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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 7  |  Issue : 3  |  Page : 111-114

Death resulting from low-grade midgut carcinoid tumor: Autopsy findings and review of the literature


1 Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Lagos, Nigeria
2 Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Web Publication29-Oct-2018

Correspondence Address:
Dr. Soyemi Sunday Sokunle
Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja-Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_42_17

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  Abstract 


Well-differentiated neuroendocrine tumors of the midgut are generally known as midgut carcinoids. These endocrine tumors have characteristic clinicopathological features with majority elaborating serotonin, present at an advanced age, and are frequently associated with carcinoid syndrome. We report an autopsy case of low-grade (G1) midgut carcinoid tumor presenting as carcinoid syndrome in a 64-year-old patient who presented with abdominal distension, diarrhea, body pain, and vomiting. Autopsy findings show a yellow tan tumor in the distal ileum measuring 0.5 × 0.5 × 0.1 cm. Histology shows tumor to be carcinoid and strongly positive for immunohistochemical markers chromogranin and cytokeratin and negative for S-100 protein.

Keywords: Carcinoid syndrome, intestinal obstruction, midgut carcinoid


How to cite this article:
Sokunle SS, Ahmed SA, Umar AK. Death resulting from low-grade midgut carcinoid tumor: Autopsy findings and review of the literature. Arch Int Surg 2017;7:111-4

How to cite this URL:
Sokunle SS, Ahmed SA, Umar AK. Death resulting from low-grade midgut carcinoid tumor: Autopsy findings and review of the literature. Arch Int Surg [serial online] 2017 [cited 2020 Jul 12];7:111-4. Available from: http://www.archintsurg.org/text.asp?2017/7/3/111/244406




  Introduction Top


Carcinoid tumors were first described over 100 years ago by Lubarsch, who found multiple tumors in the distal ileum of two patients at autopsy.[1] Carcinoids are the most common tumors arising from diffuse neuroendocrine system of the gastrointestinal tract.[2] They are derived primarily from enterochromaffin cells; these tumors are widely distributed in the body but found with greatest frequency in the gastrointestinal tract comprising 95% of all carcinoids and 1.5% of all gastrointestinal tumors. Various sites of origin of this neoplasm are small bowel 25%–35% (duodenum 2%, jejunum 7%, and ileum 19%), appendi × 30%–45%, cecum (5%), stomach (0.5%), and rectum (10%–14%).[3] Carcinoids can also rarely occur in the pancreas, lungs, biliary tract, esophagus, and the liver.

Carcinoids are often classified as APUDomas (amino precursor uptake and decarboxylation). This is due to the ability of enterochromaffin cells to take up and decarboxylate precursors of biogenic amines. In this regard, carcinoid tumors share certain pathological and biological similarities with pheochromocytomas.[4]

Diagnosis of carcinoid could sometimes be missed especially in the absence of its syndrome and where there is no obvious mass or tumor. It is against this background that we present a case of a 64-year-old male who presented in our emergency unit with classical features of intestinal obstruction. Despite the absence of any mass or tumor in the abdomen, the patient died in transit to the theater barely 48 h after hospitalization.


  Case Report Top


The patient is a 64-year-old man who presented to the emergency unit of the hospital with 10 days history of constipation, insidious abdominal distension, and generalize body pain, and 4 days history of postprandial vomiting. Constipation was later followed by passage of watery stool which was blood stained with abdominal pain, anal protrusion, no weight loss. There was no cough, headache, or fever. His medical history was unremarkable. Physical examination revealed a well-preserved elderly man, conscious and alert, not pale, acyanosed, and moderately dehydrated with severely distended abdomen. Abdominal organs were not ballotable, and bowel sounds were hyperactive. Digital rectal examination shows non-reducible anal protrusion with examination fingers stained with blood. An assessment of intestinal obstruction secondary to a colonic tumor was made by the attending physician to rule out third-degree hemorrhoid. He was immediately placed on nil per oral, rehydrated, and placed on intravenous antibiotics. Electrolytes results revealed hypokalemia which was corrected by potassium chloride. The patient became lifeless about 48 h after admission.

At autopsy, the body was that of an elderly man with a length of 173 cm. The external appearance was unremarkable. The mucosa of the tongue, pharynx, and esophagus including the stomach were also normal. Essentially all the systems were normal except the findings in the gastrointestinal tract. The small intestine was remarkably distended with watery fecal content. On opening the bowel, there was a small polypoid tumor measuring 0.5 × 0.5 × 0.4 cm in the mucosal surface of the distal ileum with yellow tan appearance on cut sections. Other organs were essentially normal.

Histological examination shows tumor cells arranged in organoid nests with pseudoglandular formation in some areas [Figure 1]. The cells have monotonous appearance with small round nuclei, prominent nucleoli, and moderate reddish cytoplasmic granules. Peripheral palisading with tumor cells extending up to muscularis propria is seen [Figure 2]. Mitosis was less than two per 10 high-power fields. Tumor cells were positive for chromogranin and cytokeratin and negative for S-100 [Figure 3], [Figure 4], [Figure 5].
Figure 1: The tumour arranged in organoid nests with partlypseudoglandularappearance. H & E X40

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Figure 2: Tumour cells with reddish cytoplasmic staining and exhibiting peripheral palisading in parts. H&E X100

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Figure 3: Tumour cells strongly positive for chromogranin X40

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Figure 4: Tumour cells positive for cytokeratin X40

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Figure 5: Tumour cells staining negative for S-100. X40

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  Discussion Top


Carcinoid tumor is the generic term traditionally applied to low-grade malignant tumors originating from diffuse endocrine system exclusive of the pancreas and thyroid c-cell. This term has been progressively replaced by well-differentiated neuroendocrine tumor/carcinoma.[4] Carcinoid tumors are thought to arise from endochromaffin cells of Kulchisky, that is, neural crest cells situated at the base of crypts of Lieberkuhn. They are characterized histologically by positive reactions to silver stains and to markers of neuroendocrine tissue. Most are strongly positive to immunohistochemical markers such as neuron-specific enolase, synaptophycin, and chromoganin; 65%–70% of cases were positive for cytokeratin and negative for S-100.[4],[5] Small bowel carcinoid tumors make up approximately one-third of small intestine neoplasms in surgical series. Patients present in the sixth and seventh decade of life, with a male: female ratio of 2:1. They are most frequently located in the distal ileum and are often multicentric. Development of the carcinoid syndrome is rare occurring mostly in younger patients.[6]

In this index case, the patient was 64 years of age and the tumor was an incidental finding in the distal part of the ileum. It also shows positive staining for chromogranin and cytokeratin and negative staining for S-100 protein. This pattern has been previously reported in carcinoids.[4],[5],[6] Small bowel carcinoids are thought to arise from serotonin producing intra-epithelial endocrine cells. It releases large amount of serotonin into the circulation which plays important role in the development of carcinoid syndrome,[6],[7] characterized by diarrhea, flushing of the face, abdominal pain, intestinal obstruction, intussusceptions, perforation or gastrointestinal hemorrhage, bronchoconstriction, and right-sided valvular heat failure (fibro sclerosis); some of these symptoms occurred in this index patient (vomiting, diarrhea, abdominal pain, intestinal obstrution) leading to electrolytes' derangement (hypokalemia). The major and striking clinical presentation of this patient is intestinal obstruction.

Chemical evaluation of carcinoid syndrome relies on measurements of serotonin and its metabolites in body fluids and tissue. In patients with carcinoid syndrome, 5-hydroxy tryptophan (5-HTP) is converted to serotonin and stored in tumor secretory granules and in platelets.[2] 5-Hydroxytryptamine (5HT) is a potent vasodilator and smooth muscle stimulant. Hence, these patients have increased blood and platelet serotonin levels and increased urinary 5-hydroxy indole acetic acid (5-HIAA). Most physicians rely on measurement of 5-HIAA to diagnose carcinoid syndrome; however, platelet serotonin has been reported to be more sensitive than urinary 5-HIAA for detecting carcinoid.[2],[7] Other substances secreted by tumor include corticotropin, histamine, dopamine, substance P, neurotensin, prostaglandin, insulin, and kallikrein.[2],[7] Other biomarkers used to diagnose carcinoid include chromogranin A and neuron-specific enolase. Carcinoid tumors have a slow growth rate but are highly invasive and have metastasizing properties. Metastases most commonly occur to regional lymph nodes and liver. Other sites include bone, thyroid, skin, and breast. None of them was seen in this patient.

Most small bowel carcinoids have loss of chromosome 18 as the commonest genetic alteration followed by loss of heterozygosity of 9p and 16q with aneuploidy present in half of ileal carcinoma.[4],[5] Recently, miRNA 133a was found to play an important role in midgut carcinoid tumor development and progression and this miRNA may have diagnostic and or prognostic utility in midgut carcinoid tumors.[7],[8]

Surgery remains the standard and only curative therapy for patients with well-differentiated carcinoid tumors of the midgut.[2] The overall 5-year survival rate of small bowel carcinoid is between 50% and 65% with difference between tumors confined to the wall and those with invasion of serosa. Also, tumor size correlates with prognosis. Tumors larger than 1.5 cm are usually associated with metastasis.[2],[7] In this patient, tumor size was less than 1.5 cm and this could probably explain why there was no metastasis (T2N0M0).[7],[8] Management of carcinoid syndrome includes the use of somastostatin analogs, interferon alpha, and antidiarrheal agents. Somastostatin analog especially octreotide blocks the release of bioactive peptides and amines and hence is the main stay for control of symptoms of carcinoid syndrome.[9] Interferon alpha acts on specific enzymes leading to degradation of peptide hormones and inhibition of protein synthesis.[10] The control of symptoms by interferon is similar to somastostatin analog, but the onset of response is more delayed. Like other causes of secretory diarrhea, opiates and loperamide have been used for symptomatic improvement of diarrhea in patients with carcinoid syndrome.


  Conclusion Top


This case has shown that elderly patients presenting with intestinal obstruction especially when there is no obvious luminal or mechanical obstruction of the bowel should be carefully investigated and carcinoid syndrome resulting from carcinoid tumor should be considered as differential diagnosis of intestinal obstruction in elderly patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest



 
  References Top

1.
Lubarsch O. Ueber den primiaren Krebs des Iileum, nebst Bemerkungenuber das gleichzeitigevorkommen von krebs and tuberkolose. Virchows Arch 1888;111:280-317.  Back to cited text no. 1
    
2.
Mattew HK, Robert JM. Carcinoid tumours. N Engl J Med 1999;340:858-68.  Back to cited text no. 2
    
3.
Kalia V, Saggar K, Sandhu P, Ahluwalia A, Vibhuti. Carcinoid tumour of the ileum. Ind J Radiol Imag 2006;16:503-4.  Back to cited text no. 3
    
4.
Gastrointestinal tract. In: Rosai J, editor. Ackerman's Surgical Pathology. 10th ed, vol. 1. Edinburgh: Mosby; 2011, p. 673-96.  Back to cited text no. 4
    
5.
Gastrointestinal system. In: In: Jean EB, Robert EP editors. Differential Diagnosis in Surgical Pathology. 2nd ed. Saunders Elsevier; 2010. p. 310-409.  Back to cited text no. 5
    
6.
Yantiss RK, Odze RD, Farraye FA, Rosenberg AE. Solitary versus multiple carcinoid tumours of the ileum: A clinical and pathologic review of 68 cases. Am J Surg Path 2003;27:811-7.  Back to cited text no. 6
    
7.
Philip JB, David SK, Manal MH, Eugene AW, Robert TJ, Stanly JG, et al. Well differentiated neuroendocrine tumors of the jejunum, ileum, appendix and cecum. Pancreas 2010;39:753-66.  Back to cited text no. 7
    
8.
Katharina R, Alexey AL, Gail AS, Shuya Z, Alberto R, Long J, et al. MicroRNA expression in ileal carcinoid tumours: Downregulation of microRNA-133a with tumour progression. Mod Pathol 2010;23:367-75.  Back to cited text no. 8
    
9.
Robin J, Ajani J, Schrmer W. Octreotide acetate long acting formulation versus open label subcutenous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 1999;17:600-6.  Back to cited text no. 9
    
10.
Biesma B, Willemse PH, Mulder NH. Recombinant interferon alpha 2b in patients with metastatic apudomas: Effect on tumours and tumour markers. Br J Cancer 1992;66:850-5.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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