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Familial Cancer Oct 2021Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue...
Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
Topics: Child; Child, Preschool; Genetic Testing; Humans; Imatinib Mesylate; Myofibromatosis; Receptor, Platelet-Derived Growth Factor beta
PubMed: 32888134
DOI: 10.1007/s10689-020-00204-2 -
BMC Medical Genomics Aug 2023Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases... (Review)
Review
BACKGROUND
Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases are detected prenatally, and the final diagnosis cannot be made until pathology is completed after birth. Here, we present a case of disseminated form IM (DFIM) with a diagnosis established on prenatal genetic grounds.
CASE PRESENTATION
A woman at 23 weeks of gestation was referred for ultrasound evaluation of fetal kidney abnormality. Generalized masses in the skin and muscle of the fetus developed at 28 weeks. Prenatal genetic testing identified the pathogenic heterozygous variant c.1681C > T (p.R561C) of the PDGFRB gene inherited from the asymptomatic father. Intrauterine demise occurred at 31 weeks. Autopsy confirmed DFIM with involvement of the heart and kidney. All cases of prenatally detected IM were reviewed, revealing an association of high mortality with DFIM.
CONCLUSIONS
Prenatal IM diagnosis is difficult. Initial detection is always based on ultrasound. DFIM has high mortality. The germline p.R561C mutation in PDGFRB may cause fetal demise due to severe visceral involvement of IM. Prenatal genetic testing provides a diagnosis before pathological results are available, leading to better counseling and management of pregnancy with a fetus with IM.
Topics: Pregnancy; Female; Humans; Myofibromatosis; Receptor, Platelet-Derived Growth Factor beta; Germ-Line Mutation; Prenatal Diagnosis
PubMed: 37568122
DOI: 10.1186/s12920-023-01612-w -
Clinical Case Reports Feb 2022Describe a novel use for a kinase inhibitor, imatinib, in young children with a known activated somatic mutation in PDGFR-beta. Two patients with infantile...
Describe a novel use for a kinase inhibitor, imatinib, in young children with a known activated somatic mutation in PDGFR-beta. Two patients with infantile myofibromatosis treated with imatinib. Case description of evaluation, diagnosis and treatment decisions for infantile myfibromatosis of the head and neck. Description of medical therapy for infantile myofibromatosis in these patients. For function threatening myofibromas of a known genotype, in infants, targeted medical therapy is a treatment option.
PubMed: 35154723
DOI: 10.1002/ccr3.5382 -
Cureus Mar 2023Infantile myofibromatosis is an uncommon soft tissue neoplasm that may present at birth or in early infancy. Although rare, this neoplasm is one of the most common...
Infantile myofibromatosis is an uncommon soft tissue neoplasm that may present at birth or in early infancy. Although rare, this neoplasm is one of the most common benign fibrous tumors of infancy. Even though these tumors do not spread, they can compress or damage nearby organs. There is not an established management protocol, but it is advisable to maintain periodic clinical and imagological control until stability. Watchful waiting is an option to consider in the absence of problematic symptoms and visceral involvement. We report a case of solitary infantile myofibromatosis, without visceral involvement. It showed an initial rapid growth, raising concern among medical doctors and motivating soft tissue biopsy, always recommended as the clinical picture deviates from the classic presentation. Histology interpretation is often challenging, making genetics and clinical evaluation essential to exclude and prevent the misdiagnosing of more aggressive lesions.
PubMed: 37033510
DOI: 10.7759/cureus.35885 -
Anales de Pediatria (Barcelona, Spain :... Jul 2015
Topics: Humans; Infant, Newborn; Male; Myofibromatosis; Soft Tissue Neoplasms
PubMed: 25616547
DOI: 10.1016/j.anpedi.2014.12.007 -
Plastic and Reconstructive Surgery.... Jan 2021Infantile myofibromatosis is an unusual and rare lesion of the bone and soft tissue, which can be seen in the craniofacial skeleton. These complex tumors present a...
Infantile myofibromatosis is an unusual and rare lesion of the bone and soft tissue, which can be seen in the craniofacial skeleton. These complex tumors present a challenge to craniofacial surgeons regarding diagnosis, management, and safe and effective surgical treatment, frequently requiring complex reconstruction. We present the case of a 7-month-old girl with multicentric infantile myofibromatosis of the right parietal and fronto-orbital region, the associated clinical presentation, histopathologic findings, and surgical management, along with a review of the relevant literature.
PubMed: 33552804
DOI: 10.1097/GOX.0000000000003261 -
European Journal of Pediatric Surgery... Dec 2016Infantile soft tissue tumors of the head are very rare and the majority of them are myofibromas. The authors present the case of a 1-day-old boy with a scalp tumor with...
Infantile soft tissue tumors of the head are very rare and the majority of them are myofibromas. The authors present the case of a 1-day-old boy with a scalp tumor with several distinct histopathological features including myofibroma, hemangiopericytoma, and fibrosarcoma consistent with the diagnosis of composite infantile myofibromatosis. Genetic testing was negative for trisomy 17, translocation (12; 15), FUS, and ETV6 translocations. Despite the ominous histopathological features, the clinical course was benign. The authors review here available literature concerning current concepts of making the diagnosis of composite infantile myofibromatosis and discuss treatment options.
PubMed: 28018804
DOI: 10.1055/s-0036-1580704 -
Children (Basel, Switzerland) Jan 2022Infantile myofibromatosis (IM) is a rare condition with a variable clinical presentation that characteristically affects young children. Most frequently it presents as...
Infantile myofibromatosis (IM) is a rare condition with a variable clinical presentation that characteristically affects young children. Most frequently it presents as one or more benign nodules of the skin, bones, soft tissues, or, rarely, visceral organs. According to the location and number of lesions, there are three different forms: solitary, multicentric without visceral involvement, and multicentric with visceral involvement (generalised), with the latter having the least favourable prognosis. We present a unique case of severe congenital generalised IM in a new-born male who required intubation and mechanical ventilation immediately after the birth due to respiratory distress. A chest radiograph showed numerous tumours involving the entire lung, resembling a metastatic lung disease. Additionally, the neonate had multiple, bluish, papular skin nodules and a biopsy of a skin nodule ultimately led to the diagnosis of IM. Diffuse lung involvement prevented adequate ventilation which resulted in multiorgan failure and death before targeted treatment could have been initiated. The presented case is unique, as such atypical extensive involvement of the lung and leptomeninges in IM has not been reported before. In this brief report, we present the findings of radiographic and ultrasonographic examinations in correlation with autopsy and histopathology.
PubMed: 35053678
DOI: 10.3390/children9010053 -
BMC Cancer Feb 2017Infantile myofibromatosis belongs to a family of soft tissue tumors. The majority of these tumors have benign behavior but resistant and malignant courses are known,...
Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene.
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Family Health; Female; Germ-Line Mutation; Heterozygote; Humans; Indoles; Infant, Newborn; Male; Molecular Targeted Therapy; Myofibromatosis; Pyrroles; Receptor, Platelet-Derived Growth Factor beta; Sunitinib; Treatment Outcome; Vinblastine
PubMed: 28183292
DOI: 10.1186/s12885-017-3115-x -
Head and Neck Pathology Sep 2011Isolated orbital infantile myofibroma are rare tumors in the head and neck. The mass-like clinical presentation and variable histologic features result in frequent... (Review)
Review
Isolated orbital infantile myofibroma are rare tumors in the head and neck. The mass-like clinical presentation and variable histologic features result in frequent misdiagnosis and potentially inappropriate clinical management. There are only a few reported cases in the English literature. Twenty-four patients with orbital infantile myofibroma or myofibromatosis were compiled from the English literature (Medline 1960-2011) and integrated with this case report. The patients included 14 males and 10 females, aged newborn to 10 years (mean, 34.8 months), who presented with a painless mass in the infra- or supraorbital regions, usually increasing in size andassociated with exophthalmos (n = 5). Females were on average older than their male counterparts (38.9 vs. 31.9 months, respectively; P = 0.71). The tumors were twice as frequent on the left (n = 16) than right (n = 8). Patients experienced symptoms for an average of 2.7 months before clinical presentation. The tumors involved the bone (n = 17) or the soft tissues (n = 7) of the orbit, with extension into the nasal or oral cavity (n = 3). The mean size was 3.0 cm, with a statistically significant difference between males and females (mean: 3.9 vs. 1.82; P = 0.0047), but without any differences based on age at presentation (P = 0.25), duration of symptoms (P = 0.66), or bone or soft tissue involvement (P = 0.51). Grossly, all tumors were well-circumscribed, firm to rubbery, homogenous, and white-grey. Histologically, the tumors were biphasic, showing whorled and nodular areas of fusiform cells with extracellular collagen, mixed with a population of small, primitive-appearing, darkly staining cells. Necrosis was not present, but mitoses could be seen. Tumors with immunohistochemistry performed showed strong and diffuse smooth muscle actin and vimentin immunoreactivity, but were negative with muscle specific actin, desmin, MYOD1, myogenin, S100 protein, GFAP, keratin, CD31, 34, Factor VIIIR-Ag, and CD45RB. The principle histologic differential diagnosis includes juvenile hyaline fibromatosis, fibrous hamartoma of infancy, fibromatosis coli, leiomyoma, infantile hemangiopericytoma, infantile fibrosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, and lymphoma. All patients were managed with surgery. Recurrences developed in two patients at 4 and 6 months, respectively. Follow-up data was available on all but two patients (n = 22). These patients were either alive without evidence of disease (n = 18), alive but with disease (n = 3), or had died unrelated to this disease (i.e., neuroblastoma, n = 1). Orbital infantile myofibroma is a rare tumor, presenting in infancy as an enlarging mass of the orbit, with characteristic histomorphologic and immunophenotypic features. Orbital disease is usually isolated rather than part of systemic disease, and shows an excellent long-term prognosis, making appropriate separation from other conditions important.
Topics: Child; Child, Preschool; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Infant; Infant, Newborn; Male; Myofibroma; Orbital Neoplasms; Soft Tissue Neoplasms
PubMed: 21512784
DOI: 10.1007/s12105-011-0260-4