Fusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1-MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1-MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1-MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion-positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion-negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1-MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.

Case of clear cell hidradenoma with mucinous metaplasia in the forehead--immunohistochemical analysis of the mucin. Rinsho Byori. 2006 Aug;54(8):781-4.

Mucinous metaplasia rarely develops in the non-neoplastic skin or its appendages, and almost exclusively confined to the genitalia, palms and soles. Similarly, mucinous metaplasia is quite uncommon in the cutaneous neoplasms and only few cases of clear cell hidradenomas and squamous cell carcinomas with mucinous metaplasia have been reported in the literature. Here we report a new case of clear cell hidradenoma with mucinous metaplasia in the forehead. Our immunohistochemical analysis revealed MUC5AC in the mucinous metaplastic cells of this tumor as in the extramammary Paget's disease, and expression of this gastric foveolar epithelial mucin core protein in these two neoplastic conditions seem to related to their common apocrine origin.