Alessandro Vanoli, Oneda Grami, Catherine Klersy, Anna Caterina Milanetto, Luca Albarello, Matteo Fassan, Claudio Luchini, Federica Grillo, Paola Spaggiari, Frediano Inzani, Silvia Uccella, Paola Parente, Gennaro Nappo, Paola Mattiolo, Massimo Milione, Andrea Pietrabissa, Lorenzo Cobianchi, Marco Schiavo Lena, Stefano Partelli, Antonio Di Sabatino, Christine Sempoux, Carlo Capella, Claudio Pasquali, Claudio Doglioni, Fausto Sessa, Aldo Scarpa, Guido Rindi, Marco Paulli, Alessandro Zerbi, Massimo Falconi, Enrico Solcia, Stefano La Rosa, Vanoli, Alessandro, Grami, Oneda, Klersy, Catherine, Milanetto, Anna Caterina, Albarello, Luca, Fassan, Matteo, Luchini, Claudio, Grillo, Federica, Spaggiari, Paola, Inzani, Frediano, Uccella, Silvia, Parente, Paola, Nappo, Gennaro, Mattiolo, Paola, Milione, Massimo, Pietrabissa, Andrea, Cobianchi, Lorenzo, Schiavo Lena, Marco, Partelli, Stefano, Di Sabatino, Antonio, Sempoux, Christine, Capella, Carlo, Pasquali, Claudio, Doglioni, Claudio, Sessa, Fausto, Scarpa, Aldo, Rindi, Guido, Paulli, Marco, Zerbi, Alessandro, Falconi, Massimo, Solcia, Enrico, and La Rosa, Stefano
Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.