Journal of Gastrointestinal Surgery

https://doi.org/10.1007/s11605-017-3664-y

GI IMAGE

Mixed Adenoneuroendocrine Carcinoma of the Gallbladder

Yi-Xin Lin 1 & Qian-Bin Jia 1 & Yi-Yun Fu 2 & Nan-Sheng Cheng 1

Received: 7 December 2017 / Accepted: 18 December 2017

# 2018 The Society for Surgery of the Alimentary Tract

Abstract
Mixed adenoneuroendocrine carcinoma rarely occurs in the gallbladder. Most cases of cholecystic mixed
adenoneuroendocrine carcinoma have been reported from Asia, North American, and Europe; however, there is scarce
literature available on this tumor in other populations. Here, we report a case of mixed adenoneuroendocrine carci-
noma in a Melanoderm woman who was initially suspected to have gallbladder cancer. No specific symptoms or
abnormal blood test results were observed preoperatively. Magnetic resonance imaging revealed a 7-cm hypointense
mass in the gallbladder fossa, which invaded the surrounding liver segments. Radical cholecystectomy, partial liver
resection, and regional lymphadenectomy were performed. Finally, she was diagnosed as mixed adenoneuroendocrine
carcinoma of the gallbladder upon postoperative pathological examination and immunohistochemical staining. She
received six cycles of systemic chemotherapy and somatostatin treatment and survived 21 months after surgery. Our
case highlights the fact that mixed adenoneuroendocrine carcinoma of the gallbladder can occur in African populations
as well. Surgical approach combined with adjuvant chemotherapy and somatostatin treatment may contribute a rela-
tively good survival outcome.

Keywords Melanoderm . Gallbladder . Neuroendocrine tumors . Adenocarcinoma

Case Presentation Gallbladder malignancy was considered preoperatively.

A 43-year-old Melanoderm woman was evaluated for a 2-
week history of right hypochondrium pain. She had no
experience in gastrointestinal illness or immunological
disease. Magnetic resonance imaging revealed a 7-cm
mass with inhomogeneous enhancement (Fig. 1a) and re-
stricted diffusion (Fig. 1b) in the gallbladder fossa, which
invaded the surrounding liver segments IV b and V.
Pertinent laboratory tests were within reference range.
* Nan-Sheng Cheng
nanshengcheng_md@126.com
1 ed neuroendocrine carcinoma (Ki-67 index, 85%) that was
Department of Bile Duct Surgery, West China Hospital, Sichuan
University, No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041,
China
2
Department of Pathology, West China Hospital, Sichuan University,
No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China
During laparotomy, periaortic lymph node biopsy was ini-
tially performed, and the result was negative. She
underwent radical cholecystectomy, partial liver resection
(segments IV b and V), and lymph node dissection around
the hepatoduodenal ligament, common hepatic artery, ce-
liac trunk, and posterior pancreaticoduodenal areas. Gross
examination revealed a large mass of 7.4 cm × 5.6 cm.
Cut surface showed grayish-yellow appearance with solid
and cauliflower-like areas (Fig. 2). Pathological examina-
tion revealed the surgical margin and lymph nodes were
negative. Histopathologically, the tumor was composed of
two ingredients: small-cell neuroendocrine carcinoma and
adenocarcinoma with a transitional mixed section
(Fig. 3a). Immunohistochemically, the poorly differentiat-
combined with poorly differentiated adenocarcinoma (Ki-
67 index, 50%) was positive for synaptophysin (Fig. 3b)
and chromogranin A (Fig. 3c). Finally, the diagnosis was
mixed adenoneuroendocrine carcinoma (MANEC) of the

Fig. 1 T1-weighted magnetic resonance imaging showed a hypointense
mass with inhomogeneous enhancement (a, arrows) in the gallbladder
fossa, which invaded the surrounding liver segments IV b and V.
Fig. 2 Macroscopic findings showed grayish-yellow appearance with
solid and cauliflower-like areas
gallbladder (T3N0M0/stage IIIA). Postoperative course
was uneventful. She received six cycles of chemotherapy
using cisplatin (75 mg/m 2 ) on day 1 and etoposide
(120 mg/m 2 ) days 1 to 3, combined with octreotide
30 mg/month, repeated every 4 weeks. She survived
21 months after surgery.
Discussion
MANEC is a rare subtype of gallbladder cancer, be-
cause the normal gallbladder mucosa does not produce
Fig. 3 Histologically, the tumor was composed of small-cell
neuroendocrine carcinoma and adenocarcinoma with a transitional
mixed section (a) (HE, × 100). Immunohistochemically, the
J Gastrointest Surg
Diffusion-weighted magnetic resonance imaging revealed this lesion
with restricted diffusion (b, arrows)
the neuroendocrine cells, which may appear after intes-
tinal or gastric metaplasia due to the influence of chron-
ic cholecystitis or cholelithiasis. 1 Most cases of
cholecystic MANEC have been reported from Asia,
North America, and Europe;2 however, there is scarce
literature available on this tumor in other populations.
Our case highlights the fact that cholecystic MANEC
can occur in African populations as well. Surgical exci-
sion might be a good option. However, considering the
malignant biologic potency of neuroendocrine carcino-
ma, the prognosis is very poor. The survival outcome
becomes even worse when the patient possesses another
poorly differentiated adenocarcinoma. In the presented
case, we encountered a patient of poorly differentiated
neuroendocrine carcinoma combined with poorly differ-
entiated adenocarcinoma in the gallbladder. We adopted
surgical methods followed by 6 cycles of adjuvant che-
motherapy and somatostatin treatment. She survived
21 months, relatively longer than the previous median
survival time.3 It seems a combination of surgical resec-
tion, adjuvant chemotherapy, and somatostatin treatment
may contribute a better prognosis. Increased reports of
cholecystic MANEC will help comprehend the epidemi-
ology, pathogenesis, and treatment options of this rare
and aggressive tumor.
neuroendocrine carcinoma cells were positive for synaptophysin (b) (×
200) and chromogranin A (c) (× 400). HE: hematoxylin and eosin
J Gastrointest Surg

Grant Support The presented case is part of a research granted by References

BSichuan Provincial Health and Family Commission, No.
16ZD010.^
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