Mixed Endocrine-Exocrine Carcinoma of Gallbladder Derived from Dysplasia

A rare case of multiple mixed endocrine-exocrine carcinoma (MEEC) of gallbladder in a 68-year-old man is described. The lesions were two separate nodules (17x13x7 mm and 17 mm in length) on the mucosa, which were composed of predominant neuroendocrine carcinoma (NEC) infiltrating into the adventitia and minor portion of adenocarcinoma (AC) or high grade dysplasia (HGD) on the surface. Surrounding mucosa showed areas of low grade dysplasia (LGD). Two nodal metastases out of 16 nodes were found containing NEC component. By immunohistochemistry, human mutL homolog 1 (hMLH1), p53, human mutS homolog 2 (hMSH2) and human mutS homolog 6 (hMSH6) showed diffuse strong positive reaction in HGD, AC and NEC, contrasting with weak positive reaction in LGD. On genetic analysis, all lesions of HGD, AC, and NEC except for LGD showed positive loss of heterozygosity in D5S346 locus. For microsatellite instability and K-ras mutation tests, all lesions showed negative results. Common immunophenotypes and molecular results among HGD, AC, and NEC suggested that NEC of this MEEC was derived from the dysplasia-AC sequence.