Appendiceal carcinoids Andrew Sutherland DOS registrar

Case Miss KM 23 year old female Presented with 24 hours lower abdominal pain Central to RIF Nausea, no vomiting/diarrhoea No urinary,gynaecological symptoms 3 previous episodes similar pain in last 6 months Previous diagnosis “mild appendicitis” Abdo US NAD

Operation Laparoscopy Omentum plastered down over caecum and appendix Blunt dissected off to reveal acute appendicitis Appendix ~3cmx2cm, anatomy unclear Open, mass in base of appendix Stapled caecal pole resection Uneventful recovery

Follow up Pathology CT abdo/pelvis Acute appendicitis and 18mm carcinoid Carcinoid has infiltrative growth pattern and extends focally to serosal resection margin, caecal margin clear No definite LVI CT abdo/pelvis No evidence metastatic disease

Appendiceal neoplasms Primary Epithelial Benign – Serrated adenoma, tubular adenoma Malignant – adenocarcinoma, mucinous neoplasms Non-epithelial Carcinoid – typical, adenocarcinoid/goblet cell carcinoid Mesenchymal – GIST, lymphoma etc Secondary

Carcinoid tumours Morphologically and biologically heterogenous tumours Now termed neuroendocrine tumours (NETs) Gastroenteropancreatic (GEP-NETs) most common Classification still inadequate

History Microscopic features first described in 1888 by Lubarsch but considered to be carcinomas Carcinoid syndrome described 1890 by Ransom Oberndorfer coined the term carcinoid (carcinoma-like) in 1907 because he believed them to be more benign than carcinomas Recognised as endocrine tumours in 1914 Classified by embryologic site of origin in 1963 Did not gain wide acceptance because of diversity within the groups especially foregut carcinoids Immunohistochemistry and assays for plasma peptides and amines has advanced understanding dramatically

Biology Derived form neuroendocrine or APUD cells scattered throughout gut mucosa and islets of Langerhans in the pancreas Up to 40 different secretory products identified and at least 12 different endocrine cell types Includes 5-hydroxytryptamine, serotonin, gastrin, VIP, insulin, glucagon, pancreatic polypeptide

Clinical Usually incidental findings at operation or autopsy Symptoms from mass effect, secreted hormones or fibrosis stimulated by the tumour Classical carcinoid syndrome in less than 10% (flushing and gut hypermotility) Association with other gut malignancies and also often multicentric Theory of common growth factor

Appendiceal carcinoids Appendix is most common site of resected GI carcinoids Small bowel probably most common site of occurrence Incidence ~1/300 appendicectomies Acute appendicitis in 50%, others found at operation, rarely present with metastases, mass or carcinoid syndrome Presence of a second primary cancer in 10-15% SVH lap appx in 2005 =51, open = 66, other = 8 ?incidence ?incidental

Average age of identification 40 years Male:female incidence equivalent Location tip of appendix 70% body 15% base 10% diffusely 5% Size <10mm 70% 10-20mm 20% >20mm 10%

Metastatic potential Overall risk of metastases up to 10% >20mm 30-60% regional and distant mets 10-20mm 0-10% <10mm virtually 0%

Cancer 1967 Mayo clinic 1930-1965 144 cases, 137 at operation (1/300), 7 autopsy (~1/4000) Carcinoids 90 of 181 appendiceal neoplasms at the Mayo 1945-65 Male:female equivalent 70% at the tip, 20% body, 10% base Incidence of carcinoid of the appendix “parallels the appearance and development of argentaffin cells” – a developmental abnormality

Metastases in 2 only – both at presentation (follow up 5-10 years) Size 70% <10 mm, 27% 10-20mm, 3% >20mm Pathology All had muscular invasion, serosal in 2/3, lymphatic invasion “almost universal” Metastases in 2 only – both at presentation (follow up 5-10 years) 9 colectomies (5 for other pathology)

Review of literature - all 35 documented cases of metastases (over 1000 primaries) occurred with primary tumour >20mm Recommend simple appendicectomy except in the rare instance of a primary appendiceal carcinoid > 20mm

Dis Colon Rectum 1997 7970 appendicectomies 33 appendicectomy alone 74 tumours (0.9%) 42 carcinoids (0.5%) 49% presented with acute appendicitis 33 appendicectomy alone 9 colectomy (5 for other pathology) 1 carcinoid developed metastases (12mm primary)

“Management of carcinoids between 1 and 2 cm is controversial” Node positive carcinoids treated by appendicectomy alone have been reported with no recurrence “Right hemicolectomy is the treatment of choice for carcinoid tumours larger than 2 cm”

Arch Surg 2006 48 patients 1980 – 2005 Massachusetts General Recurrence may occur “as late as 25 years after the initial diagnosis, and death from metastases occurs even later” No evidence for survival benefit from right hemicolectomy

No recurrence/deaths related to carcinoid in the group 5 tumours >20 mm 1 simple appendicectomy 4 secondary right hemicolectomies No evidence of residual tumour in any No recurrence/deaths related to carcinoid in the group Suggest right hemicolectomy only justified in the younger patient with carcinoid >20 mm

Recommended treatment <10mm appendicectomy with clear margins >20mm right hemicolectomy 10-20mm controversial Importance of age and health of patient Lymphovascular invasion Involvement of mesoappendix Positive lymph nodes Overall prognosis excellent 5 year survival 99%

Chromogranin A measurement is most useful serum marker Useful for screening suspected carcinoid ~80% sensitivity Post op for metastatic disease In-labelled octreotide scintigraphy most reliable imaging technique for staging

References Appendiceal tumours: Retrospective clinicopathologic analysis of appendiceal tumours from 7970 appendectomies, DCR 1998 Gastrointestinal carcinoid tumours: Current management strategies, DCR 1997 Carcinoid tumours of the vermiform appendix, Cancer 1967 Current status of gastrointestinal carcinoids, Gastroenterology 2005 Carcinoid tumours of the appendix, BJS 2003 Is right hemicolectomy for 2.0cm appendiceal carcinoids justified? Archives Surgery 2006 Management of the unexpected appendiceal neoplasm, BJS 2006