Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022; 21: 110-120
Врожденная инфантильная фибросаркома с неканоническим химерным транскриптом TPM3-NTRK1: описание клинического случая и обзор литературы
https://doi.org/10.24287/1726-1708-2022-21-1-110-120Аннотация
Инфантильная фибросаркома (ИФ) – редкая злокачественная опухоль мягких тканей, характеризующаяся местно-инвазивным ростом, низкой частотой отдаленного метастазирования (1–13%) и манифестацией в течение первых лет жизни. Показатели общей выживаемости варьируют в пределах 89–94%, бессобытийной выживаемости – 81–84%. Классическая ИФ характеризуется транслокацией t(12;15)(p13;q25) с образованием химерного транскрипта ETV6-NTRK3, однако за последние несколько лет была описана целая плеяда ИФ-подобных опухолей с неканоническими генетическими аберрациями (гены BRAF, NTRK1, MET), прогноз которых менее предсказуем. В статье описано редкое клиническое наблюдение врожденной ИФ с вовлечением подкожно-жировой клетчатки, индолентным течением и неканоническим химерным транскриптом TPM3-NTRK1, идентифицированным в различных по гистологическим характеристикам мягкотканном и интрадермальном компонентах опухоли. Родители пациента дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях. Обзор литературы посвящен современным алгоритмам диагностики и лечения ИФ у детей, включая обсуждение новых методов терапии, таких как применение ингибиторов тропомиозин-рецепторной киназы, а также алгоритмам выявления перестроек генов NTRK1, NTRK2, NTRK3 при солидных новообразованиях в целом и опухолях мягких тканей в частности.
Список литературы
1. Orbach D., Brennan B., De Paoli A., Gallego S., Mudry P., Francotte N., еt al. Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer 2016; 57: 1–9. DOI: 10.1016/j.ejca.2015.12.028. PMID: 26849118.
2. Orbach D., Rey A., Cecchetto G., Oberlin O., Casanova M., Thebaud E., еt al. Infantile fibrosarcoma: management based on the European experience. J Clin Oncol 2010; 28 (2): 318–23. DOI: 10.1200/JCO.2009.21.9972. PMID: 19917847.
3. Davis J.A., Antonescu C.R., Bahrami A. Infantile fibrosarcoma. In: WHO Classification of Tumours of Soft Tissue and Bone, 5th ed. Lyon, France: IARC Press; 2020. Рр. 119– 121.
4. Mahadeo K.M., Bajwa R., AbdelAzim H., Lehmann L.E., Duncan C., Zantek N., еt al. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement. Lancet Haematol 2020; 7 (1): e61–72. DOI: 10.1016/S2352-3026(19)30201-7. PMID: 31818728.
5. Parida L., Fernandez-Pineda I., Uffman J.K., Davidoff A.M., Krasin M.J., Pappo A., Rao B.N. Clinical management of infantile fibrosarcoma: a retrospective single-institution review. Pediatr Surg Int 2013; 29 (7): 703–8. DOI: 10.1007/s00383-013-3326-4. PMID: 23708972.
6. Knezevich S.R., McFadden D.E., Tao W., Lim J.F., Sorensen P.H. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 1998; 18 (2): 184–7. DOI: 10.1038/ng0298-184. PMID: 9462753.
7. Miettinen М., Felisiak-Golabek А., Luiña Contreras А., Glod J., Kaplan R.N., Killian J.K., еt al. New fusion sarcomas: histopathology and clinical significance of selected entities. Hum Pathol 2019; 86: 57–65. DOI: 10.1016/j.humpath.2018.12.006. PMID: 30633925; PMCID: PMC7443750.
8. Coffin C.M., Beadling C., Neff T., Corless C.L., Davis J.L. Infantile fibrosarcoma with a novel RAF1 rearrangement: The contemporary challenge of reconciling classic morphology with novel molecular genetics. Hum Pathol 2020. DOI: 10.1016/j.ehpc.2020.200434. 21212121
9. Laetsch T.W., DuBois S.G., Mascarenhas L., Turpin B., Federman N., Albert C.M., еt al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 2018; 19 (5): 705–14. DOI: 10.1016/S1470-2045(18)30119-0. PMID: 29606586; PMCID: PMC5949072.
10. DuBois S.G., Laetsch T.W., Federman N., Turpin B.K., Albert C.M., Nagasubramanian R., еt al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer 2018; 124 (21): 4241– 7. DOI: 10.1002/cncr.31701. PMID: 30204247.
11. Hong D.S., DuBois S.G., Kummar S., Farago A.F., Albert C.M., Rohrberg K.S., еt al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (4): 531–40. DOI: 10.1016/S1470-2045(19)30856-3. PMID: 32105622.
12. Bazhenova L., Liu S.V., Lin J.J., Lu S., Drilon A., Chawla S.P., et al. Efficacy and safety of entrectinib in patients with locally advanced/metastatic NTRK fusion-positive (NTRK-fp) solid tumours. Ann Oncol 2021; 32 (Suppl 5): S583–620. DOI: 10.1016/annonc/annonc699
13. Robinson G., Desai A., Basu E., Foster J., Gauvain K., Sabnis A., et al. HGG-01. Entrectinib in recurrent or refractory solid tumors including primary CNS tumors: updated data in children and adolescents. Neuro-Oncology 2020; 22 (Suppl 3): iii344. DOI: 10.1093/NEUONC/NOAA222.293
14. Orbach D., Sparber-Sauer M., Laetsch T.W., Minard-Colin V., Bielack S.S., Casanova M., et al. Spotlight on the treatment of infantile fibrosarcoma in the era of neurotrophic tropomyosin receptor kinase inhibitors: International consensus and remaining controversies. Eur J Cancer 2020; 137: 183–92. DOI: 10.1016/j.ejca.2020.06.028
15. Bokemeyer C., Vassal G., Italiano A., De La Cuesta E., Hiemeyer F., Fellous M., еt al. Impact of Disease Evolution on Efficacy Outcomes From Larotrectinib in Patients With Locally Advanced or Metastatic Tropomyosin Receptor Kinase Fusion-Positive Solid Tumors. JCO Precis Oncol 2021; 5: PO.21.00089. DOI: 10.1200/PO.21.00089. PMID: 34568715.
16. Coffin C.M., Sorensen P.H. Infantile fibrosarcoma. WHO Classification of Tumours of Soft Tissue and Bone, 4th ed. Lyon, France: IARC Press; 2013. Рр, 89–90.
17. Kallen M.E., Hornick J.L. The 2020 WHO Classification: What’s New in Soft Tissue Tumor Pathology. Am J Surg Pathol 2021; 45 (1): e1–23. DOI: 10.1097/PAS.0000000000001552. PMID: 32796172.
18. Agaram N.P., Zhang L., Sung Y.S., Chen C.L., Chung C.T., Antonescu C.R., Fletcher C.D. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors. Am J Surg Pathol 2016; 40 (10): 1407–16. DOI: 10.1097/PAS.0000000000000675. PMID: 27259011.
19. Choi J.H., Ro J.Y. The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes and New Entities. Adv Anat Pathol 2021; 28 (1): 44–58. DOI: 10.1097/PAP.0000000000000284. PMID: 32960834.
20. Suurmeijer A.J.H, Dickson B.C., Swanson D., Zhang L., Sung Y.S., Cotzia P., еt al. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer 2018; 57 (12): 611– 21. DOI: 10.1002/gcc.22671. PMID: 30276917.
21. Hung Y.P., Fletcher C.D.M., Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics. Histopathology 2018; 73 (4): 634– 44. DOI: 10.1111/his.13666. PMID: 29863809.
22. Siozopoulou V., Smits E., De Winne K., Marcq E., Pauwels P. NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects. Diagnostics (Basel) 2021; 11 (3): 478. DOI: 10.3390/diagnostics11030478. PMID: 33803146.
23. Davis J.L., Lockwood C.M., Albert C.M., Tsuchiya K., Hawkins D.S., Rudzinski E.R. Infantile NTRK-associated Mesenchymal Tumors. Pediatr Dev Pathol 2018; 21 (1): 68–78. DOI: 10.1177/1093526617712639. PMID: 28683589.
24. Yoshino T., Pentheroudakis G., Mishima S., Overman M.J., Yeh K.H., Baba E., Naito Y. JSCO-ESMOASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol 2020; 31 (7): 861–72. DOI: 10.1016/j.annonc.2020.03.299. PMID: 32272210.
25. Marchiò C., Scaltriti M., Ladanyi M., Iafrate A.J., Bibeau F., Dietel M., et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019; 30 (9): 1417–27. DOI: 10.1093/annonc/mdz204. PMID: 31268127.
Pediatric Hematology/Oncology and Immunopathology. 2022; 21: 110-120
Сongenital infantile fibrosarcoma with a non-canonical TPM3-NTRK1 fusion transcript: a case report and a literature review
https://doi.org/10.24287/1726-1708-2022-21-1-110-120Abstract
Infantile fibrosarcoma (IFS) is a rare malignant soft tissue tumor characterized by local invasion, a low rate of distant metastasis (1–13%), and manifestation during the first years of life. Overall survival rates range from 89 to 94%, event-free survival rates – from 81 to 84%. Classic IFS is characterized by t(12;15)(p13;q25) translocation resulting in the formation of the ETV6-NTRK3 fusion transcript. However, over the past few years, there have been numerous reports of IFS-like tumors with non-canonical genetic aberrations (BRAF, NTRK1, MET genes) whose prognosis is less predictable. Here we report a rare case of congenital IFS with involvement of subcutaneous fat, indolent course and a non-canonical TPM3-NTRK1 fusion transcript identified in the soft tissue and intradermal tumor components with different histological features. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. The literature review explores modern algorithms for the diagnosis and treatment of IFS in children, including the use of new therapies, such as tropomyosin receptor kinase inhibitors, as well as algorithms for detecting NTRK1, NTRK2, NTRK3 gene rearrangements in solid neoplasms in general, and soft tissue tumors in particular.
References
1. Orbach D., Brennan B., De Paoli A., Gallego S., Mudry P., Francotte N., et al. Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer 2016; 57: 1–9. DOI: 10.1016/j.ejca.2015.12.028. PMID: 26849118.
2. Orbach D., Rey A., Cecchetto G., Oberlin O., Casanova M., Thebaud E., et al. Infantile fibrosarcoma: management based on the European experience. J Clin Oncol 2010; 28 (2): 318–23. DOI: 10.1200/JCO.2009.21.9972. PMID: 19917847.
3. Davis J.A., Antonescu C.R., Bahrami A. Infantile fibrosarcoma. In: WHO Classification of Tumours of Soft Tissue and Bone, 5th ed. Lyon, France: IARC Press; 2020. Rr. 119– 121.
4. Mahadeo K.M., Bajwa R., AbdelAzim H., Lehmann L.E., Duncan C., Zantek N., et al. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement. Lancet Haematol 2020; 7 (1): e61–72. DOI: 10.1016/S2352-3026(19)30201-7. PMID: 31818728.
5. Parida L., Fernandez-Pineda I., Uffman J.K., Davidoff A.M., Krasin M.J., Pappo A., Rao B.N. Clinical management of infantile fibrosarcoma: a retrospective single-institution review. Pediatr Surg Int 2013; 29 (7): 703–8. DOI: 10.1007/s00383-013-3326-4. PMID: 23708972.
6. Knezevich S.R., McFadden D.E., Tao W., Lim J.F., Sorensen P.H. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 1998; 18 (2): 184–7. DOI: 10.1038/ng0298-184. PMID: 9462753.
7. Miettinen M., Felisiak-Golabek A., Luiña Contreras A., Glod J., Kaplan R.N., Killian J.K., et al. New fusion sarcomas: histopathology and clinical significance of selected entities. Hum Pathol 2019; 86: 57–65. DOI: 10.1016/j.humpath.2018.12.006. PMID: 30633925; PMCID: PMC7443750.
8. Coffin C.M., Beadling C., Neff T., Corless C.L., Davis J.L. Infantile fibrosarcoma with a novel RAF1 rearrangement: The contemporary challenge of reconciling classic morphology with novel molecular genetics. Hum Pathol 2020. DOI: 10.1016/j.ehpc.2020.200434. 21212121
9. Laetsch T.W., DuBois S.G., Mascarenhas L., Turpin B., Federman N., Albert C.M., et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 2018; 19 (5): 705–14. DOI: 10.1016/S1470-2045(18)30119-0. PMID: 29606586; PMCID: PMC5949072.
10. DuBois S.G., Laetsch T.W., Federman N., Turpin B.K., Albert C.M., Nagasubramanian R., et al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer 2018; 124 (21): 4241– 7. DOI: 10.1002/cncr.31701. PMID: 30204247.
11. Hong D.S., DuBois S.G., Kummar S., Farago A.F., Albert C.M., Rohrberg K.S., et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (4): 531–40. DOI: 10.1016/S1470-2045(19)30856-3. PMID: 32105622.
12. Bazhenova L., Liu S.V., Lin J.J., Lu S., Drilon A., Chawla S.P., et al. Efficacy and safety of entrectinib in patients with locally advanced/metastatic NTRK fusion-positive (NTRK-fp) solid tumours. Ann Oncol 2021; 32 (Suppl 5): S583–620. DOI: 10.1016/annonc/annonc699
13. Robinson G., Desai A., Basu E., Foster J., Gauvain K., Sabnis A., et al. HGG-01. Entrectinib in recurrent or refractory solid tumors including primary CNS tumors: updated data in children and adolescents. Neuro-Oncology 2020; 22 (Suppl 3): iii344. DOI: 10.1093/NEUONC/NOAA222.293
14. Orbach D., Sparber-Sauer M., Laetsch T.W., Minard-Colin V., Bielack S.S., Casanova M., et al. Spotlight on the treatment of infantile fibrosarcoma in the era of neurotrophic tropomyosin receptor kinase inhibitors: International consensus and remaining controversies. Eur J Cancer 2020; 137: 183–92. DOI: 10.1016/j.ejca.2020.06.028
15. Bokemeyer C., Vassal G., Italiano A., De La Cuesta E., Hiemeyer F., Fellous M., et al. Impact of Disease Evolution on Efficacy Outcomes From Larotrectinib in Patients With Locally Advanced or Metastatic Tropomyosin Receptor Kinase Fusion-Positive Solid Tumors. JCO Precis Oncol 2021; 5: PO.21.00089. DOI: 10.1200/PO.21.00089. PMID: 34568715.
16. Coffin C.M., Sorensen P.H. Infantile fibrosarcoma. WHO Classification of Tumours of Soft Tissue and Bone, 4th ed. Lyon, France: IARC Press; 2013. Rr, 89–90.
17. Kallen M.E., Hornick J.L. The 2020 WHO Classification: What’s New in Soft Tissue Tumor Pathology. Am J Surg Pathol 2021; 45 (1): e1–23. DOI: 10.1097/PAS.0000000000001552. PMID: 32796172.
18. Agaram N.P., Zhang L., Sung Y.S., Chen C.L., Chung C.T., Antonescu C.R., Fletcher C.D. Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors. Am J Surg Pathol 2016; 40 (10): 1407–16. DOI: 10.1097/PAS.0000000000000675. PMID: 27259011.
19. Choi J.H., Ro J.Y. The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes and New Entities. Adv Anat Pathol 2021; 28 (1): 44–58. DOI: 10.1097/PAP.0000000000000284. PMID: 32960834.
20. Suurmeijer A.J.H, Dickson B.C., Swanson D., Zhang L., Sung Y.S., Cotzia P., et al. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer 2018; 57 (12): 611– 21. DOI: 10.1002/gcc.22671. PMID: 30276917.
21. Hung Y.P., Fletcher C.D.M., Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics. Histopathology 2018; 73 (4): 634– 44. DOI: 10.1111/his.13666. PMID: 29863809.
22. Siozopoulou V., Smits E., De Winne K., Marcq E., Pauwels P. NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects. Diagnostics (Basel) 2021; 11 (3): 478. DOI: 10.3390/diagnostics11030478. PMID: 33803146.
23. Davis J.L., Lockwood C.M., Albert C.M., Tsuchiya K., Hawkins D.S., Rudzinski E.R. Infantile NTRK-associated Mesenchymal Tumors. Pediatr Dev Pathol 2018; 21 (1): 68–78. DOI: 10.1177/1093526617712639. PMID: 28683589.
24. Yoshino T., Pentheroudakis G., Mishima S., Overman M.J., Yeh K.H., Baba E., Naito Y. JSCO-ESMOASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol 2020; 31 (7): 861–72. DOI: 10.1016/j.annonc.2020.03.299. PMID: 32272210.
25. Marchiò C., Scaltriti M., Ladanyi M., Iafrate A.J., Bibeau F., Dietel M., et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019; 30 (9): 1417–27. DOI: 10.1093/annonc/mdz204. PMID: 31268127.
