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BMJ Case Rep. 2009; 2009: bcr12.2008.1352.
Published online 2009 May 25. doi:  10.1136/bcr.12.2008.1352
PMCID: PMC3029781
Rare disease

Primary neuroendocrine neoplasm of the gallbladder

Abstract

Carcinoid tumours are distinct neuroendocrine tumours with characteristic clinical and histological behavioural properties which arise mainly in the gastrointestinal tract (73.7%) or bronchopulmonary system (25.1%). Neuroendocrine tumours of the gallbladder are rare—to date there have been only 42 cases reported in the literature. This case was an incidental finding which was recognised during routine histopathological examination after laparoscopic cholecystectomy for symptomatic cholelithiasis. The patient recovered well from the operation. There were no concurrent lesions or metastases noted on further investigations, and the final diagnosis was a primary neuroendocrine tumour of the gallbladder.

BACKGROUND

Primary neuroendocrine tumours (NETs) of the gallbladder were first described by Joel in 1929.1 Primary NETs are distinct tumours with characteristic clinical and histological behavioural properties which arise mainly in the gastrointestinal tract (73.7%) or bronchopulmonary system (25.1%)2 from enterochromaffin cells and their precursors.3 Within the gastrointestinal system, a recent population-based study by Maggard et al4 has suggested that the small intestine is the most common site (44.7%), followed by the rectum (19.6%). Primary gallbladder NETs are rare (0.2–1%). To date there have been only 42 cases reported in the literature and most cases were detected coincidentally after cholecystectomy for acute or chronic gallbladder disease. We describe a case of NET of the gallbladder in a 52-year-old female patient who was cured by laparoscopic cholecystectomy.

CASE PRESENTATION

A 52-year-old woman had been admitted as an emergency 4 months previously with complaints of right upper quadrant pain radiating to the back, associated with nausea and a bloating sensation over the last 10 days. She gave a history of intermittent abdominal pain radiating to the shoulder and a bloating sensation for 10 years. Her past medical history included ankylosing spondylitis and emphysema. At the time of admission her vital parameters were normal and she was non-icteric. Abdominal examination revealed mild tenderness in the right upper quadrant; otherwise Murphy’s sign was negative.

INVESTIGATIONS

Laboratory investigations included full blood count and liver function tests. The inflammatory markers were slightly raised (upper limit of normal range), and the liver function tests were as follows: bilirubin 2 µmol/l (normal: <17); alkaline phosphatase 164 IU/l (normal: 35–120); aspartate aminotransferase 15 IU/l (normal: <40 IU/l); γ-glutamyl transpeptidase 83 IU/l (normal: <45 IU/l). Abdominal ultrasound revealed very small gallbladder calculi with a thickened gallbladder wall (fig 1) at 4 mm, raising the suspicion of cholecystitis in view of an acute episode of abdominal pain with associated altered liver function.

Figure 1
Ultrasonography showing the thickened gallbladder wall.

TREATMENT

The patient recovered from the acute episode of cholecystitis and was discharged with an appointment for an elective laparoscopic cholecystectomy. At her elective surgery, the gallbladder appeared thick walled with no obvious signs of malignancy. No other abnormalities were noted. She had a successful laparoscopic cholecystectomy.

OUTCOME AND FOLLOW-UP

She made an uneventful postoperative recovery and was discharged home on the same day.

The final histopathology revealed a carcinoid tumour of the neck of the gallbladder.

Histopathology

Macroscopic examination showed thickening of the gallbladder wall with some surface ulceration. Microscopic examination showed a tumour of 7 mm in maximum dimension in the thickened area of the neck of the gallbladder, composed of tubules and nests separated by dense stroma (fig 2). The tumour was confined to the wall of the gallbladder. There was no evidence of lymphovascular or perineural infiltration.

Figure 2
Microscopic appearance of the gallbladder wall, containing tubules and nests separated by stroma.

Immunohistochemistry

The tumour cells showed a strong expression of synaptophysin and chromogranin (fig 3). There was no expression of cytokeratin 7 (CK7) and CK20. The proliferation index was assessed with Ki-67 and was <1%. In other areas of the gallbladder wall there were foamy macrophages and the wall contained Rokitansky–Aschoff sinuses and a minimal chronic inflammatory cell infiltrate. The overall appearance was of a benign NET.

Figure 3
Tumour cells showed strong expression of synaptophysin and chromogranin.

Postoperative CT scan of the chest/abdomen and pelvis showed no evidence of residual disease, and an octreotide scan was normal. Further blood investigations revealed normal fasting gut hormones and 5-hydroxyindoleacetic acid levels.

DISCUSSION

Primary NETs can occur anywhere in the body wherever there are enterochromaffin cells, but the gallbladder is a rare site of occurrence (<1%).5 There have been only 42 cases of gallbladder carcinoid tumours recorded in the world literature. Godwin reported only one carcinoid tumour in the gallbladder among 2837 carcinoid tumours from the gastrointestinal tract.6 Capella et al reported 19 cases (0.2%) of gallbladder carcinoids in their analysis of 8305 cases of carcinoids of all sites.7 A review by Khetan et al showed that in all the cases examined (n=22), the diagnosis was made postoperatively or during postmortem.3 Our patient was diagnosed after surgery, during routine histopathological examination. It is interesting to know that the incidence of multiple carcinoids in the same patient may be ~10–33%, with the small bowel being the most common site (82%).8,9 In the presented case study, there was no metastasis anywhere else in the body. Due to increased incidence of gastroenteropancreatic NET (GEP-NETs), the World Health Organisation (WHO) used a prognosis-oriented definition to provide a common framework.10,11 Though the term “carcinoid tumour” is a well-recognised terminology, it may not cover all tumours arising from neuroendocrine cells present all over the body. Hence the WHO used neuroendocrine tumour or neuroendocrine carcinoma to describe these conditions instead of carcinoid tumours.12 In addition, the European Neuroendocrine Tumour Society (ENETS) proposed guidelines on Tumour–Node–Metastasis (TNM) classification for foregut, midgut and hindgut NETs.13,14 However, clear staging guidelines for NETs arising from the gallbladder have not been promulgated, perhaps because of the rarity of this condition.

While the incidence of carcinoid disease in general appears to have increased due to improved diagnostic technology, more precise specific antibodies in immunohistochemistry and awareness among clinicians and pathologists, they are commonly overlooked or misdiagnosed in uncommon sites such as the gallbladder. Following the diagnosis of carcinoid tumour in the gallbladder, further investigations should be undertaken to detect a potential concurrent lesion elsewhere or a distant metastasis. Laparoscopic curative resection is possible if the tumour is confined within the gallbladder wall.

A consensus TNM staging would be helpful for the future management of NETs arising from the gallbladder.

LEARNING POINTS

  • The incidence of neuroendocrine tumours is increasing, due to improved diagnostic tests.
  • Laparoscopic curative resection is possible if the tumour is confined to the gallbladder wall.
  • Following the diagnosis of neuroendocrine tumour in the gallbladder, further investigations should be undertaken to detect a potential concurrent lesion elsewhere or a distant metastasis.
  • A staging system should be developed to assist in the future management of this uncommon condition.

Footnotes

Competing interests: none.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

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12. Kloppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann NY Acad Sci 2004; 1014: 13–27. [PubMed]
13. Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006t; 449: 395–401. [PMC free article] [PubMed]
14. Rindi G, Kloppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007; 451: 757–62. [PubMed]

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