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...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.展开更多
Objective The occurrence of large-cell neuroendocrine carcinoma(LCNEC), a kind of neuroendocrine tumor(NET), in the cranium is extremely rare. Here we report two such cases and review the literature in order to improv...Objective The occurrence of large-cell neuroendocrine carcinoma(LCNEC), a kind of neuroendocrine tumor(NET), in the cranium is extremely rare. Here we report two such cases and review the literature in order to improve the diagnosis and treatment of intracranial LCNEC.Methods We report two cases of metastatic intracranial LCNEC. In case 1, the patient was diagnosed with lung carcinoma and underwent chemotherapy. Brain metastases were found six months later. The lung and intracranial lesions in case 2 were found at the same time. Results Intracranial multiple-tumor resection was performed in case 1 and the patient died 2 months later. Case 2 patient underwent surgery followed by chemotherapy with etoposide and carboplatin. Six months postoperatively, a recurrence lesion was found in the left cerebellar hemisphere. The patient was treated surgically. At present, a year after the diagnosis, the patient is still alive.Conclusion NETs of the intracranial region are extremely rare, and hence, most of our knowledge is based on lung NETs, and standard treatment strategies for intracranial NETs remain unclear. Our patients had different survival times probably due to different treatments, indicating that effective surgical resection and subsequent multi-agent chemotherapy should be administered to promote long-term survival of intracranial LCNEC patients.展开更多
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 includingbio...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.展开更多
Two different immunohistochemical types suggestive of Large Cell Neuroendocrine (NE) carcinoma and Adenocarcinoma in a patient with known diffusely metastatic, hormone refractory prostate carcinoma are rarities. Inter...Two different immunohistochemical types suggestive of Large Cell Neuroendocrine (NE) carcinoma and Adenocarcinoma in a patient with known diffusely metastatic, hormone refractory prostate carcinoma are rarities. Interestingly, our patient had documented history of exposure to Agent Orange during his time of service. The use of routinely used immunohistochemical stains for pathological diagnosis was a challenge in this case, though throughout his disease course, the diagnosis was confirmed as Adenocarcinoma of prostate with biopsies from all various sites of metastases. Systemic chemotherapy has been historically suboptimal in management of aggressively behaved prostate carcinomas. Finding any association of Agent Orange as a causative etiology and improving diagnosis and management of such aggressive hormone refractory prostate carcinoma need further investigations.展开更多
文摘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.
文摘Objective The occurrence of large-cell neuroendocrine carcinoma(LCNEC), a kind of neuroendocrine tumor(NET), in the cranium is extremely rare. Here we report two such cases and review the literature in order to improve the diagnosis and treatment of intracranial LCNEC.Methods We report two cases of metastatic intracranial LCNEC. In case 1, the patient was diagnosed with lung carcinoma and underwent chemotherapy. Brain metastases were found six months later. The lung and intracranial lesions in case 2 were found at the same time. Results Intracranial multiple-tumor resection was performed in case 1 and the patient died 2 months later. Case 2 patient underwent surgery followed by chemotherapy with etoposide and carboplatin. Six months postoperatively, a recurrence lesion was found in the left cerebellar hemisphere. The patient was treated surgically. At present, a year after the diagnosis, the patient is still alive.Conclusion NETs of the intracranial region are extremely rare, and hence, most of our knowledge is based on lung NETs, and standard treatment strategies for intracranial NETs remain unclear. Our patients had different survival times probably due to different treatments, indicating that effective surgical resection and subsequent multi-agent chemotherapy should be administered to promote long-term survival of intracranial LCNEC patients.
文摘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.
文摘Two different immunohistochemical types suggestive of Large Cell Neuroendocrine (NE) carcinoma and Adenocarcinoma in a patient with known diffusely metastatic, hormone refractory prostate carcinoma are rarities. Interestingly, our patient had documented history of exposure to Agent Orange during his time of service. The use of routinely used immunohistochemical stains for pathological diagnosis was a challenge in this case, though throughout his disease course, the diagnosis was confirmed as Adenocarcinoma of prostate with biopsies from all various sites of metastases. Systemic chemotherapy has been historically suboptimal in management of aggressively behaved prostate carcinomas. Finding any association of Agent Orange as a causative etiology and improving diagnosis and management of such aggressive hormone refractory prostate carcinoma need further investigations.
