Open Access

Primary hepatic carcinoid tumor: a case report and review of the literature

  • Chih-Wen Lin1,
  • Chung-Hsu Lai2,
  • Chia-Chang Hsu1,
  • Chao-Tien Hsu3,
  • Pei-Min Hsieh4,
  • Kuo-Chen Hung4 and
  • Yaw-Sen Chen4Email author
Cases Journal20092:90

https://doi.org/10.1186/1757-1626-2-90

Received: 06 January 2009

Accepted: 27 January 2009

Published: 27 January 2009

Abstract

Background

Primary hepatic carcinoid tumor (PHCT) is very rare and difficult to diagnose before biopsy or operation. We report a patient with a small PHCT and review cases in the literature.

Case presentation

A 48-year-old Chinese female with underlying hepatitis B virus (HBV) infection was found to have a low echoic hepatic nodule by abdominal ultrasound. Tumor markers were negative. Dynamic liver computed tomography scans showed enhancement of the nodule in the arterial phase and early washout in the portal phase. Hepatocellular carcinoma (HCC) was considered based on the image findings and underlying HBV infection. However, the tumor biopsy revealed a malignant neoplasm that originating from neuroendocrine cells. Pre-operative and intra-operative investigations for the possible other origin of carcinoid tumor were negative, so PHCT was confirmed.

Conclusion

A small and asymptomatic PHCT is extremely rare. PHCT should be one of the differential diagnoses in patients with small hepatic tumor, even in regions with high prevalence of HBV infection and HCC. Pre-operative biopsy is necessary to avoid misdiagnosis even when HCC is highly suspected clinically.

Background

Carcinoid tumors are neuroendocrine origin neoplasm and may produce serotonin or other functional peptide hormones. They are well-differentiated and low-grade malignant neoplasms. Approximately 74% of all carcinoid tumors arise from the gastrointestinal (GI) tract and the liver is a common site for metastases [1]. However, primary hepatic carcinoid tumor (PHCT) is very rare and the first case was documented by Edmondson in 1958 [2]. This rarity makes it difficult for clinicians to diagnose accurately before biopsy, resection of tumor, or autopsy [3]. Large-sized tumors are common presentations when they are diagnosed [4]. PHCT presents as a small and single nodule, is extremely rare and is difficult to differentiate from hepatocellular carcinoma (HCC), particularly in a region with high prevalence of HCC. Herein, we report a rare case of small PHCT with underlying HBV infection which was suspected to be a small HCC before operation and also comprehensively review 94 cases of PHCT in the literature.

Case presentation

A 48-year-old Chinese female with HBV infection for 15 years was regularly followed up at gastroenterology outpatient department by abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) screening every six months. In May 2005, abdominal US demonstrated a low echoic nodule, 1.6 × 1.6 cm in size in the sixth segment of the liver and mild parenchymal liver disease (Fig. 1A). She was asymptomatic and no abnormality was disclosed by physical examination. Noncontrast liver computed tomography (CT) showed a 1.6 × 1.6 cm well-circumscribed and low density nodule in the same liver segment (Fig. 1B). Dynamic CT scans showed enhancement of the nodule in the arterial phase and early washout in the portal phase (Figs. 1C and 1D). Serum was positive for hepatitis B surface antigen (HBsAg), but negative for HBeAg. The serum anti-HCV was also negative. AFP and CEA were within normal range. Based on the imaging findings and underlying HBV infection, small HCC was highly suspected and a US-guided liver biopsy was performed for definite diagnosis. However, the pathological finding suggested a malignant neoplasm originating form neuroendocrine cells (Fig. 2A). The result of immunohistochemical (IHC) stain was positive for neuron-specific enolase (NSE), synaptophysin, and chromogranin A (Fig. 2B). The pre-operative 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA) value was within normal limits. We undertook a more thorough investigation to rule out the possibility that the liver tumor was a metastatic carcinoid. This workup included upper and low GI endoscopy, a small bowel series, abdominal US, and chest and abdominal CT scans. All imaging findings were unremarkable. Partial hepatectomy was performed. Small bowel, appendix and large bowel were checked during operation and no tumor was found. No cirrhotic liver was noted. The surgery was performed successfully and the patient recovered well. The resected liver tissue contained a 1.6 × 1.6 × 1.5 cm circumscribed tumor (Fig. 3). Histological examination revealed the round or ovoid neoplastic cells arranged in insular pattern with a rosette formation. There was no tumor embolus in the vessels and the resection line was free from tumor invasion. The IHC stains were positive for chromogranin A, cytokeratin, NSE, and synaptophysin. The final diagnosis was PHCT. She was followed up regularly at our hospital and remained disease-free 3 years after operation.
Figure 1

(A) Abdominal ultrasound shows a low echoic nodule in the sixth segment of the liver (arrowheads). (B) Noncontrast CT scan shows a well-circumscribed, low density nodule (arrowheads). (C) Dynamic CT scan shows enhancement of the nodule in the arterial phase (arrowheads). (D) Dynamic CT scan shows enhancement in the portal phase (arrowheads).

Figure 2

(A) The tumor was composed of round or ovoid cells arranged in insular pattern with a rosette formation (hematoxylin and eosin). (B) The tumor cells were positive for chromogranin A.

Figure 3

The resected liver contained a 1.6 × 1.6 × 1.5 cm circumscribed tumor (arrowheads).

Discussion

The origin of PHCT remains unknown. The cells may originate from ectopic pancreatic or adrenal tissue found within the liver or from scattered neuroendocrine cells in the intrahepatic biliary epithelium [5]. Some were observed in animal studies such as those found in the rat liver [6]. The scarcity of such cells may explain the rarity of primary hepatic neuroendocrine tumors. It is also proposed that chronic inflammation in the biliary system may induce intestinal metaplasia that predisposes to the development of neuroendocrine tumor [5].

Including our case, we found 94 cases of PHCT (including primary hepatic neuroendocrine tumor) in the literature [15, 715] and their clinical characteristics are summarized in Table 1. This type of tumor occurs mainly in middle age (mean age, 49.8 years) and is slightly more frequent in females (58.5%). The most common symptom among 84 cases was abdominal pain (37 cases, 44.0%). Eleven cases were asymptomatic (13.1%). The overall mortality rate was 25.5% (24/94) as shown in Table 2.
Table 1

Clinical characteristics and imaging findings of 94 cases of primary hepatic carcinoid tumor

Characteristics

Number (%)

Age (y)a

49.8 ± 16.0

Gender (M/F)

39/55 (41.5/58.5)

Clinical manifestations

 

   Asymptomatic

11/84 (13.1)

   Abdominal pain

37/84 (44.0)

   Carcinoid syndrome

14/84 (16.7)

Diarrhea

8/84 (9.5)

Flushing

4/84 (4.8)

Cushing syndrome

2/84 (2.4)

   Abdominal mass

12/84 (14.3)

   Fatigue

6/84 (7.1)

   Zollinger-Ellison syndrome

5/84 (6.0)

   Dyspnea

4/84 (4.8)

   Jaundice

4/84 (4.8)

   Anemia

2/84 (2.4)

   Body weight loss

2/84 (2.4)

   Hypoglycermia

1/84 (1.2)

   Leg edema

1/84 (1.2)

Imaging finings

 

   Ultrasound

 

Solid tumor

32/39 (82.1)

Solid tumor with cystic component

7/39 (17.9)

Hyperechoic pattern

12/14 (85.7)

Hypoechoic pattern

2/14 (14.3)

   Computed tomography

 

Low density tumor in noncontrast

37/50 (74.0)

Low density tumor with cystic component in noncontrast

17/50 (34.0)

Tumor enhancement

20/50 (40.0)

Enhanced in arterial phase and washout in portal phase

13/50 (26.0)

   Magnetic resonance imaging

 

Low intensity in T1 and high intensity in T2

17/21 (81.0)

   Angiography

 

Hypervascular tumor

23/27 (85.2)

Avascular tumor

4/27 (14.8)

a Present as mean value ± standard derivation

Table 2

Location of tumor, histology and prognosis of 94 cases of primary hepatic carcinoid tumor

Characteristics

Number (%)

Location

 

   unilobar

72/94 (76.6)

Left lobe

28/94 (29.8)

Right lobe

44/94 (46.8)

   billobar

22/94 (23.4)

Number

 

   Single

59/94 (62.8)

   Multiple

35/94 (37.2)

Tumor size

 

    3 cm

7/74 (9.5)

   > 3 cm

67/74 (90.5)

Histological stains

 

   Grimelius

64/71 (90.1)

   Fontana-Masson stains

14/34 (41.2)

Immunohistochemical stains

 

   Chromogranin A

57/64 (89.1)

   Neuron specific enolase

43/58 (74.1)

   Synaptophysin

23/47 (48.9)

   cytokeratin

22/40 (55.0)

Misdiagnosed as HCC by microscopy before IHC stains

11/94 (11.7)

Prognosis

 

   Alive

70/94 (74.5)

   Death

24/94 (25.5)

Treatment

 

   Hepatectomy

73/84 (86.8)

   Liver transplantation

3/84 (3.6)

   Transcatheter arterial embolization

3/84 (3.6)

   Chemotherapy

2/84 (2.4)

   Radiotherapy

2/84 (2.4)

   Radiofrequency ablation

1/84 (1.2)

Recurrence

 

   No recurrence

53/75 (70.7)

   Recurrence

22/75 (29.3)

HCC: Hepatocellular Carcinoma; IHC: Immunohistochemical;

The case we presented was a small and asymptomatic PHCT. In the literature, only 9.5% (7/74) and 13.1% (11/84) of cases were small-sized tumors ( 3 cm) and asymptomatic PHCTs, respectively. Their prognosis was good and the survival rate was 100 % for the 7 small-sized tumor cases and 90.1% (10/11) for the asymptomatic cases, only one of which died as a result of renal cell carcinoma.

The rarity of PHCT makes it difficult to diagnose accurately before biopsy or resection. In previous reports, 4 (4.3%) and 5 (5.3%) cases were diagnosed as HCC [810] and cholagiocarcinoma [11, 12] respectively by imaging and clinical findings before operation. Moreover, PHCT is also difficult to diagnose because of the histological similarity with HCC [3]. 11.7% (11/94) of cases were misdiagnosed as HCC by light microscopy until they revealed the features of carcinoid tumor by IHC examinations [3, 7, 9, 13]. Furthermore, 6 (6.4%) cases had chronic liver disease with HBV or HCV infection and 3 (3.2%) cases with HBV infection were misdiagnosed as HCC before IHC stains [9, 14, 15]. Our case had the underlying hepatitis B liver disease and typical imaging presentation of HCC in dynamic CT scans. AFP level may not rise due to small size of tumor. In addition, Taiwan is a region with high prevalence of HBV and HCC. Thus, small HCC was highly suspected before biopsy. Carcinoid tumor was confirmed by liver biopsy and we arranged serial pre-operative and intra-operative examination to investigate the original site of tumor because the liver is a common site for metastases of carcinoid tumors [1]. The accurate diagnosis of carcinoid tumor before operation is very important because it can alert clinicians to seek possible sites of metastasis, thereby avoiding unnecessary operation or a second operation if a metastatic lesion is found.

Conclusion

A small and asymptomatic PHCT is extremely rare. PHCT should be one of the differential diagnoses in patients with small hepatic tumor, even in regions with high prevalence of HBV infection and HCC. Pre-operative biopsy is necessary to avoid misdiagnosis even when HCC is highly suspected clinically.

Consent

Written informed consent was obtained from the patient for publication of this case report, photographic and radiographic images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Abbreviations

PHCT: 

Primary hepatic carcinoid tumor

HBV: 

Hepatitis B virus

HCC: 

Hepatocellular carcinoma

GI: 

Gastrointestinal

US: 

Ultrasound

CT: 

Computed tomography

AFP: 

Alpha-fetoprotein

IHC: 

Immunohistochemical.

Declarations

Authors’ Affiliations

(1)
Division of Hepatogastroenterology, Department of Internal Medicine, E-Da Hospital/I-Shou University
(2)
Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital/I-Shou University
(3)
Department of Pathology, E-Da Hospital/I-Shou University
(4)
Department of Surgery and Organ Transplantation Center, E-Da Hospital/I-Shou University

References

  1. Knox CD, Anderson CD, Lamps LW, Adkins RB, Pinson CW: Long-term survival after resection for primary hepatic carcinoid tumor. Annals of surgical oncology. 2003, 10 (10): 1171-5. 10.1245/ASO.2003.04.533.View ArticlePubMedGoogle Scholar
  2. Edmondson. H: Tumor of the liver and intrahepatic bile duct. Atlas of tumor pathology, section 7, fascicle 25 Armed Forces Institute of Pathology, Washington, DC. 1958, 105-9.Google Scholar
  3. Sano K, Kosuge T, Yamamoto J, et al: Primary hepatic carcinoid tumors confirmed with long-term follow-up after resection. Hepato-gastroenterology. 1999, 46 (28): 2547-50.PubMedGoogle Scholar
  4. Iwao M, Nakamuta M, Enjoji M, et al: Primary hepatic carcinoid tumor: case report and review of 53 cases. Med Sci Monit. 2001, 7 (4): 746-50.PubMedGoogle Scholar
  5. Gravante G, De Liguori Carino N, Overton J, Manzia TM, Orlando G: Primary carcinoids of the liver: a review of symptoms, diagnosis and treatments. Digestive surgery. 2008, 25 (5): 364-8. 10.1159/000167021.View ArticlePubMedGoogle Scholar
  6. Payne CM, Nagle RB, Paplanus SH, Graham AR: Fibrolamellar carcinoma of liver: a primary malignant oncocytic carcinoid?. Ultrastruct Pathol. 1986, 10 (6): 539-52. 10.3109/01913128609007211.View ArticlePubMedGoogle Scholar
  7. Yasoshima H, Uematsu K, Sakurai K, et al: Primary hepatic carcinoid tumor. Acta pathologica japonica. 1993, 43 (12): 783-9.PubMedGoogle Scholar
  8. Asakawa T, Tomioka T, Abe K, et al: Primary hepatic carcinoid tumor. Journal of gastroenterology. 1999, 34 (1): 123-7. 10.1007/s005350050227.View ArticlePubMedGoogle Scholar
  9. Fenwick SW, Wyatt JI, Toogood GJ, Lodge JP: Hepatic resection and transplantation for primary carcinoid tumors of the liver. Annals of surgery. 2004, 239 (2): 210-9. 10.1097/01.sla.0000109155.89514.42.PubMed CentralView ArticlePubMedGoogle Scholar
  10. Iimuro Y, Deguchi Y, Ueda Y, et al: Primary hepatic carcinoid tumor with metachronous lymph node metastasis after long-term follow up. Journal of gastroenterology and hepatology. 2002, 17 (10): 1119-24. 10.1046/j.1440-1746.2002.02663.x.View ArticlePubMedGoogle Scholar
  11. Miura K, Shirasawa H: Primary carcinoid tumor of the liver. American journal of clinical pathology. 1988, 89 (4): 561-4.PubMedGoogle Scholar
  12. Krishnamurthy SC, Dutta V, Pai SA, et al: Primary carcinoid tumor of the liver: report of four resected cases including one with gastrin production. Journal of surgical oncology. 1996, 62 (3): 218-21. 10.1002/(SICI)1096-9098(199607)62:3<218::AID-JSO13>3.0.CO;2-2.View ArticlePubMedGoogle Scholar
  13. Wang CY, Chen A, Tseng HH, et al: Carcinoid tumor localized in the liver – two cases report: immunohistochemical and ultrastructural studies. Zhonghua yi xue za zhi = Chinese medical journal; Free China ed. 1992, 49 (5): 365-72.PubMedGoogle Scholar
  14. Andreola S, Lombardi L, Audisio RA, et al: A clinicopathologic study of primary hepatic carcinoid tumors. Cancer. 1990, 65 (5): 1211-8. 10.1002/1097-0142(19900301)65:5<1211::AID-CNCR2820650530>3.0.CO;2-M.View ArticlePubMedGoogle Scholar
  15. Barsky SH, Linnoila I, Triche TJ, Costa J: Hepatocellular carcinoma with carcinoid features. Human pathology. 1984, 15 (9): 892-4. 10.1016/S0046-8177(84)80152-5.View ArticlePubMedGoogle Scholar

Copyright

© Lin et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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