Slashchuk KIu, Reinberg MV, Bazarova EА, Kareva MА, Przhiyalkovskaya EG, Degtiarev MV, Pikin OV. Neuroendocrine tumor of thymus with ectopic production of adrenocorticotropic hormone in a 13‑year-old child. Case report, 5 year follow-up. Journal of Modern Oncology. 2024;26(1):106–111.
DOI: 10.26442/18151434.2024.1.202616
Нейроэндокринная опухоль тимуса с эктопической продукцией адренокортикотропного гормона у ребенка 13 лет. Клинический случай, 5-летнее наблюдение
Slashchuk KIu, Reinberg MV, Bazarova EА, Kareva MА, Przhiyalkovskaya EG, Degtiarev MV, Pikin OV. Neuroendocrine tumor of thymus with ectopic production of adrenocorticotropic hormone in a 13‑year-old child. Case report, 5 year follow-up. Journal of Modern Oncology. 2024;26(1):106–111.
DOI: 10.26442/18151434.2024.1.202616
Нейроэндокринные опухоли (НЭО) тимуса встречаются крайне редко и обычно ассоциированы с достаточно агрессивным течением и частым метастазированием, а те, которые характеризуются гиперсекрецией гормонов, в частности адренокортикотропного гормона (АКТГ), имеют худший прогноз. Большинство из них экспрессируют рецепторы к соматостатину, что позволяет использовать соматостатин-рецепторную сцинтиграфию и однофотонную эмиссионную компьютерную томографию с рентгеновской компьютерной томографией или позитронно-эмиссионную томографию с рентгеновской компьютерной томографией с 68Ga-меченными пептидами для топической диагностики этих опухолей и оценки распространенности заболевания. Единственным радикальным методом лечения НЭО тимуса является хирургическое удаление (макроскопически-полная резекция) первичной опухоли. На настоящий момент отсутствуют однозначные данные в пользу необходимости проведения адъювантной терапии и ее эффективности. Нами представлен клинический случай пациента детского возраста с атипичным карциноидом тимуса G2 и эктопической продукцией АКТГ. Локализация опухоли верифицирована с помощью соматостатин-рецепторной сцинтиграфии всего тела с 111In-DTPA-octreotide (Octreoscan). Пациенту проведено хирургическое лечение с наступлением ремиссии гиперкортицизма без проведения адъювантной химиотерапии. Рецидив с повторным развитием АКТГ-эктопического синдрома выявлен спустя 67 мес наблюдения.
Neuroendocrine tumors (NET) of the thymus are rare, usually aggressive, and prone to metastatic lesion. Ectopic adrenocorticotropic hormone (ACTH) secretion in thymic NET (TNEN) is associated with poor prognosis. Most of TNET express somatostatin receptors, it allows the use of somatostatin receptor scintigraphy (SRS) and SPECT/CT or PET/CT with 68Ga-labeled peptides for diagnosis and staging of the disease. Surgery (macroscopic-complete resection) is the mainstay treatment for TNET. Now, there are no unequivocal data in adjuvant therapy and its effectiveness. We present a case report of the pediatric patient with well differentiated atypical ACTH-producing thymic carcinoid. This localization was verified by whole body somatostatin receptor scintigraphy with 111In-DTPA-octreotide (Octreoscan). The patient proceeded with the surgical treatment followed by remission of hypercorticism without adjuvant chemotherapy. Tumor recurrence with redevelopment of ACTH-ectopic syndrome was detected after 67 months of observation.
1. Taal BG, Visser O. Epidemiology of neuroendocrine tumours. Neuroendocrinology. 2004;80(Suppl. 1):3‑7. DOI:10.1159/000080731
2. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063‑72. DOI:10.1200/JCO.2007.15.4377
3. Gaur P, Leary C, Yao JC. Thymic neuroendocrine tumors: A SEER database analysis of 160 patients. Ann Surg. 2010;251(6):1117‑21. DOI:10.1097/SLA.0b013e3181dd4ec4
4. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990‑3011. DOI:10.1210/jc.2012‑1230
5. Jia R, Sulentic P, Xu JM, et al. Thymic neuroendocrine neoplasms: Biological behaviour and therapy. Neuroendocrinology. 2017;105(2):105‑14. DOI:10.1159/000472255
6. Sathyakumar S, Paul TV, Asha HS, et al. Ectopic Cushing syndrome: A 10‑year experience from a tertiary care center in Southern India. Endocr Pract. 2017;23(8):907‑14. DOI:10.4158/EP161677
7. Neary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus – Experience with 12 patients over 25 years. J Clin Endocrinol Metab. 2012;97(7):2223‑30. DOI:10.1210/jc.2011‑3355
8. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord. 2010;11(2):117‑26. DOI:10.1007/s11154‑010‑9139‑z
9. Баранова О.Д., Румянцев П.О., Слащук К.Ю., Петров Л.О. Радионуклидная визуализация и терапия у пациентов с нейроэндокринными опухолями. Эндокринная хирургия. 2018;11(4):178‑90 [Baranova OD, Roumiantsev PO, Slashchuk KY, Petrov LO. Radionuclide imaging and therapy in patients with neuroendocrine tumors. Endocrine Surgery. 2017;11(4):178‑90 (in Russian)]. DOI:10.14341/serg9572
10. Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus: A clinicopathologic analysis of 80 cases. Am J Clin Pathol. 2000;114(1):100‑10. DOI:10.1309/3PDN-PMT5-EQTM-H0CD
11. Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and adrenal tumors, version 2.2021. JNCCN J Natl Compr Cancer Netw. 2021;19(7):839‑67. DOI:10.6004/jnccn.2021.0032
12. Ose N, Maeda H, Inoue M, et al. Results of treatment for thymic neuroendocrine tumours: multicentre clinicopathological study. Interact Cardiovasc Thorac Surg. 2018;26(1):18‑24. DOI:10.1093/icvts/ivx265
13. Wick MR, Scheithauer BW, Weiland LH, et al. Primary thymic carcinomas. Am J Surg Pathol. 1982;6(7):613‑30. DOI:10.1097/00000478‑198210000‑00003
14. Lau J, Ioan Cvasciuc T, Simpson D, et al. Continuing challenges of primary neuroendocrine tumours of the thymus: A concisereview. Eur J Surg Oncol. 2022;48(12):2360‑8. DOI:10.1016/j.ejso.2022.07.017
15. Lang M, Hackert T, Anamaterou C. Long-term effect of everolimus in recurrent thymic neuroendocrine neoplasia. Clin Endocrinol (Oxf). 2021;95(5):744‑51. DOI:10.1111/cen.14572
16. Yliaska I, Tokola H, Ebeling T, et al. Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Endocrine. 2022;77(3):527‑37. DOI:10.1007/s12020‑022‑03099‑4
17. Kulke MH, Lenz HJ, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008;26(20):3403‑10. DOI:10.1200/JCO.2007.15.9020
18. Pulido GE, Castellano DE, Garcia-Carbonero R, et al. PAZONET: Results of a phase II trial of pazopanib as a sequencing treatment in progressive metastatic neuroendocrine tumors (NETs) patients (pts), on behalf of the Spanish task force for NETs (GETNE) – NCT01280201. J Clin Oncol. 2012;30(15 Suppl.):4119. DOI:10.1200/jco.2012.30.15_suppl.4119
19. Wang S, Gu Z, Zhu L, et al. Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways. Chin Med J (Engl). 2023;136(22):2712‑21. DOI:10.1097/CM9.0000000000002852
20. Barroso-Sousa R, Lerario AM, Evangelista J, et al. Complete resolution of hypercortisolism with sorafenib in a patient with advanced medullary thyroid carcinoma and ectopic ACTH (adrenocorticotropic hormone) syndrome. Thyroid. 2014;24(6)1062‑6. DOI:10.1089/thy.2013.0571
21. Miyata R, Hamaji M, Omasa M, et al. The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study. Surg Today. 2021;51(4):502‑10. DOI:10.1007/s00595‑020‑02102‑7
22. Girard N. Neuroendocrine tumors of the thymus: The oncologist point of view. J Thorac Dis. 2017;9(Suppl. 15):S1491‑500. DOI:10.21037/jtd.2017.08.18
________________________________________________
1. Taal BG, Visser O. Epidemiology of neuroendocrine tumours. Neuroendocrinology. 2004;80(Suppl. 1):3‑7. DOI:10.1159/000080731
2. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063‑72. DOI:10.1200/JCO.2007.15.4377
3. Gaur P, Leary C, Yao JC. Thymic neuroendocrine tumors: A SEER database analysis of 160 patients. Ann Surg. 2010;251(6):1117‑21. DOI:10.1097/SLA.0b013e3181dd4ec4
4. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990‑3011. DOI:10.1210/jc.2012‑1230
5. Jia R, Sulentic P, Xu JM, et al. Thymic neuroendocrine neoplasms: Biological behaviour and therapy. Neuroendocrinology. 2017;105(2):105‑14. DOI:10.1159/000472255
6. Sathyakumar S, Paul TV, Asha HS, et al. Ectopic Cushing syndrome: A 10‑year experience from a tertiary care center in Southern India. Endocr Pract. 2017;23(8):907‑14. DOI:10.4158/EP161677
7. Neary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus – Experience with 12 patients over 25 years. J Clin Endocrinol Metab. 2012;97(7):2223‑30. DOI:10.1210/jc.2011‑3355
8. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord. 2010;11(2):117‑26. DOI:10.1007/s11154‑010‑9139‑z
9. Baranova OD, Roumiantsev PO, Slashchuk KY, Petrov LO. Radionuclide imaging and therapy in patients with neuroendocrine tumors. Endocrine Surgery. 2017;11(4):178‑90 (in Russian). DOI:10.14341/serg9572
10. Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus: A clinicopathologic analysis of 80 cases. Am J Clin Pathol. 2000;114(1):100‑10. DOI:10.1309/3PDN-PMT5-EQTM-H0CD
11. Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and adrenal tumors, version 2.2021. JNCCN J Natl Compr Cancer Netw. 2021;19(7):839‑67. DOI:10.6004/jnccn.2021.0032
12. Ose N, Maeda H, Inoue M, et al. Results of treatment for thymic neuroendocrine tumours: multicentre clinicopathological study. Interact Cardiovasc Thorac Surg. 2018;26(1):18‑24. DOI:10.1093/icvts/ivx265
13. Wick MR, Scheithauer BW, Weiland LH, et al. Primary thymic carcinomas. Am J Surg Pathol. 1982;6(7):613‑30. DOI:10.1097/00000478‑198210000‑00003
14. Lau J, Ioan Cvasciuc T, Simpson D, et al. Continuing challenges of primary neuroendocrine tumours of the thymus: A concisereview. Eur J Surg Oncol. 2022;48(12):2360‑8. DOI:10.1016/j.ejso.2022.07.017
15. Lang M, Hackert T, Anamaterou C. Long-term effect of everolimus in recurrent thymic neuroendocrine neoplasia. Clin Endocrinol (Oxf). 2021;95(5):744‑51. DOI:10.1111/cen.14572
16. Yliaska I, Tokola H, Ebeling T, et al. Thymic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Endocrine. 2022;77(3):527‑37. DOI:10.1007/s12020‑022‑03099‑4
17. Kulke MH, Lenz HJ, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008;26(20):3403‑10. DOI:10.1200/JCO.2007.15.9020
18. Pulido GE, Castellano DE, Garcia-Carbonero R, et al. PAZONET: Results of a phase II trial of pazopanib as a sequencing treatment in progressive metastatic neuroendocrine tumors (NETs) patients (pts), on behalf of the Spanish task force for NETs (GETNE) – NCT01280201. J Clin Oncol. 2012;30(15 Suppl.):4119. DOI:10.1200/jco.2012.30.15_suppl.4119
19. Wang S, Gu Z, Zhu L, et al. Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways. Chin Med J (Engl). 2023;136(22):2712‑21. DOI:10.1097/CM9.0000000000002852
20. Barroso-Sousa R, Lerario AM, Evangelista J, et al. Complete resolution of hypercortisolism with sorafenib in a patient with advanced medullary thyroid carcinoma and ectopic ACTH (adrenocorticotropic hormone) syndrome. Thyroid. 2014;24(6)1062‑6. DOI:10.1089/thy.2013.0571
21. Miyata R, Hamaji M, Omasa M, et al. The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study. Surg Today. 2021;51(4):502‑10. DOI:10.1007/s00595‑020‑02102‑7
22. Girard N. Neuroendocrine tumors of the thymus: The oncologist point of view. J Thorac Dis. 2017;9(Suppl. 15):S1491‑500. DOI:10.21037/jtd.2017.08.18
1ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия; 2Московский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, Москва, Россия
*e.bazarova.bq@gmail.com
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Konstantin Iu. Slashchuk1, Maria V. Reinberg1, Ekaterina А. Bazarova*1, Maria А. Kareva1, Elena G. Przhiyalkovskaya1, Mikhail V. Degtiarev1, Oleg V. Pikin2
1Endocrinology Research Center, Moscow, Russia; 2Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Moscow, Russia
*e.bazarova.bq@gmail.com