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GOBLET CELL CARCINOMAS OF THE APPENDIX: RARE BUT AGGRESSIVE TUMOURS WITH CHALLENGING MANAGEMENT
Oskar Kornasiewicz2, Ashley K. Clift*1, Panagiotis Drymousis2, Omar Faiz2, Harpreet Wasan1, Roberto Dina1, Anna Malczewska1,3, Andrea Frilling1
1Imperial College London, Sutton-in-Ashfield, Notts, United Kingdom; 2St Mark's Hospital, London, United Kingdom; 3Medical University of Silesia, Katowice, Poland

Background: Goblet cell carcinomas (GCC) are a rare, distinct sub-type of appendiceal tumors with neuroendocrine features. They are reported to possess an ‘intermediate’ aggressiveness between appendiceal neuroendocrine tumors (ANET) and adenocarcinomas, but clinical experience is limited.
Methods: Retrospective case review of patients with GCC treated at a tertiary referral centre. Histopathological and clinical data were extracted. Tumor grading was as per European Neuroendocrine Tumor Society guidelines, with staging as per the AJCC/UICC TNM classification. Histological reports were used to assign tumor ‘Tang classification’ (Type A = minimal atypia; Type B = irregular clusters, Type C = poorly differentiated). Kaplan-Meier (KM) methodology was used for survival analyses.
Results: From August 2006 to April 2015, 19 patients with GCC were identified (8 female). Median age at presentation was 56years (range 32-77). Four patients had grade (G)1, 5 had G2, and 9 had G3 tumors (unavailable, n=1). Regarding staging: stage I (n=1), stage II (n=9), stage III (n=4), stage IV (n=5). Using the Tang criteria, there were 7 type A, 9 type B, and 3 type C tumors. Initial operations included appendectomy (n=10), right hemicolectomy (RH) (n=5), appendectomy and small bowel resection (n=1), combined appendectomy, hysterectomy, oophorectomy and omentectomy (n=1), appendectomy, RH, omentectomy and hysterectomy (n=1), and appendectomy, omentecomy and oophorectomy (n=1). Eight patients received completion RH as a second operation, one of which also subsequently underwent peritonectomy and hyperthermic intra-operative chemotherapy (HIPEC). In total, six patients received cytotoxic chemotherapy. One patient underwent small bowel resection after RH. Median follow up was 31months (range 2.5-123), and there were 7 deaths. Mean overall survival (OS) was 80.3months, and 1-, 3- and 5-year OS was 78.9%, 59.7% and 59.7%, respectively. One-, 3- and 5-year disease-free survival (DFS) was 94.4%, 74% and 74%, respectively. Four patients (21%) died from disseminated tumor recurrence within 2 years of initial treatment. Mean OS (and 1-, 3- and 5-year OS) for Tang A, B and C class tumors were 73.1months (85.7%, 85.7%, 51.4%), 83.7months (all 66.7%) and 28.5months (66.7%, 66.7%, not reached), respectively.
Discussion: GCC are highly aggressive and must be clearly discriminated from ANET. Despite patients often undergoing multiple advanced surgical procedures and chemotherapy, 5-year OS and DFS was only 59.7% and 74%, respectively, in our cohort.


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