Spindle Cell-Type Undifferentiated Carcinoma of the Common Bile Duct of the Hepatic Hilus: Report of a Case

Spindle cell-type undifferentiated carcinoma arising from the extrahepatic bile duct is extremely rare. We herein report a case of this type of carcinoma in the common bile duct of the hepatic hilus. A 59-year-old man was admitted to our hospital complaining of jaundice. The laboratory data revealed an elevation of the serum carbohydrate antigen 19–9 level. Cholangiography revealed a complete obliteration of the left hepatic bile duct and stenosis of the bile duct from the superior to the right hepatic bile duct. Computed tomography showed the tumor to measure 15 × 12 mm in the hepatic hilus, with the obliteration of the right to main trunk of the portal vein and a swollen lymph node in the hepato-duodenum ligament. Arteriography revealed a kink of the right hepatic artery; therefore an encasement of the right hepatic artery was suspected. We preoperatively diagnosed hilus bile duct carcinoma and scheduled a right trisection hepatectomy. Intraoperative frozen sections taken from the tumor and tissues around the hepatic arteries showed spindle and inflammatory cells; therefore an inflammatory pseudotumor was diagnosed intraoperatively. As the right hepatic bile duct was occluded, a right lobe hepatectomy was performed. However, a permanent section revealed both spindle cells and poorly differentiated tubular adenocarcinoma cells positive for CAM5.2, AE1/AE3, and vimentin. On the basis of these findings, the tumor was finally diagnosed to be spindle cell-type undifferentiated carcinoma. Unfortunately, the patient died of pulmonary infarction 11 days after the operation.     

Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: report of a case

We report a case of undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi. A 73-year-old man presented with general malaise. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the distal common bile duct, accompanied by dilatation of the intra- and extrahepatic bile ducts. The patient underwent pancreaticoduodenectomy with regional lymphadenectomy. Gross examination revealed that the distal common bile duct was obstructed by an elastic hard mass, 3.2 × 2.6 cm, accompanied by intraductal tumor thrombi. Microscopically, the nodule was well defined and composed of atypical large tumor cells with bizarre nuclei and little cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin-7 and CAM5.2, but negative for CD56, chromogranin A, and synaptophysin. Thus, a histological diagnosis of undifferentiated carcinoma of the common bile duct was made. The patient recovered uneventfully and has remained free of any signs of recurrence for 18 months since the operation. Undifferentiated carcinomas of the extrahepatic bile duct can be detected early, with the chance of a good prognosis; however, because their biologic growth behavior is still considered aggressive, careful observation after surgery and the initiation of multidisciplinary treatment against recurrence are necessary.     

Small cell carcinoma of the cystic duct: A case report

Small cell carcinoma usually involves the lung and rarely affects the biliary tract, especially the cystic duct. In this article we report a case of small cell carcinoma of the cystic duct in a 46-year-old Japanese man. The patient presented with abdominal pain and jaundice. Imaging showed a small nodule in the cystic duct invading the common bile duct with dilatation of the proximal biliary tree. The hepatic artery and portal vein were free from invasion. Extended right hepatic lobectomy, cholecystectomy, and resection of the extrahepatic proximal bile ducts were performed together with lymph node dissection under the tentative diagnosis of carcinoma of the cystic duct. Histopathologic examination of the resected specimen revealed small cell carcinoma arising in the cystic duct and extending into the common bile duct. The postoperative clinical course was uneventful, and the patient is doing well without any signs of recurrence 1 year after the operation. To our knowledge this is the first documented case of a small cell carcinoma arising in the cystic duct.     

Undifferentiated carcinoma of the lung with osteoclast-like giant cells

We treated a patient with undifferentiated carcinoma of the lung, with osteoclast-like giant cells resembling those of the giant cell tumor of bone. The clinical and morphologic characteristics of this case are documented, and the literature concerning this type of tumor is reviewed. The tumor differed histologically from the pleomorphic carcinoma, which occurs most commonly in the lung, and showed diverse pleomorphic manifestation with benign looking osteoclast-like multinucleated cells and bizarre giant cells. In addition, and undifferentiated carcinoma with a sarcoma-like appearance containing small areas of papillary adenocarcinoma was evident in the tumor.     

Invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion but with changes in the pancreatic duct on pancreatography

We present a case of invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion in a 65-year-old man with a 45-year history of alcohol abuse and a 2-year follow-up of chronic pancreatitis. Two years previously, in May 1998, he was admitted for investigation of abdominal pain. Computed tomography (CT) showed diffuse dilation of the main pancreatic duct with atrophy of the pancreatic parenchyma. Endoscopic retrograde pancreatography (ERP) showed a diffusely dilated main pancreatic duct with irregular side branches in the head of the pancreas. Chronic alcoholic pancreatitis was diagnosed on the basis of the pancreatography findings. The patient was readmitted for investigation of progressive weight loss in August 2000. Serum CA19-9 levels were markedly elevated (750 U/ml) and CT showed enlargement of the head and body of the pancreas. ERP showed irregularity of the main pancreatic duct in the head of the pancreas, and the distal main pancreatic duct (which was dilated on initial ERP examination) was interrupted in the body of the pancreas. Suspected pancreatic carcinoma was diagnosed, and pylorus-preserving pancreatoduodenectomy was performed. Frozen section examination of the cut end of the pancreas revealed ductal carcinoma, and total pancreatoduodenectomy with portal vein resection was performed. Histologically, the resected tumor was diagnosed as an invasive carcinoma derived from intraductal papillary adenocarcinoma without mucin hypersecretion. We recommend observing changes in the pancreatic duct on pancreatography to diagnose invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma in a resectable state. Received: February 6, 2002 / Accepted: June 10, 2002 Offprint requests to: S. Ariizumi     

Mixed adenoneuroendocrine carcinoma derived from the cystic duct: A case report

IntroductionMixed adenoneuroendocrine carcinomas (MANECs) derived from cystic duct are extremely rare.Presentation of caseAn 80-year-old woman was admitted to the department of surgery, Onomichi general hospital with abnormal liver function and jaundice. Enhanced abdominal computed tomography (CT) detected a well-enhanced papillary tumor in the cystic duct, which protruded into the common bile duct. The intrahepatic bile duct was dilated due to tumor obstruction. The entire tumor showed high intensity in T2-weighted magnetic resonance imaging (MRI) imaging. Endoscopic retrograde cholangiopancreatography (ERCP) showed that the tumor ranged from part of communication of three ducts (cystic, common hepatic and common bile duct), to the middle of common bile duct. Biliary cytology determined a class V malignancy (adenocarcinoma). Endoscopic ultrasound determined that the tumor was primarily at the cystic duct with heterogeneous echoic pattern, which extended into the common bile duct. The preoperative diagnosis was cystic duct carcinoma (T3N0M0, StageIIIA). An extended cholecystectomy with regional lymph nodes dissection was performed. Histologically, the tumor had components of both well-differentiated tubular adenocarcinoma and neuroendocrine carcinoma, which is classified as MANECs according to the 2010 WHO classification of endocrine tumors. Eight months after surgery, multiple liver metastases were discovered, and treatment with adjuvant chemotherapy was initiated.DisscusionWe present a rare case of MANECs derived from cystic duct. Until now, an established adjuvant systemic chemotherapy has not emerged, and curative resection, with poor long-term prognosis, remains the only treatment option.ConclusionThough standards of treatment for MANECs have not been established,multidisciplinary theraphy is necessary to improve outcome.     

Gallbladder carcinoma associated with occult pancreatobiliary reflux in the absence of pancreaticobiliary maljunction

We herein report a case of gallbladder carcinoma associated with occult pancreatobiliary reflux (PR) in the absence of pancreatobiliary maljunction. A 67-year-old woman was referred to our hospital for the evaluation and treatment of a gallbladder tumor. Ultrasonography and computed tomography showed a nodular lesion in the fundus of the gallbladder, indicating the possibility of a gallbladder carcinoma. Endoscopic ultrasonography showed the nodular tumor and thickness of the surrounding epithelium. Endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction without the common channel and a slight dilatation of the common bile duct (15 mm in diameter). An open cholecystectomy and partial resection of the liver bed of the gallbladder with regional lymphadenectomy was performed. A C-tube was inserted from the cut end of the cystic duct into the common bile duct to prevent bile stasis. Biliary amylase and lipase levels sampled in the gallbladder were 2604 IU/l and 775 IU/l, respectively. Biliary amylase level in the bile collected from the C-tube in the common bile duct was 119 550 IU/l on postoperative day (POD) 6 and 22 265 IU/l on POD 12. These observations suggested that PR was present in this patient. The histopathological findings of the resected specimen showed a well-differentiated adenocarcinoma of the gallbladder with invasion to the muscle layer and no metastasis of the resected lymph nodes. A high index of nuclear staining for MIB-I in the cancer cells (about 10%) was exhibited, and a few cells in the normal epithelium also stained positive.     

Recent advances in pathophysiology and surgical treatment of congenital dilatation of the bile duct

The introduction of the concept of pancreaticobiliary maljunction (PBM) has led to significant progress in the pathogenetic study and surgical treatment of congenital dilatation of the bile duct (CDBD). Clinical studies of 155 patients with CDBD, and basic experimental studies of the mechanisms of bile duct dilatation and associated pancreatitis were conducted. The CDBD was morphologically classified as either cystic or cylindrical type. Clinical signs, symptoms, and laboratory findings were highly dependent on two factors: the age at onset and the reflux of pancreatic juice into the bile duct through the PBM. The canine experimental model of PBM exhibited not only significant bile duct dilatation but also morphological findings similar to those in the CDBD patients. Subsequent studies in a rat model clarified the involvement of activated pancreatic enzyme phospholipase A₂ in PBM-associated pancreatitis. For surgical treatment, cystoenterostomy has been superseded by hepatico-enterostomy after removal of the damaged bile ducts and blocking their communication with the pancreatic duct. Long-term follow-up studies have shown excellent results by confirming the surgical correction based on the pathological principles. Regarding biliary reconstruction, jejunal interposition hepatico-duodenostomy, which is, theoretically, a logical approach was unexpectedly shown to often lead to bile reflux gastritis, so it is now superseded by Roux-en-Y hepaticojejunostomy. Received: March 22, 2001 / Accepted: May 11, 2001     

Mucoepidermoid Carcinoma of the Liver Diagnosed as a Liver Abscess: Report of a Case

Mucoepidermoid carcinoma of the liver is a rare variant of cholangiocarcinoma, containing both mucus-secreting glandular cells and squamous cells mixed in nests. We report a case of mucoepidermoid carcinoma of the liver in a 69-year-old woman who presented with a 1-week history of fever, chills, and right flank pain. On admission, she was not jaundiced, and under a provisional diagnosis of liver abscess, a pigtail catheter was inserted into the abscess cavity. We performed right hepatectomy and partial excision of the diaphragm 1 month later. Microscopically, the tumor was composed of solid and invasive nests of epidermoid and mucin-producing cells with desmoplastic stroma. The epidermoid component of the tumor contained intercellular bridges and individual cell keratinization. Alcian blue and Periodic acid-Schiff (PAS) staining confirmed that there was mucin in the cytoplasm of mucus-secreting cells. The tumor cells, intrahepatic bile ducts, and ductules were consistently reactive with cytokeratin (CK) 7 and negative for CK20. The adjacent nonneoplastic liver cells were CK 7–/CK20–, and P63 immunostaining was positive in the epidermoid cells. The tumor was diagnosed as mucoepidermoid carcinoma arising from the intrahepatic bile duct. Despite aggressive surgical treatment, the patient died of multiple liver metastases 4 months after the right hepatectomy.     

Mucosal bile duct carcinoma with superficial spread

We describe a case of mucosal bile duct carcinoma with superficial spread in a 69-year-old man with gallstone pancreatitis. The patient was seen at the hospital because of abdominal pain, fever, and jaundice. Endoscopic retrograde cholangiography (ERC) demonstrated a protruding lesion in the lower third of the common bile duct (CBD) showing wall irregularity suggestive of malignancy. Percutaneous transhepatic cholangioscopy (PTCS) disclosed a papillary tumor with granular mucosa extending continuously to the middle third of the CBD. Cholangioscopic biopsy specimens taken from both the papillary tumor and surrounding granular mucosa revealed papillary adenocarcinoma. After this assessment of extent of cancer by PTCS, we performed pancreatoduodenectomy with extrahepatic bile duct resection and regional lymph node dissection. Pathology examination revealed papillary adenocarcinoma limited to the mucosal layer. The resected margin of the bile duct was free of tumor. We also reviewed 25 cases of early mucosal bile duct carcinoma described in detail in the Japanese literature, and we discuss the diagnostic advantages of PTCS. Received for publication on Nov. 25, 1997; accepted on Jan. 27, 1998     

Composite glandular-neuroendocrine carcinoma of the hilar bile duct: Report of a case

4 , S₅) and bile duct resection with lymphnode dissection were performed. A tumor measuring 6.0 3 3.0 cm was found to be located in the bile duct of the hepatic hilus. Histologically, the tumor was composed of well-differentiated adenocarcinoma and small cell neuroendocrine carcinoma cells, with a histological transition between the two components. Grimelius' method revealed the presence of diffuse positive tumor cells in neuroendocrine carcinoma. The neuroendocrine tumor cells were also diffusely immunoreactive to chromogranin A. To the best of our knowledge, only 22 previous cases of composite glandular-neuroendocrine carcinoma in the biliary tract have been reported; however, this is the first case report of a clearly composite tumor of the hilar bile duct. (Received for publication on Aug. 19, 1996; accepted on May 12, 1997)     

Primary sclerosing cholangitis in which differential diagnosis from gallbladder carcinoma was difficult

We report a case of localized primary sclerosing cholangitis (PSC) which was difficult to distinguish from gallbladder carcinoma. A 75-year-old woman with elevated serum bilirubin was hospitalized and underwent endoscopic nasobiliary drainage (ENBD). There was no history of diseases such as gallbladder stone, pancreatitis, or ulcerative colitis. Cholangiography through the ENBD tube showed localized stenosis of the common bile duct; the gallbladder could not be seen. Angiography showed no encasement of the hepatic artery. Ultrasonography showed a tumor in the cystic duct, and the tumor had invaded the gallbladder and common bile duct. We diagnosed gallbladder carcinoma on radioimaging, and performed an S4aS5 subsegmentectomy of the liver and resection of the extrahepatic biliary tree. Pathologically, no malignant cells were detected, and fibrosis around bile ducts and infiltration of inflammatory cells into hepatic tissue were found. It is well known that PSC is sometimes difficult to differentially diagnose from cholangiocarcinoma. Our case is of high interest because ultrasonography showed findings suggestive of gallbladder carcinoma. It is therefore necessary to keep the possibility of PSC in mind for the diagnosis and treatment of such localized biliary stenosis.     

胆管癌表皮生长因子受体,增殖细胞核抗原的表达

为研究胆管癌组织中表皮生长因子受体（ＥＧＦＲ）、增殖细胞核抗原（ＰＣＮＡ）的表达及其生物学意义，并探讨ＥＧＦＲ表达与血型Ａ抗原的关系，通过应用免疫组织化学方法（ＡＢＣ法）检测３０例肝外胆管癌。结果发现１５例（５０％）为ＥＧＦＲ阳性，ＰＣＮＡ阳性７例（２３．３３％），对照组５例为非肿瘤胆总管，ＥＧＦＲ、ＰＣＮＡ均为阴性。胆管癌与非肿瘤胆总管组ＥＧＦＲ及ＰＣＮＡ表达率有显著差异，细胞分化差、有胆管外转移的胆管癌ＥＧＦＲ的表达率高于细胞分化好、无胆管外转移病例。胆管癌各组间ＰＣＮＡ表达率均无显著性差异。ＥＧＦＲ表达与血型Ａ抗原无关。结果提示：检测ＥＧＦＲ表达是判断胆管癌增生活性的有效手段，而ＰＣＮＡ尚需进一步研究。     

Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.     

Congenital web of the common bile duct in association with cholelithiasis

Congenital web formations are extremely rare anomalies of the extrahepatic biliary tree. The age at presentation and the clinical symptomatology of these anomalies depend on the grade of the biliary obstruction. We report a case of a common bile duct septum in association with cholelithiasis in a 30-year-old woman. The diagnosis was made on preoperative magnetic resonance cholangiopancreatography (MRCP) and confirmed with intraoperative cholangiography. Because all known causes of acquired web formation were excluded, a congenital origin of the web was assumed. The patient was treated with a hepaticoduodenostomy above the level of the septum. The embryological aspects of this rare anomaly are described. Received: September 21, 2001 / Accetped: February 8, 2002     

An Icteric Type Hepatocellular Carcinoma with No Detectable Tumor in the Liver: Report of a Case

A 70-year-old man was admitted to our hospital with obstructive jaundice. Computed tomography revealed a tumor in the left intrahepatic bile duct extending to the common bile duct without any significant lesions in the liver. Cholangiography showed a filling defect due to an intraductal tumor. Cytology of the bile juice was negative and tumor markers were carcinoembryonic antigen 5.7 ng/ml, carbohydrate antigen 19-9 49 U/ml, α-fetoprotein 9 ng/dl, and PIVKA-II 19 200 AU/ml. With a preoperative diagnosis of hilar bile duct carcinoma, a laparotomy was performed. The common bile duct was filled with a tumor and it extended into the bilateral intrahepatic bile ducts. The intraductal tumor was removed together with the extrahepatic bile ducts. An intraoperative histological examination of the tumor showed a well-differentiated hepatocellular carcinoma. No lesions were detected in the liver by ultrasonography, palpation during the operation, or a computed tomography scan after the operation. At 1 year postoperatively, no recurrence has been seen in this patient.     

Well-Differentiated Endocrine Carcinoma Originating From the Bile Duct in Association With a Congenital Choledochal Cyst

We encountered a rare case of a well-differentiated endocrine carcinoma originating from the bile duct in association with a congenital choledochal cyst (CCC). The patient is a 28-year-old woman referred to our clinic for pruritus. Laboratory data showed mild elevation of serum hepatobiliary enzymes. Computed tomography and magnetic resonance imaging demonstrated pancreatobiliary maljunction and a Todani type IV-A CCC from the inferior bile duct to the bilateral intrahepatic bile ducts. A solid tumor was detected in the middle portion of the common bile duct. Pancreatoduodenectomy and total extrahepatic bile duct resection was performed. Based on pathologic and immunohistochemical examinations, a diagnosis of well-differentiated endocrine carcinoma was made according to the World Health Organization criteria. To our knowledge, this is the third report of a neuroendocrine tumor originating from the bile duct in association with a CCC.     

人胆管癌细胞神经周围浸润模型的构建与初步观察

目的构建人胆管癌细胞神经周围浸润模型,观察培养神经细胞的生长、人胆管癌细胞的增殖与神经周围浸润的过程的形态学变化。方法应用小鼠背根神经节(DorsalRootGanglia,DRG)置于Matrigel基质中体外培养,同时在其表面接种人胆管癌细胞QBC939,观察神经纤维的生长、QBC939细胞粘附、浸润神经纤维的过程及其形态学变化。结果小鼠DRG置于Matrigel基质中体外培养时,神经纤维生长迅速,人胆管癌细胞QBC939能够穿过人工基质粘附并浸润神经纤维,形成包绕神经纤维的细胞团。结论DRG/神经细胞-肿瘤细胞共培养模型较好的模拟了肿瘤细胞穿过细胞基质,浸润神经纤维的过程,人胆管癌细胞QBC939细胞对神经纤维具有亲嗜性。     

Small cell neuroendocrine carcinoma of the ampulla of Vater with foci of squamous differentiation: a case report

A 54-year-old woman with obstructive jaundice was found to have a 4-cm ulcerated, elevated tumor, located at the papilla of Vater by endoscopy and radiographic investigation. Based on a clinical diagnosis of carcinoma of the ampulla of Vater, a pylorus-preserving pancreaticoduodenectomy was performed. The histologic appearance of the lesion was identical to extrapulmonary small cell carcinoma, with diffuse proliferation of small, spindle-shaped, atypical tumor cells with numerous mitoses. Neuroendocrine differentiation was demonstrated by immunoreactivity with neuron-specific enolase (NSE) and Leu-7, and by the presence of dense core granules ultrastructurally. The tumor was composed mainly of small cell neuroendocrine carcinoma, and partially of an area of squamous differentiation, showing transition from one to the other. Histopathologic investigation disclosed direct invasion deep to the lamina propria, and infiltration of the pancreatic parenchyma, duodenum, and bile duct. Lymph node metastases were present in the superior pancreaticoduodenal chain. The patient died of liver metastases 8 months later. As in previously reported cases of small cell neuroendocrine carcinoma of the ampullary region, the present case showed extremely aggressive clinical behavior with early metastases resulting in fatal outcome.     

Does bile spillage during an operation present a risk for peritoneal metastasis in bile duct carcinoma?

Whether bile spillage during operation presents a risk for peritoneal metastasis in the treatment of bile duct carcinoma was studied in 15 patients (12 with bile duct cancer, 3 with cancer of the papilla of Vater) who had all undergone a pancreatoduodenectomy. Preoperative bile was sampled through a percutaneous transhepatic biliary drainage catheter. Nine patients with bile duct cancer and one with cancer of the papilla of Vater showed positive bile cytology. The operative bile was obtained at the hepatic duct stump after a resection of the tumor-bearing bile duct. The operative bile in 10 patients with positive preoperative bile was found to be positive, while that in the five patients with negative preoperative bile was negative. Thus, the specificity of operative bile was identified as 100%. Moreover, in five patients with preoperative positive bile, saline irrigation of intrahepatic bile duct after a full recovery of hepatic bile revealed cancer cells to remain in the intrahepatic biliary trees. The viability of preoperative bile was 61%–97% with 10⁴–2.4×10⁵ tumor cells, whereas there was a 41%–97% viability with 7.6×10⁴–10.4×10⁵ tumor cells in the operative or irrigated bile. Accordingly, the patients with preoperative positive bile are thus suggested to be at high risk of inducing peritoneal metastasis due to the inadvertent spillage of hepatic bile at the time of resection of a bile duct tumor.