BRAF and KRAS mutations in tubular apocrine adenoma and papillary eccrine adenoma of the skin

Abstract

Tubular apocrine adenoma (TAA) and papillary eccrine adenoma (PEA) are benign sweat gland tumors. Their names imply that they exhibit apocrine and eccrine differentiation, respectively. However, morphologically they are very similar and are often indistinguishable. The molecular pathogenesis of either tumor is poorly understood at present. On the basis of an index case of nipple adenoma that was morphologically reminiscent of cutaneous TAA/PEA and harbored a BRAFV600E mutation, we investigated whether a similar genetic change is also present in TAA/PEA. BRAF, RAS, and PIK3CA mutation analyses, and BRAFV600E-specific immunohistochemistry were performed for 24 TAAs/PEAs, 10 eccrine poromas, 7 apocrine cystadenomas, 2 TAA-like adenomas associated with nevus sebaceus, and one apocrine adenoma probably arising in anogenital mammary-like glands (AGMLGs). The results demonstrated that BRAFV600E mutations were present in TAAs (9/15, 60%) and PEAs (7/9, 78%), but not in other neoplasms. Two additional TAAs harbored KRASG12D mutations. In addition, a KRASG12C mutation was identified in one nevus sebaceus-associated TAA-like adenoma. The speculated AGMLG-related apocrine adenoma had a PIK3CAH1047R mutation. We concluded that activating BRAF and KRAS mutations were commonly present in TAAs/PEAs, indicating that in addition to a morphological resemblance, they are closely related genetically. Therefore, they could be considered to be united as a single entity. By contrast, the apocrine adenoma probably arising in AGMLG harbored a PIK3CA mutation, which is also commonly present in hidradenoma papilliferum. Further studies are necessary to determine whether the pathogenesis of AGMLG-related tumors is similar to breast tumors.