title: The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin.
abstract: Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11-22% and 5% of metastatic cutaneous metastases, respectively. Both cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using chi(2) analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value=0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm.
authors.affiliation: Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA 02114, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Mahalingam
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Nguyen
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Richards
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000378:metabolism*; D064032:Calbindin 2; D016009:Chi-Square Distribution; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053569:Keratin-15 / Q000378:metabolism; D018294:Neoplasms, Adnexal and Skin Appendage / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D012044:Regression Analysis; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C576764:CALB2 protein, human; D064032:Calbindin 2; D007381:Intermediate Filament Proteins; D053569:Keratin-15; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D064030:S100 Calcium Binding Protein G; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C500987:monoclonal antibody D2-40