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J Cutan Pathol. 2013 Apr;40(4):363-70. doi: 10.1111/cup.12085. Epub 2013 Feb 11.

The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers.

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Department of Dermatology, Cleveland Clinic Foundation, Cleveland, OH, USA.



Microcystic adnexal carcinoma (MAC), desmoplastic trichoepithelioma (DTE) and morpheaform basal cell carcinoma (BCC) frequently impose a considerable differential diagnostic challenge and immunohistochemistry is often used as a differentiating diagnostic adjunct.


Using standard immunohistochemical techniques, we examined 21 examples of DTE, 17 examples of morpheaform BCC and 10 examples of MAC for the expression of BerEP4, a marker of epithelial cells, and of three stem cell markers, pleckstrin homology-like domain, family A, member 1 (PHLDA1) [T cell death-associated gene 51 (TDAG51)], cytokeratin 15 (CK15) and cytokeratin (CK19).


All but one MAC was negative for BerEP4 and all morpheaform BCC expressed BerEP4. Sixteen out of 21 DTE were immunoreactive for BerEP4. All 21 DTE were PHLDA1 positive and all 17 morpheaform BCC were PHLDA1 negative. MAC showed a mixed staining pattern for PHLDA1. CK15 was expressed in 20/21 DTE, whereas the majority of cases of MAC and morpheaform BCC were CK15 negative. CK19 stained more MAC than DTE and morpheaform BCC.


BerEP4 differentiates between MAC and morpheaform BCC but not between MAC and DTE whereas PHLDA1 differentiates between DTE and morpheaform BCC but shows variable staining in MAC. CK15 and CK19 are helpful adjuncts in the differential diagnosis of sclerosing adnexal neoplasms but are second in line to BerEP4 and PHLDA1. We propose an algorithm for the immunohistochemical work-up of sclerosing adnexal neoplasms.

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