BACKGROUND: Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known, namely in tumors with visceral involvement. The standard of care is surgical resection. Observations suggest that low dose chemotherapy is beneficial. The treatment of resistant or relapsed patients with multifocal disease remains challenging. Patients that harbor an actionable mutation in the kinase domain are potential subjects for targeted tyrosine kinase inhibitor therapy. CASE PRESENTATION: An infant boy with inborn generalized infantile myofibromatosis that included bone, intracranial, soft tissue and visceral involvement was treated according to recent recommendations with low dose chemotherapy. The presence of a partial but temporary response led to a second line of treatment with six cycles of chemotherapy, which achieved a partial response again but was followed by severe toxicity. The generalized progression of the disease was observed later. Genetic analyses were performed and revealed a PDGFRB gene c.1681C>A missense heterozygous germline mutation, high PDGFRβ phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome 657del5 mutation in the NBN gene. Targeted treatment with sunitinib, the PDGFRβ inhibitor, plus low dose vinblastine led to an unexpected and durable response without toxicities or limitations to daily life activities. The presence of the Slavic NBN gene mutation limited standard chemotherapy dosing due to severe toxicities. Sister of the patient suffred from skull base tumor with same genotype and histology. The same targeted therapy led to similar quick and durable response. CONCLUSION: Progressive and resistant incurable infantile myofibromatosis can be successfully treated with the new approach described herein. Detailed insights into the biology of the patient's tumor and genome are necessary to understand the mechanisms of activity of less toxic and effective drugs except for up to date population-based chemotherapy regimens.

Central European Institute of Technology Masaryk University Kamenice 753 5 Brno 625 00 Czech Republic

Department of Pathology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic

Department of Pediatric Oncology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic

Department of Pediatric Oncology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic International Clinical Research Center St Anne's University Hospital Brno Pekarska 53 Brno 656 91 Czech Republic

Department of Pediatric Oncology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic Laboratory of Tumor Biology Department of Experimental Biology School of Science Masaryk University Kotlarska 2 Brno 611 37 Czech Republic International Clinical Research Center St Anne's University Hospital Brno Pekarska 53 Brno 656 91 Czech Republic

Department of Pediatric Radiology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic

Division of Medical Genetics Department of Biology University Hospital Brno and School of Medicine Masaryk University Cernopolni 9 Brno 613 00 Czech Republic

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