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Home , Synaptophysin

Efficient immunohistochemical differential diagnosis of undifferentiated neoplasia

Conventional histomorphology: pleomorph and/or high-grade spindle-cell Conventional histomorphology: epitheliod, intermediate-cell to large-cell Conventional histomorphology: small-cell

Localisation of tumour Localisation of tumour Localisation of tumour Antibody panel Marker constellation and valuation Antibody panel Marker constellation and valuation Antibody panel Marker constellation and valuation infiltrates infiltrates infiltrates

CK8/18 + (diffuse), Ber-EP4 +/-, GFAP -/+ (focal) p63 +, WT1 -, D2-40 (Podoplanin) -/+ metastasis if plexus carcinoma has been excluded pleura carcinosis due to non-keratinising squamous cell carcinoma CK8/18, Ber-EP4, GFAP, CK8/18 + (diffuse), Synaptophysin +, TTF-1 +/- Central nervous system GFAP +, CK8/18 -/+ (focal), CD34-positive microvascular proliferates WT1 + and/or D2-40 (Podoplanin) +, p63 -, Pan-CK + Melan A, CD34 metastasis of a small-cell carcinoma glioblastoma epithelioid or biphasic mesothelioma, Central nervous system CK8/18, GFAP, Melan A, p63, WT1, Podoplanin Attention: Pleura carcinosis due to serous ovarian carcinoma TTF-1, Synaptophysin GFAP +, CK8/18 -/+ (focal), Synaptophysin - Melan A + malignant (metastasis) Pleura small-cell fraction of a glioblastoma (D2-40), S100, Pan-CK Pan-CK +, other markers negative Pleura carcinosis due to macrocellular carcinoma Melan A + small-cell malignant melanoma (metastasis) Pan-CK + (diffuse or focal, other markers negative) S100 + (diffuse nuclear and cytoplasmic), Pan-CK -/+ (focal) carcinoma metastasis metastasis of a malignant melanoma Pan-CK + (diffuse), -, CK20 -, Synaptophysin +/- S100 + (diffuse nuclear and cytoplasmic) small-cell carcinoma (if Synaptophysin –: differential diagnosis small- metastasis of malignant melanoma cell squamous cell carcinoma) Pan-CK, S100, CD30, kappa/lambda +, CD20 - immature (anaplastic) plasmocytoma (myeloma) Ber-EP4 + or Ber-EP4 -, Pan-CK +, Calretinin - peritoneal carcinosis Lymph node CK20 + (punctual perinuclear), Synaptophysin + CD20, kappa/lambda Calretinin +, Pan-CK +, Ber-EP4 - Merkel cell carcinoma CD30 + (diffuse membrane-associated and in the Golgi region), epithelioid or biphasic mesothelioma, Pan-CK -/+ (focal), CD20 - anaplastic large-cell lymphoma (ALCL) Ber-EP4, Pan-CK, CD99 + (diffuse membrane-associated), Pan-CK -/+ (focal), Synaptophy- S100 + (diffuse nuclear and cytoplasmic), Pan-CK -/+ (focal), CD20 +, CD30 +/- Peritoneum Calretinin, S100, Pan-CK, S100, CD99, sin +/-, TdT -, S100 -/+ (focal), MPO - PNET HMB45, Inhibin α Ber-EP4 -, Inhibin α - diffuse large-cell B-cell lymphoma, anaplastic variation metastasis of a malignant melanoma other localisation Desmin, Synaptophysin, Synaptophysin +, CD99 -, Pan-CK -, S100-positive sustentacular cells TdT, Myeloperoxidase olfactory ? (rhinopharynx) all markers negative Inhibin α +, Calretinin +, Ber-EP4 -, S100 –/+ (focal) granulosa-cell tumour? carcinoma with loss of CK expression or histiocytic sarcoma? (MPO), CK20 S100 + (diffuse nuclear and cytoplasmic) HMB45 +, S100 - perivascular epithelioid-cell tumour small-cell malignant melanoma

Pan-CK + (diffuse or focal, other markers negative) Pan-CK+/-, Desmin + (point-shaped), CD99 -/+, TdT- (sarcomatoid) carcinoma CK8/18 + (diffuse), GFAP -/+ (focal) desmoplastic small- and round-cell tumour? S100 + (diffuse nuclear and cytoplasmic), HMB45 +/- carcinoma metastasis if plexus carcinoma has been excluded TdT +, CD99 +/-, Pan-CK -, MPO - malignant melanoma GFAP +, CK8/18 -/+ (focal) anaplastic glioma or glioblastoma lymphoblastic lymphoma/leukaemia, NK cell lymphoma Gastrointestinal tract, CK8/18, GFAP, Melan A, Central nervous system MPO + myeloid sarcoma genito-urinary system, Pan-CK, S100, CD30 + (diffuse membrane-associated and in the Golgi region), OCT4, CD117 Melan A + malignant melanoma (metastasis) parenchymatous organs, HMB45, CD30, CD20 Pan-CK -/+ (focal), CD20 - anaplastic large-cell lymphoma (ALCL) OCT4 +, CD117 - embryonary carcinoma head/neck area CD20 +, CD30 +/- OCT4 +, CD117 + diffuse large-cell B-cell lymphoma, anaplastic variation all markers negative carcinoma with loss of CK expression? Pan-CK + (diffuse), OCT4 - carcinoma metastasis Markers for immunohistochemical diagnostics of CUP (Carcinoma of Unknown Primary) S100 + (diffuse nuclear and cytoplasmic), Pan-CK -/+ (focal) metastasis of a malignant melanoma Predicted localisation of Pan-CK+/-, CK5/6 +/-, CD31 -, h-Caldesmon -, S100 -/+ (focal) Marker primary tumour Type of carcinoma Comments (sarcomatoid) carcinoma, differential diagnosis metastasis OCT4 +, Pan-CK + (diffuse), CD30 + Pan-CK, CD20, S100, metastasis of an embryonary carcinoma Arginase-1 liver HCC (Hepato Cellular Carcinoma) more specific than HePar1 and Glypican-3 S100 + (diffuse nuclear and cytoplasmic) Lymph node OCT4, CD30 OCT4 +, Pan-CK -/+ (diffuse), CD30 - metastasis of a seminoma adenocarcinoma of stomach, oesophagus, pancreas, (spindle-cell) malignant melanoma colorectum, ovary, bladder adenocarcinomas (ovary only in and biliary ducts frequently show heterogeneous CD30 + (diffuse membrane-associated and in the Golgi region), Pan-CK -/+ (focal), CDX-2 case of gastrointestinal mucinous Pan-CK, CK5/6, CD31, CD31 + angiosarcoma (diffuse immunoreactivity) immunoreactivity. Adenocarcinomas of the lung are CD20 - anaplastic large-cell lymphoma, „small-cell” variant differentiation) rarely positive. (mainly mucinous carcinoma) Skin S100, CD30, h-Caldesmon h-Caldesmon + (more than few cells) leiomyosarcoma CD20 + diffuse large-cell B-NHL CK7/CK20 colorectum adenocarcinomas (CK7-/CK20+) CD30 + (diffuse membrane-associated and in the Golgi region), Pan-CK -/+ (focal) (sarcomatoid) anaplastic large-cell lymphoma DPC4/SMAD4 pancreas, biliary ducts adenocarcinomas only the loss of expression is relevant for diagnosis! all markers negative Pan-CK +, EMA +/-, Inhibin α -, OCT4 - more sensitive for mamma as GCDFP-15 and Mam- atypical fibroxanthoma (head/neck, actinic lesion?) carcinoma (primary tumour or metastasis) maglobin in poorly differentiated tumours, but less GATA3 breast, urinary tract adenocarcinomas specific; among others mesothelioma and ductal S100 + (diffuse nuclear and cytoplasmic), Pan-CK -/+ (focal), Inhibin α - pancreas carcinoma malignant melanoma high specificity but low sensitivity in poorly diffe- S100 + (diffuse nuclear and cytoplasmic), HMB45 + Pan-CK, EMA, S100, GCDFP-15 breast adenocarcinomas Ovary Inhibin α +, EMA -, S100 -/+ (focal) germ band or stroma tumour rentiated tumours; rare immunoreactivity in lung malignant melanoma, differential diagnosis clear cell sarcoma (if HMB45 –: Inhibin α, OCT4, CD20 differential diagnosis malignant peripheral nerve sheath tumour, MPNST) OCT4 +, Pan-CK + (diffuse) embryonary carcinoma positive in malignant , in a minority of squamous cell carcinoma, and in yolk sack OCT4 +, Pan-CK -/+ (focal) Glypican-3 liver HCC (Hepato Cellular Carcinoma) CD31 + angiosarcoma tumours (> 90%); otherwise more sensitive and Myf4 + (nuclear, attention: immunoreactivity in regenerative skeletal CD20 + diffuse large-cell B-NHL specific than HepPar1 muscle fibres in tumour-infiltrated areas) positive in appr. 50% of all adenocarcinomas of S100, HMB45, Myf4, Soft tissue pleomorphic or other tumour with focal rhabdo- stomach and to a lesser degree in other primary lo- CD31, h-Caldesmon, CD30 myoblastic differentiation Pan-CK + (diffuse) carcinoma HepPar1 liver HCC (Hepato Cellular Carcinoma) calisations (colon, lung, pancreas); therefore minor positive predictive value for differentiation from HCC h-Caldesmon + (more than few cells) S100 + (diffuse nuclear and cytoplasmic), Pan-CK -/+ (focal), Inhibin α - and liver metastases. pleomorphic leiomyosarcoma malignant melanoma, (if HMB45 -: differential diagnosis epithelioid Gastrointestinal tract, ductal/lobular , high specificity, but low sensitivity in poorly diffe- malignant nerve sheath tumour) Mammaglobin breast, endometrium CD30 + (diffuse membrane-associated and in the Golgi region) Respiratory tract, Pan-CK, S100, HMB45, endometrial adenocarcinomas rentiated breast carcinoma HMB45 +, S100 - perivascular epithelioid-cell tumour (sarcomatoid) anaplastic large-cell lymphoma genito-urinary system, CD20, CD30, kappa/ high specificity and sensitivity; positive in some NKX3.1 prostate adenocarcinomas other marker combination parenchymatous organs, lambda CD20 + diffuse large-cell B-NHL PSA-neg., poorly differentiated adenocarcinomas. head/neck area sarcoma; needs further investigation CD30 + (diffuse membrane-associated and in the Golgi region), Pan-CK -/+ (focal), negative in mucinous carcinomas of the ovary and CD20 - anaplastic large-cell lymphoma, „small-cell” variant Estrogen Receptor mamma, ovary, corpus uteri adenocarcinomas serouse corpus carcinoma Kappa/lambda +, CD20 - lower sensitivity in mucinous ovary carcinomas; carcinoma of the kidney (all types), plasmoblastic lymphoma? (HIV + ?), ALK-1-positive diffuse large-cell Pax-8 kidney, ovary, uterus, mullerian tumours; thyroid carcino- more sensitive than Thyreoglobulin in insular and B-NHL? thyroid gland anaplastic carcinomas of the thyroid; mesothelioma ma (including medullary) negative more specific than CDX-2, larger proportion of SATB2 colon adenocarcinomas Pan-CK + (diffuse) epithelioid sarcoma, differential diagnosis stained medullary carcinoma carcinoma metastasis PSA prostate adenocarcinomas S100 + (diffuse nuclear and cytoplasmic), HMB45 +/- malignant melanoma, differential diagnosis clear-cell sarcoma differentiated and insular thyroid lower sensitivity in insular carcinomas Pan-CK, S100, CD31, Thyreoglobulin thyroid gland gland carcinomas Soft tissue (if HMB45 -: differential diagnosis epithelioid malignant nerve sheath tu- HMB45, CD117 mour) TTF-1 nuclear adenocarcinomas (non mucinous), with clone 8G7G3/1 also rare immunoreactivity in (only clone 8G7G3/1, large-cell non-neuroendocrine endometrial adenocarcinomas. HMB45 +, S100 - perivascular epithelioid-cell tumour lung, thyroid gland CD31 + epithelioid angiosarcoma other clones mostly carcinomas; insular and medullar expression in small cell carcinomas is not location less specific thyroid carcinomas specific CD117 + epithelioid gastro-intestinal stroma tumour (GIST)? Uroplakin II urinary tract urothelial carcinoma very specific, more sensitive than Uroplakin III mesotheliomas and mucinous mamma carcinomas WT1 nuclear ovary serous adenocarcinoma are positive; serous corpus carcinoma are negative

CDX-2, liver metastasis Estrogen Receptor, liver metastasis HepPar1, Lokalisation of the primary of neuroendocrine tumours (NET), G1 and G2 of colon carcinoma of breast carcinoma midgut CDX-2 NET G1/2 (ileum, appendix, colon)

NKX6.1 pancreas, duodenum NET G1/2 alternative to polyclonal Pax-8 This IHC algorithm was prepared to the best of our knowledge. However, in special cases (for example childhood tumours) the information can be incomplete and the user has to be aware of this. The use of this diagram is solely the responsibility of the user. UnderPax-8 no circumstances polyklonal shall Zytomed Systempancreas, be liable duodenum for any damages arising out of theNET use G1/G2of this table. due to cross reactivity to Pax-6 We kindly would like to thank Dr. med. habil. Olaf Kaufmann for his expert advice in the preparation of this diagram. ©TTF-1 ZYTOM EDnuclear SYSTEMS 2015 lung

Synaptophysin, GATA3, 20, Oct-4, Calretinin, TTF-1, neuroendocrine tumour breast carcinoma colon carcinoma seminoma mesothelioma pulmonary adenocarcinoma