Pure and mixed gallbladder neuroendocrine neoplasms: rare and orphan lesions

neoplasms of the gallbladder are rare since they represent around0,5% of all gallbladder cancers. Mixed adeno-neuroendocrine carcinomas(MANEC) are combined neoplasms in which both componentsrepresent at least 30% of the tumour. In the last 2 years wefound 2 MANEC of the gallbladder, so we retrospectively investigatedour Archive to define their frequency in our Hospital and estimatethe incidence of the disease.Methods: We searched for gallbladder “MANEC” in our database fromJanuary 2009 to March 2019, and then we defined how many gallbladderswere neoplastic in these last 10 years.Results: Of the 8087 sampled gallbladders, 200 were neoplastic (2,4%).In particular, 4 of them were diagnosed as MANEC (0,05%), the otherswere dysplastic (1% low-moderate grade, 0,4% high grade), adenocarcinomas(1,4%) and a pure moderately differentiated NEC (0,012%).All MANECs displayed a poorly differentiated adenocarcinoma plus aneuroendocrine carcinoma with Ki67 higher than 30%. Two cases presentedwell distinct counterparts with numerous Paneth cells CDX-2+ inthe neuroendocrine population, whilst in the other cases the two populationswere deeply intermingled.Conclusion: The neuroendocrine neoplasms of the gallbladder are veryrare and only a few reports are found in the literature (pure NEC = around500, MANEC= 33 cases). Since they are frequently aggressive lesions,the collections and characterization of these neoplasms could help inbetter defining prognosis and treatment.