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.

방광의 소세포 신경내분비 암종의 요 세포학적 소견 - 1 예 보고 -

김동훈,강동욱,김경희,김주헌,박미자,Kim, Dong-Hoon,Kang, Dong-Wook,Kim, yuug-Hee,Kim, Ju-Heon,Park, Mee-Ja 대한세포병리학회 2002 대한세포병리학회지 Vol.13 No.2

We report the cytologic features of a case of primary small cell carcinoma of the urinary bladder with high grade transitional cell and signet ring cell carcinomatous components. A 64-year-old male presented with gross hematuria for one week. Computed tomography revealed an ill-defined mass in the left lateral wall of the urinary bladder. Urinary cytology showed hypercellularity with predominantly isolated single cells and clustered cells. They have scanty cytoplasm and naked hyperchromatic nuclei with finely granular nuclear chromatin and rare nucleoli. The tumor cells occurred predominantly singe cells, but a few in clusters. Nuclear molding was prominent. No glandular formation or nesting was noted. The second tumor cells had high nuclear/cytoplasmic ratio, irregular nuclear membrane, and coarse granular chromatin. The background was inflamed and necrotic. The histoiogic findings of transurethral resection were mainly composed of small cell carcinoma, and partly transitional cell and signet ring cell carcinomatous components. Small cell neuroendocrine carcinoma have distinctive cytologic features to make a proper diagnosis.

Morphologic Analysis of Pulmonary Neuroendocrine Tumors

이승숙,하승연,강명희,안정석,노미숙,하창원,한정호 대한병리학회 2013 Journal of Pathology and Translational Medicine Vol.47 No.1

Background: Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis. Methods: Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes. Results: The mean nuclear area was 0.318±0.101 μm2 in typical carcinoid tumors, 0.326±0.119 μm2 in atypical carcinoid tumors, 0.314±0.107 μm2 in small cell carcinomas, and 0.446±0.145 μm2 in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 μm in typical carcinoid tumors, 2.408±0.680 μm in atypical carcinoid tumors, 2.158±0.438 μm in small cell carcinomas, and 3.247±1.276 μm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001). Conclusions: Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

A Case of Mixed Small and Large Cell Neuroendocrine Carcinoma of the Uterine Cervix

Aeli Ryu,Seong Taek Mun,Shi Sun Kim 순천향대학교 순천향의학연구소 2014 Journal of Soonchunhyang Medical Science Vol.20 No.2

A rare case of mixed carcinoma of the cervix is reported, composed of a small and large cell neuroendocrine carcinoma. Neuroendocrine cervical carcinomas are very rare and aggressive. The prognosis is very poor despite multimodal treatment. Earlier reports have shown that the majority of patients present with advanced stage disease, have lymph node metastasis, and are at a high risk for recurrence and disease progression. In this study, we report the case of a 26-year-old woman with composite small and large cell neuroendocrine carcinoma of the cervix. A woman presented with vaginal bleed since 2 months of presentation. Gynecologic examination revealed cervical enlargement, and punch biopsy of the cervical lesion was performed. The biopsy was disclosed a large cell neuroendocrine carcinoma. The patient underwent a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The final histopathologic findings are mixed small and large cell neuroendocrine carcinoma of cervix.

Maclurin exerts anti-cancer effects on PC3 human prostate cancer cells via activation of p38 and inhibitions of JNK, FAK, AKT, and c-Myc signaling pathways

Lee, Yu Jin,Jung, Okkeun,Lee, Jongsung,Son, Juhyeon,Cho, Jae Youl,Ryou, Chongsuk,Lee, Sang Yeol Elsevier 2018 Nutrition research Vol.58 No.-

<P><B>Abstract</B></P> <P>Maclurin is a phenolic compound extracted from purple mangosteen and mulberry twigs. Earlier reports indicated that it exerts antioxidant activity. We hypothesized that maclurin exerts antioxidant activity and anti-cancer effects in small cell neuroendocrine carcinomas (SCNCs), a very aggressive type of human prostate cancer. To verify our hypothesis, we selected PC3 cells as a model system and investigated the antioxidant activity and anti-cancer effects of maclurin. In the reactive oxygen species (ROS) detection assay for the verification of antioxidant activity, we observed the unexpected prooxidant activity of maclurin in PC3 cells. For the anti-cancer activities, we investigated the effects of maclurin on induction of apoptosis and inhibition of metastatic characteristics of PC3 cells. In the apoptosis assay, maclurin significantly induced apoptosis of PC3 cells. Maclurin also showed significant anti-metastatic effects. Maclurin inhibited cell migration in a dosage-dependent manner. In addition, the gelatin zymography assay indicated that maclurin inhibited activities of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) that affect cell migration and extracellular matrix (ECM) degradation. Then, we investigated the effects of maclurin on the cancer-related signaling molecules. Maclurin activated p38 signaling and inhibited c-Jun N-terminal kinase (JNK), focal-adhesion kinase (FAK), AKT, and c-Myc signalings in PC3 cells. Finally, we observed prooxidant activity and anti-SCNC effects of maclurin in DU145 cells. This suggests that the effects of maclurin may not be specifically limited to PC3 cells. Our findings suggest that maclurin exerts anti-cancer effects on SCNC cells via activation of p38 and inhibitions of JNK, FAK, AKT and c-Myc signalings.</P>

Small-cell neuroendocrine carcinoma of the breast

Jin Kyung An,Jeong Joo Woo,Jae Hee Kang,Eun Kyung Kim 대한외과학회 2012 Annals of Surgical Treatment and Research(ASRT) Vol.82 No.2

A small-cell carcinoma is one of the histologic subtypes of primary neuroendocrine carcinomas of the breast. A small-cell carcinoma is a rare entity of the breast and exhibits similar morphologic features as neuroendocrine tumors of the gastrointestinal tract and lung. We present the imaging and pathologic findings of a primary small-cell neuroendocrine carcinoma of the breast. This is the first report of a primary small-cell carcinoma arising from the breast in Korea.

간에 발생한 원발 소세포 신경내분비암종 1예

김경진 ( Kyung Jin Kim ),임형준 ( Hyung Joon Yim ),김민정 ( Min Jeong Kim ),정록선 ( Rok Son Choung ),연종은 ( Jong Eun Yeon ),이홍식 ( Hong Sik Lee ),변관수 ( Kwan Soo Byun ),이상우 ( Sang Woo Lee ),최재현 ( Jai Hyun Choi ),류호 대한소화기학회 2006 대한소화기학회지 Vol.48 No.1

Small cell neuroendocrine carcinoma is a type of undifferentiated, malignant neuroendocrine tumor. Most of neuroendocrine tumors exhibit well-differentiated features and are classified as carcinoid tumors. However, carcinomas of the liver with anaplastic characters, which are classified as small-cell carcinomas are extremely rare and only few cases have been reported in the literature. We report an unusual case of primary small cell neuroendocrine carcinoma of the liver in a 67-year-old man. The patient was found to have a palpable mass on right upper quadrant of abdomen on physical examination. The diagnosis was made by immunohistochemical stains of biopsied specimen from the liver. Other possible primary site was excluded by radiologic and endoscopic evaluations. The tumor was composed of small monotonous and hyperchromatic poorly differentiated cells with higher nuclear to cytoplasmic ratio, and were positive for neuroendocrine tissue markers such as synaptophysin, c-kit, and CD56. (Korean J Gastroenterol 2006;48:37-41)

비강에 발생한 신경내분비성 소세포암 1예

강준명,이흥엽,이근석,고석윤 대한이비인후과학회 2003 대한이비인후과학회지 두경부외과학 Vol.46 No.2

Small cell neuroendocrine carcinomas of the sinonasal tract are extremely uncomon tumors, and they have been recognized as a highly agresive neoplasm with poor prognosis. The authors experienced a case of small cell neuroendocrine carcinoma of e round or oval and hyperchromatic. Imunohistochemical study showed small cell neuroendocrine carcinoma. The chest X-ray and CT scan of chest showed no evidence of primary lung lesion. The patient received chemotherapy, but died from cerebral infarction and its complication. We report our case with a brief review of the literatures.(Korean J Otolaryngol 2003 ;46 :164-7)

Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis

하승연,노미숙,한정호,김완섭,서병성 대한병리학회 2012 Journal of Pathology and Translational Medicine Vol.46 No.1

Background: Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability. Methods: One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as “unanimous” if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases. Results: Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement. Conclusions: Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

Merkel 세포암양 조직 소견을 동반한 전이성 소형 신경내분비 세포암

김재왕 ( Jae Wang Kim ),김순택 ( Soon Taek Kim ),김상석 ( Sang Seok Kim ),이종주 ( Chong Ju Lee ) 대한피부과학회 2003 대한피부과학회지 Vol.41 No.6

Metastatic small cell neuroendocrine carcinomas(MSCNC) from distant sites, such as the lung, are high grade tumors with poor prognosis. Histopathologically, it is difficult to distinguish between MSCNC and Merkel cell carcinoma solely on the basis of histologic morphology, electron microscopy, and immunohistochemistry. In recent years, differential expression of cytokeratin(CK) 20 and thyroid transcription factor(TTF)-1 has been proposed as useful distinguishing features. It must be emphasized that clinical correlation(e.g. symptomatology, chest X-ray) and a combination of CK 20 and TTF-1 markers, are essential to differentiate these two disease entities. We herein present a case of MSCNC of the lung that might be misdiagnosed as Merkel cell carcinoma. (Korean J Dermatol 2003;41(6) : 714~779)