Management of a rare type of Ca appendix Dr. Lam Tang Yu Tuen Mun Hospital Joint Hospital Surgical Grand Round

introduction  primary tumor of the appendix are rare  account for ~0.4-1 % of all gastrointestinal malignancy  ~1 % of all appendicectomy specimen

41 neoplasms in 8560 specimen adenocarcinoma (16) and carcinoid (15) Richard K.Englehardt et al. Journal of Cancer Therapy, 2010  17 neoplasms in 1492 specimen Ma, KW et al. HK MJ neoplasms in 7970 appendicectomy specimen 20 are malignant Conor SJ et al. Dis Colon Rectum 1998

primary appendiceal carcinoma classification epithelial: - mucinous (low grade to high grade, pseudomyxoma peritonei) - adenocarcinoma non-epithelial: - classical carcinoid (neuroendocrine) - goblet cell carcinoid / adenocarcinod - mesenchymal tumors: GIST, leiomyoma, sarcoma Misdraji J et al. Semin Diagn Pathol 2004

E.M.A. Murphy et al. British Journal of Surgery tumor recognized at time of surgery tumor < 2cm base of appendix and mesoappendix clear right hemicolectomy appendicectomy yes no

case presentation  55 years old gentleman, non-smoker, good past health  admitted in 08/2012 for RLQ pain, WCC 14  laparoscopy to open appendicectomy: - rupture acute inflamed appendix in retro-caecal position - ~7cm abscess around - base healthy

pathology : - 9cm long, diffuse dilated appendix with 1.5cm diameter at proximal end and 2cm at distal end - carcinoid tumor, mesenteric and lymphovascular invasion, margin involved

our patient, CT 09/2012: - heterogenous caecal mass - another mass medial to caecum, suggestive peritoneal involvement

laparoscopic right hemi-colectomy in 09/2012: - 5cm tumor growth at caecum with multiple enlarged mesenteric lymph node - another 5cm tumor bulk wrapped by omentum medial to caecum - loop of small bowel ~80cm from ileo-caecal valve invaded by tumor - a small pelvic nodule excised

pathology: - right hemi-colectomy: mixed adeno- neuroendocrine carcinoma (high grade neuroendocrine carcinoma and moderate differentiated adenocarcinoma), margin clear - pelvic nodule: high grade neuroendocrine metastatic carcinoma - no lymph node involvement (0/15)

goblet cell carcinoid (GCC) of appendix  variety of names: adenocarcinoid, adeno- neuroendocrine carcinoma, goblet cell carcinoid, intermediate type of carcinoid, etc  all names except GCC were omitted from WHO classification  biphasic histopathological appearance, recognized since 1960s

 GCC accounts less than 5% of primary tumors of the appendix Gallegos NC et al. Eur J Surg Oncol 1992  3 GCC over 41 appendiceal neoplasm over 8560 specimen Richard K.Englehardt et al. Journal of Cancer Therapy, 2010

Payam S Pahlaven et al. world journal of surgical oncology 2005 a review from 1966 to 2004, nearly 600 cases:  mean age of presentation: 58.9 years (mean age of carcinoid: 35.9 years)  most common presentation: acute appendicitis  tend to present as diffuse thickening of whole appendix  ovaries and disseminated abdominal carcinomatosis most common distant metastasis  liver or other distant organ metastasis rare

Payam S Pahlaven et al. world journal of surgical oncology 2005 a review from 1966 to 2004, nearly 600 cases:  right hemicolectomy recommended if any one of following criteria are noted: - tumor size > 2cm; involvement of the base / lymph node - cellular undifferentiation; increase mitotic activity  bilateral salpingo-oophorectomy also advocated  chemotherapy 5 flurouracil and leucovorin advised  overall 5-year survival between 60% to 84%

Laura H. Tang, et al. Am J Surg Pathol 2008 a single center study, 63 cases:  most common growth pattern: circumferential involvement of appendiceal wall with longitudinal extension  63% patients present with stage IV disease  spectrum of histologic features and correlated with clinical behavior

Laura H. Tang, et la. Am J Surg Pathol 2008 a single center study, 63 cases: typical GCC (group A)minimal atypia and minimal distortion of appendiceal wall adenocarcinoma ex GCC, signet ring cell type (group B ) signficant cytologic atypia, associated destruction of the appendiceal wall adenocarcinoma ex GCC, poorly differentiated carcinoma type (group C) poorly differentiated carcinoma or a high grade neuroendocrine carcinoma for the stage IV-matched 5 year survival, group A: 100%; group B: 38% group C: 0%

our patient…  5 flurouracil and leucovorin, 6 cycles given  admitted in Jan 2013 for abdominal distension / sub-acute IO, resolved with conservative treatment  early FU CT arranged

 CT 30/01/2013: - heterogenous mass at right upper abdomen in close vicinity to adjacent small bowel - another soft tissue mass in left pelvic region

3 rd operation with debulking done 03/ cm tumour mass arising from previous ileo- colonic anastomosis - 5cm peritoneal mass at left iliac fossa - another 7cm mass at greater omentum pathology : all are metastatic neuroendocrine carcinoma

H.Mahteme et al. British Journal of Surgery 2004 what else can we do… - cyto-reductive surgery and intra-peritoneal chemotherapy may help - 5-year survival: 25% - as invasive as that from colorectal adenocarcinoma with peritoneal carcinomatosis

follow up… - In-labeled octreotide scintigraphy - CT scan - plasma chromogranin A corresponding to tumor load - colonscopy: colorectal neoplasms found in 10% with carcinoid ; >50% with malignant epithelial tumour Conor SJ et al. Dis Colon Rectum 1998

bring home message…  diffuse “abnormally” dilated appendix, ?not simple appendicitis, ?goblet cell carcinoid of appendix  spectrum of clinical behavior for GCC  cyto-reductive surgery and intra-peritoneal chemotherapy may be a good option for GCC with peritoneal carcinomatosis  long term follow up for any type of Ca appendix

thank you any question…