|
Key Words:
Carcinoid, midgut tumors, anemia, capsule endoscopy
Abstract:
A patient was evaluated for recurrent blood loss/iron deficiency anemia. Capsule endoscopy identified several abnormalities in the small bowel which at surgery were found to be carcinoid tumors. The patient's father had died from metastatic carcinoid tumors 25 years previously. The inheritability of small intestinal carcinoid disease is discussed.
Introduction:
A 56-year-old gentleman had a history of severe iron deficiency anemia, but no signs of intestinal bleeding. Eighteen months prior to evaluation, the patient had unexplained severe anemia with a hemoglobin of 8 and MCV of 58 fl. This appears to recover following transfusion and 3 months his hemoglobin was 15. A source of bleeding was not identified on endoscopy at an outside institution. One month later, he presented with a hemoglobin of 7, an elevated TIBC, 678 (normal less than 400) and a low ferritin level, 4 mcg/L (normal greater than 15 mcg/L). EGD and colonscopy performed at an outside institution were relatively unremarkable.
His past medical history was unremarkable. He was without any symptoms of any disease process, and was working full time without difficulties. His family history was significant in that his father had died from metastatic carcinoid tumor, with a presumptive ileal origin 25 years earlier. No other familial neoplastic or endocrine diseases were identified. The patient's physical exam was completely normal for age. Rectal examination revealed brown stool that was hemoccult positive on 2/3 cards.
At our institution, evaluation included a small bowel capsule endoscopy (Pill Cam SB, Given Imaging Ltd).
This showed several nodular areas including some with lymphangiectasia. Figures 1-3, Video 1. No active intra-luminal bleeding or mucosal changes of celiac disease were identified. Due to a concern for potential carcinoid tumor, a chromogranin A level was obtained and revealed a marked elevation at 6850ng/ml (normal 225 ng/ml). A 5-HIAA level was slightly elevated at 8.2 (nl less than 6). CT of the abdomen was normal.
|
|
|
Figure 1 |
Figure 2 |
Figure 3 |
Based on the capsule endoscopy and supporting laboratory evaluation the patient underwent exploratory surgery. Two nodules were palpated in a short section of ileum and 20 cm of mid-ileum was resected. A liver biopsy of a small nodule was also done. Four discrete mucosal and submucosal tan-yellow tumor nodules were identified in the ileum ranging from 0.3 to 0.5 cm in greatest dimension (Figure 4,5). No tumor was found in 12 lymph nodes. The small liver lesion revealed a bile duct hamartoma. The patient has not had recurrent anemia in the 6 months following surgery. His MCV is now 98 fl. A repeat chromogranin A level at 6 months was 1600 (Normal less than 225).
Discussion
Carcinoid tumors are small neuroendocrine neoplasms which can occur throughout the body, and commonly in the gastrointestinal tract.1 Intestinal carcinoid tumors are characterized by location: foregut, midgut and hindgut, Table 1.2-4 Familial neuroendocrine tumor syndromes of the foregut and pancreas which can include carcinoid tumors, seem to be associated with the MEN1 syndrome.5,6 MEN1 Syndrome does not appear to be related to the development of midgut (ileal) carcinoids2,4
| Table 1: Location of Intestinal Carcinoid Tumors. |
Foregut |
Midgut |
Hindgut |
Esophagus |
Jejunum |
Descending colon |
Stomach |
Ileum |
Sigmoid colon |
Duodenum |
Appendix |
Rectum |
Liver |
Right colon |
|
Gallbladder |
Transverse colon |
|
Bile ducts |
|
|
Pancreas |
|
|
Familial carcinoid tumors of the ileum (midgut) and hindgut consist of case reports.6-12 Mutations in the tumor-suppressor gene succinate-ubiquinone oxidoreductase subunit D (SDHD) gene have been detected in midgut carcinoid tumors, it is unclear if there are inherited cases with this mutation due to the rarity of the event. Two recent reviews indicate that for an individual with one affected first degree relative, the risk of carcinoid is four times greater than the general population.4,13
Our patient presented with an apparent blood loss anemia. The cause was not identified during upper and lower endoscopies. Further assessment lead to small bowel capsule endoscopy. An active bleeding site was not found, but findings worrisome for carcinoid tumor were identified. Following clinical assessment which revealed both a family history of carcinoid tumor, and elevated chromogranin A levels14,15 with a marginal 5HIAA level, surgical exploration was pursued, and four carcinoid tumors were uncovered. It is important to emphasize that nodal (40-85%) and liver metastasis (10-60%) are commonly associated with midgut carcinoids. Risk for metastasis correlates with size of the primary tumor. In our case, preoperative abdominal CT scan was negative, but careful surgical exploration identified a solitary hepatic lesion histology consistent with incidental hamartoma, emphasizing the need for careful preoperative staging for midgut carcinoid.
The findings at capsule endoscopy can be subtle. However, capsule endoscopy has been reported to be effective in identifying tumors of the small bowel, including carcinoid tumors.16,17 Still, the decision to pursue further evaluation of a potential carcinoid tumor by either double balloon endoscopy or surgery can be difficult. In our case, the findings at capsule endoscopy, supportive laboratory work, and a family history of carcinoid tumors helped us to pursue a surgical option. This patient is obviously at risk for reoccurrence and will require close, lifelong follow up.
References
1. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005 128:1717-51.
2. Sutton R, Doran HE, Williams EMI, Vora J, Vinjamuri S, et al. Neuroendocrine tumors: Surgery for midgut carcinoid. Endocrine-Related Cancer. 10:469-481, 2003.
3. Debelenko, L. V.; Brambilla, E.; Agarwal, S. K.; Swalwell, J. I.; Kester, M. B.; Lubensky, I. A.; Zhuang, Z.; Guru, S. C.; Manickam, P.; Olufemi, S.-E.; Chandrasekharappa, S. C.; Crabtree, J. S.; Kim, Y. S.; Heppner, C.; Burns, A. L.; Spiegel, A. M.; Marx, S. J.; Liotta, L. A.; Collins, F. S.; Travis, W. D.; Emmert-Buck, M. R. Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum. Molec. Genet. 6: 2285-2290, 1997.
4. Babovic-Vuksanovic D, Costantinou CL, Rubin J, Rowland CM, Schaid DJ, Karnes PS. Familial occurrence of carcinoid tumors and association with other malignant neoplasms. Cancer Epidemiology, Biomarkers & Prevention. 8:715-719, 1999.
5. Leotlela PD, Jauch A, Holtgreve-Grez H, Thakker RV. Genetics of neuroendocrine and carcinoid tumours. Endocr Relat Cancer. 2003;10:437-50.
6. Anderson, R. E. A familial instance of appendiceal carcinoid. Am. J. Surg. 111: 738-740, 1966.
7. Eschbach, J. W.; Rinaldo, J. A., Jr. Metastatic carcinoid: a familial occurrence. Ann. Intern. Med. 57: 647-650, 1962.
8. Moertel, C. G.; Dockerty, M. B. Familial occurrence of metastasizing carcinoid tumors. Ann. Intern. Med. 78: 389-390, 1973.
9. Katdare MV, Fichera A, Heimann TM. Familial rectal carcinoid: report of two first-degree relatives with rectal carcinoid and review of the literature. Tech Coloproctol. 2006 10:143-6.
10. Pal T, Liede A, Mitchell M, Calender A, Narod SA. Intestinal carcinoid tumours in a father and daughter. Can J Gastroenterol. 2001 15:405-9.
11. Wale RJ, Williams JA, Beeley AH, Hughes ES. Familial occurrence in carcinoid tumours. Aust N Z J Surg. 1983 Aug;53(4):325-8.
12. Kytola, S.; Nord, B.; Elder, E. E.; Carling, T.; Kjellman, M.; Cedermark, B.; Juhlin, C.; Hoog, A.; Isola, J.; Larsson, C. Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. Genes Chromosomes Cancer 34: 325-332, 2002.
13. Hemminki K and Li X. Familial carcinoid tumors and subsequent cancers: a nationwide epidemiologic study from Sweden. International Journal of Cancer. 94;444-448, 2001.
14. Woltering EA, Hilton RS, Zolfoghary CM, Thomson J, Zietz S, Go VL, Vinik AI, Vinik E, O'Dorisio TM, Mamikunian G. Validation of serum versus plasma measurements of chromogranin a levels in patients with carcinoid tumors: lack of correlation between absolute chromogranin a levels and symptom frequency. Pancreas. 2006 33:250-4.
15. Kölby L, Bernhardt P, Swärd C, Johanson V, Ahlman H, Forssell-Aronsson E, Stridsberg M, Wängberg B, Nilsson O. Chromogranin A as a determinant of midgut carcinoid tumour volume. Regul Pept. 2004 Aug 15;120(1-3):269-73.
16. Nathan SR, Biernat L, Tang D. Multifocal small-bowel carcinoid tumor causing obscure recurrent gastrointestinal bleeding diagnosed by capsule endoscopy. Endoscopy. 2007 Oct 24.
17. van Tuyl SA, van Noorden JT, Timmer R, Stolk MF, Kuipers EJ, Taal BG. Detection of small-bowel neuroendocrine tumors by video capsule endoscopy. Gastrointest Endosc. 2006 Jul;64(1):66-72.
|
