Stem cell markers can help identify adnexal tumor differentiation when evaluated in the context of morphology: methodology matters.

Modern medicine is increasingly being influenced by the concepts of stem cell biology. In dermatopathology, one of the most intriguing yet unresolved questions is the lineage of adnexal neoplasms. With an expanding arsenal of stem cell markers, we have the tools available to address this question. The application of stem cell markers in dermatopathology requires intimate familiarity with the underlying basic science in order to avoid misinterpretation of their staining pattern. At the same time, the basic science itself can be misleading when immunohistochemical staining patterns for adnexal tumors are under consideration. The markers critically reviewed in this manuscript include B-lymphocyte-induced maturation protein 1 (Blimp-1), nestin, CD34, p63, cytokeratins 15 and 19 and the most recent ones appearing on the horizon: pleckstrin homology-like domain, family A, member 1 (PHLDA1) (TDAG51) and CD200. Of those, cytokeratin 15, PHLDA1 (TDAG51) and CD200 offer the most promise. A combined approach of modern morphology with basic science holds potential to advance one important aspect of our field further with the final goal of logically classifying adnexal tumors based on stem cell biology.