Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

Abstract

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.

Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Standard of Care and Treatment Recommendations from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

“…Various degrees of response were reported, with some authors in favor of low-morbidity regimens like those used for desmoid fibromatosis. 30 , 120 , 121 …”

“…Various degrees of response were reported, with some authors in favor of low-morbidity regimens like those used for desmoid fibromatosis. 30,120,121 The treatment strategy has changed substantially in recent years, however, with emerging evidence of the high levels of activity of ALK inhibitors (crizotinib, ceritinib, alectinib, and brigatinib), and -more recently -ROS1, RET and NTRK inhibitors (for cases with the corresponding molecular abnormality). 122,123 The EpSSG recommends no adjuvant therapy after initial R0 or R1 resection, but chemotherapy (vinblastine plus low-dose methotrexate) is still a valid first option in cases of unresectable disease.…”

Comment on: Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

“…In a recent issue of Pediatric Blood and Cancer, Pire et al characterized a large, unselected pediatric population with inflammatory myofibroblastic tumor (IMT) and emphasized the role of surgery in combination with novel therapeutics to improve outcomes. 1 IMTs are rare mesenchymal tumors that usually occur isolated but can metastasize. [2][3][4] A combination of unspecific symptoms on presentation and an inflammatory infiltrate on histology contributes to a challenging diagnosis.…”

Ileal Inflammatory Myofibroblastic Tumor in a Two-Month-Old Girl: Long-Term Follow-up

“…

to have a benign course, but they can sometimes be invasive and cause local recurrences. Metastasization has also been described in relation to these tumors [4]. Clinically, the presentation is highly variable, including asymptomatic cases.

…”

“…The etiology of IMT has not been determined. However, isolated associations with Epstein-Barr virus and chromosomal translocations have been described [3,4]. IMT tends…”