Neuroendocrine carcinoma of the extrahepatic bile duct: Case report and literature review

Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is rare, and only 22 cases have been reported. Only two of these were large-cell NEC (LCNEC); the vast majority were small-cell NEC. Here, we report a third case of LCNEC of the extrahepatic bile duct. A 76-year-old male presented to a local hospital with painless jaundice. Imaging studies revealed a tumor at the hepatic hilum. The patient underwent right hepatic lobectomy, bile duct resection, and cholecystectomy. The resection specimen showed a 5.0-cm invasive neoplasm involving the hilar bile ducts and surrounding soft tissue. Histologically, the tumor consisted of nests of medium to large cells with little intervening stroma. The tumor invaded a large portal vein branch. All four excised lymph nodes were positive for metastasis, and metastatic deposits were also present in the gallbladder wall. The tumor was diffusely positive for synaptophysin and focally positive for chromogranin A. Approximately 70%-80% of the tumor cells were positive for Ki-67, indicating strong proliferative activity. A diagnosis of LCNEC was made. A few bile ducts within and adjacent to the invasive tumor showed dysplasia of the intestinal phenotype and were focally positive for synaptophysin and chromogranin A, suggesting that the dysplastic intestinal-type epithelium played a precursor role in this case. A postoperative computer tomography scan revealed rapid enlargement of the abdominal and retroperitoneal lymph nodes. The patient died 21 d after the operation. NEC of the bile duct is an aggressive neoplasm, and its biological characteristics remain to be better defined.     

Large-cell neuroendocrine carcinoma of the distal bile duct

Large-cell neuroendocrine carcinoma (LCNEC) in the distal bile duct is very rare and different from common distal bile duct adenocarcinoma. A 77-year-old man was admitted with obstructive jaundice. Severe stenosis of the distal bile duct was revealed by percutaneous transhepatic cholangiography. Subtotal stomach-preserving pancreaticoduodenectomy was performed. A tumor measuring 1.8 cm in diameter was located in the distal bile duct. Both histopathological and immunohistochemical examination of the resected specimen revealed features of LCNEC of the bile duct. The patient developed multiple liver metastases, lung metastases, and local recurrence and died of disease 3 months after the operation. The clinical behavior of LCNEC in the distal bile duct appears to be highly aggressive with early metastases and a fatal outcome.     

Granular cell tumor of the common bile duct: A Japanese case

Granular cell tumor (GCT) of the biliary system is rare. It is reported that it occurs more commonly in young black women. We report here our seldom experience of a Japanese case in whom icterus was found as a first symptom just after a caesarean operation. A 36-year-old Japanese woman developed icterus after delivery by the Caesarean operation. A surgical operation was performed without can deny that there was a tumor-related change in a bile duct as a result of examination for various images. As a result of pathological evaluation, GCT was diagnosed. By the preoperative organization biomicroscopy result, it was not able to be attachd a right diagnosis. It was thought that this tumor, although rare, should be considered as one of the causes of biliary stenosis in the younger population.     

Neuroendocrine carcinoma of the extrahepatic bile duct: A case report

Neuroendocrine carcinoma(NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma(cT 4N1M0, c Stage Ⅳ). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis.     

Benign giant-cell tumor of the common bile duct: A case report

Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor’s possible confusion with other malignant tumors.     

处置困难胆总管结石1例治疗体会

采用常规取石技术仍未能取出的结石,被认为是处置"困难"的胆总管结石。现将我院收治的1例处置困难的胆总管结石患者治疗经过和治疗体会报道如下。     

Undifferentiated carcinoma of the common bile duct: case report and review of the literature

A 78‐year‐old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 × 10mm. Microscopically, the nodule was ill‐defined and composed of atypical spindle‐shaped and pleomorphic tumor cells. The spindle‐shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.     

Metastatic melanoma to the common bile duct causing obstructive jaundice： A case report

Metastatic melanoma to the common bile duct is very rare with only 18 cases reported so far. We report a 46 year old women who, 18 mo after excision of a skin melanoma, developped a painless progressive obstructive jaundice. At operation a melanoma within the distal third of the common bile duct was found. There were no other secondaries within the abdomen. The common bile duct, including the tumor, was resected and anastomosed with Roux-en-Y jejunal limb. The patient survived 31 mo without any sign of local recurrence and was submitted to three other operations for axillar and brain secondaries, from which she finally died. Radical resection of metastatic melanoma to the common bile duct may result in lifelong relief of obstructive jaundice. It is safe and relatively easy to perform. In other cases, a less aggressive approach, stenting or bypass procedures, should be adopted.     

Double common bile duct： A case report

Double common bile duct （DCBD） is a rare congenital anomaly in which two common bile ducts exist. One usually has normal drainage into the papilla duodeni major and the other usually named accessory common bile duct （ACBD） opens in different parts of upper gastrointestinal tract （stomach, duodenum, ductus pancreaticus or septum）. This anomaly is of great importance since it is often associated with biliary lithiasis, choledochal cyst, anomalous pancreaticobiliary junction （APBJ） and upper gastrointestinal tract malignancies. We recently recognized a rare case of DCBD associated with APB3 with lithiasis in better developed common bile duct. The opening site of ACBD was in the pancreatic duct. The anomaly was suspected by transabdominal ultrasonography and finally confirmed by endoscopic retrograde cholangiopancreatography （ERCP） followed by endoscopic sphincterotomy and stone extraction. According to the literature, the existence of DCBD with the opening of ACBD in the pancreatic duct is most frequently associated with APB3 and gallbladder carcinoma. In case of DCBD, the opening site of ACBD is of greatest clinical importance because of its close implications with concomitant pathology. The adequate diagnosis of this rare anomaly is significant since the operative complications may occur in cases with DCBD which is not recognized prior to surgical treatment.     

Signet ring cell carcinoma of the extrahepatic bile duct

Most tumors affecting the extrahepatic bile duct are adenocarcinomas; the other histologic types occur only rarely. We herein report the extremely rare case of signet ring cell carcinoma (SRCC) originating from the extrahepatic bile duct. A 55-year-old man was hospitalized for jaundice and pruritus. Computed tomography and positron emission tomography suggested the presence of distal extrahepatic bile-duct cancer. He underwent a pylorus preserving pancreaticoduodenectomy. A histologic study confirmed a signet ring cell neoplasm of the distal common bile duct. Because the upper resection margin was invaded by the tumor, he received postoperative concurrent chemoradiotherapy and four cycles of chemotherapy. The patient has survived with no evidence of recurrence for 2 years. This is the second case of primary SRCC of the distal extrahepatic bile duct reported in the literature; further reports of cases are warranted to determine the nature of SRCC in the extrahepatic bile duct.     

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.     

Carcinoma in situ arising in a tubulovillous adenoma of the distal common bile duct： A case report

Tubulovillous adenomas are common in the colon and rectum, but are rare in the common bile duct. Biliary adenomas may produce obstructive jaundice, which can be easily confused with a malignant neoplasm or stone. We report a case of a carcinoma in situ arising in a tubulovillous adenoma of the distal common bile duct causing obstructive jaundice. A 55-year-old male presented with a 10-d history of pruritus and progressive jaundice. Abdominal sonography and computed tomography showed a mass in the distal common bile duct. Endoscopic retrograde cholangiopancreatography showed luminal narrowing of the bile duct due to a polypoid mass. Positron emission tomography demonstrated no abnormal uptake. It was thought that this mass was a malignant tumor, thus a pylorus-preserving panceaticoduodenectomy was performed. The final pathology showed a tubulovillous adenoma with carcinoma in situ of the distal common bile duct. At follow-up 8 mo later, endoscopy showed multiple polyps in the rectum, colon and stomach. The polyps were removed by endoscopic mucosal resection and shown to be tubular adenomas with high grade dysplasia. Biliary adenomas require careful follow-up for early detection of recurrence and malignant transformation.     

Establishment,functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line

AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response prediction.METHODS Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid cancers.RESULTS The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC.     

Duplication of the common bile duct manifesting as recurrent pyogenic cholangitis: A case report

BACKGROUNDDuplication of the extrahepatic bile duct (DCBD) is an extremely rare congenital anomaly of the biliary system. There are five types of DCBD according to the latest classification. Among them, Type V is characterized by single drainage of the extrahepatic bile ducts. Reports on DCBD Type V are scarce.CASE SUMMARYA 77-year-old woman presented with recurrent epigastric pain but without fever or chills. Computed tomography revealed a dilated common bile duct (CBD) that harboured multiple choledocholithiasis. Endoscopic retrograde cholangio-pancreatography (ERCP) was performed, and the stones were extracted using a Dormia basket. She was discharged without any complications; however, she visited the emergency department a day after she was discharged due to epigastric pain and fever. Laboratory findings were suggestive of cholestasis. After urgent ERCP for stone removal, magnetic resonance cholangiopancrea-tography was performed to evaluate remnant choledocholithiasis. Magnetic resonance cholangiopancreatography revealed a DCBD Type Va and remnant choledocholithiasis in the right CBD. Both CBDs were accessed, and the stones were cleared successfully during a subsequent ERCP.CONCLUSIONIn this article, we report an extremely rare case of DCBD manifesting as recurrent pyogenic cholangitis. This case highlights the importance of recognizing DCBD because stones in the unrecognized bile duct could make the patient’s prognosis critical.     

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.     

Primary pure large cell neuroendocrine carcinoma of the ovary: A rare case report and review of literature

Introduction:Ovarian large cell neuroendocrine carcinoma (LCNEC), or ovarian non-small cell neuroendocrine carcinoma, which is a newly described tumour in the classification of primary ovarian neoplasms by the World Health Organization, is a rare entity that is frequently associated with a surface epithelial and germ cell neoplasm component. Few cases have been reported in the literature, and only 18 primary pure ovarian LCNEC cases have been reported so far, including our 1 case. Ovarian LCNEC is a highly aggressive tumor with a poor prognosis even at an early stage.Patient concerns:We report a case of a 55-year-old postmenopausal woman who complained of abdominal pain. CT examination revealed a mass in the right adnexial region and CA125 level was elevated.Diagnosis:She underwent a exploratory laparotomy, and diagnosed as LCNEC histopathologically.Interventions:Cytoreductive surgery was administered to the patient, and had accepted 5 cycles of chemotherapy consisting of paclitaxel and cisplatin.Outcomes:Follow-up for 12 months showed no clinical or radiological evidence of disease recurrence.Conclusion:This case is 1 of the ovarian LCNEC which is a rare and extremely malignant tumor. Diagnosis requires histopathology and immunohistochemistry. The treatment includes primary cytoreductive surgery followed by chemotherapy.     

EUS diagnosis of ectopic opening of the common bile duct in the duodenal bulb： A case report

Among the various congenital anomalies of the biliary system, an ectopic opening of the common bile duct (CBD) in the duodenal bulb is extremely rare. ERCP is essential for diagnosing the anomaly. A 55-year-old male was admitted to hospital for severe right upper quadrant abdominal pain, followed by fever, chills, elevated body temperature and mild icterus. The diagnosis of ectopic opening of CBD in the duodenal bulb was established on endoscopic ultraso-nography (EUS), which clearly demonstrated dilated CBD, with multiple stones and air in the lumen, draining into the bulb. A normal pancreatic duct, which did not drain into the bulb, was also observed. This finding was confirmed on ERCP and surgery. As far as we know, this is the first case of this anomaly diagnosed by EUS. Ectopic opening of the CBD in the duodenal bulb is not an incidental finding, but a pathologic condition which can be associated with clinical entities such as recurrent or intractable duodenal ulcer, recurrent biliary pain, choledocholithiasis or acute cholangitis. Endoscopic ultrasonography features allow preoperative diagnosis of this anomaly and can replace ERCP as a first diagnostic tool in such clinical circumstances. Embryology of the anomalies of the extrahepatic biliary tree has been also reviewed.     

Small-cell carcinoma of the extrahepatic bile duct: a case report and review of the literature

A small-cell carcinoma of the extrahepatic bile duct in a 69-year-old woman is herein reported. A tumor measuring approximately 3 cm in diameter was located at the confluence of the common bile duct, cystic duct, and common hepatic duct. Histopathologically, the tumor was small-cell neuroendocrine carcinoma without any gland formation or differentiation to squamous cell carcinoma. Tumor cells were immunoreactive for epithelial markers such as epithelial membrane antigen and cytokeratin and for the neuroendocrine markers such as neuron-specific enolase, chromogranin A, and synaptophysin. Although the carcinomas in more than half of the reported cases have been reported to be associated with well-to-moderately differentiated squamous or glandular components, seven cases, including our case, showed the carcinomas without squamous or glandular components. According to the review of 16 previously reported cases and our case of small-cell carcinoma of the extrahepatic bile ducts, there is no significant difference in the clinicopathological findings, namely, age, sex, site of carcinoma, and prognosis between the cases with or without squamous or glandular components. No CD34-positive multipotent adult progenitor cells, which might be the origin of the small-cell carcinoma, were detected in the bile duct epithelium in our case.     

Solitary pituitary metastasis resulting from pulmonary large cell neuroendocrine carcinoma

Solitary pituitary metastasis is a rare phenomenon in human neoplasms. We report a case of lung cancer with the initial manifestation of endocrinopathy resulting from pituitary metastasis. The patient's initial diagnosis was a poorly differentiated carcinoma, however, morbid anatomy revealed a definite diagnosis of large cell neuroendocrine carcinoma(LCNEC). Clinical physicians should be aware of potential initial manifestations such as endocrine abnormalities including panhypopituitarism and diabetes insipidus due to solitary pituitary metastasis. This case demonstrates that an endocrine abnormality such as panhypopituitarism could be an initial manifestation of LCNEC.