• Journal of Gastric Cancer
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• v.16 no.4
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• pp.266-270
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• 2016

We report a unique case of synchronous double primary gastric cancer consisting of adenocarcinoma components with micropapillary features and composite glandular-endocrine cell carcinoma components. The patient was a 53-year-old man presenting with a 6-month history of epigastric pain and diarrhea. A subtotal gastrectomy was performed. Histologically, one tumor was composed of micropapillary carcinoma components (50%) with tight clusters of micropapillary aggregates lying in the empty spaces, admixed with moderately differentiated adenocarcinoma components. MUC-1 was expressed at the stromal edge of the micropapillary component. The other tumor was composed of atypical carcinoid-like neuroendocrine carcinoma (50%), adenocarcinoid (30%), and adenocarcinoma components (20%). The neuroendocrine components were positive for CD56, synaptophysin, chromogranin, and creatine kinase. The adenocarcinoid components were positive for both carcinoembryonic antigen and neuroendocrine markers (amphicrine differentiation). This case is unique, due to the peculiar histologic micropapillary pattern and the histologic spectrum of adenocarcinoma adenocarcinoid-neuroendocrine carcinoma of the synchronous composite tumor.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.17-26
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• 2000

The regional distribution and relative frequencies of endocrine cells were studied immunohistochemically (PAP methods) in the alimentary tract and pancreas of the toad, Bufo bufo gargarizans Cantor using specific antisera against bovine Sp-1/chromogranin (BCG), serotonin, bombesin, gastrin, substance P (SP), somatostatin, insulin, glucagon, pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP) and secretin. Nine kinds of endocrine cells were identified in this study. Spherical or spindleshaped immunoreactive (IR) cells were located in the gastric glands of stomach regions, in the basal portion of the epithelium of intestinal tract or esophagus, and in the exocrine or pancreatic islets with variable frequencies. In the alimentary tract, BCG-IR cells were found in the fundus and pylorus with rare and a few frequencies, respectively. Serotonin-IR cells were demonstrated in the whole alimentary tract including the esophagus. Bombesin- and SP-IR cells were restricted to the stomach regions and gastrin-IR cells were restricted to the pylorus. Somatostatin-IR cells were detected throughout the whole alimentary tract except for the large intestine, However, insulin-, glucagon-, PP-, VIP- and secretin-IR cells were not detected in the alimentary tract. In the pancreas of toad, the distribution and relative frequency of endocrine cells were similar to those of other mammals. Insulin-IR cells were located in the central portion of the pancreatic islets and interspaces of exocrine portions, and glucagon-, somatostatin- and PP-IR cells were detected in the marginal regions of the pancreatic islets and interspaces of exocrine. However, other IR cells were not found in the pancreas. In conclusion, the regional distribution and relative frequency of the endocrine cells in the alimentary tract and pancreas of the toad were similar to other anuran species but some differences which might be caused by feeding habits and species specification were also observed.

• Animal cells and systems
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• v.4 no.2
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• pp.187-193
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• 2000

Regional distribution and relative frequency of endocrine cells in the pancreas of the red-eared slider, Trachemys scripta elegans, were investigated by immunohistochemical methods. Chromogranin (Cg) A-, serotonin-, insulin-, glucagon-, somatostatin-, bovine pancreatic polypeptide (BPP)- and human pancreatic polypeptede (HPP)-immunoreactive cells were identified in this study. Most of immunoreactive cells in the exocrine and endocrine pancreas (Langerhans islet) were generally spherical or spindle-shaped (open-typed cell), while occasionally cells round in shape (close-typed cell) were found in the basal portion or interepithelial regions of the pancreatic duct. These immunoreactive cells were located in the exocrine, endocrine pancreas and/or basal or interepithelial portion of the pancreatic duct. Serotonin-immunoreactive cells were found in the basal portion of epithelia of the pancreatic duct at a low frequency and interacinar region of the exocrine at a moderate frequency. Insulin-immunoreactive cells were found in the central portion of the endocrine pancreas, interacinar regions of the exocrine pancreas and basal portion of the epithelia of the pancreatic duct at high, moderate and low frequencies, respectively. Glucagon-immunoreactive cells were detected in the periphery of the endocrine pancreas, interacinar region of the exocrine pancreas and basal portion of the epithelia or interepithelia of the pancreatic duct at high, moderate and moderate frequencies, respectively. Somatostatin-immunoreactive cells were dispersed in the whole area of the endocrine pancreas, interacinar regions of exocrine pancreas and basal portion of the epithelia or interepithelia of the pancreatic duct at a moderate frequency. BPP- and HPP-immunoreactive cells were detected in the iinteracinar region of the exocrine pancreas at moderate and hige frequencies, respectively. However, no Cg A- and motilin-immunoreactive cells were detected in this study.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.448-454
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• 1999

The regional distribution and relative frequency of the endocrine cells in the pancreas of the bean goose were investigated by immunohistochemical methods using 6 types of the specific antisera. Spindle shaped serotonin-immunoreactive cells were detected in the exocrine portions. Spherical or spindle shaped glucagon-immunoreactive cells were observed in the exocrine and dark and mammalian type islets. In the dark type islets, numerous cells were dispersed throughout whole islets but they were located in the peripheral regions of the mammalian type islets. No glucagon-immunoreactive cells were detected in light type islets. Round or spherical shaped insulin-immunoreactive cells were observed in the exocrine and dark, light and mammalian type islets. They were observed in the exocrine regions with a few numbers. Extremely rare cells were detected in central portion of the dark type islets but moderate to numerous cells were found in the central regions of the mammalian and light type islets, respectively. Spherical or spindle shaped somatostatin-immunoreactive cells were observed in the exocrine and dark, light and mammalian type islets. A few single cells were detected in the exocrine portions. In the dark type islets, numerous cells were dispersed throughout whole islets but a few to moderate numbers of cells were located in the peripheral regions of the light and mammalian type islets. Moderate numbers of the bovine pancreatic polypeptide-immunoreactive cells were found in the exocrine portions with round, spherical or spindle shape. But no bovine Sp-1/chromogranin-immunoreactive cells were observed in this study.

• Korean Journal of Veterinary Research
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• v.39 no.6
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• pp.1038-1048
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• 1999

The regional distributions and relative frequencies of the gastrointestinal endocrine cells in the bean goose (Anser fabalis Latham) were investigated by immunohistochemical methods using bovine Sp-1/chromogranin (CG), serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin and glucagon antisera. BCG-immunoreactive cells were widespread throughout the gastrointestinal tract (GIT) with moderated frequencies except for the gizzard and proventriculus which were a few frequencies. Serotonin-immunoreactive cells were detected throughout the GIT except for the proventriculus and gizzard. These cells were observed in the pylorus with rare frequencies but numerous cells were detected in the intestinal tract. Gastrin-immunoreactive cells were restricted to the gizzard, pylorus and duodenum. These cells were most predominant in the pylorus and a few or rare in the gizzard and duodenum, respectively. CCK-8-immunoreactive cells were observed from the gizzard to ileum. The highest frequencies of endocrine cells were observed in the duodenum. These cells were increased from the gizzard to duodenum but thereafter decreased. Somatostatin-immunoreactive cells were detected in the GIT except for the large intestine. In the proventriculus and pylorus, numerous immunoreactive cells were demonstrated but a few cells were present in the other regions. Glucagon cells were observed in the gizzard, pylorus, ileum, colon and rectum with a few or moderated numbers.

• The Korean Journal of Gastroenterology
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• v.72 no.6
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• pp.318-321
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• 2018

Primary neuroendocrine tumors originating from the extrahepatic bile duct are rare. Among these tumors, large cell neuroendocrine carcinomas (NECs) are extremely rare. A 59-year-old man was admitted to Sanggye Paik Hospital with jaundice that started 10 days previously. He had a history of laparoscopic cholecystectomy, which he had undergone 12 years previously due to chronic calculous cholecystitis. Laboratory data showed abnormally elevated levels of total bilirubin 15.3 mg/dL (normal 0.2-1.2 mg/dL), AST 200 IU (normal 0-40 IU), ALT 390 IU (normal 0-40 IU), and gamma-glutamyl transferase 1,288 U/L (normal 0-60 U/L). Serum CEA was normal, but CA 19-9 was elevated 5,863 U/mL (normal 0-37 U/mL). Abdominal CT revealed a 4.5 cm sized mass involving the common bile duct and liver hilum and dilatation of both intrahepatic ducts. Percutaneous transhepatic drainage in the left hepatic duct was performed for preoperative biliary drainage. The patient underwent radical common bile duct and Roux-en-Y hepaticojejunostomy for histopathological diagnosis and surgical excision. On histopathological examination, the tumor exhibited large cell NEC (mitotic index >20/10 high-power field, Ki-67 index >20%, CD56 [+], synaptophysin [+], chromogranin [+]). Adjuvant concurrent chemotherapy and radiotherapy were started because the tumor had invaded the proximal resection margin. No recurrence was detected at 10 months by follow-up CT.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.95-103
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• 2013

Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.230-234
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• 2008

The incidence of appendiceal metastatic cancer is quite low. In particular, in small cell lung cancer, there is a very low incidence of a metastasis to the appendix. A 75-years old man with right lower quadrant pain, cough and sputum was transferred to our hospital. Abdominal CT revealed acute appendicitis with a perforation. The patient underwent surgery. The frozen sections of the tissue obtained during surgery, indicated a malignancy, but a right hemicolectomy was not performed due to the patient's poor general condition. The histology findings of the appendix were identified as a small cell carcinoma. The abdominal CT scan and chest x-ray at admission day showed a mass in the right lower lobe, and a further evaluation of the lesion was performed including positron emission tomography and flexible bronchoscopy with a biopsy. The pathology findings of the lung mass were also small cell lung cancer. The specimens from both sites stained positive for cytokeratin, cluster designation 56, synaptophysin, chromogranin-A and thyroid transcription factor 1. It was concluded that the appendiceal small cell cancer originated from the lung.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5775-5781
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• 2013

Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (${\chi}^2=32.825$, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.