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1
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Manatakis DK, Tsouknidas I, Mylonakis E, Tasis N, Antonopoulou MI, Acheimastos V, Mastoropoulou A, Korkolis DP. Primary adrenal Ewing sarcoma: A systematic review of the literature. World J Clin Cases 2023; 11:6782-6791. [PMID: 37900999 PMCID: PMC10600854 DOI: 10.12998/wjcc.v11.i28.6782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/18/2023] [Accepted: 09/12/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Ewing sarcoma (ES) is a malignant neoplasm of neuroectodermal origin and is commonly observed in children and young adults. The musculoskeletal system is the main body system impacted and ES is rarely seen in the visceral organs particularly the adrenal gland. AIM To present a comprehensive review of primary adrenal ES, with emphasis on diagnosis, therapy and oncological outcomes. METHODS A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020. PubMed/ MEDLINE, EMBASE and Google Scholar bibliographic databases were searched to identify articles from 1989 to 2022 and included patients with ES/primitive neuroectodermal tumor (PNET) of the adrenal gland. PubMed, Google Scholar and EMBASE medical databases were searched, combining the terms "adrenal", "ES" and "PNET". Demographic, clinical, pathological and oncological data of patients were analyzed by SPSS version 29.0. RESULTS A total of 52 studies were included for review (47 case reports and 5 case series) with 66 patients reported to have primary adrenal ES. Mean age at diagnosis was 26.4 ± 15.4 years (37.9% males, 57.6% females, sex not reported in 3 cases). The most frequent complaint was abdominal/flank pain or discomfort (46.4%) followed by a palpable mass (25.0%), and the average duration of symptoms was 2.6 ± 3.1 mo. The imaging modality of choice was computed tomography scan (81.5%), followed by magnetic resonance imaging (20.4%). Preoperative staging revealed that 17 tumors (27.9%) were metastatic and 14 patients had inferior vena cava or renal vein neoplastic thrombus at initial diagnosis. Open adrenalectomy was performed in the majority of cases (80.0%), of which 27.9% required more extensive resection. Minimally invasive surgery was attempted in 8.2% of tumors. Complete surgical resection was achieved in 89.4% of the patients. Adjuvant therapy was administered to 32 patients, in the form of chemotherapy (62.5%), radiotherapy (3.1%) or combination (34.4%). Median overall survival was 15 mo and 24-mo overall survival was 40.5%. Median disease-free survival was 10 mo and 24-mo disease-free survival was 33.3%. CONCLUSION The significant progress in molecular biology and genetics of ES does not reflect on patient outcomes. ES remains an aggressive tumor with a poor prognosis and high mortality.
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Affiliation(s)
| | - Ioannis Tsouknidas
- General Surgery, Lankenau Medical Center, Main Line Health, Wynnewood, PA 19096, United States
| | - Emmanouil Mylonakis
- 2nd Department of Surgery, Athens Naval and Veterans Hospital, Athens 11521, Greece
| | - Nikolaos Tasis
- 2nd Department of Surgery, Athens Naval and Veterans Hospital, Athens 11521, Greece
- Department of Surgical Oncology, St Savvas Cancer Hospital, Athens 11522, Greece
| | | | | | | | - Dimitrios P Korkolis
- Department of Surgical Oncology, St Savvas Cancer Hospital, Athens 11522, Greece
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2
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Roy D, Pereira M, Shivdasani D, Singh N. 18 F-FDG PET-CT Evaluation of Primary Adrenal Ewing Sarcoma with Venous Thrombosis: An Unusual Presentation. World J Nucl Med 2023; 22:26-28. [PMID: 36923977 PMCID: PMC10010853 DOI: 10.1055/s-0042-1757251] [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: 10/14/2022] Open
Abstract
Ewing sarcoma (EWS) is primarily an osseous malignancy of childhood and young adults. Extraskeletal occurrence is less frequent and primary adrenal involvement is an even rare presentation. We present such a case of a 7-year-old boy diagnosed with adrenal EWS with associated venous thrombosis and pulmonary embolism detected on 18 F-fluorodeoxyglucose positron emission tomography-computed tomography scan.
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Affiliation(s)
- Debdip Roy
- Department of Nuclear Medicine and Molecular Imaging, P. D. Hinduja National Hospital and MRC, Mahim, Mumbai, Maharashtra, India
| | - Melvika Pereira
- Department of Nuclear Medicine and Molecular Imaging, P. D. Hinduja National Hospital and MRC, Mahim, Mumbai, Maharashtra, India
| | - Divya Shivdasani
- Department of Nuclear Medicine and Molecular Imaging, P. D. Hinduja National Hospital and MRC, Mahim, Mumbai, Maharashtra, India
| | - Natasha Singh
- Department of Nuclear Medicine and Molecular Imaging, P. D. Hinduja National Hospital and MRC, Mahim, Mumbai, Maharashtra, India
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3
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Roundhill EA, Chicon-Bosch M, Jeys L, Parry M, Rankin KS, Droop A, Burchill SA. RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma. Cell Oncol (Dordr) 2021; 44:1065-1085. [PMID: 34403115 PMCID: PMC8516792 DOI: 10.1007/s13402-021-00619-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2021] [Indexed: 12/02/2022] Open
Abstract
PURPOSE The development of biomarkers and molecularly targeted therapies for patients with Ewing sarcoma (ES) in order to minimise morbidity and improve outcome is urgently needed. Here, we set out to isolate and characterise patient-derived ES primary cell cultures and daughter cancer stem-like cells (CSCs) to identify biomarkers of high-risk disease and candidate therapeutic targets. METHODS Thirty-two patient-derived primary cultures were established from treatment-naïve tumours and primary ES-CSCs isolated from these cultures using functional methods. By RNA-sequencing we analysed the transcriptome of ES patient-derived cells (n = 24) and ES-CSCs (n = 11) to identify the most abundant and differentially expressed genes (DEGs). Expression of the top DEG(s) in ES-CSCs compared to ES cells was validated at both RNA and protein levels. The functional and prognostic potential of the most significant gene (neurexin-1) was investigated using knock-down studies and immunohistochemistry of two independent tumour cohorts. RESULTS ES-CSCs were isolated from all primary cell cultures, consistent with the premise that ES is a CSC driven cancer. Transcriptional profiling confirmed that these cells were of mesenchymal origin, revealed novel cell surface targets for therapy that regulate cell-extracellular matrix interactions and identified candidate drivers of progression and relapse. High expression of neurexin-1 and low levels of regulators of its activity, APBA1 and NLGN4X, were associated with poor event-free and overall survival rates. Knock-down of neurexin-1 decreased viable cell numbers and spheroid formation. CONCLUSIONS Genes that regulate extracellular interactions, including neurexin-1, are candidate therapeutic targets in ES. High levels of neurexin-1 at diagnosis are associated with poor outcome and identify patients with localised disease that will relapse. These patients could benefit from more intensive or novel treatment modalities. The prognostic significance of neurexin-1 should be validated independently.
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MESH Headings
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/metabolism
- Antineoplastic Agents/pharmacology
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Bone Neoplasms/genetics
- Bone Neoplasms/metabolism
- Calcium-Binding Proteins/genetics
- Calcium-Binding Proteins/metabolism
- Cell Adhesion Molecules, Neuronal/genetics
- Cell Adhesion Molecules, Neuronal/metabolism
- Cell Line, Tumor
- Child
- Doxorubicin/pharmacology
- Gene Expression Regulation, Neoplastic
- Humans
- Kaplan-Meier Estimate
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- Neural Cell Adhesion Molecules/genetics
- Neural Cell Adhesion Molecules/metabolism
- Prognosis
- Sarcoma, Ewing/genetics
- Sarcoma, Ewing/metabolism
- Sequence Analysis, RNA/methods
- Transcriptome/genetics
- Tumor Cells, Cultured
- Vincristine/pharmacology
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Affiliation(s)
- Elizabeth Ann Roundhill
- Children's Cancer Research Group, Leeds Institute of Medical Research, St. James's University Hospital, Leeds, LS9 7TF, UK
| | - Mariona Chicon-Bosch
- Children's Cancer Research Group, Leeds Institute of Medical Research, St. James's University Hospital, Leeds, LS9 7TF, UK
| | - Lee Jeys
- Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Northfield, Birmingham, B31 2AP, UK
| | - Michael Parry
- Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Northfield, Birmingham, B31 2AP, UK
| | - Kenneth S Rankin
- Translational and Clinical Research Institute, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne, NE2 4AD, UK
| | - Alastair Droop
- Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
| | - Susan Ann Burchill
- Children's Cancer Research Group, Leeds Institute of Medical Research, St. James's University Hospital, Leeds, LS9 7TF, UK.
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4
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Adrenal mass of unusual etiology: Ewing sarcoma in a young man. Radiol Case Rep 2018; 12:838-844. [PMID: 29484083 PMCID: PMC5823311 DOI: 10.1016/j.radcr.2017.07.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 06/19/2017] [Accepted: 07/03/2017] [Indexed: 11/21/2022] Open
Abstract
Ewing sarcoma and peripheral primitive neuroectodermal tumor belong to the Ewing sarcoma (ES) family of tumors originating from a primitive neural tube. We report a 31-year-old man who was admitted to the urology clinic with complaints of fever, nausea, and dysuria. A right-sided adrenal mass was detected during ultrasonography. The lesion was then evaluated with magnetic resonance imaging, which showed areas of necrosis amid heterogeneous solid areas. Whole body scan with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography and bone scan studies showed pulmonary and osseous metastatic foci. The mass and right kidney were removed by an open approach. An immunohistochemical and molecular workup enabled the diagnosis of ES. The patient also underwent radiotherapy and chemotherapy. The patient remained in fairly good health during the 18-month follow-up period, but showed progression of all metastatic foci and died 26 months after treatment. In conclusion, adrenal ES should be included in the differential diagnosis of nonfunctional adrenal lesions despite its rare occurrence.
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5
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VandenBussche CJ, Adams CL, McDonald OG, Whitworth SA, Ali SZ. The fine needle aspiration of translocation sarcomas. Cytopathology 2017; 28:356-363. [DOI: 10.1111/cyt.12446] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2017] [Indexed: 12/18/2022]
Affiliation(s)
- C. J. VandenBussche
- Department of Pathology; The Johns Hopkins University School of Medicine; Baltimore MD USA
| | - C. L. Adams
- Department of Pathology; The Johns Hopkins University School of Medicine; Baltimore MD USA
| | - O. G. McDonald
- Department of Pathology, Microbiology and Immunology; Vanderbilt University Medical Center; Nashville TN USA
| | - S. A. Whitworth
- Department of Pathology; The Johns Hopkins University School of Medicine; Baltimore MD USA
| | - S. Z. Ali
- Department of Pathology; The Johns Hopkins University School of Medicine; Baltimore MD USA
- Department of Radiology; The Johns Hopkins University School of Medicine; Baltimore MD USA
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6
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Guo H, Chen S, Liu S, Wang K, Liu E, Li F, Hou Y. Rare adrenal gland incidentaloma: an unusual Ewing's sarcoma family of tumor presentation and literature review. BMC Urol 2017; 17:24. [PMID: 28376845 PMCID: PMC5379633 DOI: 10.1186/s12894-017-0217-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 03/27/2017] [Indexed: 01/10/2023] Open
Abstract
Background Members of the Ewing’s sarcoma family of tumor (ESFT) are malignant neoplasms and rarely observed in the adrenal gland. Case presentation We report an extremely exceptional case of ESFT rising from the adrenal gland in a 57-year-old Chinese man. The patient was hospitalized with abdominal swelling for 2 months. Computed tomography (CT) scan revealed a nearly-circular mass measuring about 8.1 × 10.6 cm in the right adrenal region. The patient underwent right adrenal resection. Histopathologic examination found the tumor was composed of small round blue cells forming typical Homer-Wright rosettes in focal area. The immunohistochemical analysis confirmed the case to be ESFT, which was positive for membranous CD99 and nuclear FLI-1. The patient was scheduled for four courses of large doses of chemotherapy and died for cancer metastasis one year later after surgery. Conclusions Histopathological evidence of Homer-Wright rosettes and immunohistochemical markers positivity, such as CD99 and FLI-1, are valuable factors for ESFT diagnosis, although cytogenetic analysis is considered as the gold standard. Complete surgery is the treatment of choice for ESFT and adjuvant radiotherapy and combination chemotherapy can significantly improve the survival rate of postoperative patients.
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Affiliation(s)
- Hui Guo
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Shuaiqi Chen
- Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
| | - Shukun Liu
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Kaixuan Wang
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Erpeng Liu
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Faping Li
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China
| | - Yuchuan Hou
- Department of Urology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
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7
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Pal DK, Chandra V, Ranjan KR, Chakrabortty D, Banerjee M. Ewing's Sarcoma of the Adrenal Gland. APSP J Case Rep 2016; 7:20. [PMID: 27398321 PMCID: PMC4921217 DOI: 10.21699/ajcr.v7i3.406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 04/28/2016] [Indexed: 12/27/2022] Open
Abstract
Ewing’s sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing’s sarcoma is very rare. Here we report a case of Ewing’s sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.
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Affiliation(s)
- Dilip Kumar Pal
- Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata
| | - Vipin Chandra
- Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata
| | - Kumar Rajiv Ranjan
- Department of Urology, Institute of Post Graduate Medical Education and Research, Kolkata
| | - Debasis Chakrabortty
- Department of Pathology, Institute of Post Graduate Medical Education and Research, Kolkata
| | - Manju Banerjee
- Department of Surgery, Institute of Post Graduate Medical Education and Research, Kolkata
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8
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Roncati L, Gatti AM, Capitani F, Barbolini G, Maiorana A, Palmieri B. Heavy Metal Bioaccumulation in an Atypical Primitive Neuroectodermal Tumor of the Abdominal Wall. Ultrastruct Pathol 2016; 39:286-92. [PMID: 26270725 DOI: 10.3109/01913123.2015.1013655] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Heavy metals are able to interfere with the function of vital cellular components. Besides in trace heavy metals, which are essential at low concentration for humans, there are heavy metals with a well-known toxic and oncogenic potential. In this study, for the first time in literature, we report the unique adulthood case of an atypical primitive neuroectodermal tumor of the abdominal wall, diagnosed by histology and immunohistochemistry, with the molecular hybridization support. The neoplasia occurred in a patient chronically exposed to a transdermal delivery of heavy metal salts (aluminum and bismuth), whose intracellular bioaccumulation has been revealed by elemental microanalysis.
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Affiliation(s)
- Luca Roncati
- Department of Diagnostic and Clinical Medicine and of Public Health, Section of Pathology, University of Modena and Reggio Emilia , Modena (MO) , Italy
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9
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Ewing sarcoma/peripheral primitive neuroectodermal tumor in the adrenal gland of an adolescent: a case report and review of the literature. J Pediatr Hematol Oncol 2014; 36:e456-9. [PMID: 24276043 DOI: 10.1097/mph.0000000000000058] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Ewing sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNETs) typically occur in the long or flat bones, the chest wall, extraskeletal soft tissue, or less frequently, in solid organs. They can arise from anywhere in the body; however, ES/pPNETs arising from the adrenal gland are very rare, especially in children and adolescents. Herein, the authors report a case of an ES/pPNET in the adrenal gland of a 17-year-old girl, who was successfully treated with a multimodal treatment, with a brief review of the pertinent literature.
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10
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Latent adrenal Ewing sarcoma family of tumors: A case report. Leg Med (Tokyo) 2013; 15:96-8. [DOI: 10.1016/j.legalmed.2012.08.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2012] [Accepted: 08/15/2012] [Indexed: 11/18/2022]
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11
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Abstract
Purpose. Examine the benefits and limitations of fine-needle aspiration cytology (FNA) used as the definitive diagnostic method before treatment. Method. Review of the 25 year experience at a multidisciplinary musculo-skeletal centre where FNA is the primary diagnostic approach to soft tissue sarcoma in the extremities and trunk wall and the experience of various experts in the field. Results. FNA has several benefits compared with coarse needle or open surgical biopsy. The most important are rapid preliminary diagnosis, no need for hospitalization and anaesthesia, negligible complications and fear for tumour cell spread. With the collected experience gained during the years a reliable diagnosis of sarcoma is the rule in general and specific-type diagnoses are possible in many histotypes, especially when the cytologic examination is supplemented with ancillary diagnostics. The most important limitations are inability to hit small deep-seated sarcoma and some diagnostic pitfalls such as the correct diagnosis of spindle cell neoplasms, variants of benign lipomatous tumours and ‘new soft tissue tumour entities’. Discussion. Optimal use of FNA calls for certain requirements such as centralization, experience in soft tissue tumour cytology–histopathology, the FNA technique and close co-operation between the orthopaedic surgeon and cytopathologist.
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Affiliation(s)
- M Akerman
- Department of Pathology and Cytology University Hospital Lund S-221 85 Sweden
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12
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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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13
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Llombart-Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P, Alberghini M, Karzeladze A, Savelov N, Petrov S, Alvarado-Cabrero I, Mihaila D, Terrier P, Lopez-Guerrero JA, Picci P. Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 2009; 455:397-411. [PMID: 19841938 DOI: 10.1007/s00428-009-0842-7] [Citation(s) in RCA: 147] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2009] [Revised: 09/15/2009] [Accepted: 09/25/2009] [Indexed: 12/31/2022]
Abstract
Ewing's sarcoma (ES)/peripheral neuroectodermal tumor (PNET) are malignant neoplasms affecting children and young adults. We performed a study to typify the histological diversity and evaluate antibodies that may offer diagnostic/prognostic support. In total, 415 cases of genetically confirmed paraffin-embedded ES/PNET were analyzed on whole sections and in tissue microarrays. This study confirms the structural heterogeneity of ES/PNET, distinguishing three major subtypes: conventional ES (280 cases); PNET (53 cases); and atypical ES/PNET (80), including large cells, vascular-like patterns, spindle pattern, and adamantinoma-like configuration. All cases presented positivity for at least three of the four tested antibodies (CD99, FLI1, HNK1, and CAV1). CAV1 appeared as a diagnostic immunomarker of ES/PNET being positive in CD99-negative cases. Hence, the immunohistochemical analysis confirmed the diagnostic value of all four antibodies, which together cover more than 99% of the tumors, independently of the histological variety. The univariate analysis for survival revealed atypical ES as the only histological parameter apparently associated with less favorable clinical outcome, particularly in the subgroup of patients treated with surgery. In conclusion, the diagnosis of atypical ES is a challenge for the pathologist and needs support from molecular techniques to perform an optimal differential diagnosis with other small round cell tumors.
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MESH Headings
- 12E7 Antigen
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antibodies
- Antigens, CD/biosynthesis
- Biomarkers, Tumor/analysis
- Bone Neoplasms/metabolism
- Bone Neoplasms/pathology
- CD57 Antigens/biosynthesis
- Caveolin 1/biosynthesis
- Cell Adhesion Molecules/biosynthesis
- Child
- Child, Preschool
- Disease Progression
- Female
- Humans
- Immunohistochemistry
- In Situ Hybridization, Fluorescence
- Infant
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Neuroectodermal Tumors, Primitive, Peripheral/metabolism
- Neuroectodermal Tumors, Primitive, Peripheral/pathology
- Prognosis
- Proto-Oncogene Protein c-fli-1/biosynthesis
- Sarcoma, Ewing/metabolism
- Sarcoma, Ewing/pathology
- Young Adult
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Affiliation(s)
- Antonio Llombart-Bosch
- Department of Pathology, University of Valencia, Ave. Blasco Ibañez, 17, 46010, Valencia, Spain.
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14
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Favorable outcome of Ewing sarcoma family tumors to multiagent intensive preoperative chemotherapy: a single institution experience. J Surg Oncol 2005; 89:239-43. [PMID: 15726621 DOI: 10.1002/jso.20206] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Aim of our study was to evaluate the efficacy of multiagent intensive preoperative chemotherapy in patients with Ewing sarcoma family tumors (ESFT), in order to succeed a better percentage of necrosis before surgical resection. PROCEDURE Eighteen patients with ESFT were treated with the same multiagent intensive preoperative protocol. 5/18 patients had bone Ewings sarcoma (EWS) and 13/18 had peripheral primitive neuroectodermal tumor (PNET). None had metastases at diagnosis. Chemotherapy consisted of 5 or 6 cycles with vincristine, cisplatin, cyclophosphamide, and Adriamycin, followed by 12 cycles of vincristine, cyclophosphamide, and actinomycin-D. Five patients with EWS underwent total resection after 5-6 cycles of preoperative chemotherapy and prosthetic replacement was performed in two of them. In 3/13 patients with PNET the tumor was resected at diagnosis and in 1/13 after 5 cycles of chemotherapy, while 9/13 patients received chemotherapy only and/or radiotherapy. RESULTS In patients with EWS, the histologic specimens of the resected tumors showed that tissue necrosis was 100% in four patients and 95% in one patient. The good histologic response reflects the effectiveness of this regimen in all ESFT. No patient had topical recurrence or developed metastatic disease during follow-up period (2-13 years, mean time 7.4 years). All patients had the scheduled cycles without delays or dose reductions. There were no major side effects of chemotherapy. CONCLUSIONS The intensive chemotherapy schedule, comprising of 5-6 cycles preoperatively, seems to maximize the percentage of tumor necrosis, thus improving outcome. Our study implies that this combined therapy may improve the prognosis of ESFT.
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15
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Leon ME, Hou JS, Galindo LM, Garcia FU. Fine-needle aspiration of adult small-round-cell tumors studied with flow cytometry. Diagn Cytopathol 2004; 31:147-54. [PMID: 15349982 DOI: 10.1002/dc.20074] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Immunophenotypic study is critical for the diagnosis of adult small-round-cell tumors (SRCTs). We describe three patients with Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) and one patient with neuroblastoma in which flow cytometry immunophenotyping (FCI) on the fine-needle aspirate (FNA) and bone marrow aspirate (BMA) demonstrated an abnormal population of cells that were CD45(-) and CD16/CD56(+). Four patients with mean age of 30 years, three male and one female, clinically suspicious for a lymphoma or SRCT are described. FNA, BMA, and biopsy specimens were obtained for routine cytologic and histologic evaluation. Fresh tissue was studied by FCI. In all cases, the cytology smears showed small cells with round nuclei, slightly irregular nuclear membranes, fine chromatin, and scant cytoplasm. FCI showed CD16/56(+) and CD45(-) neoplastic cells in all cases. In one case, 76% of these cells were CD99(+). The diagnoses of ES/PNET were confirmed by immunohistochemical, ultrastructural, and cytogenetic studies. ES/PNET in FNA and BMA can be efficiently and rapidly diagnosed by combining cytologic examination with FCI using a panel including CD45, CD16/56, and CD99.
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Affiliation(s)
- Marino E Leon
- Department of Pathology and Laboratory Medicine, Drexel University, College of Medicine, Philadelphia, Pennsylvania 15212, USA.
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16
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Riley RD, Burchill SA, Abrams KR, Heney D, Sutton AJ, Jones DR, Lambert PC, Young B, Wailoo AJ, Lewis IJ. A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family. Eur J Cancer 2003; 39:19-30. [PMID: 12504654 DOI: 10.1016/s0959-8049(02)00500-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFT's were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.
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Affiliation(s)
- R D Riley
- Department of Epidemiology and Public Health, University of Leicester, 22-28 Princess Road West, Leicester LE1 6TP, UK.
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Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia 2002; 39:162-73. [PMID: 12112367 DOI: 10.1002/glia.10083] [Citation(s) in RCA: 191] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Highly migratory neuroectodermal cells share a common embryonic origin with cells of the central nervous system (CNS). They include enteric, parasympathetic, sympathoadrenal, and sensory neurons of the peripheral nervous system, Schwann cells, melanocytes, endocrine cells, and cells forming connective tissue of the face and neck. Because of their common embryologic origin, these cells and the tumors that derive from them can share genetic and antigenic phenotypes with gliomas, tumors derived from CNS glia. We recently discovered that chlorotoxin (ClTx), a 4-kD peptide purified from Leiurus quinquestriatus scorpion, is a highly specific marker for glioma cells in biopsy tissues (Soroceanu et al. Cancer Res 58:4871-4879, 1998) that can target tumors in animal models. We report on the specificity of ClTx as a marker for tumors of neuroectodermal origin that include peripheral neuroectodermal tumors (PNET) and gliomas. Specifically, we histochemically stained frozen and paraffin tissue sections of human biopsy tissues from 262 patients with a synthetically manufactured and biologically active ClTx bearing an N-terminal biotin. The vast majority (74 of 79) of primary human brain tumors investigated showed abundant binding of ClTx with greater than 90% ClTx-positive cells in each section. By comparison, 32 biopsies of uninvolved brain used for comparison were largely ClTx-negative, with only a few isolated reactive astrocytes showing some ClTx binding. However, as with gliomas, the vast majority of PNETs examined showed specific ClTx binding (31 of 34). These include medulloblastomas (4 of 4), neuroblastomas (6 of 7), ganglioneuromas (4 of 4), melanomas (7 of 7), adrenal pheochromocytomas (5 of 6), primitive PNET (1), small cell lung carcinoma (2 of 3), and Ewing's sarcoma (2 of 2). Under identical staining conditions, normal tissues from brain, skin, kidney, and lung were consistently negative for ClTx. These results suggest that chlorotoxin is a reliable and specific histopathological marker for tumors of neuroectodermal origin and that chlorotoxin derivatives with cytolytic activity may have therapeutic potential for these cancers.
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Affiliation(s)
- Susan A Lyons
- TransMolecular, Inc., Birmingham, Alabama 35294, USA
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Sápi Z, Antal I, Pápai Z, Szendröi M, Mayer A, Jakab K, Pajor L, Bodó M. Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques. Diagn Cytopathol 2002; 26:232-42. [PMID: 11933269 DOI: 10.1002/dc.10096] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing.
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Affiliation(s)
- Zoltán Sápi
- Department of Oncopathology, Semmelweis University of Health Sciences, Budapest, Hungary.
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Kato K, Kato Y, Ijiri R, Misugi K, Nanba I, Nagai J, Nagahara N, Kigasawa H, Toyoda Y, Nishi T, Tanaka Y. Ewing's sarcoma family of tumor arising in the adrenal gland--possible diagnostic pitfall in pediatric pathology: histologic, immunohistochemical, ultrastructural, and molecular study. Hum Pathol 2001; 32:1012-6. [PMID: 11567233 DOI: 10.1053/hupa.2001.27121] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
We present an adrenal Ewing's sarcoma family of tumor (ESFT) arising in an 11-year-old Japanese boy. Although intensive chemoradiotherapy and radical surgery were performed, the patient died of obstinate disease 1 year and 3 months after the initial presentation. The primary site (adrenal gland) with radiologic findings (with foci of calcification), high titer of serum neuron specific enolase, and sheets of monotonous primitive rounded cells on histology mostly favored neuroblastoma. However, a diagnosis of ESFT was confirmed by immunohistochemical profile, including MIC2-positivity and molecular study disclosing EWS-FLI1 chimera gene verified by direct sequencing. Recognition of adrenal ESFT and use of newly developed diagnostic techniques are required for differential diagnosis of undifferentiated small round cell tumor of the adrenal gland.
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Affiliation(s)
- K Kato
- Division of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan
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Sandberg AA, Bridge JA. Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumors. CANCER GENETICS AND CYTOGENETICS 2000; 123:1-26. [PMID: 11120329 DOI: 10.1016/s0165-4608(00)00295-8] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- A A Sandberg
- Department of DNA Diagnostics, St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA.
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Helsel JC, Mrak RE, Hanna E, Parham DH, Bardales RH. Peripheral primitive neuroectodermal tumor of the parotid gland region: report of a case with fine-needle aspiration findings. Diagn Cytopathol 2000; 22:161-6. [PMID: 10679996 DOI: 10.1002/(sici)1097-0339(20000301)22:3<161::aid-dc6>3.0.co;2-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
A case of peripheral primitive neuroectodermal tumor of the parotid gland region in a 38-yr-old woman is reported. She had a 1-yr history of a large, firm, and slightly tender left parotid-region mass. CT scan showed an invasive tumor involving the parotid gland, mandible, infratemporal fossa, and parapharyngeal space. Fine-needle aspiration cytology of the mass showed a highly cellular, poorly cohesive smear pattern exhibiting small cuboidal cells, with fibrillary cytoplasm forming occasional rosette-like structures. Numerous intact single cells with fragile cytoplasm, finely granular chromatin, and inconspicuous nucleoli were present together with free-lying nuclei in the background. Histologic, immunohistochemical, and ultrastructural findings confirmed the diagnosis. Diagn. Cytopathol. 2000;22:161-166. Published 2000 Wiley-Liss, Inc.
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Affiliation(s)
- J C Helsel
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Fine needle aspiration (FNA) of bone tumours: with special emphasis on definitive treatment of primary malignant bone tumours based on FNA. ACTA ACUST UNITED AC 1998. [DOI: 10.1016/s0968-6053(98)80012-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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