWS translocation (>50%); also t(9;17) & t(9;15) Fibromatosis (desmoid) β-catenin (nuclear) SMA Fibrosarcoma Vimentin GI Stromal Tumor CD117 DOG1 CD34 SMA Desmin S100 Mutations in KIT (80%) & PDGFRA (8%) Inflammatory myofibroblastic tumor ALK1 FISH for ALK translocation Kaposi's sarcoma HHV8 ERG CD31 Leiomyosarcoma Desmin H- Caldesmon SMA MSA Calponin CD117 DOG1 CD34 S100 CD10 Uterine leiomyosarcs are ER (30-80%) and PR positive (40-80%) vs other (0-25% and (0-13%) respectively Liposarcoma, well-diff. MDM2 CDK4 SMA Desmin S100 FISH for MDM2, Ring chromosomes/markers from 12q13-15 Liposarcoma, de-diff. MDM2 CDK4 SMA Desmin S100 FISH for MDM2, Ring chromosomes/markers from 12q13-15 Liposarcoma, myxoid t(12;16) or t(12;22) FISH for FUS gene translocation Low grade fibromyxoid sarcoma FISH for t(7;16) (FUS gene translocation, 75% of cases) Lymphangioma D2-40 LYVE1 CD31 CD34 ERG Malignant Peripheral Nerve Sheath Tumor S100 (40%) SOX10 (27%) INI1 loss TLE Lost in 50% of epithelioid variant Mesenchymal chrondrosarcoma CD99 SOX10 Neurofibroma S100 SOX10 Neurothekeoma (skin tumor) NK1/C3, NSE, CD68 S100 Osteosarcoma CDK4 MDM2 Perineurioma EMA GLUT1 S100 PEComa SMA Calretinin HMB45 Desmin (50%) Melan A (50%) S100 (25%) Pleomorphic rhabdomyosarcoma Desmin MSA Myogenin (10-30% cells) Schwannoma S100 SOX10 Solitary fibrous tumor CD34 BCL-2 β-catenin (nuclear; in 40%) CD117 DOG1 S100 Synovial sarcoma TLE EMA CKCKT CD99 INI1 (loss) SOX10 FISH for t(x;18) (SYT gene translocation)
4 Angiomyolipoma HMB45 Caldesmon Melan-A SMA S100 Carcinoid tumors: Foregut Synapto Chromogr Hindgut Synapto CDX-2 Chromogr Pulmonary Synapto Chromogr TTF1 (~30%) Dendritic cell sarcoma CD21 CD23 CD35 lysozyme (muramidase) Germ cell tumors: Seminoma/Dysgerminoma PLAP CD117 OCT 3/4 D2-40 CD30 CKCKT Glypican Emybronal carcinoma CD30 OCT 3/4 Glypican Yolk sac tumor Glypican AFP D2-40 Choriocarcinoma HCG Glypican hpl Teratoma No special markers (common to all types) FISH for i12p (retained in carcinomas arising out of teratomas; has treatment implications) Glomus tumor SMA Granular cell tumor S100 SOX10 Infantile hemangioma GLUT1 Lymphangioma D2-40 LYVE1 CD31 CD34 ERG Malignant melanoma (all types) Melan-A (MART-1) HMB45 S100 SOX10 CD117 SOX 10 is superior to S100 for desmoplastic melanoma Mesothelioma CK5/6 Calretinin WT1 D2-40 HBME CK7 HMWCK CEA TTF1 CD15 ER Napsin Pancreas - neuroendocrine tumor Synapto Chromogr PR Pancreas - solid pseudopap. tumor b-catenin (nuclear) E-cadherin (loss) Pheochromocytoma Synapto Chromogr S100 (sustentacular cells)inhibin Renal oncocytoma CKIT PAX-2 EMA CK7 (rare intense positive cells in negative background) RCC CD10 Sex cord stromal tumors Inhibin* ER* Calretinin* CD99 Melan-A WT1 Vimentin
5 Morphology Suggestions For Starting Panel High grade undiff. CKCKT S100/SOX10 CD45 CD30 CD34 OCT3/4 Small round blue cell CD99 CD45 CKCKT Desmin Myogenin S100/SOX10 Synapto Chromogr GI Spindle Cell CD117 CD34 DOG1 Desmin S100 Adenoca vs Mesothelioma Calretinin WT1 CK5/6 TTF1 CEA CD15 HBME D2-40 Endometrial vs Cervical ER Vimentin p16 CEA
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