Case Report GASTRIC CARCINOID WITH TYPICAL CARCINOID SYNDROME - A CASE REPORT WITH REVIEW OF LITERATURE. J JAIN*, GUPTA OP*, VV JAIN**, A RAWOOL*** ABSTRACT Neuroendocrine tumours (NETs) are rare tumours in humans which originate from endocrine cells of alimentary tract, lung, biliary tract and ovary. Carcinoid syndrome (CS) is disorder characterized diarrhoea and flushing. Classic CS is rarely caused by gastric NETs. We report a case of a 50 year woman who presented with diarrhoea, flushing and weight loss and was found to have Carcinoid tumour of stomach with classic CS. Despite advances in the understanding of pathophysiology of carcinoid tumour its complications remains enigmatic. Early, accurate diagnosis and aggressive treatment is recommended.
Introduction : Gastric carcinoids (GC) are rare human Neuro Endocrine Tumours (NETs) and represent only 2%-3% of the alimentary tract carcinoids and 0.3% of the gastric neoplasm1, 2. The original description of Carcinoids was made by Langhans in 1867. They are characterized by secretory granules and ability to produce biogenic amines and polypeptide hormones. GC may present with anaemia caused by bleeding from an ulcerative mass, abdominal pain, or wi th Carcinoid Syndrome(CS). Typical CS is carcinoid tumours along with specific set of symptoms including flushing, diarrhoea, weight loss, palpitations, congestive heart failure, asthma and Cushing's syndrome2.
mm Hg , respiratory rate of 18/min. She was afebrile, anicteric with no pedal oedema and no lymphadenopathy. Red flush was noticed over face and trunk, lasting for few minutes, without leaving a permanent discoloration. Systemic examination did not reveal any abnormality. Her investigations revealed haemoglobin of 9.6 gm/dl, normal peripheral smear with hypoalbuminaemia (albumin of 2.9).Her random blood glucose level at admission was 263mg/dl. Her levels of 5hydroxyindoleacetic acid (5 HIAA) were found to be higher. On ultrasonography multiple ill defined heterogenous lesion in the both lobes of liver with raised vascularity were seen. Computerized tomography(CT) scan of abdomen with oral contrast showed evidence of enhancing irregular nodular thickening (22 mm) of the greater curvature of stomach and evidence of multiple (largest 3.9 x 3.9 cm size) heterogenous and peripherally enhancing hypodense areas in both lobes of liver (Figure 1). Upper gastrointestinal endoscopy revealed an irregular ulcerated mass lesion in body of stomach (Fig. 2). Histopathological
Case History : A 50-years-female presented with history of pain in epigastrium, distension of abdomen, palpitations, nausea and weight loss since one month. On examination patient was conscious, pale, pulse of 90/min, blood pressure of 110/80 * Professor, ** Assistant Professor, Deptt of Medicine, MGIMS *** Ex resident E-mail -
[email protected]
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examination of gastric mass was suggestive of carcinoid tumors (Fig. 3a, 3b). She was not willing for any surgical intervention so she was treated symptomatically and her diarrhea responded well. We have followed up the patient at six months interval and she is well after one year.
Discussion : Gastrointestinal carcinoids arise from neoplastic proliferation of enterochromaffin cells or Kulchitsky cells3. Incidence of clinically significant carcinoid is estimated at 0.8 - 2.1 new cases per 100,000 people per year and majority are sporadic in nature4. The incidence of GC is less as kulchitsky cells are found occasionally in the stomach. In 2000, World Health Organization revised the classification of GEP-NETs, abandoning the term carcinoid in favour of NET 5. The age of presentation ranges from 4th to 8 decade6. The exact aetiology of carcinoid tumourogenesis is not known. Carcinoid are classified, depending on the site of origin, as foregut (lung, thymus, stomach, duodenum) or midgut (distal ileum ,proximal colon) or hindgut (distal colon, rectum) 7. The biological and clinical characteristics of the tumours vary considerably. Most of the GC shows no evidence of endocrine function 3. They may synthesise and secret serotonin (5-HT) which is metabolised to 5hydroxyindoleacetic acid (5-HIAA). Other hormones secreted are ACTH, histamine, dopamine, substance P, prostaglandins, kallikrein and tachykinins8. Highly aggressive tumours present as CS and have high mortality rate7. The CS is usually a consequence of a synergistic interaction of 5-HT, kinins, kallikrein and prostaglandins gaining access to the circulation. The prevalence of CS is 4%.CS may be classic (typical) more common (95%) and the atypical syndrome. The classic CS present with flushing (pink to red, over face and trunk, lasting for few minutes, without leaving a permanent discoloration and triggered by alcohol or tyramine-containing foods), diarrhoea, abdominal pain, valvular heart disease, palpitations, telangiectasia , wheezing , weight loss and pellagra7. th
Figure : 1 - Computed tomography scan of abdomen with oral contrast showing evidence of enhancing irregular nodular thickening (block arrow) of the greater curvature of stomach and evidence of multiple, heterogeneous (arrow head) and peripherally enhancing hypodense areas in both lobes of liver suggestive of secondaries in liver.
Figure : 2 - Endoscopic view of the body of stomach showing large, irregular and friable mass lesion.
Figure 3a and 3b : Histology slides (H&E Stain) (3a - 40X magnification) - Section showing presence of small blue tumour cells (arrow head) with areas of haemorrhage (block arrow). (3b- 400X magnification)- Section showing presence of relatively monomorphic small round cells with salt and pepper nuclear chromatin.
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In our patient flushing, diarrhoea, weight loss, palpitations were present. Carcinoid crisis (severe episode of CS) can be triggered by surgery or chemotherapy. In contrast atypical syndrome consists of flush (tends to be for hours, purplish colour, over the face, neck and limbs, leaves telangiectasia), headache, lacrimation, cutaneous edema and bronchoconstriction. The most common metastatic sites are liver, lymph nodes and bones. The typical CS and hepatic metastases is rarely observed with GC. They secrete predominantly 5- hydroxytryptophan and not serotonin. GC presents with an atypical CS and have the potential to metastasize to bone1. In our patient GC presented as multiple hepatic metastases and classic CS. The differential diagnoses of the CS include inflammatory bowel disease, gut neoplasia, diverticular disease and irritable bowel syndrome. Endoscopy and endosonography are common diagnostic tools. CT and MRI are required to assess the presence of metastases and plan surgery8. Measurement of urinary 5-HIAA levels (73% sensitivity and 100% specificity) is used for confirming the diagnosis and monitoring patients with metastatic disease8. Other markers help in diagnosis are chromogranin-A, neuron-specific enolase, synaptophysin and CDX-2.Somatostatin receptor scintigraphy, Gallium-68 receptor PET are newer modalities for diagnosis. Patients with foregut carcinoids rarely secrete serotonin, and only the rare existence of CS justifies measurement of 5-HIAA as measured in our patient8. Surgery is the only curative therapy for NETs if performed before metastasis2.9. Nonsurgical therapeutic options include chemotherapy, which is reported to be ineffective. Somatostatin-analogbased therapies are given for symptomatic relief. Peptide receptor radionuclide therapy also called
as hormone-delivered radiotherapy utilizes radioligands (indium-111, lutetium-177,yttrium90) conjugated with hormones. It safely delivers higher dose of radiation than external beam radiation. Hepatic artery chemoinfusion, chemoembolization radiofrequency ablation and cryoablation are used for liver metastases1. Interferon at low doses, growth factor inhibitors, vascular endothelial growth factor receptors and angiopoietin-related growth factor are in the experimental stage. A cumulative analysis of carcinoids showed that in 45% of cases metastases were seen at the time of diagnosis Survival rates are substantially lower for GC (5-yr survival rate -50%) and tumour size, stage and lymph node status are important predictors of survival 4. The prognosis of the gastric carcinoids is significantly better than that of adenocarcinoma even in the presence of regional or hepatic metastasis9. Our case represents type III gastric carcinoid. (Table1) CS is primarily associated with midgut carcinoids, but in our case it was associated with GC. Table : Clinico-pathologic types of gastric carcinoid neoplasm: 7,10 Type I - Small benign gastric carcinoids tumours along with chronic atrophic gastritis type A hypochlorhydria, chronic hypergastrinemia and pernicious anaemia. Type II - Large and polypoid gastric carcinoid associated with MEN I and Zollinger and Ellison syndrome. Lymph node metastasis may be seen. Type III (Sporadic) - Large, solitary gastric carcinoids unassociated with hypergastrinemic states and atypical CS. highly proliferative, show ulceration and are invasive with distant metastases.
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6. Borch K, Ahrén B, Ahlman H, Falkmer S , Granérus G, Grimelius L. Gastric Carcinoids :Biologic Behavior and Prognosis After Differentiated Treatment in Relation to Type. Ann Surg. 2005; 242: 64-73.
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