근치적 전립샘적출술을 시행한 699예의 전립샘암종에서 신경내분비 분화가 예후에 미치는 영향

김태훈,신은,김백희,최기영 대한병리학회 2008 Journal of Pathology and Translational Medicine Vol.42 No.6

Background : Neuroendocrine differentiation of prostatic carcinoma is known to be associated with a poor prognosis, tumor progression and androgen-independency, and there is currently no successful therapy for this type of tumor. The purpose of this study is to evaluate the prognostic implications of neuroendocrine differentiation in prostatic carcinoma in Korean men. Methods : Six hundreds and ninety nine consecutive cases of radical prostatectomy specimens were systematically processed for topographic mapping. Neuroendocrine differentiation was detected by immunohistochemistry by using antibody to chromogranin. We analyzed the relationship between neuroendocrine differentiation and the clinicopathological prognostic factors, as well as biochemical failure. The neuroendocrine differentiation was evaluated according to the presence of chromogranin-positive cells, the pattern of neuroendocrine cells and the number of neuroendocrine cells, respectively. Results : Neuroendocrine differentiation was detected in 150 out of 699 cases (21.5%). The presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells was correlated with biochemical failure and the other clinicopathological prognostic factors such as the Gleason score, the pathologic stage, the tumor volume, angiolymphatic invasion, perineural invasion, and the Ki-67 proliferative index (p<0.05). Conclusions : We suggest that neuroendocrine differentiation of prostatic carcinoma is a prognostic factor even in radical prostatectomy specimens for localized prostate cancer. Evaluation of the presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells is recommended in radical prostatectomy specimens.

자궁경부 소세포암종의 방사선치료

정은지(Eun Ji Chung),이용희(Yong Hee Lee),김귀언(Gwi Eon Kim),서창욱(Chang Ok Suh) 대한방사선종양학회 1997 Radiation Oncology Journal Vol.15 No.4

목 적 : 자궁경부 소세포암종으로 진단되어 방사선치료를 받은 환자에서 조직병리학적인 재검사를 시행하여 조직병리학적 특성을 알아보고, 환자 및 종양의 특징, 방사선치료 후의 치료 성적 등을 조직병리학적 유형에 따라 후향적으로 비교 분석해 보았다. 대상 및 방법 : 1981년 10월부터 1995년 4월까지 연세의대 연세암센터 치료방사선과에서 자궁경부암으로 방사선치료를 받은 환자 총 2890명 중 조직학적 유형이 소세포암종이었던 환자는 60명으로 2.08%였다. 타병원에서 조직검사 및 병기 결정 후 방사선치료 만을 위해 전과되었던 36예에서는 자궁경부 생검 조직을 확보할 수 없었고, 이들을 제외한 24명에서 조직에 대한 병리학적 재검사가 가능하여 H & E 염색 및 신경내분비 표지인 neuron-specific enolase(NSE), chromogranin, synaptophysin, Grimelius 면역조직화학 염색을 시행하였다. 이들 24예의 환자 및 종양의 특성, 방사선치료에 대한 반응, 치료 실패 양상, 5년 생존율 및 5년 무병 생존율 등을 후향적으로 분석하였다. 결 과 : H & E 염색 및 4가지 neuroendocrine marker 검사 후 13예는 신경내분비암종으로 진단되었고 11예는 소세포 유형의 편평상피암종으로 진단되어 병리학적으로 크게 2가지 군으로 분류하였다. 신경내분비암종으로 분류된 13예 중 5예는 중등도 이상으로 분화가 좋은 편이었으나 8예는 분화가 나쁘거나 미분화되었다. 전체 24예 대상 환자들의 연령은 23-79세로 중앙 연령치 54세였으며 FIGO 병기 분포는 Ib 8예(33.3%), IIa 1예(4.2%), IIb 11예(45.8%), IIIa 2예(8.3%), IIIb 1예(4.2%), IV 1예(4.2%)로 병기 I- II가 20예로 대다수를 차지하였다. 골반 림프절에 전이가 있었던 환자가 5예(20.8%) 있었는데 이 중 3예는 수술후 조직학적으로 확인되었고(2예는 근치적 수술, 1예는 골반 림프절 생검) 다른 2예는 전산화 단층 촬영상 골반 림프절이 커져 있어 전이로 판단되었다. 이들 2가지 병리학적 분류군에 따라 환자 및 종양의 특성을 비교해 보았는데 특별한 차이는 발견할 수 없었으며, 방사선치료에 대한 반응, 치료 실패 양상, 5년 생존율 및 5년 무병 생존율 등의 치료 결과를 비교해 보았을 때 치료 실패 양상에 있어서 소세포형의 편평상피암종에서는 원격 전이가 2예(18.2%)인데 반해 신경내분비암종에서는 6예(46.2%)로 신경내분비암종(neuroendocrine carcinoma)에서 원격 전이율이 높았으나 환자 수가 적어 통계학적인 유의성은 없었다(P>0.05). 결 론 : 병리조직학적 재검사가 가능하였던 24예의 자궁경부 소세포암종 환자 중 13예가 신경내분비암종으로 진단되었으며 나머지 11예는 소세포형의 편평상피암종으로 분류되었는데 환자 및 종양의 특징, 방사선치료 성적을 비교해 볼 때 신경내분비암종에서 원격 전이가 호발하였으나(46.2% vs. 18.2%), 5년 생존율과 5년 무병 생존율의 차이는 없었다. 이런 결과로 자궁경부에서 발생한 소세포암종 중 신경내분비암종의 경우는 원격 전이가 많으므로 방사선치료, 수술 등의 국 소 치료와 더불어 적절한 항암화학요법을 추가하여 치료 결과를 증진시킬 수 있으리라 생각한다. 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 II, 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 neuroendocrine 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.

직장 신경내분비종양의 국소절제술 후 추적관찰 결과

권유민(Yoomin Kwon),유승범(Seung-Bum Ryoo),송인호(Inho Song),권윤혜(Yoon-Hye Kwon),이동운(Dong Woon Lee),문상희(Sang Hui Moon),박지원(Ji Won Park),정승용(Seung-Yong Jeong),박규주(Kyu Joo Park) 대한종양외과학회 2016 Korean Journal of Clinical Oncology Vol.12 No.2

Purpose: Neuroendocrine tumor is a rare tumor in the rectum, but incidence has been increasing. Local excision is an option for treatment of small tumors, and transanal excision or endoscopic resection can be undergone. But indications for local excision have not been established yet. This study was to compare the long-term oncologic outcomes between transanal excision and endoscopic resection for rectal neuroendocrine tumor. Methods: Patients diagnosed and treated with rectal neuroendocrine tumor from 2000 to 2015 were collected prospectively, and medical records were analyzed retrospectively. Results: Forty patients were included, mean age was 50.20±13.35 years (male:female=23:17). Transanal excision and endoscopic resection were performed in 28 (70%) and 12 (30%) patients, respectively. Mean tumor size was 0.63±0.37 cm, and tumor location was 5.45±1.89 cm from anal verge. Tumor location was more distal rectum in transanal excision (5.04±1.73 cm vs. 6.42±1.98 cm, P=0.049). Pathologic T stage was T1 in all patients. Most of the patients (90%) showed tumor grade 1. After median 24 months (range, 0–86 months) follow-up, one patient (2.5%) experienced local recurrence. The patient underwent further transanal excision. There was no mortality after local excision. Conclusion: Local excision is a safe and effective treatment for small-sized neuroendocrine tumors in rectum.

대세포 신경내분비암종과 선암종이 혼합된 난소암

유원정 ( Won Jeong Yoo ),박노현 ( Noh Hyun Park ),조현일 ( Hoen Il Jo ),채수진 ( Soo Jin Chae ),박인애 ( In Ae Park ),설혜실 ( Hye Sil Seol ),김재원 ( Jae Weon Kim ),송용상 ( Yong Sang Song ),강순범 ( Soon Beom Kang ),이효표 ( Hyo 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.9

Neuroendocrine tumor is a very heterogenous group arising from the neuroendocrine cells. Especially, large cell neuroendocrine tumor of the ovary is a extremely rare aggressive neoplasm, characteristically arising in association with a surface epithelial tumor. This report describes a mixed type of large cell neuroendocrine carcinoma and adenocarcinoma of the ovary. A 63-year old woman presented with abdominal distension and discomfort underwent staging laparotomy under the impression of ovarian cancer. The operation revealed an small ovarian mass with invasion of multiple region in peritoneal cavity by the tumor. Immunohistochemical and ultrastructural analysis confirmed the neuroendocrine nature of the tumor. The adenocarcinoma in this case is mixture of mucinous and endometrioid type. A diagnosis of stage IIIc mixed large cell neuroendocrine tumor and adenocarcinoma of the ovary was rendered. She is subsequently being treated with Paclitaxel and Carboplatin combination chemotherapy.

같은 종양에서 깊이에 따라 분포된 혼합형 신경내분비-비신경내분비암의 증례: 2010년 세계보건기구에서 정의한 혼합형 샘-신경내분비암 정의에 부합하지 않는 암

정준호,정경원,김재현,김성은,문원,박무인,박선자 대한소화기학회 2019 대한소화기학회지 Vol.74 No.6

A mixed adenoneuroendocrine carcinoma (MANEC) of the stomach is a rare disease entity that was first defined by the World Health Organization (WHO) classification (2010) for tumors of the digestive system. According to the WHO classification (2010), MANEC is referred to as a tumor with both neuroendocrine and non-neuroendocrine neoplasms; each component of the tumor should be at least 30%. On the other hand, this cut-off value lacks clinical evidence and does not explain the characteristics and heterogeneity of this tumor. A 66-year-old male diagnosed with early gastric cancer (EGC) at a community hospital was referred to the Kosin University Gospel Hospital for further evaluation of gastric cancer. Esophagogastroduodenoscopy and EUS performed at the Kosin University Gospel Hospital revealed a sub-mucosal tumor-like component. In addition, a re-biopsy revealed a neuroendorine tumor at different depths of the same tumor. The final pathologic-diagnosis through surgery revealed a mixed neuroendocrine- non-neuroendocrine neoplasm, which is inconsistent with the definition of MANEC. Clinicians should consider EUS when a tumor has atypical endoscopic findings, even if EGC has already been diagnosed.

REVIEW : Variable Clinical Classifications and Diagnostic Coding Systems of Colorectal Neuroendocrine Tumor

( Byung Chang Kim ),( Cheol Hee Park ),( Tae Il Kim ),( Suck-Ho Lee ),( Jin-Oh Kim ),( Hyun Soo Kim ),( Dong-Hoon Yang ),( Bora Keum ),( Sung Pil Hong ),( Seong-Eun Kim ),( Hyun Gun Kim ),( Jeong Eun 대한장연구학회 2013 Intestinal Research Vol.11 No.1

The incidence of colorectal carcinoid tumor is recently increasing as screening colonoscopy increased. Traditional carcinoid tumor had been known as low grade, malignant neuroendocrine cell orign tumor. In 2000, World Health Organization (WHO) suggested that carcinoid was called well-differentiated neuroendocrine tumor (NET). It recently updated in 2010 by WHO; according to the differentiation and malignant potential, NET classified with NET Grade 1, Grade 2, and neuroendocrine carcinoma. They suggested that NET had malignant potential in accordance with histopathologic characteristics. Therefore, WHO recommended the behavior code of NET as malignant. However, European Neuroendocrine Tumor Society (ENETS) proposed the behavior of NET to four grades based on the histopathologic features; benign, benign or low grade malignant, low grade malignant, and high grade malignant. Also, American Joint Committee on Cancer (AJCC) suggested that topography codes of NET were defined as malignant. Korean Standard Classification of Diseases (KCD) described the different codings of carcinoid (NET). The discrepancies of behavior code or coding system exist among WHO, ENETS, AJCC and KCD. Also, there were differences in the perception for topographic coding system between clinicians and pathologists. NETs of colorectum were reported with the variable clinical characteristics (especially, metastasis) and long term prognosis from many studies. Especially, risk of metastasis and long term prognosis of small sized NET (<1 cm) had some discrepancies and should be investigated prospectively. Therefore, the consensus about topographic codes of NET should be needed with multidisplinary approach among gastroenterologists, pathologists and surgeons. (Intest Res 2013;11:14-22)

Digestive Neuroendocrine Tumor Distribution and Characteristics According to the 2010 WHO Classification: a Single Institution Experience in Lebanon

Kourie, Hampig Raphael,Ghorra, Claude,Rassy, Marc,Kesserouani, Carole,Kattan, Joseph Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Background: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in gastro-intestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NEN in a Lebanese population. Materials and Methods: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in $H\hat{o}tel$ Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site. Results: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC). Conclusions: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports.

Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastases in Korea: A Clinicopathological Analysis of 72 Cases in a Single Institute

신유주,하상윤,현지연,이보람,이지연,장기택,김경미,박영석,박철근 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4

Purpose Management of gastroenteropancreatic (GEP) neuroendocrine tumors with liver metastases(NETLM) presents many clinical challenges. Assessment of the extent of disease and primarytumor site is crucial for management. In this study, we investigated the primary tumor sitesand prognostic factors in GEP NETLM among Korean patients. Materials and MethodsWe reviewed the medical records of 72 Korean patients diagnosed with GEP NETLMbetween January 1999 and May 2013, focusing on their clinical and pathologic characteristics. ResultsThe most frequently encountered primary tumor sites were the pancreas (n=25, 35%), stomach(n=8, 11%), gall bladder (n=4, 6%) and rectum (n=3, 4%). Twenty-five patients (35%)had occult primary tumor. Twelve patients (17%) had histological grade G1 tumors, 30patients (42%) had G2 tumors, and 30 patients (42%) had G3 tumors. The mean follow-upperiod after histological confirmation of hepatic metastases was 11.30±2.44 months forG3 tumors, 19.67±4.09 months for G2 tumors, and 30.67±6.51 months for G1 tumors. Multivariate analyses revealed that an unknown primary tumor site (p=0.001) and higherhistological grade (p < 0.001) were independent prognostic indicators for shorter overallsurvival (OS). Most long-term survivors (OS > 24 months) had received antitumor treatment. ConclusionThe primary tumor site most frequently associated with GEP NETLM was the pancreas. Unknown primary tumor and higher histological grade were independent prognostic indicatorsfor shorter OS. Patients identified as being at a risk of shorter OS should be followedup closely.

Clinical outcomes of ligation-assisted endoscopic resection for duodenal neuroendocrine tumors

Park, Su Bum,Kang, Dae Hwan,Choi, Cheol Woong,Kim, Hyung Wook,Kim, Su Jin Williams & Wilkins Co 2018 Medicine Vol.97 No.18

<P><B>Abstract</B></P><P>Duodenal carcinoid tumors, a type of neuroendocrine tumors, are relatively rare and are usually found incidentally during endoscopy. Small duodenal carcinoid tumors (≤10–20 mm), embedded in the submucosa, can be resected endoscopically because of the low risk of metastasis. The aim of this study was to assess the safety and efficacy of ligation-assisted endoscopic mucosal resection (EMR) for the treatment of small duodenal carcinoid tumors. The clinical outcomes of the endoscopic procedures were also evaluated.</P><P>Between November 2008 and November 2017, a total of 15 duodenal carcinoid tumors embedded in the submucosa were resected using EMR. Two types of EMR (conventional EMR and ligation-assisted EMR) were performed according to tumor morphology (narrow-based and broad-based).</P><P>The mean tumor size was 6.6 ± 3.9 mm and the mean procedure time was 11.0 ± 11.2 minutes. Most of the lesions (80.0%) were located in the duodenal 1st portion. Broad-based tumors were more common than narrow-based tumors (66.7% vs 33.3%). All broad-based tumors were resected successfully using ligation-assisted EMR. Although en-bloc resection and complete resection rates were higher in ligation-assisted EMR than in conventional EMR ([100% vs 87.5%], and [85.7% vs 62.5%], respectively), the difference was not significant (<I>P = </I>.333 and <I>P = </I>.310, respectively). Moreover, there was no evidence of local or distant metastasis during the follow-up (26.1 ± 20.7 months).</P><P>Ligation-assisted EMR showed a higher complete resection rate than conventional EMR. Ligation-assisted EMR may be an optimal treatment option for duodenal carcinoid tumors with a broad base.</P>

폐의 신경내분비 종양의 세침흡인 세포검사 소견

고재수,Koh, Jae-Soo 대한세포병리학회 2008 대한세포병리학회지 Vol.19 No.1

The major categories of neuroendocrine tumors of lung are typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The histologic classification criteria of neuroendocrine tumors are well documented in the "WHO Classification of Tumors" based on mitotic figures and necrosis. Cytologic characteristics of neuroendocrine tumors are trabecular, acinar, and solid arrangement of tumor cells and occasional rosette formation. Nuclear chromatin patterns are characteristically described as "salt and pepper chromatin pattern". Many of cytologic classifications documented in the literature are before the "WHO Classification". In this review, the cytologic features of pulmonary neuroendocrine tumors are documented according to the WHO classification, and recent concepts of neuroendocrine tumors of lung are discussed.