Gallbladder small cell carcinoma: a case report and literature review
© The Author(s). 2016
Received: 1 April 2016
Accepted: 12 July 2016
Published: 25 July 2016
Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.
KeywordsSmall cell carcinoma Gallbladder Neuroendocrine tumor
Primary gallbladder neuroendocrine tumors are rare, representing 0.2 % of all tumors . Neuroendocrine neoplasms of the gallbladder are classified as grades 1 and 2 neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) (large cell or small cell type), and mixed adenoneuroendocrine carcinoma (MANEC) . In particular, gallbladder small cell carcinoma (SCC) is extremely rare. Gallbladder SCC carries a grave prognosis with the survival rates worse than gallbladder adenocarcinoma due to its high malignant potential and late stage at presentation . The overall median survival is 4–6 months despite aggressive management. According to the Surveillance, Epidemiology and End Results (SEER) data, the 1-year survival of gallbladder SCC was 21 % and 5-year was 0 % . In recent years, gallbladder SCC has attracted increasing attention for improved understanding and diagnosis. Herein, we describe the latest review of the English-language literature, including our present gallbladder SCC case [2–17].
Characteristics of patients with gallbladder small cell carcinoma
Gender (n = 121)
42 (35 %)
79 (65 %)
Median age in years (n = 120)
Histopathology (n = 104)
Pure small cell carcinoma
82 (79 %)
22 (21 %)
Cholelithiasis (n = 120)
59 (49 %)
Surgery (n = 90)
67 (74 %)
Chemotherapy (n = 90)
53 (59 %)
Stage (n = 117)
39 (33 %)
78 (67 %)
Lymph nodes (n = 118)
83 (70 %)
Liver (n = 117)
66 (56 %)
Lung (n = 117)
7 (6 %)
Pancreas (n = 117)
7 (6 %)
Peritoneum (n = 117)
6 (5 %)
Omentum (n = 117)
5 (4 %)
Median survival in months
Gallbladder SCC usually presents as a large mass containing extensive necrosis with marked propensity for invasive submucosal growth . Histopathologically, about 80 % of cases are pure SCC and the remaining 20 % are combined SCC (Table 1). Microscopically, the WHO classification defines small cell carcinomas as neuroendocrine tumors with >20 mitoses/2 mm2 (mean 75/10 hpf) and small cell cytological features . Immunohistochemically, the tumor cells expressed neuroendocrine markers, such as chromogranin A, synaptophysin, and/or CD56. In comparison to NETs which usually are diffusely positive for neuroendocrine markers, SCCs show more focal staining . Surgical treatment remains the best curative option and appears to prolong life, with chemotherapy adding a marginal advantage. The operative procedures that we deem appropriate range from cholecystectomy alone to extensive surgical resections, including regional lymph node clearances and hepatic lobectomy. However, therapeutic options are limited because the disease presents in an advanced stage. In fact, stage IV is found in 67 % of cases (Table 1). In cases of nonresectable tumors, the primary management is chemotherapy, and the chemotherapeutic agents of choice are cisplatin, etoposide, and 5-fluorouracil. Actually, there are few papers that showed specific chemotherapy regimens [2, 7]. Surgical treatment and chemotherapy are found in 74 and 59 % of cases, respectively (Table 1). The role of radiotherapy remains undefined due to paucity of data . As shown in Table 1, distant metastasis at presentation is present and is most often located in adjacent lymph nodes (70 %) and the liver (56 %). Median survival for gallbladder SCC is only 8 months. Based on SEER data, gallbladder SCC has no survivors at 10 years, in contrast to the 10-year survival of 36 % for carcinoid tumors .
We have presented the latest review of English-language literature concerning gallbladder SCC. However, despite the finding of a few recent useful papers, we could not give unequivocal directions on preoperative diagnostic methods and treatments including specific chemotherapy regimens. As with previous reports, we can assume that aggressive multimodal treatment may prolong survival of gallbladder SCC patients if they could be provided with early diagnosis with prompt surgical intervention. But, we do not have more effective targeted treatment modalities for gallbladder SCC as yet. Thus, prospective studies on a larger scale need to be conducted in the future.
Written informed consent was obtained from the next of kin of the patient for publishing this case report with accompanying images because the patient had died. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors would like to thank Charles de Kerckhove for review as per his training through the American Medical Writers Association.
MHar and TA were primary writers of the manuscript; additionally, MHar organized the figures and TA prepared the literature search. SE assisted in writing the manuscript. TY, RU, SI, HT, KN, NT, MHir, KI, and SM attended to the patient; JI performed the pathological examination and provided the slides. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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