Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents.
inflammatory myofibroblastic tumors
nonmutilating surgery
target therapy
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
01
10
2021
received:
04
08
2021
accepted:
18
10
2021
pubmed:
3
12
2021
medline:
6
5
2022
entrez:
2
12
2021
Statut:
ppublish
Résumé
Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized. A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019. This series included 39 cases of IMT, with a median age at diagnosis of 7 years (range 20 days to 16 years). Tumor location included pelvis-abdomen (n = 16), thorax (n = 14), head and neck (n = 7), and limbs (n = 2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)-positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33 months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7 months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p < .001) or after incomplete surgery with no adjuvant therapy (p = .027). Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.
Sections du résumé
BACKGROUND
Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized.
METHODS
A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019.
RESULTS
This series included 39 cases of IMT, with a median age at diagnosis of 7 years (range 20 days to 16 years). Tumor location included pelvis-abdomen (n = 16), thorax (n = 14), head and neck (n = 7), and limbs (n = 2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)-positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33 months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7 months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p < .001) or after incomplete surgery with no adjuvant therapy (p = .027).
CONCLUSION
Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.
Substances chimiques
Proto-Oncogene Proteins
0
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29460Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Coffin CM, Watterson J, Priest JR, et al. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995;19(8):859-872.
Kovach SJ, Fischer AC, Katzman PJ, et al. Inflammatory myofibroblastic tumors. J Surg Oncol. 2006;94(5):385-391.
Marie-Cardine A, Berrebi D, Orbach D. Guidelines for management of localized inflammatory myofibroblastic tumours in children. Bull Cancer. 2011;98(2):209-216.
Telugu RB, Prabhu AJ, Kalappurayil NB, et al. Clinicopathological study of 18 cases of inflammatory myofibroblastic tumors with reference to ALK-1 expression: 5-year experience in a tertiary care center. J Pathol Transl Med. 2017;51(3):255-263.
Gleason BC, Hornick JL. Inflammatory myofibroblastic tumours: where are we now? J Clin Pathol. 2008;61(4):428-437.
Coffin CM, Hornick JL. Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol. 2007;31(4):509-520.
Li J, Yin WH, Takeuchi K, et al. Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a report of two cases and literature review. Diagn Pathol. 2013;8:147.
Butrynski JE, D'Adamo DR, Hornick JL, et al. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010;363(18):1727-1733.
Lovly CM, Gupta A, Lipson D, et al. Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions. Cancer Discov. 2014;4(8):889-895.
Preobrazhenskaya E, Iyevleva A, Suleymanova A, et al. Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors. Pediatr Blood Cancer. 2020;67:e28220.
Hornick JL, Sholl LM, Dal Cin P, et al. Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory myofibroblastic tumors. Mod Pathol. 2015;28(5):732-739.
Alassiri AH, Ali RH, Shen Y, et al. ETV6-NTRK3 is expressed in a subset of ALK-negative inflammatory myofibroblastic tumors. Am J Surg Pathol. 2016;40(8):1051-1061.
Casanova M, Brennan B, Alaggio R, et al. Inflammatory myofibroblastic tumor: the experience of the European pediatric Soft Tissue Sarcoma Study Group (EpSSG). Eur J Cancer. 2020;127:123-129.
Trahair T, Gifford A, Fordham A, et al. Crizotinib and surgery for long-term disease control in children and adolescents with ALK-positive inflammatory myofibroblastic tumors. JCO Precis Oncol. 2019;3:1-11. https://doi.org/10.1200/PO.18.00297
Kube S, Vokuhl C, Dantonello T, et al. Inflammatory myofibroblastic tumors-a retrospective analysis of the Cooperative Weichteilsarkom Studiengruppe. Pediatr Blood Cancer. 2018;65(6):e27012.
Felkai L, Bánusz R, Kovalszky I, et al. The presence of ALK alterations and clinical relevance of crizotinib treatment in pediatric solid tumors. Pathol Oncol Res. 2019;25(1):217-224.
Qiu X, Montgomery E, Sun B. Inflammatory myofibroblastic tumor and low-grade myofibroblastic sarcoma: a comparative study of clinicopathologic features and further observations on the immunohistochemical profile of myofibroblasts. Hum Pathol. 2008;39(6):846-856.
Kallen ME, Hornick JL. The 2020 WHO classification: what's new in soft tissue tumor pathology? Am J Surg Pathol. 2021;45(1):e1-e23. https://doi.org/10.1097/pas.0000000000001552
Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO classification of soft tissue tumours: news and perspectives. Pathologica. 2021;113(2):70-84.
Zhang N, Zeng Q, Chen C, et al. Clinical characteristics and prognosis of pulmonary inflammatory myofibroblastic tumor: an over 10-year retrospective analysis. Pediatr Investig. 2020;4(3):192-197
Wittekind C, Compton CC, Greene FL, et al. TNM residual tumor classification revisited. Cancer. 2002;94(9):2511-2516.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-213.
Favini F, Resti AG, Collini P, et al. Inflammatory myofibroblastic tumor of the conjunctiva: response to chemotherapy with low-dose methotrexate and vinorelbine. Pediatr Blood Cancer. 2010;54:483-485.
Gaudichon J, Jeanne-Pasquier C, Deparis M, et al. Complete and repeated response of a metastatic ALK-rearranged inflammatory myofibroblastic tumor to crizotinib in a teenage girl. J Pediatr Hematol Oncol. 2016;38(4):308-311.
Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital. Arch Pathol Lab Med. 2008;132(7):1079-1103.
Rafee S, Elamin YY, Joyce E, et al. Neoadjuvant crizotinib in advanced inflammatory myofibroblastic tumour with ALK gene rearrangement. Tumori. 2015;101(2):e35-e39.
Mossé YP, Voss SD, Lim MS, et al. Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: a Children's Oncology Group study. J Clin Oncol. 2017;35(28):3215-3221.
Sparber-Sauer M, Orbach D, Navid F, et al. Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis. Br J Cancer. 2021;124(10):1637-1646.
Orbach D, Sparber-Sauer M, Laetsch TW, 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;137:183-192.
Mehta B, Mascarenhas L, Zhou S, Wang L, Venkatramani R. Inflammatory myofibroblastic tumors in childhood. Pediatr Hematol Oncol. 2013;30(7):640-645.