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Zhang X, Zhang Y, Peng D, Shi X, Zhang Z, Wang J, Zhang X, Leng J, Li W. Adrenal ganglioneuroblastoma with metastasis near the renal hilum in an adult female: A case report and review of the literature. Oncol Lett 2024; 27:187. [PMID: 38486945 PMCID: PMC10938287 DOI: 10.3892/ol.2024.14319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/12/2024] [Indexed: 03/17/2024] Open
Abstract
Ganglioneuroblastoma (GNB), predominantly observed in children, is an uncommon malignant tumor in adults, with established treatment protocols notably lacking. The present study details the case of a 20-year-old woman who presented with a left adrenal gland mass, identified during a physical examination. Additionally, an unidentified mass was noted near the renal hilum in the preoperative evaluation. Following thorough preoperative preparation, both the primary adrenal gland mass and the renal hilar mass were surgically removed. The procedure concluded successfully. Pathological analysis confirmed that the left adrenal mass was a GNB and identified the renal hilar mass as a metastatic extension. Postoperative examination revealed a new formation at the original surgical site, later verified as a postoperative scar. Through the publication of a case report and extensive literature review, the present study aims to enhance our understanding of this condition, providing valuable diagnostic, therapeutic and post-recovery references for this rare adult disease.
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Affiliation(s)
- Xinzhang Zhang
- Department of Urology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650100, P.R. China
- Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Yiwen Zhang
- Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Dan Peng
- Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Xin Shi
- Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Zhuorui Zhang
- Department of Urology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650100, P.R. China
| | - Junfeng Wang
- Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Xue Zhang
- Department of Management Science and Information System, Faculty of Management and Economics, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China
| | - Jinjun Leng
- Department of Urology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650100, P.R. China
| | - Wei Li
- Department of Urology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650100, P.R. China
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Wang H, Xie M, Chen X, Zhu J, Zhang L, Ding H, Pan Z, He L. Radiomics analysis of contrast-enhanced computed tomography in predicting the International Neuroblastoma Pathology Classification in neuroblastoma. Insights Imaging 2023; 14:106. [PMID: 37316589 DOI: 10.1186/s13244-023-01418-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 03/30/2023] [Indexed: 06/16/2023] Open
Abstract
PURPOSE To predict the International Neuroblastoma Pathology Classification (INPC) in neuroblastoma using a computed tomography (CT)-based radiomics approach. METHODS We enrolled 297 patients with neuroblastoma retrospectively and divided them into a training group (n = 208) and a testing group (n = 89). To balance the classes in the training group, a Synthetic Minority Over-sampling Technique was applied. A logistic regression radiomics model based on the radiomics features after dimensionality reduction was then constructed and validated in both the training and testing groups. To evaluate the diagnostic performance of the radiomics model, the receiver operating characteristic curve and calibration curve were utilized. Moreover, the decision curve analysis to assess the net benefits of the radiomics model at different high-risk thresholds was employed. RESULTS Seventeen radiomics features were used to construct radiomics model. In the training group, radiomics model achieved an area under the curve (AUC), accuracy, sensitivity, and specificity of 0.851 (95% confidence interval (CI) 0.805-0.897), 0.770, 0.694, and 0.847, respectively. In the testing group, radiomics model achieved an AUC, accuracy, sensitivity, and specificity of 0.816 (95% CI 0.725-0.906), 0.787, 0.793, and 0.778, respectively. The calibration curve indicated that the radiomics model was well fitted in both the training and testing groups (p > 0.05). Decision curve analysis further confirmed that the radiomics model performed well at different high-risk thresholds. CONCLUSION Radiomics analysis of contrast-enhanced CT demonstrates favorable diagnostic capabilities in distinguishing the INPC subgroups of neuroblastoma. CRITICAL RELEVANCE STATEMENT Radiomics features of contrast-enhanced CT images correlate with the International Neuroblastoma Pathology Classification (INPC) of neuroblastoma.
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Affiliation(s)
- Haoru Wang
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Mingye Xie
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Xin Chen
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Jin Zhu
- Department of Pathology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Li Zhang
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Hao Ding
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China
| | - Zhengxia Pan
- Department of Cardiothoracic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China.
| | - Ling He
- Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, No. 136 Zhongshan Road 2, Yuzhong District, Chongqing, 400014, China.
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Tanaka J, Sasaguri M, Yada N, Tanaka M, Habu M, Yoshiga D, Matsuo K, Tominaga K, Yoshioka I. A case of cervical ganglioneuroma incidentally detected during surgery for oral cancer. JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, MEDICINE, AND PATHOLOGY 2023. [DOI: 10.1016/j.ajoms.2022.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Mills CM, Turner J, Piña IC, Garrabrant KA, Geerts D, Bachmann AS, Peterson YK, Woster PM. Synthesis and evaluation of small molecule inhibitors of LSD1 for use against MYCN-expressing neuroblastoma. Eur J Med Chem 2022; 244:114818. [DOI: 10.1016/j.ejmech.2022.114818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/27/2022] [Accepted: 09/29/2022] [Indexed: 11/04/2022]
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Liu Y, Jia Y, Hou C, Li N, Zhang N, Yan X, Yang L, Guo Y, Chen H, Li J, Hao Y, Liu J. Pathological prognosis classification of patients with neuroblastoma using computational pathology analysis. Comput Biol Med 2022; 149:105980. [PMID: 36001926 DOI: 10.1016/j.compbiomed.2022.105980] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 08/08/2022] [Accepted: 08/14/2022] [Indexed: 11/18/2022]
Abstract
Neuroblastoma is the most common extracranial solid tumor in early childhood. International Neuroblastoma Pathology Classification (INPC) is a commonly used classification system that provides clinicians with a reference for treatment stratification. However, given the complex and subjective assessment of the INPC, there will be inconsistencies in the analysis of the same patient by multiple pathologists. An automated, comprehensive and objective classification method is needed to identify different prognostic groups in patients with neuroblastoma. In this study, we collected 563 hematoxylin and eosin-stained histopathology whole-slide images from 107 patients with neuroblastoma who underwent surgical resection. We proposed a novel processing pipeline for nuclear segmentation, cell-level image feature extraction, and patient-level feature aggregation. Logistic regression model was built to classify patients with favorable histology (FH) and patients with unfavorable histology (UH). On the training/test dataset, patient-level of nucleus morphological/intensity features and age could correctly classify patients with a mean area under the receiver operating characteristic curve (AUC) of 0.946, a mean accuracy of 0.856, and a mean Matthews Correlation Coefficient (MCC) of 0.703,respectively. On the independent validation dataset, the classification model achieved a mean AUC of 0.938, a mean accuracy of 0.865 and a mean MCC of 0.630, showing good generalizability. Our results suggested that automatically derived image features could identify the differences in nuclear morphological and intensity between different prognostic groups, which could provide a reference to pathologists and facilitate the evaluation of the pathological prognosis in patients with neuroblastoma.
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Affiliation(s)
- Yanfei Liu
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China
| | - Yuxia Jia
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China; International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Chongzhi Hou
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China
| | - Nan Li
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China; International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Na Zhang
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China
| | - Xiaosong Yan
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China
| | - Li Yang
- Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi, 710032, China
| | - Yong Guo
- Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi, 710032, China
| | - Huangtao Chen
- Department of Neurosurgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710032, China
| | - Jun Li
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China; International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
| | - Yuewen Hao
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China.
| | - Jixin Liu
- The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710003, China; Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China; International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
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Deslarzes P, Djafarrian R, Matter M, La Rosa S, Gengler C, Beck-Popovic M, Zingg T. Neuroblastic Tumors of the Adrenal Gland in Elderly Patients: A Case Report and Review of the Literature. Front Pediatr 2022; 10:869518. [PMID: 35656383 PMCID: PMC9152181 DOI: 10.3389/fped.2022.869518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 04/20/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Neuroblastic neoplasms (NN) include ganglioneuromas (GN), ganglioneuroblastomas (GNB), and neuroblastomas (NB). They generally arise in childhood from primitive sympathetic ganglion cells. Their incidence in adults, especially among elderly, is extremely low. CASE PRESENTATION This is the case of a 74-year-old woman with history of abdominal pain, weakness and night sweating since several months. Blood pressure was normal. CT-scan showed a 10 cm left adrenal mass, without other pathologic findings. An open left-sided adrenalectomy was performed. Recovery was uneventful with hospital length of stay of 8 days. Based on morphological, immunohistochemical, and molecular features the diagnosis was a nodular GNB. A positron emission tomography (PET) performed 6 weeks after the resection did not show any residual tumor or distant metastases. The patient was followed-up with annual clinical and radiological exams. CONCLUSION This case presentation, associated with a review of the literature, illustrates the importance to include NN in the preoperative differential diagnosis of adrenal tumors in adults and highlights the need for multidisciplinary patient work-up and management.
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Affiliation(s)
- Philip Deslarzes
- Department of Visceral Surgery, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Reza Djafarrian
- Department of Visceral Surgery, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Maurice Matter
- Department of Visceral Surgery, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Stefano La Rosa
- Department of Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
| | - Carole Gengler
- Department of Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
| | - Maja Beck-Popovic
- Department "Woman-Mother-Child", Lausanne University Hospital, Lausanne, Switzerland
| | - Tobias Zingg
- Department of Visceral Surgery, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
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Gifford AJ, Murray J, Fletcher JI, Marshall GM, Norris MD, Haber M. A Primer for Assessing the Pathology in Mouse Models of Neuroblastoma. Curr Protoc 2021; 1:e310. [PMID: 34826366 DOI: 10.1002/cpz1.310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Neuroblastoma, the most common extracranial solid tumor in young children, arises from the sympathetic nervous system. Our understanding of neuroblastoma has been improved by the development of both genetically engineered and xenograft mouse models of the disease. Anatomical pathology is an essential component of the phenotyping of mouse models of cancer, characterizing the morphologic effects of genetic manipulation and drug treatment. The Th-MYCN model, the most widely used of several genetically engineered mouse models of neuroblastoma, was established by targeted expression of the human MYCN gene to murine neural crest cells under the control of the rat tyrosine hydroxylase promoter. Neuroblastoma development in Th-MYCN mice is preceded by neuroblast hyperplasia-the persistence and proliferation of neural crest-derived neuroblasts within the sympathetic autonomic ganglia. The neuroblastomas that subsequently develop morphologically resemble human neuroblastoma and carry chromosomal gains and losses in regions syntenic with those observed in human tumors. In this overview, we describe the essential pathologic features for investigators when assessing mouse models of neuroblastoma. We outline human neuroblastoma as the foundation for understanding the murine disease, followed by details of the murine sympathetic ganglia from which neuroblastoma arises. Sympathetic ganglia, both with and without neuroblast hyperplasia, are described. The macroscopic and microscopic features of murine neuroblastoma are explained, including assessment of xenografts and tumors following drug treatment. An approach to experimental design is also detailed. Increased understanding of the pathology of murine neuroblastoma should improve reproducibility and comparability of research findings and assist investigators working with mouse models of neuroblastoma. © 2021 Wiley Periodicals LLC.
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Affiliation(s)
- Andrew J Gifford
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.,Anatomical Pathology, NSW Heath Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.,School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jayne Murray
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jamie I Fletcher
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.,School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia
| | - Glenn M Marshall
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.,School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.,Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
| | - Murray D Norris
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.,UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, New South Wales, Australia
| | - Michelle Haber
- Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.,School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia
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Vassallo L, Fasciano M, Baralis I, Pellegrino L, Fortunato M, Orcioni GF, Sorrentino S. A rare case of adrenal ganglioneuroblastoma-intermixed in an adult and a review of literature. Radiol Case Rep 2021; 16:2351-2356. [PMID: 34306280 PMCID: PMC8258789 DOI: 10.1016/j.radcr.2021.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 11/04/2022] Open
Abstract
Peripheral neuroblastic tumors are extremely rare in the adult with less just over 20 cases involving adrenal gland described in the literature. We reported herewith the case of a 22-year-old young male who presented with epigastric pain and diarrhea. Imaging studies documented a 3.5cm x 3cm x 4cm solid well-circumscribed right adrenal mass, of heterogeneous structure and with fine calcifications. The lesion turned negative at MIBG scintigraphy. A right robotic-assisted adrenalectomy was performed leading to complete excision of the lesion without complications. Histology was consistent with intermixed stroma-rich ganglioneuroblastoma. A wait-and-see strategy was considered adequate. Two years after diagnosis patient is alive disease-free. Although the definitive diagnosis of a peripheral neuroblastic tumor is obtained after histopathological analysis, CT, and MRI are helpful to further characterize masses and useful in pretreatment risk stratification. Clinicians should be aware of the possibility of GNB development in adult population and its malignant potential.
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Key Words
- ADC, Apparent Diffusion Coefficient
- Adrenal gland
- Adult
- CT, Computed Tomography
- Computed tomography
- GN, Ganglioneuroma
- GNB, Ganglioneuroblastoma
- Ganglioneuroblastoma
- INPC, International Neuroblastoma Pathology Classification
- INRG, International Neuroblastoma Risk Group
- INSS, International Neuroblastoma Staging System
- MRI, Magnetic Resonance Imaging
- Magnetic resonance imaging
- NB, Neuroblastoma
- Neuroblastoma
- PNT, Neuroblastic tumors
- RT, Radiotherapy
- US, Ultrasound
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Affiliation(s)
- Lorenzo Vassallo
- Unit of Radiology, S.S. Annunziata Hospital, ASLCN1, Via degli Ospedali 9, 12038, Cuneo, Italy
| | - Mirella Fasciano
- Unit of Radiology, S.S. Annunziata Hospital, ASLCN1, Via degli Ospedali 9, 12038, Cuneo, Italy
| | - Ilaria Baralis
- Department of Diagnostic and Interventional Radiology, S. Croce e Carle Hospital, Via Michele Coppino 26, 12100, Cuneo, Italy
| | - Luca Pellegrino
- General and Oncologic Surgery Unit, Department of Surgery, Santa Croce e Carle Hospital, Via Michele Coppino 26, 12100, Cuneo, Italy
| | - Mirella Fortunato
- Department of Pathology, Santa Croce e Carle Hospital, Via Michele Coppino 26, 12100, Cuneo, Italy
| | | | - Stefania Sorrentino
- Unit of Pediatric Oncology, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genoa, Italy
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Xiao J, Zhao Z, Li B, Zhang T. Primary Retroperitoneal Ganglioneuroma: A Retrospective Cohort Study of 32 Patients. Front Surg 2021; 8:642451. [PMID: 34095202 PMCID: PMC8176303 DOI: 10.3389/fsurg.2021.642451] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/06/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose: To investigate the clinical characteristics, diagnosis, differential diagnosis, therapy options, and outcomes of retroperitoneal ganglioneuroma. Methods: In this retrospective study, we collected and analyzed the clinical data of 32 patients diagnosed with retroperitoneal ganglioneuroma and admitted to Peking Union Medical College Hospital from October 2012 to August 2019. Results: Among our 32 cases with retroperitoneal ganglioneuroma, the male-to-female ratio was 1:3 and the mean age was 35. Only 25% of the cases presented with abdominal pain while more than 65% had no specific symptoms. The masses could be found through physical examination in only five patients. Most of the tumors are located near the renal area. They were usually single and displayed an embedded growth pattern with diameters <10 cm, clear borders, and soft texture. For radiological imaging, the majority of tumors demonstrated soft tissue density with mild-to-moderate enhancement on CT imaging and showed hypoecho with moderate blood flow signals in ultrasound. No significantly abnormal laboratory examinations were found in most patients. Of all the 32 patients, 2 chose surveillance after biopsy due to difficulties in operation, while others chose surgical resection. The mean follow-up time was 15.8 months among 26 patients. The tumor remained stable in the surveillance cases. Residual tumors were found in four cases receiving operations with no progress and discomfort. No recurrence was seen in all patients. Conclusions: The retroperitoneal ganglioneuroma is a benign tumor without specific clinical manifestations or significant laboratory findings. Typically, it is shown as low density with a clear border and an embedded growth pattern in radiological imaging. The overall prognosis is good. Surgery is an effective approach with possible severe complications. Incomplete resection or surveillance can be considered for some cases where complete resection is difficult to achieve.
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Affiliation(s)
- Jianchun Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Zixuan Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.,School of Medicine, Tsinghua University, Beijing, China
| | - Binglu Li
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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10
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ÇALAPKULU M, SENCAR ME, ÖZTÜRK ÜNSAL İ, DÜĞER H, ÖZBEK M, ÇAKAL E. Large ganglioneuroma case mimicking as an adrenal adenoma. TURKISH JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.46310/tjim.877025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Fliedner SMJ, Winkelmann PER, Wesley R, Vonthein R, Lehnert H. Ganglioneuromas across age groups: Systematic review of individual patient data. Clin Endocrinol (Oxf) 2021; 94:12-23. [PMID: 32702779 DOI: 10.1111/cen.14297] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 06/23/2020] [Accepted: 07/13/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Ganglioneuromas are very rare tumours of the sympathetic nervous system. Clinical and pathological knowledge is currently based on largely incomparable registries and case series that focus on paediatric or adrenal cases. To comprehensively characterize the full clinical spectrum across ages and locations, a meta-analysis was performed where amenable and complemented by systematic literature review of individual patient data (IPD). DESIGN Articles containing "ganglioneuroma" in English on humans, published from 1/1/1995-6/27/2018, were identified from PubMed. Aggregate data from 10 eligible patient series on 19 variables were considerably inhomogeneous, restricting meta-analysis to age and gender distribution. To determine basic disease characteristics across ages and locations, IPD were retrieved from case reports and small case series (PROSPERO CRD42018010247). RESULTS Individual patient data representing 364 cases revealed that 65.7% (60.6%-70.4%) were diagnosed in adults, more frequently in females (62%, 56.9%-66.9%). 24.5% (20.3%-39.1%) were discovered incidentally. Most often, ganglioneuromas developed in abdomen/pelvis (66.2, 32.1% adrenal). With age, the proportion of ganglioneuroma localizations with high post-surgical complication rate (35.6% head/neck and 16.3% thorax) decreased. Contrarily, the diagnosis of adrenal ganglioneuromas (<1% post-surgical complications) increased with age. Hormone production, hypertension or coincidence with another non-neuroblastic neural-crest-derived tumour component was more common for adrenal location. Recurrence and metastatic spread have not been reported for ganglioneuromas without secondary tumour component. CONCLUSIONS This work summarizes characteristics of the currently largest number of international GN patients across all ages. The data confirm a benign nature of GN, independent of age. Age-related differences in predominant tumour location, associated post-surgical complications and hormone production suggest case-centred management strategies.
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Affiliation(s)
- Stephanie M J Fliedner
- 1st Department of Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, University of Lübeck, Lübeck, Germany
| | - Philipp E R Winkelmann
- Department of Hematology and Medical Oncology, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany
| | | | - Reinhard Vonthein
- Institut für Medizinische Biometrie, Universität zu Lübeck, Lübeck, Germany
- Institut für Statistik, Ludwig-Maximilians-Universität München, München, Germany
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Zhang Y, He W. Primary orbital ganglioneuroblastoma in a child: A case report. Medicine (Baltimore) 2020; 99:e22922. [PMID: 33157934 PMCID: PMC7647574 DOI: 10.1097/md.0000000000022922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
RATIONALE Ganglioneuroblastoma (GNB) is a transitional tumor of sympathetic origin that has never been described as primarily involving the orbit. Herein we report an extremely rare case of GNB with primary orbital involvement and its treatment strategies. PATIENT CONCERNS A 9-year-old girl presented with progressive and recurring right orbital mass for 2 years. DIAGNOSIS Computed tomography (CT) showed a well-defined, well-circumscribed, and homogeneous extraconal soft tissue mass occupying most of the right superior orbital area. Magnetic resonance imaging (MRI) revealed that there was a neoplasm of the right superior orbit molding around the globe with long T1 and T2 signals, and contrast-enhanced MR image showed a heterogeneous enhancement of the mass. Histopathologic examinations were performed after surgery and the characteristics were consistent with a diagnosis of GNB. INTERVENTIONS Surgery was performed and the mass was completely resected. OUTCOMES Postoperatively, the patient was on a regular follow-up for 19 months and so far, has had no orbital mass recurrence. LESSONS Herein we present a rare case of GNB primarily involving the orbit, and the findings showed that GNB could originate from the orbit. The patient underwent surgical tumor resection. The histopathological and immunohistochemical features were consistent with the diagnosis of GNB. For this case, there was no recurrence for 19 months after complete surgical excision of the tumor; however, a regular long-term follow-up is required.
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13
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Occurrence of paratesticular ganglioneuroma 18 years after concurrent adrenal ganglioneuroma and papillary thyroid carcinoma - a case report. BMC Cancer 2019; 19:1265. [PMID: 31888521 PMCID: PMC6937970 DOI: 10.1186/s12885-019-6440-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 12/08/2019] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare. CASE PRESENTATION Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later. CONCLUSIONS We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.
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Duan K, Dickson BC, Marrano P, Thorner PS, Chung CT. Adult‐onset neuroblastoma: Report of seven cases with molecular genetic characterization. Genes Chromosomes Cancer 2019; 59:240-248. [DOI: 10.1002/gcc.22826] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 11/13/2019] [Accepted: 11/19/2019] [Indexed: 01/10/2023] Open
Affiliation(s)
- Kai Duan
- Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
| | - Brendan C. Dickson
- Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
- Department of Pathology and Laboratory Medicine Mount Sinai Hospital Toronto Ontario Canada
| | - Paula Marrano
- Division of Pathology The Hospital for Sick Children Toronto Ontario Canada
| | - Paul S. Thorner
- Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
- Division of Pathology The Hospital for Sick Children Toronto Ontario Canada
| | - Catherine T. Chung
- Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
- Division of Pathology The Hospital for Sick Children Toronto Ontario Canada
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15
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Raghav S, Gupta P, Ahuja A, Bhardwaj M. Anterior neck swelling in a child: Cytological consideration of an uncommon diagnosis. Cytojournal 2019; 16:7. [PMID: 31031817 PMCID: PMC6444900 DOI: 10.4103/cytojournal.cytojournal_17_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 07/17/2018] [Indexed: 11/04/2022] Open
Affiliation(s)
- Sonia Raghav
- Address: Department of Pathology, Postgraduate Institute of Medical Education and Research, Dr. RML Hospital, New Delhi, India
| | - Prajwala Gupta
- Address: Department of Pathology, Postgraduate Institute of Medical Education and Research, Dr. RML Hospital, New Delhi, India
| | - Arvind Ahuja
- Address: Department of Pathology, Postgraduate Institute of Medical Education and Research, Dr. RML Hospital, New Delhi, India
| | - Minakshi Bhardwaj
- Address: Department of Pathology, Postgraduate Institute of Medical Education and Research, Dr. RML Hospital, New Delhi, India
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16
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Shi C, Li F, Wang Y, Pei L, Wang T. Retroperitoneoscopic resection of retroperitoneal nonadrenal ganglioneuromas: our technique and clinical outcomes. Int Braz J Urol 2019; 44:1166-1173. [PMID: 29570257 PMCID: PMC6442184 DOI: 10.1590/s1677-5538.ibju.2017.0460] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 01/10/2018] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To report our experience of retroperitoneoscopic technique in semi-lateral decubitus position for the retroperitoneal nonadrenal ganglioneuromas in 18 patients, and to evaluate its clinical outcomes. MATERIALS AND METHODS From January 2012 to May 2016, 18 patients with retroperitoneal nonadrenal ganglioneuromas underwent retroperitoneoscopic resection. With the patients in semi-lateral decubitus position, a 4-port retroperitoneal approach was used. Data were collected on the tumor size, tumor location, perioperative outcomes, pathology, and lastknown disease status. We reviewed the operative videos to identify surgical tips and tricks. RESULTS All procedures were carried out successfully without converting to open surgery. The tumors had an average size of 5.2cm. The mean operative time was 86.5 min, with a mean estimated blood loss of 85.4mL. There were three patients suffering from intraoperative complications. Postoperatively, all patients achieved an uneventful recovery; the mean postoperative hospital stay was 5.5 days. The postoperative pathology revealed to be retroperitoneal ganglioneuromas. With a mean follow-up of 39.5 months, all patients were recurrence free. The review of the operative videos revealed several tips and tricks, including keeping peritoneum and posterior Gerota fascia intact to provide a favorable operative exposure of tumors, and placing the harmonic scalpel through different ports during tumor dissection. CONCLUSIONS With the patient in semi-lateral decubitus position and a 4-port retroperitoneal approach, retroperitoneoscopic resection of retroperitoneal nonadrenal ganglioneuroma is a feasible, effective, and safe procedure. This approach has distinct advantages including direct access to the tumor, optimal exposure of tumor and less intraperitoneal interference.
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Affiliation(s)
- Changjin Shi
- Department of Urology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Feng Li
- Department of Urology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanchao Wang
- Department of Urology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Long Pei
- Department of Urology, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tao Wang
- Department of Nephrology, Hebei Provincial General Hospital, Shijiazhuang, China
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17
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Abstract
A mass was found at the base of the dorsum linguae of a male 11-year-old Labrador retriever. The tumor comprised of ganglion cells and Schwannian cells with Verocay bodies. The ganglion cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and beta III tubulin. The Schwannian cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and glial fibrillary acidic protein. The lingual mass was diagnosed as a ganglioneuroma. To our knowledge, there has been no previous report of a lingual ganglioneuroma in a dog.
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Affiliation(s)
- Minami Goto
- Laboratory of Veterinary Pathology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Kayoko Yonemaru
- Laboratory of Veterinary Pathology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.,Comparative Cancer Center Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Akihiro Hirata
- Comparative Cancer Center Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.,Division of Animal Experiment, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Hidenari Furuhashi
- Furuhashi Animal Hospital, 2-7-20 Kagoya, Ichinomiya, Aichi 494-0002, Japan
| | - Tokuma Yanai
- Laboratory of Veterinary Pathology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Hiroki Sakai
- Laboratory of Veterinary Pathology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.,Comparative Cancer Center Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
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18
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Raza MZ, Allegrini S, Dumontet C, Jordheim LP. Functions of the multi-interacting protein KIDINS220/ARMS in cancer and other pathologies. Genes Chromosomes Cancer 2017; 57:114-122. [PMID: 29181864 DOI: 10.1002/gcc.22514] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 11/07/2017] [Accepted: 11/24/2017] [Indexed: 12/20/2022] Open
Abstract
Development of an organ and subsequently the whole system from an embryo is a highly integrated process. Although there is evidence that different systems are interconnected during developmental stages, the molecular understanding of this relationship is either not known or only to a limited extent. Nervous system development, amongst all, is maybe the most crucial and complex process. It relies on the correct distribution of specific neuronal growth factors and hormones to the specific receptors. Among the plethora of proteins that are involved in downstream signalling of neuronal growth factors, we find the kinase-D interacting substrate of 220 kDa (KIDINS220), also known as ankyrin-rich repeat membrane spanning (ARMS) protein. KIDINS220 has been shown to play a substantial role in the nervous system and vascular system development as well as in neuronal survival and differentiation. It serves as a downstream regulator for many important neuronal and vascular growth factors such as vascular endothelial growth factor (VEGF), the neurotrophin family, glutamate receptors and ephrin receptors. Moreover, activation and differentiation of B- and T-cells, as well as tumour cell proliferation has also shown to be related to KIDINS220. This review comprehensively summarises the existing research data on this protein, with a particular interest in its role in cancer and in other pathologies.
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Affiliation(s)
- Muhammad-Zawwad Raza
- Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
| | - Simone Allegrini
- Department of Biology, Biochemistry Unit, University of Pisa, Pisa, Italy
| | - Charles Dumontet
- Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
| | - Lars Petter Jordheim
- Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, 69008, France
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19
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Barth TFE, von Witzleben A, Möller P, Scheil-Bertram S. [Notochordal tumors : Benign notochordal tumors and chordomas]. DER PATHOLOGE 2017; 39:117-124. [PMID: 29236139 DOI: 10.1007/s00292-017-0399-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Benign notochordal tumors (BNCT) and chordomas are primary bone tumors of the spine with a predominant localization in the sacrum and clival region followed by the vertebral bodies. Besides the most common variant (NOS [not otherwise specified] with hepatoid or renal carcinoma cell-like differentiation) chordomas with chondroid, and polymorphic to anaplastic morphology are described. An unfavorable variant are pediatric chordomas with a loss of INI-1. BNCT and chordomas are characterized by the following immunohistological profile: vimentin+, cytokeratin+/-, epithelial membrane antigen (EMA)+/-, S100 protein+/-, brachyury+. This profile helps to distinguish these tumors from other lesions such as chondrosarcoma, chordoid meningioma, and metastases of carcinoma.
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Affiliation(s)
- T F E Barth
- Institut für Pathologie, Universität Ulm, Ulm, Deutschland
| | | | - P Möller
- Institut für Pathologie, Universität Ulm, Ulm, Deutschland
| | - S Scheil-Bertram
- Institut für Pathologie, Universität Ulm, Ulm, Deutschland.
- Institut für Pathologie und Zytologie, HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Ludwig-Erhard-Str. 100, 65199, Wiesbaden, Deutschland.
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20
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Mylonas KS, Schizas D, Economopoulos KP. Adrenal ganglioneuroma: What you need to know. World J Clin Cases 2017; 5:373-377. [PMID: 29085827 PMCID: PMC5648998 DOI: 10.12998/wjcc.v5.i10.373] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 06/14/2017] [Accepted: 07/10/2017] [Indexed: 02/05/2023] Open
Abstract
Adrenal ganglioneuromas (GNs) constitute rare, differentiated tumors which originate from neural crest cells. GNs are usually hormonally silent and tend to be discovered incidentally on imaging tests. Adrenalectomy is the gold standard for the treatment of primary adrenal GNs. Nevertheless, preoperative differential diagnosis of GNs remains extremely challenging, and thus histopathological examination is required in order to confirm the diagnosis of GN. Overall, prognosis after surgical resection seems to be excellent, without any recurrences or need for adjuvant therapy.
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Affiliation(s)
- Konstantinos S Mylonas
- Division of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
- Surgery Working Group, Society of Junior Doctors, 11852 Athens, Greece
| | - Dimitrios Schizas
- Surgery Working Group, Society of Junior Doctors, 11852 Athens, Greece
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Konstantinos P Economopoulos
- Surgery Working Group, Society of Junior Doctors, 11852 Athens, Greece
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, United States
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21
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Zhao L, Mu J, Du P, Wang H, Mao Y, Xu Y, Xin X, Zang F. Ultrasound-guided core needle biopsy in the diagnosis of neuroblastic tumors in children: a retrospective study on 83 cases. Pediatr Surg Int 2017; 33:347-353. [PMID: 27990597 DOI: 10.1007/s00383-016-4037-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/05/2016] [Indexed: 02/06/2023]
Abstract
AIM Ultrasound-guided biopsy technique with the large-core needle has widely been applied in the diagnosis of adult abdominopelvic cavity, thyroid, and neck tumors. There are few reports on ultrasound-guided biopsy using large-core needle in pediatric abdominopelvic cavity tumors. This study was to evaluate the ultrasound features and the diagnostic value of ultrasound-guided core needle biopsy for pediatric neuroblastic tumors. METHODS The pediatric patients with neuroblastic tumor that underwent ultrasound examination and ultrasound-guided core needle biopsy from January 2009 to November 2015 were reviewed. A minimum of two cores in each case was obtained. The biopsy results were confirmed by subsequent surgical histopathology. The ultrasound features and the diagnostic accuracy of ultrasound-guided core needle biopsy were evaluated. RESULTS Eighty-three patients were enrolled into the study. Conventional ultrasound examination showed irregular hypoechoic or mixed echo masses and calcification and liquefied necrosis. The diagnostic accuracy of ultrasound-guided core needle biopsy was 96.4% (80/83). Three cases were misdiagnosed because of inadequate tissue sample. No serious complication, infection, or needle track seeding occurred. CONCLUSIONS Ultrasound-guided core needle biopsy seems to be an accurate, minimally invasive, and safe diagnostic method of pediatric neuroblastic tumor.
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Affiliation(s)
- Lihui Zhao
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Jie Mu
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Ping Du
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Hailing Wang
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China.
| | - Yiran Mao
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Yong Xu
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Xiaojie Xin
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin, 300060, China
| | - Fenglin Zang
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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22
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Marrano P, Irwin MS, Thorner PS. Heterogeneity of MYCN amplification in neuroblastoma at diagnosis, treatment, relapse, and metastasis. Genes Chromosomes Cancer 2016; 56:28-41. [PMID: 27465929 DOI: 10.1002/gcc.22398] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 07/24/2016] [Accepted: 07/25/2016] [Indexed: 12/14/2022] Open
Abstract
Amplification of the MYCN gene in neuroblastoma is associated with a poor prognosis and is considered to remain unchanged in post-treatment specimens and metastases. While heterogeneity of MYCN copy number in tumor cells has been reported, serial samples have only been studied in a limited way, and the biologic relevance of this finding is not well understood. We used in situ hybridization on paraffin sections of 102 specimens from 30 patients with MYCN-amplified neuroblastoma to determine MYCN copy number in the primary tumor, pre- and post-treatment, and in metastatic samples. Nineteen cases (63%) showed diffuse MYCN amplification in all samples tested. Nine cases (30%) showed a reduction in MYCN copy number: five cases with diffuse amplification subsequently showed focal amplification, one case with diffuse MYCN amplification showed MYCN gain after treatment, and three focally amplified cases were non-amplified in later specimens. In two cases (7%), focal amplification became diffuse in subsequent samples. Histology was not predictive of the temporal or spatial pattern of MYCN amplification for a particular tumor. If extent of amplification (focal vs. diffuse) is not considered, 26/30 (87%) of cases were consistently MYCN-amplified. However, our data suggest that MYCN status can be heterogeneous between tumor sites, during tumor progression or following treatment, challenging the notion that MYCN copy number does not change for a particular neuroblastoma. Assessing the biologic significance of MYCN heterogeneity will require larger studies of clinically annotated tumor samples, and will depend on interpreting heterogeneity in MYCN status in combination with other genetic changes. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Paula Marrano
- Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Canada
| | - Meredith S Irwin
- Department of Pediatrics, the Hospital for Sick Children, Toronto, Canada.,Department of Pediatrics, University of Toronto, Toronto, Canada
| | - Paul S Thorner
- Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
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23
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Samardzija G, Stevovic TK, Djuricic S, Djokic D, Djurisic M, Ciric D, Martinovic T, Bumbasirevic V, Vujic D. Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria. Ultrastruct Pathol 2016; 40:240-8. [PMID: 27669398 DOI: 10.1080/01913123.2016.1187689] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.
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Affiliation(s)
- Gordana Samardzija
- a Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic ," Belgrade , Serbia
| | | | - Slavisa Djuricic
- a Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic ," Belgrade , Serbia
| | - Dragomir Djokic
- a Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic ," Belgrade , Serbia
| | - Marina Djurisic
- a Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic ," Belgrade , Serbia
| | - Darko Ciric
- b School of Medicine , University of Belgrade , Belgrade , Serbia
| | | | | | - Dragana Vujic
- a Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic ," Belgrade , Serbia.,b School of Medicine , University of Belgrade , Belgrade , Serbia
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24
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Intermittent Fever, Progressive Weight Gain, and Personality Changes in a Five-Year-Old Girl: Unusual Paraneoplastic Syndrome due to Presacral Ganglioneuroma. Case Rep Endocrinol 2016; 2016:2743576. [PMID: 27413558 PMCID: PMC4931079 DOI: 10.1155/2016/2743576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 01/06/2016] [Indexed: 11/18/2022] Open
Abstract
Ganglioneuromas are rare tumors in the neuroblastoma group. Paraneoplastic syndrome (PNS) due to presacral ganglioneuromas was hardly reported in previous literature. Here, we reported that a case of a 5-year-old girl with a presacral ganglioneuroma presented with PNS, who presented with intermittent fever, progressive weight gain, and personality changes. Our report revealed intermittent fever, progressive weight gain, and personality changes may represent rare paraneoplastic syndromes in ganglioneuromas.
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25
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Masserot C, Liu Q, Nguyen E, Gattolliat CH, Valteau-Couanet D, Bénard J, Huber C, Ségal-Bendirdjian E. WT1 expression is inversely correlated with MYCN amplification or expression and associated with poor survival in non-MYCN-amplified neuroblastoma. Mol Oncol 2015; 10:240-52. [PMID: 26482175 DOI: 10.1016/j.molonc.2015.09.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2015] [Revised: 09/05/2015] [Accepted: 09/25/2015] [Indexed: 02/07/2023] Open
Abstract
Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. A striking feature of this tumor is its clinical heterogeneity. Several tumor progression markers have been delineated so far, among which MYCN amplification, which occurs in about 25% of total NB cases, with the percentage increasing to 30% in advanced stage NB. Although MYCN amplification is strongly correlated with NB of poor outcome, the MYCN status cannot alone predict all cases of poor survival in NB. Indeed NB without MYCN amplification (about 70-80% of NB) are not always favorable. WT1 was initially identified as a tumor suppressor gene involved in the development of a pediatric renal tumor (Wilms' tumor). Here, we describe an inverse correlation between WT1 expression and MYCN amplification and expression. However and most notably, our results show that WT1 gene expression is associated with a poor outcome for patients showing non-MYCN-amplified tumors. Thus WT1 expression is clinically significant in NB and may be a prognostic marker for better risk stratification and for an optimized therapeutic management of NB.
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Affiliation(s)
- Caroline Masserot
- INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France
| | - Qingyuan Liu
- INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France
| | - Eric Nguyen
- INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France
| | - Charles-Henry Gattolliat
- Université Paris-Sud 11, Orsay, France; Signalisation, Noyaux et Innovations Thérapeutiques en Cancérologie CNRS-UMR 8126, Gustave Roussy, Villejuif, France
| | | | - Jean Bénard
- Université Paris-Sud 11, Orsay, France; Signalisation, Noyaux et Innovations Thérapeutiques en Cancérologie CNRS-UMR 8126, Gustave Roussy, Villejuif, France
| | - Catherine Huber
- MAP5, Université Paris Descartes, Sorbonne Paris Cité, France; INSERM UMR-S 1018, 16 bis Avenue Paul Vaillant-Couturier, 94804, Villejuif, France
| | - Evelyne Ségal-Bendirdjian
- INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France.
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26
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Bleeker G, Tytgat GAM, Adam JA, Caron HN, Kremer LCM, Hooft L, van Dalen EC. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma. Cochrane Database Syst Rev 2015; 2015:CD009263. [PMID: 26417712 PMCID: PMC4621955 DOI: 10.1002/14651858.cd009263.pub2] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose ((18)F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. OBJECTIVES PRIMARY OBJECTIVES 1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. SECONDARY OBJECTIVES 2.1 To determine the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. This was performed within and between included studies. ¹²³I-MIBG (SPECT-CT) scintigraphy was the comparator test in this case. SEARCH METHODS We searched the databases of MEDLINE/PubMed (1945 to 11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially relevant articles. Also we checked the reference lists of relevant articles and review articles, scanned conference proceedings and searched for unpublished studies by contacting researchers involved in this area. SELECTION CRITERIA We included studies of a cross-sectional design or cases series of proven neuroblastoma, either retrospective or prospective, if they compared the results of ¹²³I-MIBG (SPECT-CT) scintigraphy or (18)F-FDG-PET(-CT) imaging, or both, with the reference standards or with each other. Studies had to be primary diagnostic and report on children aged between 0 to 18 years old with a neuroblastoma of any stage at first diagnosis or at recurrence. DATA COLLECTION AND ANALYSIS One review author performed the initial screening of identified references. Two review authors independently performed the study selection, extracted data and assessed the methodological quality.We used data from two-by-two tables, describing at least the number of patients with a true positive test and the number of patients with a false negative test, to calculate the sensitivity, and if possible, the specificity for each included study.If possible, we generated forest plots showing estimates of sensitivity and specificity together with 95% confidence intervals. MAIN RESULTS Eleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of ¹²³I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of ¹²³I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies.One study reported on the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging (add-on test) in patients with negative ¹²³I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative ¹²³I-MIBG scan and a positive (18)F-FDG-PET(-CT) scan.The sensitivity of (18)F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to ¹²³I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of (18)F-FDG-PET(-CT) imaging was 100% versus 92% of ¹²³I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities. AUTHORS' CONCLUSIONS The reported sensitivities of ¹²³-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma.Only one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made.As described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate ¹²³I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be (18)F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed.The diagnostic accuracy of (18)F-FDG-PET(-CT) imaging in case of a negative ¹²³I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test ¹²³I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search.At the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term "the sensitivity to assess the presence of neuroblastoma" instead of "diagnostic accuracy" for the objectives.
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Affiliation(s)
- Gitta Bleeker
- Northwest ClinicsRadiology and Nuclear MedicinePO box 501AlkmaarNetherlands1800 AM
| | - Godelieve AM Tytgat
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
| | - Judit A Adam
- Amsterdam UMC, University of AmsterdamNuclear Medicine and RadiologyP.O. Box 22660AmsterdamNetherlands1100 DD
| | - Huib N Caron
- F. Hoffmann‐La Roche AGiPODD Pediatric Oncology team, Pharma Development OncologyBldg/Room 682/332BaselSwitzerland4070
| | - Leontien CM Kremer
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
| | - Lotty Hooft
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityCochrane NetherlandsRoom Str. 6.127P.O. Box 85500UtrechtNetherlands3508 GA
| | - Elvira C van Dalen
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
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von Witzleben A, Goerttler LT, Lennerz J, Weissinger S, Kornmann M, Mayer-Steinacker R, von Baer A, Schultheiss M, Möller P, Barth TFE. In chordoma, metastasis, recurrences, Ki-67 index, and a matrix-poor phenotype are associated with patients’ shorter overall survival. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2015; 25:4016-4024. [DOI: 10.1007/s00586-015-4242-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 08/07/2015] [Accepted: 09/10/2015] [Indexed: 10/23/2022]
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Magro G, Salvatorelli L, Di Cataldo A, Musumeci G, Spoto G, Parenti R. Cyclin D1 in human neuroblastic tumors recapitulates its developmental expression: An immunohistochemical study. Acta Histochem 2015; 117:415-24. [PMID: 25765113 DOI: 10.1016/j.acthis.2015.01.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 01/21/2015] [Accepted: 01/28/2015] [Indexed: 01/18/2023]
Abstract
The protein cyclin D1 (CD1), which belongs to a family of proteins functioning as regulators of CDKs (cyclin-dependent kinases) throughout the cell cycle, has been immunohistochemically detected in a wide variety of human malignant tumors. The aim of the present study was to investigate immunohistochemically the expression and distribution of CD1 in the developing human peripheral sympathetic nervous system (PSNS) and in childhood peripheral neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas). The above mentioned fetal and neoplastic tissues represent an in vivo model in which undifferentiated neuroblastic cells undergo ganglion cell differentiation. During development, a strong nuclear expression of CD1 was restricted to neuroblasts, disappearing progressively from the maturing ganglion cells with increasing gestational age. In neoplastic tissues, CD1 immunoreactivity was restricted to neuroblastic cell component of all neuroblastomas and ganglioneuroblastomas, whereas it was absent or only focally detectable in maturing/mature ganglion cell component of differentiating neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. We conclude that CD1 is a reliable marker, which can be used routinely to stain neuroblastic cells in both developing and neoplastic tissues. Furthermore, our results indicate that CD1 expression in childhood peripheral neuroblastic tumors recapitulates the changes during normal development of PSNS, as previously reported for Bcl-2 oncoprotein, c-ErbB2, insulin-like growth factor 2, β-2-microglobulin, and cathepsin D. This is consistent with the current view that childhood peripheral neuroblastic tumors exhibit gene expression profiles mirroring those occurring during PSNS development.
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Affiliation(s)
- Gaetano Magro
- Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, AziendaOspedaliero-Universitaria "Policlinico-Vittorio Emanuele", Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy.
| | - Lucia Salvatorelli
- Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, AziendaOspedaliero-Universitaria "Policlinico-Vittorio Emanuele", Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Andrea Di Cataldo
- Department of Paediatric Haematology and Oncology, University of Catania, Catania, Italy
| | - Giuseppe Musumeci
- Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Graziana Spoto
- Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, AziendaOspedaliero-Universitaria "Policlinico-Vittorio Emanuele", Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, Section of Physiology, School of Medicine, University of Catania, Catania, Italy
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Angelini P, Baruchel S, Marrano P, Irwin MS, Thorner PS. The neuroblastoma and ganglion components of nodular ganglioneuroblastoma are genetically similar: evidence against separate clonal origins. Mod Pathol 2015; 28:166-76. [PMID: 25081755 DOI: 10.1038/modpathol.2014.90] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Revised: 04/18/2014] [Accepted: 04/19/2014] [Indexed: 12/12/2022]
Abstract
Nodular ganglioneuroblastoma is characterized by a macroscopic nodule of neuroblastoma within a ganglioneuromatous component. These two components have been considered to originate from separate clones, with the neuroblastoma clone accounting for the clinical behavior of nodular ganglioneuroblastoma. In order to investigate the clonal origin of the cellular components (neuroblasts, ganglion cells, and Schwann cells) of nodular ganglioneuroblastoma, paraffin-embedded tumor samples from eight cases were analyzed by single nucleotide polymorphism array and in situ hybridization. DNA was extracted separately from neuroblastomatous and ganglioneuromatous areas. By in situ hybridization, MYCN gain (4-10 gene copies/nucleus) was detected in 7/8 neuroblastoma samples. In ganglioneuromatous regions, gains were also detected in ganglion cells but not in Schwann cells. Single-nucleotide polymorphism array studies identified chromosome losses (11q and 14q) and gains (12, 13q, 17q and 18q) in the neuroblastoma component, whereas the ganglioneuromatous component showed fewer or no genetic alterations. There were no unique copy number changes distinguishing nodular ganglioneuroblastoma from other subtypes of neuroblastoma. By in situ hybridization, ganglion cells but not Schwann cells showed the same alterations detected in neuroblasts. Thus, neuroblasts and ganglion cells in nodular ganglioneuroblastoma are genetically related and may arise from the same clone. In contrast, the Schwann cells have a different origin and may be derived from a non-neoplastic neural crest precursor. Our results suggest that the clinical behavior of nodular ganglioneuroblastoma cannot be explained by the presence of separate clones with distinct genetic signatures.
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Affiliation(s)
- Paola Angelini
- Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Sylvain Baruchel
- 1] Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada [2] Department of Pediatrics, University of Toronto, University of Toronto, Toronto, ON, Canada
| | - Paula Marrano
- Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Meredith S Irwin
- 1] Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada [2] Department of Pediatrics, University of Toronto, University of Toronto, Toronto, ON, Canada
| | - Paul S Thorner
- 1] Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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Adas M, Koc B, Adas G, Ozulker F, Aydin T. Ganglioneuroma presenting as an adrenal incidentaloma: a case report. J Med Case Rep 2014; 8:131. [PMID: 24779851 PMCID: PMC4031973 DOI: 10.1186/1752-1947-8-131] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Accepted: 02/17/2014] [Indexed: 12/12/2022] Open
Abstract
Introduction Ganglioneuromas are rare benign tumors arising from the neural crest tissue and are most commonly located in the posterior mediastinum and retroperitoneum; they are rarely found in the adrenal gland. This tumor is usually asymptomatic and in the majority of cases is detected incidentally. Although the characteristics of adrenal ganglioneuroma on computerized tomography and magnetic resonance imaging have been well described, the exact diagnosis is difficult. Histopathological examination is currently the mainstay of diagnosis. Ganglioneuromas have a very good prognosis with surgical removal. We report the case of a male patient with an incidentally identified adrenal ganglioneuroma with high standardized uptake values in a positron emission tomography scan. Case presentation An 18-year-old Turkish male patient with no previous comorbidities was admitted to our hospital with lower-quadrant pain. He had no significant past medical or surgical history. A physical examination did not reveal any signs and the results of routine laboratory tests were all within the normal ranges. Our patient underwent computed tomography of his abdomen, which showed a relatively homogenous left adrenal tumor measuring 5.2×4.3×7.1cm. On a positron emission tomography scan, the left adrenal gland disclosed a standardized uptake value of 4.1. Our patient underwent an exploratory laparotomy with left adrenalectomy without any related complications. Conclusion Ganglioneuroma may sometimes be similar to other adrenal malignancies. Careful evaluation with endocrine tests and imaging procedures is necessary to provide an accurate diagnosis. Definitive diagnosis can be made by histological examination. The prognosis is very good with surgical removal.
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Affiliation(s)
| | - Bora Koc
- Department of Surgery, Okmeydani Training and Research Hospital, 34200 Şişli, İstanbul, Turkey.
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ALK amplification and protein expression predict inferior prognosis in neuroblastomas. Exp Mol Pathol 2013; 95:124-30. [PMID: 23797004 DOI: 10.1016/j.yexmp.2013.06.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Accepted: 06/06/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL. METHODS We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients. RESULTS Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P<0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P<0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P=0.044). CONCLUSION ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice.
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Paramythiotis D, Vasiliadou K, Panagiotou D, Panidis S, Grigoriadou M, Basdanis G. Multiple Presacral Ganglioneuroma in an Adult Patient: Report on a Rare Case and a Literature Review. J Gynecol Surg 2013. [DOI: 10.1089/gyn.2012.0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Daniel Paramythiotis
- 1st Propedeutic Surgical Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kalliopi Vasiliadou
- 1st Propedeutic Surgical Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Panagiotou
- 1st Propedeutic Surgical Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stavros Panidis
- 1st Propedeutic Surgical Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Grigoriadou
- Department of Pathology,Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgios Basdanis
- 1st Propedeutic Surgical Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Rogers DA, Schor NF. Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model. Exp Cell Res 2013; 319:660-9. [PMID: 23333500 DOI: 10.1016/j.yexcr.2012.12.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Revised: 12/17/2012] [Accepted: 12/19/2012] [Indexed: 11/16/2022]
Abstract
Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells.
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Affiliation(s)
- Danny A Rogers
- Departments of Pediatrics, Neurology, and Neurobiology & Anatomy, University of Rochester Medical Center, 601 Elmwood Avenue, Box 777, Rochester, NY 14642, USA.
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Abstract
OBJECTIVE Ganglioneuromas are rare benign tumors originating from ganglion cells. Ganglioneuromas are detected incidentally because they are asymptomatic. We report a case of laparoscopic excision of a retroperitoneal ganglioneuroma. CASE DESCRIPTION A 49-y-old female was admitted to our medical center with the complaint of abdominal pain. Abdominal ultrasound showed a hypoechoic solid lesion at the level of the liver hilum, adjacent to the pancreas. Computerized tomography scan confirmed the presence of a thin walled mass 44 mm in diameter, adjacent to the pancreas and liver. Laparoscopic excision of the retroperitoneal mass was planned. The tumor was removed en bloc, and the pathologic diagnosis was ganglioneuroma. The patient was discharged from the hospital on the third postoperative day without any complications. CONCLUSION Minimally invasive surgery has been shown to be safe and reliable in patients with retroperitoneal tumors.
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Affiliation(s)
- Orhan Alimoglu
- Department of General Surgery, Umraniye Education and Research Hospital, Istanbul, Turkey.
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George RE, Perez-Atayde AR, Yao X, London WB, Shamberger RC, Neuberg D, Diller L. Tumor histology during induction therapy in patients with high-risk neuroblastoma. Pediatr Blood Cancer 2012; 59:506-10. [PMID: 22162143 DOI: 10.1002/pbc.24013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Accepted: 10/28/2011] [Indexed: 11/11/2022]
Abstract
BACKGROUND In high-risk neuroblastoma patients, response to induction chemotherapy is emerging as an important determinant of overall survival. We sought to determine whether histological changes in the primary tumor following induction therapy could be used as a marker of response. PROCEDURE Second-look primary tumor specimens from 43 patients were reviewed according to specific morphological features. RESULTS In the majority, induction therapy resulted in a shift from an intermediate/high to low mitosis-karyorrhexis index (MKI) (P = 0.0009) and from undifferentiated/poorly differentiated to differentiating tumors (P < 0.0001). Following induction therapy, persistence of intermediate/high tumor MKI and ≥90% persistent neuroblastic cells were predictive of a poor outcome (P = 0.001 and 0.03, respectively). Less than 10% tumor necrosis was associated with a trend towards lower survival. CONCLUSIONS High proliferative activity in the primary tumor following induction therapy portends a poor outcome in patients with high-risk neuroblastoma. If confirmed in a larger cohort, tumor histology at second-look surgery could be used to define a subset of very high risk patients who would benefit from alternative therapies prior to myeloablative dose-intensive transplant.
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Affiliation(s)
- Rani E George
- Department of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA 02115, USA.
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Shuangshoti S, Shuangshoti S, Nuchprayoon I, Kanjanapongkul S, Marrano P, Irwin MS, Thorner PS. Natural course of low risk neuroblastoma. Pediatr Blood Cancer 2012; 58:690-4. [PMID: 21922650 DOI: 10.1002/pbc.23325] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Accepted: 08/02/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND Neuroblastoma is characterized by heterogeneity of histology, biology, and clinical behavior. Most epidemiology studies are based on Western and Japanese populations; there are very few studies on neuroblastoma from Southeast Asia. PROCEDURE Cases of Thai children with neuroblastoma were retrospectively reviewed to determine if the epidemiology of the disease differs from Western populations. Sixty-two cases were assembled from two pathology centers in Bangkok. Histologic prognostic category and MYCN copy number were determined. RESULTS The median age at diagnosis was 2.9 years. Only 11% of cases presented at less than 1 year of age and 12% cases had low stage disease (1, 2, and 4S). The majority of tumors had unfavorable histology (48/62); this was at least partly due to the higher age at diagnosis for most patients. MYCN amplification was detected in 18/52 (35%) tumors, all in stage 3 or 4 tumors. We assigned patients to high, intermediate and low risk categories using the Children's Oncology Group risk stratification criteria. In contrast to Western studies, the majority of cases (50/59 or 85%) in our series had high risk disease. CONCLUSIONS Since there is no evidence to date that the biology of neuroblastoma varies by geographic region, the paucity of low risk cases in our study may reflect spontaneous resolution/differentiation of tumors that are not clinically detected. Moreover, a delay in diagnosis of intermediate risk cases could result in higher tumor burden at the time of diagnosis, increasing the proportion of high risk cases observed.
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Affiliation(s)
- Somruetai Shuangshoti
- Institute of Pathology, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand
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Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model. Neoplasia 2012; 13:991-1004. [PMID: 22028624 DOI: 10.1593/neo.11800] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 08/30/2011] [Accepted: 09/06/2011] [Indexed: 01/06/2023] Open
Abstract
Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically "profile" the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB.
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Gawecka JE, Geerts D, Koster J, Caliva MJ, Sulzmaier FJ, Opoku-Ansah J, Wada RK, Bachmann AS, Ramos JW. PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma. Int J Cancer 2012; 131:1556-68. [PMID: 22213050 DOI: 10.1002/ijc.27415] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2011] [Accepted: 12/09/2011] [Indexed: 12/29/2022]
Abstract
ERK and RSK2 drive proliferation and invasion of many cancers. Phosphoprotein enriched in astrocytes 15 (PEA15) binds ERK and RSK2 and high PEA15 levels can impair ERK- and RSK2-dependent transcription. PEA15 expression also inversely correlates with cell motility and invasiveness. We therefore tested PEA15 effects on neuroblastoma cells in vitro. We further analyzed PEA15 expression in the context of clinical and genetic features of neuroblastoma in tumor samples to determine its correlation with disease progression. Affymetrix microarray analysis was performed using 24 different neuroblastoma cell lines. Cell lines expressing low to intermediate levels of PEA15 were chosen for in vitro functional studies. The cell line results were verified by Affymetrix analysis of three different neuroblastic tumor types (total of 110 samples) PEA15 overexpression inhibited neuroblastoma migration in vitro. We verified that inhibition of motility required PEA15 interaction with its binding partners ERK and RSK2. Additionally, synthetic inhibitors of RSK2 suppressed integrin-dependent migration. PEA15 expression correlates with clinical parameters and a 25% increase in patient survival rate. The highest PEA15 levels were found in low stage, more differentiated and less metastatic neuroblastic tumors, and correlated with lack of MYCN amplification. PEA15 blocks neuroblastoma migration through inhibition of ERK/RSK2 signaling. PEA15 expression levels correlate with favorable clinical features suggesting that PEA15 limits metastatic progression of neuroblastoma. Thus, PEA15 and its partners ERK and RSK2 are potential targets for the development of new therapeutics to impede progression of minimal residual disease in patients with high-risk neuroblastoma.
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Affiliation(s)
- Joanna E Gawecka
- Cancer Biology Program, University of Hawai'i Cancer Center, University of Hawai'i at Manoa, Honolulu, HI 96813, USA
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Simultaneous diagnosis of acute lymphoblastic leukemia and peripheral neuroblastic tumor in a child. J Pediatr Hematol Oncol 2012; 34:72-5. [PMID: 21646915 DOI: 10.1097/mph.0b013e31820db67b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
We report the case of a 3-year-old girl with a mediastinal mass, severe anemia, leukocytosis and neutropenia, in whom, after initial suspicion of metastatic neuroblastoma, a final diagnosis of concurrent ganglioneuroblastoma and acute lymphoblastic leukemia was made. The mediastinal tumor was surgically excised and the child subsequently underwent chemotherapy for acute lymphoblastic leukemia. The patient remains in complete remission from both diseases 4 years after the diagnosis and 24 months after completion of all treatment. The simultaneous occurrence of 2 different neoplasms in a child is very infrequent, and no comparable cases are reported in the literature.
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41
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Aktüre E, Salamat M, Korkmaz H, Başkaya M. Ganglioneuroma of the sphenoid wing: a case report and literature review. Clin Neuropathol 2011; 30:313-7. [PMID: 22011737 PMCID: PMC3663467 DOI: 10.5414/np300376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2011] [Accepted: 06/23/2011] [Indexed: 11/18/2022] Open
Abstract
Ganglioneuromas (GNs) are well-differentiated, slow-growing, benign tumors that are quite rare and usually found in the posterior mediastinum and retroperitoneum. They are composed of ganglion and Schwann cells and their origin remains in dispute. GNs have been reported as intraosseous lesions, such as in temporal and orbital bones. There are rare reports of intracranial lesions, mostly in the pituitary fossa. Most GN patients are children and are clinically asymptomatic. Diagnosis of GN requires histopathologic evaluation since no specific clinical or radiologic diagnostic features have been identified. We report the case of a 35-year-old man with recurrent sinusitis whose radiologic workup revealed a lytic right sphenoid wing lesion with microcalcifications. He underwent gross-total resection of the lesion and the pathologic findings were diagnostic of ganglioneuroma. To the best of our knowledge, this is the first reported case of sphenoid wing GN. The nature and origin of this tumor are discussed, and the GN literature is reviewed.
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Affiliation(s)
| | - M.S. Salamat
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
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Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer. Clin Dev Immunol 2011; 2011:245181. [PMID: 21941577 PMCID: PMC3177098 DOI: 10.1155/2011/245181] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2011] [Accepted: 07/22/2011] [Indexed: 11/20/2022]
Abstract
The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.
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Reddy S JR, Purushottam G, Pandurangarao K, Ravi Chander PT. Para aortic ganglioneuroma presenting as Cushing's syndrome. Indian J Urol 2011; 23:471-3. [PMID: 19718307 PMCID: PMC2721583 DOI: 10.4103/0970-1591.36725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
We present a case of an eight-year-old female presenting with four months history of progressive weight gain, short stature, obesity, mild acanthosis, moon facies and buffalo hump. Biochemically, low-dose and high-dose Dexamethasone tests were not suppressible, ACTH was raised and 24h urinary metanephrines were normal. The CECT scan showed a 3cm paraganglioma. Tumor was excised via 11th rib transcostal approach and the mass was found arising from the sympathetic chain. Histopathology was suggestive of ganglioneuroma positive for ACTH immunostaining.
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Affiliation(s)
- Jaya Ram Reddy S
- Department of Urology, Osmania General Hospital, Hyderabad, India
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Haug BH, Henriksen JR, Buechner J, Geerts D, Tømte E, Kogner P, Martinsson T, Flægstad T, Sveinbjørnsson B, Einvik C. MYCN-regulated miRNA-92 inhibits secretion of the tumor suppressor DICKKOPF-3 (DKK3) in neuroblastoma. Carcinogenesis 2011; 32:1005-12. [PMID: 21572098 DOI: 10.1093/carcin/bgr073] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
The MYCN oncogene is frequently amplified in neuroblastoma. It is one of the most consistent markers of bad prognosis for this disease. Dickkopf-3 (DKK3) is a secreted protein of the DKK family of Wnt regulators. It functions as a tumor suppressor in a range of cancers, including neuroblastoma. MYCN was recently found to downregulate DKK3 mRNA. In this study, we show that MYCN knockdown in MYCN-amplified (MNA) neuroblastoma cell lines increases secretion of endogenous DKK3 to the culture media. MicroRNAs (miRNAs) are ∼20 nt long single-stranded RNA molecules that downregulate messenger RNAs by targeting the 3' untranslated region (3'UTR). Many miRNAs regulate genes involved in the pathogenesis of cancer and are extensively deregulated in different tumors. Using miRNA target prediction software, we found several MYCN-regulated miRNAs that could target the 3'UTR sequence of DKK3, including mir-92a, mir-92b and let-7e. Luciferase expression from a reporter vector containing the DKK3-3'UTR was decreased when this construct was cotransfected with mir-92a, mir-92b or let-7e in HEK293 cells. Mutation of the mir-92 seed sequence in the 3'UTR completely rescued the observed decrease in reporter expression when cotransfected with mir-92a and mir-92b. Antagomir and miRNA-mimic transfections in neuroblastoma cell lines confirmed that DKK3 secretion to the culture media is regulated by mir-92. Consistent with reports from other cancers, we found DKK3 to be expressed in the endothelium of primary neuroblastoma samples and to be absent in tumors with MYCN amplification. Our data demonstrate that MYCN-regulated miRNAs are able to modulate the expression of the tumor suppressor DKK3 in neuroblastoma.
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Affiliation(s)
- Bjørn Helge Haug
- Department of Pediatrics, University Hospital of North-Norway, NO-9038 Tromsø, Norway
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Jung HR, Kang KJ, Kwon JH, Kang YN. Adrenal ganglioneuroma with hepatic metastasis. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2011; 80:297-300. [PMID: 22066051 PMCID: PMC3204680 DOI: 10.4174/jkss.2011.80.4.297] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 02/23/2010] [Indexed: 11/30/2022]
Abstract
Ganglioneuroma is the most differentiated tumor of neural crest origin and rarely arises in the adrenal gland. Ganglioneuroma is typically known to be benign, but very rarely can metastasize to distant sites. We report a case of a 31-year-old man with a huge adrenal mass with hepatic metastases.
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Affiliation(s)
- Hye Ra Jung
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
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SAKAI H, YONEMARU K, TAKEDA M, NIIMI K, MURAKAMI M, HIRATA A, YANAI T. Ganglioneuroma in the Urinary Bladder of a Dog. J Vet Med Sci 2011; 73:801-3. [DOI: 10.1292/jvms.10-0523] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hiroki SAKAI
- Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University
| | | | | | - Kenta NIIMI
- Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University
| | - Mami MURAKAMI
- Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University
| | - Akihiro HIRATA
- Division of Animal Experiment, Life Science Research Center, Gifu University
| | - Tokuma YANAI
- Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University
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Abstract
Small cell malignancies of children constitute a continuing diagnostic challenge for surgical pathologists, although modern methods of ancillary diagnosis provide powerful tools that resolve most difficult cases. Current techniques range from identification of DNA alternations, including gene fusions, chromosome translocations, and genetic deletions, to recognition of characteristic patterns of protein expression, usually visualized with immunohistochemistry. In spite of these advances, recognition of key cellular and histologic features remains the keystone of diagnosis but requires adequately fixed and carefully stained histologic sections. Cytologic features now suffice for diagnosis if confirmed by appropriate testing. This article outlines key histologic features of pediatric small cell neoplasms and the algorithms that allow diagnostic confirmation and the initiation of appropriate therapy.
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Affiliation(s)
- David M Parham
- Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Room BMSB 451, Oklahoma City, OK 70104, USA.
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48
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TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene 2010; 29:6172-83. [PMID: 20729920 PMCID: PMC3007621 DOI: 10.1038/onc.2010.340] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor β(2) transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
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49
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Mizuno S, Iida T, Fujita S. Adult-onset adrenal ganglioneuroblastoma - Bone metastasis two years after surgery: report of a case. Surg Today 2010; 40:482-6. [PMID: 20425556 DOI: 10.1007/s00595-008-4084-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2008] [Accepted: 08/10/2009] [Indexed: 11/29/2022]
Abstract
Ganglioneuroblastoma (GNB) is a common type of tumor in children but is rarely seen in adults. This report presents a case of an adrenal GNB in a 53-year-old man with bone metastasis after surgery. The patient experienced an increased frequency of urination and was found to have a nonfunctioning tumor in the right adrenal gland. The tumor was 11 cm in diameter with no local invasion or distant metastasis, and was completely removed. Histologically, on gross examination the tumor contained a visible neuroblastomatous nodule with ganglioneuromatous component, and was diagnosed as GNB nodular classical type. Two years after surgery, multiple metastatic lesions were found in the patient's lumbar spine. Only 48 GNB cases have been reported in the literature. According to these reports, large GNB tumors, more than 8 cm in diameter, tend to arise from the retroperitoneal cavity and develop to metastasize to nearby bone or lymph nodes. Because the prognosis was not favorable, despite surgery and radiation therapy or chemotherapy, it is necessary to closely follow patients with large GNB tumors.
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Affiliation(s)
- Shugo Mizuno
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, P.O. Box 100286, Gainesville, FL 32610-0286, USA
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50
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Kattepura S, Alexander B, Kini U, Das K. Sporadic synchronous ganglioneuromas in a child--case report and review. J Pediatr Surg 2010; 45:822-5. [PMID: 20385294 DOI: 10.1016/j.jpedsurg.2010.01.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2009] [Revised: 01/20/2010] [Accepted: 01/20/2010] [Indexed: 10/19/2022]
Abstract
An 8-year-old girl presented with a relatively asymptomatic abdominopelvic mass that was detected in the neonatal period. She harbored a presacral mass with intraspinal extension and a right posterior mediastinal mass; all were excised completely and were ganglioneuromas. The report discusses the maturation of neuroblastoma-ganglioneuromas and details the staged management of sporadic synchronous ganglioneuromas in a child, probably the first in published English literature.
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Affiliation(s)
- Subramanya Kattepura
- Department of Paediatric Surgery, St. John's Medical College Hospital, St. John's National Academy of Health Sciences, Johnnagara, Bangalore 560034, India
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