Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022; 21: 142-151
Злокачественная гастроинтестинальная нейроэктодермальная опухоль
https://doi.org/10.24287/1726-1708-2022-21-4-142-151Аннотация
Злокачественная гастроинтестинальная нейроэктодермальная опухоль (ЗГНО) – редкая агрессивная мезенхимальная опухоль желудочно-кишечного тракта (ЖКТ), отличающаяся высоким потенциалом злокачественности. Характерным является поражение ЖКТ с преимущественным развитием в стенке тонкой кишки. В основе развития ЗГНО лежат хромосомные транслокации t(12;22)(q13;q12) и t(2;22) (q34;q12), приводящие к формированию химерных транскриптов EWSR1–ATF1 и EWSR1–CREB1 соответственно. В международной литературе представлены единичные случаи развития данного вида новообразования у детей и подростков. В настоящей статье описан случай развития метастатической формы ЗГНО у мальчика в возрасте 6 лет. Родители пациента дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях. Диагноз был подтвержден гистологически и методом высокопроизводительного секвенирования «РНК экзом», по результатам которого выявлен характерный химерный транскрипт EWSR1–ATF1. Описана терапия заболевания, включающая помимо применения интенсивной химиотерапии назначение c-Met/ALKингибитора кризотиниба с транзиторным противоопухолевым эффектом. Представлен обзор литературы, описывающий клинические особенности, патогенез, дифференциальную диагностику и подходы к терапии ЗГНО.
Список литературы
1. Wang J., Thway K. Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: An Evolving Entity. Arch Pathol Lab Med 2015; 139 (3): 407–12.
2. Miettinen M., Sciot R., Tsui W.M. Gastrointestinal clear cell sarcoma/ malignant gastrointestinal neuroectodermal tumor. WHO classification of tumours. 5th edition. Digestive System Tumours. Lyon (France). International Agency for Research on Cancer; 2019. P. 494–496.
3. Kandler T., Cortez E., Clinton L., Hemmerich A., Ahmed O., Wong R., еt al. A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases. Curr Oncol 2022; 29 (2): 1279–97. DOI:10.3390/curroncol29020109
4. Stockman D.L., Miettinen M., Suster S., Spagnolo D., Dominguez-Malagon H., Hornick J.L., at al. Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract. Am J Surg Pathol 2012; 36 (6): 857–68. DOI:10.1097/PAS.0b013e31824644ac
5. Wolak P., Wincewicz A., Czauderna P., Spałek M., Kruczak A., Urbaniak-Wąsik S., еt аl. Malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like tumor of the gastrointestinal tract) of the small intestine in a 12-year-old boy. Dev Period Med 2018; 22 (4): 358–63.
6. Alyousef M.J., Alratroot J.A., ElSharkawy T., Shawarby M.A., Al Hamad M.A., Hashem T.M., Alsayyah A. Malignant gastrointestinal neuroectodermal tumor: a case report and review of the literature. Diagn Pathol 2017; 12 (1): 29. DOI:10.1186/s13000-017-0620-9
7. Green C., Spagnolo D.V., Robbins P.D., Fermoyle S., Wong D.D. Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. Pathology 2018; 50 (5): 490–8. DOI:10.1016/j.pathol.2018.05.001
8. Fritchie K.J., van de Rijn M. Clear cell sarcoma of soft tissue. In book WHO Classification of Tumours of Soft Tissue and Bone, 5th ed. Lyon, France: IARC Press; 2020. Рр. 300–302.
9. Klingebiel T., Boos J., Beske F., Hallmen E., Int-Veen C., Dantonello T., et al. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer 2008; 50 (4): 739–45. DOI:10.1002/pbc.21494
10. Subbiah V., Holmes O., Gowen K., Spritz D., Amini B., Wang W.L., еt аl. Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion. Oncology 2016; 91 (6): 348–53. DOI:10.1159/000449204
11. Bisogno G., De Salvo G.L., Bergeron C., Gallego Melcón S., Merks J.H., Kelsey A., еt аl.; European paediatric Soft tissue sarcoma Study Group. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2019; 20 (11): 1566–75. DOI:10.1016/S1470-2045(19)30617-5
12. Zambrano E., Reyes-Mugica M., Franchi A., Rosai J. An osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol 2003; 11 (2): 75–81. DOI:10.1177/106689690301100202
13. Li R., Cao J., Chen L., Cui F., Chen S., Feng Z., Li N. Malignant Gastrointestinal Neuroectodermal Tumors: Clinicopathological and Prognostic Features of 96 Patients. Onco Targets Ther 2020; 13: 9731–40. DOI:10.2147/OTT.S275633
14. Thway K., Judson I., Fisher C. Clear cell sarcoma-like tumor of the gastrointestinal tract, presenting as a second malignancy after childhood hepatoblastoma. Case Rep Med 2014; 2014: 984369. DOI:10.1155/2014/984369
15. Yang J.C., Chou A.J., Oeffinger K.C., La Quaglia M.P., Wolden S.L. Clear cell sarcoma of the gastrointestinal tract after very low-dose therapeutic radiation therapy: a case report. J Pediatr Surg 2012; 47 (10): 1943–5. DOI:10.1016/j.jpedsurg.2012.08.014
16. Balkaransingh P., Saad S.A., Govil S.C., Thind P.K., Ballance C.M., Weiss A.R. Clear cell sarcoma of the gastrointestinal tract presenting as a second malignant neoplasm following neuroblastoma in infancy. Pediatr Blood Cancer 2012; 58 (3): 481–2. DOI:10.1002/pbc.23330
17. Zhan M.N., Yu J., Luo R.K., Hou Y.Y. Malignant gastrointestinal neuroectodermal tumor, presenting as a second malignancy after gastric adenocarcinoma: a case report and literature review. J Gastrointest Oncol 2019; 10 (6): 1144–50. DOI:10.21037/jgo.2019.08.04
18. Yagi T., Nagata S., Yamamoto T., Wakamatsu T., Imura Y., Tamiya H., et al. Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report. Mol Clin Oncol 2021; 14 (2): 23. DOI:10.3892/mco.2020.2185
19. Chang B., Yu L., Guo W.W., Sheng W.Q., Wang L., Lao I., et al. Malignant Gastrointestinal Neuroectodermal Tumor: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 19 Cases. Am J Surg Pathol 2020; 44 (4): 456–66. DOI:10.1097/PAS.0000000000001396
20. Antonescu C.R., Nafa K., Segal N.H., Dal Cin P., Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 2006; 12 (18): 5356–62. DOI:10.1158/1078-0432.CCR-05-2811
21. Thway K., Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol 2012; 36 (7): e1–11. DOI:10.1097/PAS.0b013e31825485c5
22. Libertini M., Thway K., Noujaim J., Puls F., Messiou C., Fisher C., Jones R.L. Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: Clinical Outcome and Pathologic Features of a Molecularly Characterized Tertiary Center Case Series. Anticancer Res 2018; 38 (3): 1479–83. DOI:10.21873/anticanres.12374
23. Schöffski P., Wozniak A., Stacchiotti S., Rutkowski P., Blay J.Y., Lindner L.H., еt al. Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 “CREATE”. Ann Oncol 2017; 28 (12): 3000–8. DOI:10.1093/annonc/mdx527
Pediatric Hematology/Oncology and Immunopathology. 2022; 21: 142-151
Malignant gastrointestinal neuroectodermal tumor
https://doi.org/10.24287/1726-1708-2022-21-4-142-151Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare, aggressive, highly malignant mesenchymal tumor of the gastrointestinal tract. It commonly arises within the gastrointestinal tract, mostly involving the small intestine. The molecular features of GNET include chromosomal translocations t(12;22)(q13;q12) and t(2;22)(q34;q12) resulting in EWSR1–ATF1 and EWSR1–CREB1 gene fusions, respectively. Only a few cases of GNET in children and adolescents have been described in the international literature. Here, we report a case of metastatic GNET in a 6-year-old boy. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications. The diagnosis was confirmed histologically and by high-throughput RNA exome sequencing which revealed the typical EWSR1–ATF1 fusion transcript. In this article, we give the details of the patient's treatment that included intensive chemotherapy and the administration of the c-Met/ ALK inhibitor crizotinib with a transient antitumor effect. We also provide a literature review describing the clinical features and pathogenesis of GNET, its differential diagnosis and treatment approaches.
References
1. Wang J., Thway K. Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: An Evolving Entity. Arch Pathol Lab Med 2015; 139 (3): 407–12.
2. Miettinen M., Sciot R., Tsui W.M. Gastrointestinal clear cell sarcoma/ malignant gastrointestinal neuroectodermal tumor. WHO classification of tumours. 5th edition. Digestive System Tumours. Lyon (France). International Agency for Research on Cancer; 2019. P. 494–496.
3. Kandler T., Cortez E., Clinton L., Hemmerich A., Ahmed O., Wong R., et al. A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases. Curr Oncol 2022; 29 (2): 1279–97. DOI:10.3390/curroncol29020109
4. Stockman D.L., Miettinen M., Suster S., Spagnolo D., Dominguez-Malagon H., Hornick J.L., at al. Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract. Am J Surg Pathol 2012; 36 (6): 857–68. DOI:10.1097/PAS.0b013e31824644ac
5. Wolak P., Wincewicz A., Czauderna P., Spałek M., Kruczak A., Urbaniak-Wąsik S., et al. Malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like tumor of the gastrointestinal tract) of the small intestine in a 12-year-old boy. Dev Period Med 2018; 22 (4): 358–63.
6. Alyousef M.J., Alratroot J.A., ElSharkawy T., Shawarby M.A., Al Hamad M.A., Hashem T.M., Alsayyah A. Malignant gastrointestinal neuroectodermal tumor: a case report and review of the literature. Diagn Pathol 2017; 12 (1): 29. DOI:10.1186/s13000-017-0620-9
7. Green C., Spagnolo D.V., Robbins P.D., Fermoyle S., Wong D.D. Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. Pathology 2018; 50 (5): 490–8. DOI:10.1016/j.pathol.2018.05.001
8. Fritchie K.J., van de Rijn M. Clear cell sarcoma of soft tissue. In book WHO Classification of Tumours of Soft Tissue and Bone, 5th ed. Lyon, France: IARC Press; 2020. Rr. 300–302.
9. Klingebiel T., Boos J., Beske F., Hallmen E., Int-Veen C., Dantonello T., et al. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer 2008; 50 (4): 739–45. DOI:10.1002/pbc.21494
10. Subbiah V., Holmes O., Gowen K., Spritz D., Amini B., Wang W.L., et al. Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion. Oncology 2016; 91 (6): 348–53. DOI:10.1159/000449204
11. Bisogno G., De Salvo G.L., Bergeron C., Gallego Melcón S., Merks J.H., Kelsey A., et al.; European paediatric Soft tissue sarcoma Study Group. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2019; 20 (11): 1566–75. DOI:10.1016/S1470-2045(19)30617-5
12. Zambrano E., Reyes-Mugica M., Franchi A., Rosai J. An osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol 2003; 11 (2): 75–81. DOI:10.1177/106689690301100202
13. Li R., Cao J., Chen L., Cui F., Chen S., Feng Z., Li N. Malignant Gastrointestinal Neuroectodermal Tumors: Clinicopathological and Prognostic Features of 96 Patients. Onco Targets Ther 2020; 13: 9731–40. DOI:10.2147/OTT.S275633
14. Thway K., Judson I., Fisher C. Clear cell sarcoma-like tumor of the gastrointestinal tract, presenting as a second malignancy after childhood hepatoblastoma. Case Rep Med 2014; 2014: 984369. DOI:10.1155/2014/984369
15. Yang J.C., Chou A.J., Oeffinger K.C., La Quaglia M.P., Wolden S.L. Clear cell sarcoma of the gastrointestinal tract after very low-dose therapeutic radiation therapy: a case report. J Pediatr Surg 2012; 47 (10): 1943–5. DOI:10.1016/j.jpedsurg.2012.08.014
16. Balkaransingh P., Saad S.A., Govil S.C., Thind P.K., Ballance C.M., Weiss A.R. Clear cell sarcoma of the gastrointestinal tract presenting as a second malignant neoplasm following neuroblastoma in infancy. Pediatr Blood Cancer 2012; 58 (3): 481–2. DOI:10.1002/pbc.23330
17. Zhan M.N., Yu J., Luo R.K., Hou Y.Y. Malignant gastrointestinal neuroectodermal tumor, presenting as a second malignancy after gastric adenocarcinoma: a case report and literature review. J Gastrointest Oncol 2019; 10 (6): 1144–50. DOI:10.21037/jgo.2019.08.04
18. Yagi T., Nagata S., Yamamoto T., Wakamatsu T., Imura Y., Tamiya H., et al. Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report. Mol Clin Oncol 2021; 14 (2): 23. DOI:10.3892/mco.2020.2185
19. Chang B., Yu L., Guo W.W., Sheng W.Q., Wang L., Lao I., et al. Malignant Gastrointestinal Neuroectodermal Tumor: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 19 Cases. Am J Surg Pathol 2020; 44 (4): 456–66. DOI:10.1097/PAS.0000000000001396
20. Antonescu C.R., Nafa K., Segal N.H., Dal Cin P., Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 2006; 12 (18): 5356–62. DOI:10.1158/1078-0432.CCR-05-2811
21. Thway K., Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol 2012; 36 (7): e1–11. DOI:10.1097/PAS.0b013e31825485c5
22. Libertini M., Thway K., Noujaim J., Puls F., Messiou C., Fisher C., Jones R.L. Clear Cell Sarcoma-like Tumor of the Gastrointestinal Tract: Clinical Outcome and Pathologic Features of a Molecularly Characterized Tertiary Center Case Series. Anticancer Res 2018; 38 (3): 1479–83. DOI:10.21873/anticanres.12374
23. Schöffski P., Wozniak A., Stacchiotti S., Rutkowski P., Blay J.Y., Lindner L.H., et al. Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 “CREATE”. Ann Oncol 2017; 28 (12): 3000–8. DOI:10.1093/annonc/mdx527
