title: Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases.
abstract: High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy, and spreads along peritoneal surfaces with only rare hematogenous metastasis. It appears to be significantly more aggressive than appendiceal mucinous neoplasms.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Reid
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI, USA.
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Walid L
authors.initials: WL
authors.lastname: Shaib
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Serdar
authors.identifier: 0000-0002-7852-3851
authors.initials: S
authors.lastname: Balci
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Gizem
authors.initials: G
authors.lastname: Akkas
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Bahar
authors.initials: B
authors.lastname: Memis
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Robinson
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Staley
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Winer
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Russell
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Knight
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001063:Appendiceal Neoplasms / Q000473:pathology*; D002276:Carcinoid Tumor / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*