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J Cutan Pathol. 2011 Jul;38(7):542-50. doi: 10.1111/j.1600-0560.2011.01693.x. Epub 2011 Feb 24.

Follicular stem cell marker PHLDA1 (TDAG51) is superior to cytokeratin-20 in differentiating between trichoepithelioma and basal cell carcinoma in small biopsy specimens.

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



Biopsies submitted to dermatopathologists are becoming increasingly smaller in size and thus the available diagnostic material is reduced. The distinction between trichoepithelioma and basal cell carcinoma remains challenging, particularly if tissue is limited. Merkel cells, which can be highlighted by means of cytokeratin-20 (CK20) immunostaining, are used as a surrogate marker for the diagnosis of trichoepithelioma, as Merkel cells commonly colonize trichoepithelioma but are generally lacking in basal cell carcinomas. In the current study, we examined the expression of a recently characterized follicular stem cell marker, PHLDA1 (pleckstrin homology-like domain, family A, member 1), also known as TDAG51 (T-cell death-associated gene 51).


Using standard immunohistochemical techniques, we examined 19 trichoepitheliomas and 11 basal cell carcinomas for the expression of PHLDA1 and compared it with CK20 expression.


All 19 trichoepitheliomas were immunoreactive for PHLDA1 and all 11 basal cell carcinomas lacked PHLDA1 expression. Two of eleven basal cell carcinomas harbored CK20-positive Merkel cells. Three trichoepitheliomas lacked secondary CK20-positive cells.


Our results suggest that PHLDA1 represents a practical and easily used tool that can be applied to the differentiation of trichoepithelioma and basal cell carcinoma in small biopsy specimens. Rather than searching for CK20-positive Merkel cells, assessing PHLDA1 expression allows the differential diagnosis between trichoepithelioma and basal cell carcinoma to be solved at scanning magnification.

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