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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
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Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

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On April 2011
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On Jan 2020

Important Notice

Case report
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : PD03 - PD05 Full Version

Ileal Neuroendocrine Tumour Causing Carcinoid Syndrome in Absence of Hepatic Metastasis


Published: January 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/58953.17414
Iti Jain, Ameet Kumar, Balram Goyal, Prerna Guleria

1. Postgraduate Student, Department of Surgery, AFMC, Pune, Maharashtra, India. 2. Professor, Department of Surgery, AFMC, Pune, Maharashtra, India. 3. Assisstant Professor, Department of Surgery, AFMC, Pune, Maharashtra, India. 4. Assisstant Professor, Department of Pathology, AFMC, Pune, Maharashtra, India.

Correspondence Address :
Ameet Kumar,
Professor, Department of Surgery, AFMC, Pune, Maharashtra, India.
E-mail: ameetsurg@gmail.com

Abstract

Carcinoid syndrome consists of the classic symptom triad of flushing, diarrhoea, and valvular heart disease. It occurs in the majority of patients with liver metastases. This report presents a 68-year-old female who suffered from chronic diarrhoea with a history of multiple admissions for the same. On evaluation, a Computed Tomography (CT) scan showed a terminal ileal lesion and bulky ovaries. Suspecting Neuroendocrine Tumour (NET) with carcinoid syndrome, a Gallium 68 DOTANOC (DOTA-1-Nal3-octreotide) scan was done which revealed somatostatin receptor expression in enhancing soft tissue lesion in terminal ileum as well as in bilateral adnexa. This confirmed the diagnosis of NET of the ileum and bilateral ovarian metastases. The patient underwent laparoscopic curative resection of the primary tumour along with bilateral oophorectomy. The patient was diagnosed with ileal NET and presented with clinical symptoms of carcinoid syndrome, yet did not have evidence of hepatic metastasis, but instead had bilateral ovarian metastasis which itself is a rare entity.

Keywords

Diarrhoea, Ileal carcinoid, Laparoscopic resection, Ovarian metastasis

Case Report

A 68-year-old postmenopausal female presented with recurrent episodes of watery diarrhoea for the last 18 months. There was no history of fever, blood in stools, weight loss, flushing, breathlessness, or wheezing. She had multiple Outpatient Department (OPD) consultations and admissions where she received symptomatic treatment without definite relief. Her physical examination and routine haematological and biochemical parameters were unremarkable. The stool examination was normal. CT scan of the abdomen revealed a focal non obstructive submucosal lesion in the terminal ileum showing homogenous enhancement and measuring 17 mm in maximum thickness and 2.8 cm in length. It also showed bulky ovaries (left>right) (Table/Fig 1).

With suspicion of NET, a Ga-68 DOTANOC scan was done, which revealed somatostatin receptor expression in enhancing soft tissue lesion in the terminal ileum as well as in bilateral adnexa, which confirmed the diagnosis of NET of the ileum with bilateral ovarian metastases. Furthermore, serum chromogranin A levels and 24 hours urinary 5-Hydroxyindoleacetic Acid (5-HIAA) levels were elevated- 2580 ng/mL (normal <108 ng/mL) and 12 mg (normal 2-9 mg), respectively. Echocardiography was normal.

The patient underwent laparoscopic segmental resection with primary anastomosis of the distal ileum and bilateral oophorectomy (Table/Fig 2). To prevent carcinoid crisis intraoperatively, the surgery was performed under octreotide infusion cover at 50 ug/hr started 12 hours before surgery, and continued for 24 hours postoperatively.

Histopathological examination showed a well-differentiated NET (World Health Organisation (WHO) Grade-2) (1) in the ileum and bilateral ovaries. On Immunohistochemistry, tumour cells were positive for synaptophysin and chromogranin (Table/Fig 3). On the four week follow-up, the patient was completely asymptomatic.

Discussion

Gastrointestinal NETs (GI-NETS), frequently called carcinoid tumours, are tumours derived from diffuse amine and acid-producing cells of the GI tract with different hormonal profiles, depending on the site of origin. Small Intestinal (SI) NETS comprise >50% of all SI tumours with an annual incidence of approximately, 0.8/100,000 (2). The ileum is the most common site of origin. Patients with GI-NETs must have liver metastasis before they develop carcinoid syndrome unlike ovarian or bronchial tumours, which may have carcinoid syndrome even in absence of liver metastasis (3).

Among the NET ectopic hormonal syndromes, carcinoid syndrome is the second oldest to be described, after insulinoma, with the earliest publication in 1954 (4). Approximately, 30-40% of patients with well-differentiated NETs present with carcinoid syndrome (5).

The occurrence of Carcinoid syndrome associated diarrhoea among NET patients is as high as 60-80%. One of the main secretory products of GI-NETS is serotonin. It acts on 5-HT3 receptors, stimulating intestinal motility and secretion and inhibiting absorption. High levels of serotonin cause increased frequency of bowel movements and decrease stool consistency, clinically seen as diarrhoea (6).

Two plausible explanations have been given to explain why carcinoid syndrome in such a case cannot occur in absence of liver metastasis (7):

• The liver contains a huge amount of monoamine oxidase activity, which inactivates most of the serotonin produced by the tumour (7).
• Primary GI-NETs are usually small and secrete a lesser amount of hormones than a metastatic liver lesion, which is much larger in size and secretory function (7).

Primary ovarian carcinoid tumours or ovarian metastasis as in this case, release serotonin or other vasoactive substances directly into the systemic circulation bypassing the liver and thus, can produce carcinoid syndrome. To the best of our knowledge, there have been only a limited number of such cases in the literature so far. A review of the literature yielded 19 cases of GI-NET with features of carcinoid syndrome in the absence of liver metastasis (Table/Fig 4) (7),(8),(9),(10),(11),(12),(13),(14),(15),(16),(17),(18). As mentioned in the table, the site of primary tumours in these patients was the middle and distal ileum, jejunum, caecum, appendix and mesentery. All the patients had evidence of carcinoid syndrome in the absence of hepatic metastasis. Only eight patients had metastatic deposits in the ovaries (Case 2,3,4,5,6,8,9,10), while in others the most common site of tumour spread was lymph nodes (Case 1,11,12,13,14,15,17). Most of the patients received surgical management and five patients (Case 5,10,12,14,17) showed complete remission without any postoperative complications or recurrence.

Conclusion

Management of chronic diarrhoea can challenge clinicians and the possibility of a carcinoid syndrome should be entertained in them. Further, carcinoid syndrome in absence of liver metastasis, though rare, can occur when vasoactive substances are released directly into systemic circulation as in this case with ovarian metastasis.

References

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Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, et al. A common classification framework for neuroendocrine neoplasms: An International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol. 2018;31:1770-86. [crossref] [PubMed]
2.
Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK, et al. Neuroendocrine tumour epidemiology: Contrasting Norway and North America. Cancer. 2008;113(10):2655-64. [crossref] [PubMed]
3.
Haq AU, Yook CR, Hiremath V, Kasimis BS. Carcinoid syndrome in the absence of liver metastasis: A case report and review of literature. Medical and Pediatric Oncology. 1992;20(3):221-23. [crossref] [PubMed]
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Ito T, Lee L, Jensen RT. Carcinoid-syndrome: recent advances, current status and controversies. Current Opinion in Endocrinology, Diabetes, and Obesity. 2018;25(1):22. [crossref] [PubMed]
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Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP. Carcinoid syndrome: Update on the pathophysiology and treatment. Clinics. 2018;73(suppl 1):e490s. [crossref] [PubMed]
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Boutzios G, Kaltsas G. Clinical syndromes related to gastrointestinal neuroendocrine neoplasms. Front Horm Res. 2015;44:40-57. [crossref] [PubMed]
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Feldmann MJ, Jones SR. Carcinoid syndrome from gastrointestinal carcinoids without liver metastases. Ann Surg. 1982;196:33-37. [crossref] [PubMed]
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Robboy SJ, Scully RE, Norris HJ. Carcinoid metastatic to the ovary. A clinicopathologic analysis of 35 cases. Cancer. 1974;33(3):798-811. 3.0.CO;2-L>[crossref] [PubMed]
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Qninn BF. Argentaffin carcinoma in the ovary-A report of 2 cases. Med J Aust. 1965;2:120-25. [crossref]
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Morris JM, Scully RE. Endocrine pathology of the ovary. London H. Kimpton, 1958.
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Hopping RA, Dockerty MB, Masson JC. Carcinoid tumour of the appendix: Report of a case in which extensive intra-abdominal metastases occurred, including involvement of the right ovary. Archives of Surgery. 1942;45:613-22. [crossref]
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Rosenberg JM, Welch JP. Ileal tumour causing carcinoid syndrome without hepatic metastases. Arch Surg. 1984;119(4):485. [crossref] [PubMed]
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Hossain J, al-Mofleh I, Tandon R, Dhahada NM. Carcinoid syndrome without liver metastasis. Postgrad Med J. 1989;65(766):597-99. [crossref] [PubMed]
14.
Zavras N, Schizas D, Machairas N, Damaskou V, Economopoulos N, Machairas A. Carcinoid syndrome from a carcinoid tumor of the pancreas without liver metastases: A case report and literature review. Oncol Lett. 2017;13(4):2373- 76. Doi: 10.3892/ol.2017.5678. Epub 2017 Feb 6. PMID: 28454406; PMCID: PMC5403383. [crossref] [PubMed]
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Datta S, Williams N, Suortamo S, Mahmood A, Oliver C, Hedley N, Ray P. Carcinoid syndrome from small bowel endocrine carcinoma in the absence of hepatic metastasis. Age Ageing. 2011;40(6):760-62. [crossref] [PubMed]
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Jahagirdar V, Kamal A, Steeds R, Ayuk J. Metastatic small bowel neuroendocrine tumour with bilateral carcinoid heart disease. BMJ Case Rep. 2016;2016:bcr2015213693. [crossref] [PubMed]
17.
Shogbesan O, Abdulkareem A, Pappachen B, Altomare J. Primary mesenteric carcinoid tumour presenting with carcinoid syndrome. Case Rep Gastroenterol. 2018;12(2):396-401. [crossref] [PubMed]
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Famerée L, Van Lier C, Borbath I, Yildiz H, Lemaire J, Baeck M. Misleading clinical presentation of carcinoid syndrome. Acta Gastroenterol Belg. 2021;84(3):501-03. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/58953.17414

Date of Submission: Jul 12, 2022
Date of Peer Review: Aug 28, 2022
Date of Acceptance: Oct 26, 2022
Date of Publishing: Jan 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 13, 2022
• Manual Googling: Oct 10, 2022
• iThenticate Software: Oct 24, 2022 (7%)

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