Primer of Immunohistochemistry (Epithelial Markers) Paul K. Shitabata, M.D. Dermatopathology Institute Torrance, CA. Monday, April 2, 12
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1 Primer of Immunohistochemistry (Epithelial Markers) Paul K. Shitabata, M.D. Dermatopathology Institute Torrance, CA
2 DETERMINANTS OF VALUE IN DDX OF SQUAMOID BCC VARIANTS VS. SQUAMOUS CARCINOMA bcl-2 Protein Functions in the governance of apoptosis, together with products of bax, p53, and other genes Expressed by basal cell carcinoma (Br J Dermatol 1993; 131: 28) but not by squamous cell carcinoma BER-EP4 Monoclonal antibody directed against a cell surface glycoprotein found on most but not all epithelial cells Expressed by basal cell carcinoma (Am J Dermatopathol 1993; 15: 45) but not by squamous cell carcinoma
3 Metatypical BCC
4 bcl-2 Protein Ber-EP4
5 IMMUNOHISTOLOGIC DDX OF BCC AND ADNEXAL CARCINOMAS OF THE SKIN Epithelial Membrane Antigen Cell membranous glycoprotein that is observed in the majority of human epithelial cells Expressed in a diffuse fashion by truly glandular or sebaceous neoplasms; if present at all in BCC, EMA is restricted to areas of divergent differentiation Carcinoembryonic Antigen Cell surface glycoprotein that is produced by a wide variety of glandular and other epithelial cells, including normal sweat glands and sudoriferous neoplasms Expressed in adenoid cystic carcinoma of the skin and other forms of adnexal neoplasia that may be confused with adenoid basal cell carcinoma, whereas all BCC variants except eccrine epithelioma are non-reactive for this marker
6 Adenoid BCC Adenoid Cystic Carcinoma of Skin
7 EMA- Adenoid BCC CEA+ Adenoid Cystic CA of Skin
8 DDX OF MORPHEAFORM BCC AND DESMOPLASTIC TRICHOEPITHELIOMA -Epithelial Membrane Antigen Expressed by approximately 75% of desmoplastic trichoepitheliomas, but not by any BCC variant except for possibly focal reactivity in eccrine epitheliomas Chromogranin Expressed in most DTEs but not most BCCs
9 Morphea BCC DTE Morphea BCC DTE
10 DTE-- Positive EMA DTE-- Positive Chromogranin
11 IMMUNOHISTOLOGIC DDX OF BCC & CLASSICAL TRICHOEPITHELIOMA bcl-2 protein One report (Smoller BR, et al.: Br J Dermatol 1993; 131:28) found immunostains for bcl-2 protein to be useful in separating BCC from classic trichoepithelioma (Fitzpatrick M, et al.: Am J Clin Pathol 1995; 103: 508) has not borne out that contention; at present, morphology alone must be used to make the distinction between BCC and usual trichoepithelioma
12 Trichoepithelioma
13 bcl-2 in BCC
14
15 DDX OF SARCOMATOID BCC/SCC FROM MESENCHYMAL NEOPLASMS Keratin & Epithelial Membrane Antigen Reproducibly expressed multifocally in sarcomatoid carcinomas of the skin, but not in true cutaneous mesenchymal malignancies
16 Sarcomatoid Carcinoma of Skin
17 DDX OF SARCOMATOID BCC & SCC OF THE SKIN TUMOR KER EMA S100 VIM SCC + +/- 0 +/- Melanoma AFX & OTHER SARCOMAS
18 Keratin Positivity in Sarcomatoid Carcinoma of Skin
19 Angiosarcoma-like Squamous Cell Carcinoma of Skin
20 Cytokeratin + Pseudovascular Squamous Carcinoma of Skin
21 Epithelioid (Carcinoma-like) Angiosarcoma
22 IMMUNOHISTOLOGICAL QUIRKS OF EAS Potential positivity for keratin Reactivity with B72.3
23 IMMUNOREACTIVITY FOR KERATIN IN EAS... WHY?? Some reported cases of keratin+ EASDST represent simple technical artifacts due to faulty antibody titering; HOWEVER, Other examples have had confirmation of keratin content by Western blot and/or mrna hybridization... The latter probably reflects atavistic activation of the keratin gene complex in EASDST, which, among all soft tissue tumors, exhibits this aberrant trait most often for reasons that are currently unknown
24 HOW TO AVOID MISDIAGNOSIS OF EAS BECAUSE OF ABERRANT KERATIN REACTIVITY PANEL APPROACH!!! Epithelial membrane antigen - Ulex europaeus I+ CD31+ CD34+ von Willebrand factor +/-
25 CD31 Positivity CD34 Positivity Epithelioid Angiosarcoma of the Skin
26 DDX OF ADENOID SCC AND SWEAT GLAND CARCINOEMBRYONIC ANTIGEN Present in roughly 75% of sweat gland carcinoma variants but not in primary cutaneous SCC S100 PROTEIN Observed in approximately 60% of sudoriferous malignancies but not in SCC of the skin CONJOINT EFFICACY OF CEA+S % B72.3 Discriminating power between SCC and SGC is still being studied
27 Adenoid (Pseudoglandular) Squamous Cell Carcinoma Sweat Gland Carcinoma with Squamous Metaplasia
28 B72.3+ Sweat Gland Carcinoma
29 MALIGNANT CLEAR CELL TUMORS OF THE SKIN: Differential Diagnosis Clear cell (hydropic) BCC & SCC Clear cell eccrine adenocarcinoma Sebaceous carcinoma Tricholemmal carcinoma Metastatic clear cell adenocarcinoma of viscera Clear (balloon) cell malignant melanoma
30 Clear Cell Basal Cell Carcinoma
31 CLEAR CELL BASAL CELL CARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 + AE13/AE14 (-) EMA (-) CEA (-)
32 Clear Cell Squamous Cell Carcinoma
33 CLEAR CELL SQUAMOUS CELL CARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 (-) AE13/AE14 (-) EMA (+/-) CEA (-) S100 protein (-)
34 Clear Cell Eccrine Carcinoma
35 CLEAR CELL ECCRINE CARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 (+/-) AE13/AE14 (-) EMA (+) CEA (+/-) S100 protein (+/-)
36 CEA+ Clear Cell Eccrine Carcinoma
37 Sebaceous Carcinoma
38 SEBACEOUS CARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 (+/-) AE13/AE14 (-) EMA (+ with multivacuolar cytoplasmic pattern) CEA (-) S100 protein (-)
39 Trichilemmal Carcinoma
40 TRICHILEMMAL CARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 (-) AE13/AE14 + EMA (+/-) CEA (-) S100 protein (-)
41 Metastatic Renal Cell Carcinoma
42 Metastatic Clear-Cell Carcinoma of Ovary
43 METASTATIC CLEAR CELL ADENOCARCINOMA: Immunophenotype Pan-Keratin + BER-EP4 (+/-) AE13/AE14 (-) EMA + CEA (+/-) S100 protein (+/-) [CA-125 or PLAP may be +]
44 CA-125+ Metastatic Clear Cell Ovarian Carcinoma
45 Balloon Cell Melanoma
46 CLEAR (BALLOON) CELL MELANOMA: Immunophenotype Pan-Keratin (-) BER-EP4 (-) AE13/AE14 (-) EMA (-) CEA (-) S100 protein +
47 Primer of Immunohistochemistry (Epithelial Markers) Paul K. Shitabata, M.D. Dermatopathology Institute Torrance, CA
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