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 Table of Contents     
CASE REPORT
Year : 2013  |  Volume : 28  |  Issue : 1  |  Page : 39-41  

Dual tracer functional characterization of metastatic gastric carcinoid


1 Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication22-Aug-2013

Correspondence Address:
Rakesh Kumar
E-81, Ansari Nagar (East), All India Institute of Medical Sciences Campus, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-3919.116817

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   Abstract 

Because of the increasing clinical importance of gastric carcinoids and the difficulty in diagnosing them, the need for non-invasive diagnostic methods is growing. Currently, the only reliable method is upper gastrointestinal endoscopy with biopsy. We report the case of a 32-year-old male where a combination of functional imaging studies ( 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography [PET/CT] and 68 Ga-DOTA-NOC PET/CT) not only helped in the correct staging, but also highlighted certain important biological aspects of these tumors, which are important from the management point of view and can prognosticate the patients.

Keywords: 18 F-fluorodeoxyglucose, 68 Ga-DOTA-NOC, carcinoid, positron emission tomography/computed tomography, stomach


How to cite this article:
Naswa N, Sharma P, Agarwal S, Kumar R, Bal C. Dual tracer functional characterization of metastatic gastric carcinoid. Indian J Nucl Med 2013;28:39-41

How to cite this URL:
Naswa N, Sharma P, Agarwal S, Kumar R, Bal C. Dual tracer functional characterization of metastatic gastric carcinoid. Indian J Nucl Med [serial online] 2013 [cited 2019 Dec 9];28:39-41. Available from: http://www.ijnm.in/text.asp?2013/28/1/39/116817


   Introduction Top


Gastric carcinoids are of increasing clinical importance. Whereas, in older studies these composed only 2-3.8% of all carcinoids, [1],[2] more recently investigators have suggested that the incidence may be significantly higher-11-30% of all carcinoids. [3],[4] In addition, to the increased frequency of gastric carcinoids, they are receiving more attention because of recognition that they occur not only sporadically (type-III), but also with increased frequency in chronic hypergastrenemic states (atrophic gastritis type-I) and Zollinger-Ellison syndrome, type-II. [5],[6] Recognition of gastric carcinoids is important because each type can, on occasion, become malignant and metastasize to lymph nodes or the liver (type-I, 5%; type-II, 30%; and type III, 71%). [5],[6] In particular the type-III carcinoid tumors are sporadic, large solitary tumors not associated with a hypergastrenemic state, are highly proliferating due to intense over expression of a mutated p53 gene, [7] have a high propensity to ulcerate and are more likely to be invasive with metastasis. They appear with striking predominance in men; 80% patients diagnosed with type-III carcinoids are men. Accurate pre-therapy staging with other non-invasive imaging modalities is therefore mandatory to select the appropriate mode of therapy.

In this context, we report a case of a patient having gastric carcinoid with liver metastases (type-III) with classic textbook description except that the tumor was non-functional and the patient did not have any of the clinical syndromes. Accurate pre-therapy localization was carried out by positron emission tomography using two different radiotracers. The diagnosis was confirmed by fine needle aspiration cytology (FNAC) from a liver space occupying lesion (SOL) and a gastric biopsy.


   Case Report Top


A 32-year-old man presented with features of abdominal pain and enlargement of 6 months duration. Clinical examination revealed a massively enlarged liver reaching up to the umbilicus with no other positive clinical findings. Biochemical examination, liver function tests, and viral markers were within normal limits except for an elevation of serum alkaline phosphatase. A preliminary high-resolution dual phase computed tomography (CT) revealed a grossly enlarged liver with multiple enhancing hypodense lesions suggestive of hypervascular secondaries and thickening of the greater curvature of the stomach [Figure 1]. An upper gastrointestinal (UGI) endoscopy done during the same time revealed a 3 cm × 2 cm ulcer with rolled up edges along the greater curvature of the stomach. FNAC from one of the liver SOL revealed features of neuroendocrine tumor (NET) with positive immunohistochemistry and a Ki-67 index of 40-50%, following which the patient underwent positron emission tomography/CT (PET/CT) using two different radiotracers with differing imaging perspectives: 18 F-fluorodeoxyglucose ( 18 F-FDG) (a metabolic tracer) and 68 Gallium-DOTA-NOC (somatostatin receptor expressing tumor seeking tracer).
Figure 1: Non-contrast computed tomography (a) and dual phase contrast enhanced computed tomography (b and c) images of abdomen showing multiple hypodense lesions in an enlarged liver with significant marginal contrast enhancement and rapid washout on the venous phase suggestive of hypervascular metastasis. Thickening along the greater curvature of the stomach is also evident (arrow)

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18 F-FDG PET/CT revealed multiple hypodense lesions in liver with focally increased radiotracer uptake, suggestive of poorly differentiated secondaries with high metabolic activity, which was earlier proven on FNAC from a liver SOL [Figure 2]a while foci of increased tracer uptake in a soft-tissue mass at the greater curvature of the stomach was seen on a 68 Ga-DOTA-NOC PET/CT scan suggesting a well-differentiated primary somatostatin receptor expressing NET in addition to regional lymph node involvement while the liver lesions showed no tracer uptake [Figure 2]b. A gastric biopsy later confirmed this finding (well-differentiated NET; Ki-67 index-2%) [Figure 3]. Based on a combination of these findings the patient was deferred from surgery and instead underwent chemotherapy protocol with etoposide and cisplatin, following which he went into a near total clinical and radiological remission [Figure 4]. The patient however had recurrence later on and despite aggressive treatment even including a bone marrow transplant, he succumbed to his disease.
Figure 2: (a) 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) images showing multiple focal areas of increased radiotracer uptake in both lobes of the liver, implicating metabolically active lesions. No significant tracer uptake was noted in the greater curvature of the stomach (arrow) (b) 68Ga-DOTA-NOC PET/CT showing increased radiotracer uptake in the mass at the greater curvature (arrow) while the liver lesions show only minimal radiotracer uptake

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Figure 3: Gastric biopsy showing superficial mucosal fragments with tumor cells arranged as nests and as acini (H and E, ×200) had a small rim of cytoplasm and had a stippled nuclear chromatin (a). They were strongly immunopositive for chromogranin and synaptophysin, two of the common markers used for detection and demonstration of neuroendocrine differentiation (b and c) FNAC from the liver mass (d) showed sheets and fragments of tumor cells with cells having moderately pleomorphic nuclei and coarse chromatin (Papanicolaou, ×200). The tumor was more poorly differentiated as compared to the gastric primary

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Figure 4: Six months after, chemotherapy (A) 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) showing normal physiological distribution the radiotracer. The multiple liver lesions, which previously had intense tracer uptake, have disappeared (b) 68Ga-DOTA-NOC PET/CT showing that the greater curvature of the stomach has normalized and no lesion is visible on the post-therapy image

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   Discussion Top


Among the gastrointestinal carcinoids, small intestine is the most frequent site (28%), followed by rectum (19%) and colon (8%). The incidence of gastric carcinoids is 6%. The average age at diagnosis of patients with gastric carcinoids is 62 years with an equal male to female distribution. Patients are often asymptomatic; carcinoids being found incidentally at the time of UGI endoscopy. When symptomatology occurs they are usually dyspeptic. It has been reported that almost all patients with gastric carcinoids have elevations of plasma chromogranin-A, a peptide secreted by all neuroendocrine cells, although prospective studies for its use as a tumor marker for carcinoids have not yet been proposed.

The management of gastric carcinoids is controversial; sporadic carcinoids have a higher rate of regional lymph node involvement and thus surgical resection with lymph node sampling is generally recommended. Liver is a common site of metastasis. The CT appearance of these lesions is similar to other hepatic metastasis: Multiple, low-density lesions that are rarely calcified and with variable density after intravenous contrast enhancement.

Gastric carcinoids, similar to other carcinoids have a high density of somatostatin receptors (SSTR). [8],[9] With recent studies showing that somatostatin receptor scintigraphy (SRS) are highly sensitive and specific in localizing carcinoids in other locations, [10],[11] the possibility exists that SRS can be used to localize gastric carcinoids. Recently 68 Ga coupled to Octreotide via a bifunctional chelate DOTA (1, 4, 7, 10 tetraazacyclododecane-1, 4, 7, 10 tetra acetic acid) have been used as radiotracers for SRS PET imaging because they exhibit better tumor-to-background ratio. [12],[13] However, because NETs are mostly well-differentiated tumors, they have a low metabolic activity and cannot be visualized efficiently with 18 F-FDG, which is more useful in, less differentiated NETs without expressing (SSTR). [14],[15] Our results also demonstrate similar findings as described with 68 Gallium labeled octreotide (DOTA-NOC) showing the presence of a well-differentiated NET primary in the gastric wall while the less differentiated secondaries in the liver were accurately shown on 18 F-FDG imaging. It therefore represents a unique example of combining two functional imaging modalities, which are complementary to each other for accurately functional mapping of tumor lesions and predicting response to therapy. Furthermore, the positivity of liver lesions on 18 F-FDG imaging meant that this patient had a poor prognosis despite the primary showing increased uptake on 68 Ga-DOTA-NOC imaging.

In conclusion, our observations suggest that these functional imaging findings are characteristic of neuroendocrine cellular differentiation and are very useful in the pre-therapy localization/staging of tumors, predicting, and monitoring response to therapy and follow-up of the patient for future recurrences/relapse and also for prognostication.

 
   References Top

1.Godwin JD 2 nd . Carcinoid tumors. An analysis of 2,837 cases. Cancer 1975;36:560-9.  Back to cited text no. 1
    
2.Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer 1997;79:813-29.  Back to cited text no. 2
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3.Gilligan CJ, Lawton GP, Tang LH, West AB, Modlin IM. Gastric carcinoid tumors: The biology and therapy of an enigmatic and controversial lesion. Am J Gastroenterol 1995;90:338-52.  Back to cited text no. 3
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4.Sjöblom SM. Clinical presentation and prognosis of gastrointestinal carcinoid tumours. Scand J Gastroenterol 1988;23:779-87.  Back to cited text no. 4
    
5.Rindi G, Azzoni C, La Rosa S, Klersy C, Paolotti D, Rappel S, et al. ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: Prognostic evaluation by pathological analysis. Gastroenterology 1999;116:532-42.  Back to cited text no. 5
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7.Peny MO, Donckier V, Gelin M, Haot J, Noel JC. Sporadic carcinoid of the stomach: A highly proliferative disease with a probable role for p53 protein dysregulation. Eur J Gastroenterol Hepatol 1999;11:677-9.  Back to cited text no. 7
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8.Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with 111In-DTPA-D-Phe1- and 123I-Tyr3-octreotide: The Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716-31.  Back to cited text no. 8
    
9.Jensen RT. Peptide therapies: Recent advances in the use of somatostatin and other peptide receptor agonists and antagonists. In: Lewis JH, Dubois A, editors. Current Clinical Topics in Gastrointestinal Pharmacology. Malden, MA: Blackwell Science; 1997. p. 144-223.  Back to cited text no. 9
    
10.Nilsson O, Kölby L, Wängberg B, Wigander A, Billig H, William-Olsson L, et al. Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours. Br J Cancer 1998;77:632-7.  Back to cited text no. 10
    
11.Jensen RT. Presence of somatostatin receptors on gastro enteropancreatic endocrine tumors (GEP's): Impact on clinical management with somatostatin receptor imaging and other uses of somatostatin analysis. In: Lamberts SW, editor. Octreotide: The Next Decade. Bristol, UK: Bioscientific Ltd.; 1999. p. 149-78.  Back to cited text no. 11
    
12.Hofland LJ, Lamberts SW. Somatostatin receptor subtype expression in human tumors. Ann Oncol 2001;12 Suppl 2:31-6.  Back to cited text no. 12
    
13.Anderson CJ, Dehdashti F, Cutler PD, Schwarz SW, Laforest R, Bass LA, et al. 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J Nucl Med 2001;42:213-21.  Back to cited text no. 13
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14.Erasmus JJ, McAdams HP, Patz EF Jr, Coleman RE, Ahuja V, Goodman PC. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 1998;170:1369-73.  Back to cited text no. 14
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15.Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 1998;25:79-83.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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