1. Appendiceal carcinoids
Andrew Sutherland
DOS registrar

2. 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

3. 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

4. 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

6. 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

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

8. 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

9. 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

10. 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

11. 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

12. 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%

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

14. Cancer 1967
Mayo clinic
144 cases, 137 at operation (1/300), 7 autopsy (~1/4000)
Carcinoids 90 of 181 appendiceal neoplasms at the Mayo
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

15. 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)

16. 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

17. 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)

18. “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”

19. 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

20. 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

21. 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%

22. 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

23. 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