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

摘要

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 aBRAFV600Emutation, we investigated whether a similar genetic change is also present in TAA/PEA.BRAF,RAS, andPIK3CAmutation 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 thatBRAFV600Emutations were present in TAAs (9/15, 60%) and PEAs (7/9, 78%), but not in other neoplasms. Two additional TAAs harboredKRASG12Dmutations. In addition, aKRASG12Cmutation was identified in one nevus sebaceus-associated TAA-like adenoma. The speculated AGMLG-related apocrine adenoma had aPIK3CAH1047Rmutation. We concluded that activatingBRAFandKRASmutations 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 aPIK3CAmutation, 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.