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.     

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.     

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.     

Endocrine cells in extrahepatic bile duct carcinoma

Summary A total of 44 extrahepatic bile duct carcinomas comprising 13 well-differentiated adenocarcinomas, 25 moderately differentiated adenocarcinomas, and 6 poorly differentiated adenocarcinomas were examined histologically and immunohistochemically for somatostatin, gastrin, and glicentin. Argyrophil cells, argentaffin cells, and somatostatin- and gastrin-immunoreactive cells within the tumor were detected in 46.2%, 15.4%, 23.1%, and 15.4% of well-differentiated adenocarcinomas, and in 16.0%, 8.0%, 12.0%, and 4.0% of moderately differentiated adenocarcinomas, respectively. No tumor tissues of poorly differentiated adenocarcinomas contained endocrine cells. A statistically significant difference in the frequency of argyrophil cells was observed between well and poorly differentiated adenocarcinoma. The incidence of argyrophil cells and somatostatin-immunoreactive cells in nonneoplastic mucosa adjacent to well-differentiated adenocarcinoma was higher than in that adjacent to poorly differentiated adenocarcinoma. Glicentin-immunoreactive cells could not be demonstrated either in tumor tissue or in nonneoplastic mucosa of the extrahepatic bile duct. With reference to the histogenesis of extrahepatic bile duct carcinoma, it was assumed from these results that the development of well-differentiated adenocarcinoma might be closely related to the occurrence of endocrine cells and that poorly differentiated adenocarcinoma might develop from ordinary mucosa.     

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.     

Primary large cell neuroendocrine carcinoma in the common bile duct: First Asian case report

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.     

Cholangiographic findings of early-stage extrahepatic bile duct carcinoma

BACKGROUND: To clarify the cholangiographic findings of early-stage (T1, tumor confined to the mucosal or fibromuscular layer) extrahepatic bile duct carcinoma. METHODS: Cholangiographic images were retrospectively analyzed without other information in 55 patients with extrahepatic bile duct carcinoma who underwent surgical treatment. Tumor stages were T1 (n = 10). T2 (n = 17), and T3 (n = 28). Cholangiographic findings were classified as "diffuse sclerosis," "stenosis," "papillary polypoid filling defect," or "nodular polypoid filling defect". "Papillary polypoid filling defect" was the term used when the width of the base was smaller than the width of the polypoid filling defect. RESULTS: T1 patients showed papillary polypoid filling defects (n = 8) or nodular polypoid filling defects (n = 2) on cholangiography. When cholangiography showed papillary polypoid filling defects, 8 of the 14 resected patients showed T1 stage tumor histologically. CONCLUSIONS: In this study, 57% (8/14) of resected patients with papillary polypoid filling defects showed T1 stage tumor. No T1 stage tumor showed stenosis or diffuse sclerosis.     

Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site

Extrahepatic bile duct(EHBD)cancer may occur metachronously,and these cancers are resectable with a favorable prognosis.We aimed to identify the pattern of metachronous EHBD cancer.We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer.A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor(pT-1N0M0).A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer(pT2N1M0).Imaging studies of both patients taken at 14 and 24mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy(PD).Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas(pT3N0M0).Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery.Through a review of the literature on these cases,we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia.The proximal remnant bile duct was most commonly involved.Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor.Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors.     

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.     

Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data revealed jaundice and liver injury.Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary growth.Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated orifice.Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic imaging.Therefore,the initial diagnosis was IPNB.After endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was performed.Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type IPNB.In addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident.Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET.     

Hilar bile duct resection for bile duct carcinoma at the hilus of the liver

Hilar bile duct resection, by which only the bile duct is resected, was carried out in 31 patients with bile duct carcinoma at the hepatic hilus. However, curative resection was possible in only 4 patients (12.9%). The postoperative 1-, 3-, and 5-year survival rates were 58.1%, 19.4%, and 7.7%, respectively. These results indicate that treatment of this hilar bile duct carcinoma by hilar bile duct resection is of limited value. We believe that this operative procedure should be used only for papillary or nodular carcinoma at the hepatic confluence at relatively early stages of Bismuth's type I or II.     

Limitations of three-dimensional intraductal ultrasonography in the assessment of longitudinal spread of extrahepatic bile duct carcinoma

We investigated the utility and limitations of three-dimensional intraductal ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight patients with extrahepatic bile duct carcinoma, 3D-IDUS was used to assess longitudinal cancer extension to the hepatic side prior to resection. When the linear dimension of 3D-IDUS showed bile duct wall thickening that was connected to the tumor and which became thin at a point, it was determined to be the front formation of longitu-dinal cancer extension. The findings were examined in relation to histologic information from the resected specimen. Although 3D-IDUS showed front formation of wall thickening in two patients, it accurately reflected the histological margin of the longitudinal cancer extension in only one patient. In the other patient, the wall thickening was longer than the histological margin. When 3D-IDUS showed bile duct wall thickening without front formation (n = 2), the wall thickening was longer than the histological margin of the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening (n = 4), one of these patients showed cancer spread histologically. As a result, the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%. Even if the linear dimension of 3D-IDUS demonstrated front formation of thickening of the bile duct, it reflected not only cancer extension but also inflammatory wall thickening. Received: March 21, 2000 / Accepted: July 7, 2000     

Common bile duct schwannoma： A case report and review of literature

Schwannoma is a myelin sheath tumor complicated with neurofibroma, neurofibromatosis and neurogenic sarcoma. Peripheral nerve sheath tumors represent 2%-6% of gastrointestinal tract stromal tumors (GIST), but there are deficient data about location of neurogenic tumors in the biliary system and only nine cases of schwannoma of the extrahepatic biliary tract have been reported. These tumors are clinically non-specific. They are usually symptomatic by compressing the close or adjacent structures when being retroperitoneal, and their preoperative diagnosis is extremely difficult. This paper reviews the literature data and describes a case of schwannoma of the common bile duct associated with cholestasis in a healthy young woman, diagnosed and treated in our department. This case is of interest on account of the complexity of its diagnosis and the atypical macroscopic growth pattern of the tumor.     

Neuroendocrine carcinoma of the gastric stump:A case report and literature review

We herein report a case of neuroendocrine carcinoma of the gastric stump found 47 years after Billroth II gastric resection for a benign gastric ulcer. A 74-yearold man was referred to another hospital with melena. Endoscopic examination revealed a localized ulcerative lesion at the gastrojejunal anastomosis. The diagnosis by endoscopic biopsy was neuroendocrine carcinoma. A total gastrectomy of the remnant stomach with D2 lymphadenectomy was performed at our hospital. The lesion invaded the subserosa, and metastasis was found in two of nine the lymph nodes retrieved. The lesion was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 60%. The diagnosis of neuroendocrine carcinoma of the gastric stump was confirmed using World Health Organization 2010 criteria. Subsequently, the patient underwent one course of adjuvant chemotherapy with the etoposide plus cisplatin(EP) regimen; however, treatment was discontinued due to grade 3 myelosuppression. The patient showed lymph node metastasis in the region around the gastrojejunal anastomosis in the abdominal cavity 7 mo post-surgery. He then underwent radiotherapy and platinum-based combination chemotherapy; however, the disease progressed and liver recurrence was observed on follow-up computedtomography at 16 mo post-surgery. The patient then received chemotherapy with regimens used for the treatment of small cell lung cancer in first-and secondline settings. The patient died of disease progression 31 months after surgery.     

腹腔镜胆囊切除术中肝外胆管横断损伤原因及对策

目的　探讨腹腔镜胆囊切除术中肝外胆管横断损伤发生的原因及预防措施。方法　回顾分析了６ ０００ 例腹腔镜胆囊切除术中９例肝外胆管横断损伤的原因,探讨了预防肝外胆管横断损伤的措施。结果　指出Ｃａｌｏｔ三角解剖结构不清或存在解剖变异,误把胆总管当胆囊管钳夹、切断是肝外胆管横断损伤的主要原因。结论　严格掌握手术适应证,沿胆囊壶腹向下分离,仔细辨别Ｃａｌｏｔ三角解剖结构,术中始终想着Ｃａｌｏｔ三角解剖结构存在的变异,避免盲目自信、莽撞行事是预防肝外胆管横断损伤的关键。     

Carcinosarcoma of the extrahepatic bile duct

A rare case of a carcinosarcoma of the extrahepatic bile duct demonstrating interesting features is described. A 75-year-old woman with a history of choledocholithotomy presented with acute obstructive suppurative cholangitis. Ultrasonography and computed tomography showed a thickened choledochal wall, with calcification. Percutaneous transhepatic and endoscopic retrograde cholangiography revealed a round filling defect accompanied by an irregular obstruction in the common bile duct. Carcinosarcoma was diagnosed from a protruding lesion in the common bile duct obtained by intraoperative frozen sectioning, and pylorus-preserving pancreatoduodenectomy was performed. Histological examination by light microscopy showed a transition between the carcinomatous and sarcomatous components and positive immunoreactivity for epithelial markers in the sarcomatous component. The patient died of a local recurrence 2 years after the surgery. Polypoid growth and ossification in the tumor could be representative features of carcinosarcoma of the extrahepatic bile duct.     

Limitation of cholangiography in assessing longitudinal spread of extrahepatic bile duct carcinoma to the hepatic side

BACKGROUND: Preoperative assessment of longitudinal spread of bile duct carcinoma (BDC) to the hepatic side remains a difficult problem for diagnostic imaging. METHODS: We studied the accuracy of cholangiography in assessing BDC. In 54 patients with extrahepatic bile duct cancer, cholangiographic findings were compared retrospectively with the histological findings of the resected specimens. RESULTS: Histological examination of specimens indicated longitudinal spread of the tumour to the hepatic side in 22 of 54 patients. The accuracy of cholangiography in assessing the extent of the longitudinal spread was only 34/54 (63%). When the cholangiographic images showed a main tumour with a collapsed edge, there was a significantly higher frequency of longitudinal spread compared with tumours with sharp edges (P< 0.05). In contrast, the accuracy of mapping biopsy under percutaneous transhepatic cholangioscopy (n=24) was 83%. CONCLUSIONS: Cholangiography cannot accurately assess the extent of the longitudinal spread of bile duct cancer. When cholangiographic images show a tumour with a collapsed edge, preoperative or intraoperative histological examination is essential to determine a suitable surgical line.     

Intraductal papillary neoplasm of the bile ducts: A case report and literature review

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries, it is very rare and the etiology is unknown. In this article, we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-year-old female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB, gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of PubMed database, we collected 354 IPNB patients reported in 22 articles. In these patients, 52.8% were from Japan and 27.7% were from western countries including the United States (11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically, 57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically, pancreato-biliary subtype accounted for 41.8%, intestinal 28.0%, gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Defined clinico-pathologic features are in demand for the accurate diagnosis and proper treatment.     

Intraductal papillary neoplasm of the bile duct extending superficially from the intrahepatic to extrahepatic bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) or liver is a recently noted rare disease, and its pathogenesis remains unclear. Here we present a case of IPNB with an interesting morphology, which was treated by resection of the right hemiliver and extrahepatic bile duct. A 79-year-old woman was found to have a high alkaline phosphatase level and slight dilatation of the right intrahepatic bile duct on imaging studies. The right intrahepatic bile duct became dilated over a 2-year period; however, no solid mass could be detected, and tumor markers were not elevated. Hepatic resection was scheduled because a mucin-producing bile duct carcinoma of the liver was suspected. A right hemihepatectomy was conducted, and the extrahepatic bile duct was also resected after malignant cells were found in the surgical stump of the right bile duct and in the bile itself. Macroscopically, diffuse dilatation of the intrahepatic bile duct was noted, but no solid component or mucin within the duct was found. Histopathological findings revealed carcinoma in situ, IPNB, in the majority of intrahepatic bile ducts, with no lymph node metastasis, and it extended continuously to the epithelium of the common bile duct. No tumor recurrence or biliary dilatation was observed at follow-up 2 years after surgery. It is important to consider malignancy in the presence of a dilated bile duct and in the absence of any cause of occlusion. Complete resection of IPNB results in a good prognosis and no recurrence.     

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.