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

Background 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. Methods 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 ). Results 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 . Conclusions 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.