title: Mixed Adeno-neuroendocrine Carcinoma: An Aggressive Clinical Entity.
abstract: Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathologic diagnosis recently defined by the World Health Organization in 2010. Due to poor understanding of MANEC as a clinical entity, there is significant variation in the management of these patients. The purpose of our study was to characterize MANEC to develop evidence-based treatment strategies.
  
  
  
  The Ohio State University patient database was queried for the diagnosis of MANEC and 46 patients were identified. For comparison, the database also was queried for goblet cell carcinoid (GCC) of the appendix, signet ring cell carcinoma, and carcinoid/neuroendocrine tumor of the appendix. Charts were then retrospectively reviewed for clinicopathologic characteristics, patient treatment, and survival data.
  
  
  
  The mean age of diagnosis of MANEC was 54 years. Eighty-seven percent of MANEC arose from the appendix, with 28 % of patients undergoing appendectomy and 35 % undergoing right hemicolectomy as their index operation. Immunohistochemical staining was positive for chromogranin (82 %), synaptophysin (97 %), and CD56 (67 %). Sixty-seven percent of patients presented with stage IV disease and 41 % had nodal metastases. Overall survival was 4.1 years, which was statistically significantly different (p ≤ 0.05) compared with carcinoid tumors (13.4 years), GCC (15.4 years), and signet ring carcinoma (2.2 years).
  
  
  
  MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid/neuroendocrine tumors of the appendix. Based on these findings, we recommend patients with MANEC tumors undergo aggressive multidisciplinary cancer management and close surveillance.
authors.affiliation: Department of General Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Shayna
authors.initials: S
authors.lastname: Brathwaite
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rock
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Yearsley
authors.affiliation: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.affiliation: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hays
authors.affiliation: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, M256 Starling Loving Hall, 320 W. 10th Avenue, Columbus, OH, 43210, USA. sherif.abdel-misih@osumc.edu.
authors.forename: Sherif
authors.initials: S
authors.lastname: Abdel-Misih
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001062:Appendectomy; D001063:Appendiceal Neoplasms / Q000473:pathology* / Q000601:surgery; D002276:Carcinoid Tumor / Q000473:pathology* / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000473:pathology* / Q000601:surgery; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology* / Q000601:surgery; D003082:Colectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult