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 v 2 analysis, statistically significant P-values (o0.05) 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: o0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value ¼ 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.

An immunohistochemical comparison of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in differentiating porocarcinoma from squamous cell carcinoma

“…The expression of CK19 in porocarcinoma has been previously documented only in case reports [20,21]. As we have previously reported (41%) [17], 49% of the current cases of porocarcinoma expressed CK15. Expression of nestin, an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells, has not been extensively studied in porocarcinomas [13,17].…”

“…A variety of markers have been reported in the diagnosis of porocarcinoma; however, there is overlapping staining pattern seen in SCC (Table 1) [4,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Both porocarcinoma [4,11,12] and SCC [10,11,25] can express EMA.…”

“…CD10, reported negative in porocarcinoma, labels only 25% of cases of SCC [16]. P63 and cytokeratin (CK) 5/6, reportedly sensitive markers for adnexal carcinomas including porocarcinoma, label the most cutaneous SCC including the spindle cell variant (Table 1) [13,14,17,26,27]. [27] In this study, we performed CK7, CK15, CK19, CAM 5.2, CEA, and nestin immunohistochemistry in a series of cases to determine the following:…”

Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evaluation using tissue microarray samples

“…This statistical test has been used in previous study to test the diagnostic utility of a panel of immune markers to differentiate primary adnexal skin carcinoma from metastatic neoplasms of the skin. 21 Both the linear and logistic regression analyses showed agreement between the discriminatory patterns and markers better able to distinguish trichoepithelioma from basal cell carcinoma (Table 3), but the arrangement of the data in the linear regression study highlights that among the markers used in this work there was not a single marker/ pattern that was completely effective in the differential diagnosis of trichoepithelioma and basal cell carcinoma. Although the data from D2-40 labeling pattern was considered the best identifier of trichoepithelioma tumors, this marker is not entirely reliable because in our series 16 basal cell carcinoma biopsies only expressed this antigen (see Table 4).…”

Atypical Hidradenoma Mimicking Primary Mammary Carcinoma on Breast Fine-Needle Aspiration: A Case Report with Long-Term Follow-Up

“…Importantly, ER and PR are often negative in higher-grade breast cancers and rare morphologic variants. In such cases, a panel including p63, CK5/6 and D2-40 reportedly helps differentiate breast and adnexal neoplasia, although these stains are not entirely specific [39,40,41]. …”