Primary cutaneous neuroendocrine neoplasms: understanding concepts and approaching the differential diagnosis

Cutaneous tumours with neuroendocrine differentiation are not uncommon. Many of these tumours share similar clinical, cytological and immunohistochemical features rendering the final diagnosis challenging. Furthermore, some cutaneous tumours may rarely show aberrant expression of neuroendocrine markers, while true neuroendocrine differentiation in these remains debatable. Nomenclature and classification of some entities have also been confusing, reflecting the difficulty in histological interpretation as well as rarity of some of the tumours described, and the evolving understanding of their pathogenesis. For instance, low-grade neuroendocrine carcinoma of the skin has been re-named to sweat gland carcinoma with neuroendocrine differentiation, indicating a likely sweat gland origin. Another example is polymorphous sweat gland carcinoma, of which existence has been debated. In this article, we review the basic histological definitions, discuss incorporating clinicopathological findings and immunohistochemical interpretation when approaching the differential diagnoses of neuroendocrine tumours. We also review the most recently described entities and their evolution in the literature.