Lymph node melanocytic nevi: pathogenesis and differential diagnoses, with special reference to p16 reactivity

Lymph node nevi (NN) have been occasionally described, yet little is currently known on their origin. According to a theoretical model of nevogenesis, the dissemination of nevus progenitor cells through lymphatic routes is responsible for the development of both nodal and skin nevi. The true incidence of NN is largely unknown but it has been reported to vary from 0.017% to as high as 22%. The frequency of NN nevi has increased since the introduction of sentinel lymph node mapping as a routine prognostic procedure in breast cancer and melanoma. The aim of this study was to analyze the frequency and morphological findings of NN, to discuss possible pathogenetic pathways in their evolution, and to verify the consistency of p16 immunostaining in the critical differential approach between NN and melanoma metastases. We therefore morphologically and immunohistochemically evaluated a series of 60 NN from 58 patients. In 21 patients, the lymph nodes had been removed during the staging for a skin melanoma; in all these patients NN immunostaining with p16 was strongly positive and p16 proved to be a reliable marker for the crucial differential diagnosis between NN and melanoma metastasis, strongly reacting in NN and lacking in melanoma deposits. A deeper knowledge on NN could help to clarify some important topics such as lymph node metastatic melanoma with unknown primary and the current debate on the lymph node involvement from atypical spitzoid tumors.