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Pediatric Dermatology 2010Infantile myofibromatosis is a rare fibrous tumor of infancy that can be solitary or multiple. Although most of the cases are limited to the skin, in some instances...
Infantile myofibromatosis is a rare fibrous tumor of infancy that can be solitary or multiple. Although most of the cases are limited to the skin, in some instances systemic involvement can be present. Solitary tumors limited to the skin usually present a good prognosis with spontaneous regression. We performed a retrospective observational review of the clinical and pathologic characteristics of nine patients diagnosed as having infantile myofibromatosis, followed during a 10-year period in a Pediatric Dermatology Department.
Topics: Age of Onset; Biopsy; Female; Humans; Infant, Newborn; Male; Myofibromatosis; Prognosis; Retrospective Studies; Skin; Skin Neoplasms; Soft Tissue Neoplasms
PubMed: 20199406
DOI: 10.1111/j.1525-1470.2009.01073.x -
Disease Models & Mechanisms Jan 2021Infantile myofibromatosis (IMF) is a benign tumor form characterized by the development of nonmetastatic tumors in skin, bone, muscle and sometimes viscera. Autosomal...
Infantile myofibromatosis (IMF) is a benign tumor form characterized by the development of nonmetastatic tumors in skin, bone, muscle and sometimes viscera. Autosomal dominant forms of IMF are caused by mutations in the gene, but a family carrying a L1519P mutation in the gene has also recently been identified. In this report, we address the molecular consequences of the NOTCH3 mutation and the relationship between the NOTCH and PDGFRB signaling in IMF. The NOTCH3 receptor generates enhanced downstream signaling in a ligand-independent manner. Despite the enhanced signaling, the NOTCH3 receptor is absent from the cell surface and instead accumulates in the endoplasmic reticulum. Furthermore, the localization of the NOTCH3 receptor in the bipartite, heterodimeric state is altered, combined with avid secretion of the mutated extracellular domain from the cell. Chloroquine treatment strongly reduces the amount of secreted NOTCH3 extracellular domain and decreases signaling. Finally, NOTCH3 upregulates PDGFRB expression in fibroblasts, supporting a functional link between Notch and PDGF dysregulation in IMF. Collectively, our data define a NOTCH3-PDGFRB axis in IMF, where an IMF-mutated NOTCH3 receptor elevates PDGFRB expression. The functional characterization of a ligand-independent gain-of-function NOTCH3 mutation is important for Notch therapy considerations for IMF, including strategies aimed at altering lysosome function.
PubMed: 33509954
DOI: 10.1242/dmm.046300 -
Journal Francais D'ophtalmologie Sep 2022
Topics: Diagnosis, Differential; Exophthalmos; Humans; Infant, Newborn; Myofibromatosis; Ophthalmologists
PubMed: 35764508
DOI: 10.1016/j.jfo.2022.02.022 -
JBJS Case Connector Jan 2024A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in...
CASE
A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in the left femoral neck. The patient was avoiding weight-bearing on the affected extremity; thus, stabilization of the femoral neck was performed using a proximal femur locking plate. Postoperatively, he achieved all gross motor developmental milestones.
CONCLUSION
This report is the first to describe a solitary infantile myofibroma in the femoral neck and demonstrates the utility of operative stabilization of these lesions.
Topics: Male; Humans; Infant; Myofibromatosis; Femur Neck; Myofibroma; Femur
PubMed: 38363879
DOI: 10.2106/JBJS.CC.23.00478 -
Annales de Dermatologie Et de... 2017
Topics: Child; Child, Preschool; Humans; Infant; Mutation; Myofibromatosis; Receptor, Notch3; Receptor, Platelet-Derived Growth Factor beta
PubMed: 28756885
DOI: 10.1016/j.annder.2017.05.010 -
Clinical Imaging 2019Infantile myofibromatosis (IM) is the most common fibrous tumor of infancy. MRI is considered the gold standard in IM evaluation. Very little has been published about IM...
BACKGROUND
Infantile myofibromatosis (IM) is the most common fibrous tumor of infancy. MRI is considered the gold standard in IM evaluation. Very little has been published about IM with histopathology correlation in the pediatric age.
PURPOSE
Describe imaging findings in IM and correlate MRI findings with histopathology.
MATERIAL AND METHODS
Imaging findings of 17 patients with IM were retrospectively analyzed including CT, US and MRI. Signal characteristics on T1-, T2-weighted and STIR imaging, extent of T2-hyperintensity, degree & pattern of enhancement, diffusion restriction, location & margins, & involvement of adjacent structures were tabulated. Histopathology findings included cellularity, collagenization, myxoid changes, atypia, mitosis & microscopic invasion. Established grading scores were utilized.
RESULTS
Relative to normal skeletal muscle, on T1-weighted imaging, 9 lesions had similar signal while the remaining had a mixture of iso & hypo intensity; whereas on T2-weighted and STIR imaging, all 12 lesions demonstrated a mixture of iso, hypo & hyperintensity. T2-hyperintensity was grade 2 in one, grade 3 in 8 & grade 4 in 3 lesions. Intensity of enhancement was grade 2 in one, grade 3 in 8 & grade 4 in 3 lesions. Enhancement was predominantly peripheral in all 12 lesions. Extent of T2-hyperintensity & degree of enhancement corresponded to variable grades on histopathology. CT and US showed nonspecific findings.
CONCLUSION
On MRI, IM has a mixture of signal intensity with predominant hyperintense signal on T2W images. However various signal & enhancement features correlated poorly with specific histopathologic grades.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Muscle, Skeletal; Myofibromatosis; Pediatrics; Retrospective Studies; Young Adult
PubMed: 30529421
DOI: 10.1016/j.clinimag.2018.11.003 -
Journal of Surgical Case Reports May 2023Infantile myofibromatosis (IM) is the most common fibrous disorder of infancy and early childhood. Solitary intracranial involvement is rare and often unrecognized. This...
Infantile myofibromatosis (IM) is the most common fibrous disorder of infancy and early childhood. Solitary intracranial involvement is rare and often unrecognized. This makes its early diagnosis and adequate management difficult. The majority of lesions are localized to the skull or dura with variable intracranial extension. Herein, we report a misdiagnosed and aggressive presentation of a solitary IM of the petrous bone. Our aim is to discuss histopathological differential diagnoses and management difficulties.
PubMed: 37192874
DOI: 10.1093/jscr/rjad237 -
Journal of Stomatology, Oral and... Jun 2018Aggressive paediatric myofibromatosis is an autosomal recessive disease characterized by fibroblastic proliferation from cells originated in muscle-aponeurotic tissue....
INTRODUCTION
Aggressive paediatric myofibromatosis is an autosomal recessive disease characterized by fibroblastic proliferation from cells originated in muscle-aponeurotic tissue. Its etiology is unknown, and the average age of the reported cases is 7 years old. The tumor exhibits rapid painless growth and appears attached to muscle tissue and/or bone. The treatment of choice is conservative surgical excision despite of early relapses has been reported.
OBSERVATION
A 2-year-old patient, with no morbid history, presented with a large swelling in the left submandibular region, firm, neither defined limits nor inflammatory characteristics. Its size doubled 2 months after an incisional biopsy. CT images showed great compromise of the left mandibular body with expanded and thinned cortical bone. The MRI showed extension towards the pharynx. Histopathological findings were elongated fibroblastic and ovoid cells arranged in bundles and fascicles within fibromyxoid stroma, an image consistent with the diagnosis. The treatment consisted in a conservative exeresis of the tumor, preserving the jaw. Control 1 year after surgical removal shows no signs of relapse and the mandibular structure has been restored.
DISCUSSION
The large size of the lesion and bone involvement at such an early age evidenced a very aggressive lesion, however, supported by a previous biopsy, we performed a conservative treatment, which only caused the loss of a dental germ, impossible to take off from the intraosseous tumor. The control of this type of lesions requires a longer follow-up.
Topics: Biopsy; Child; Child, Preschool; Humans; Magnetic Resonance Imaging; Mandible; Myofibromatosis; Neoplasm Recurrence, Local
PubMed: 29274401
DOI: 10.1016/j.jormas.2017.11.018 -
Clinical Cases in Mineral and Bone... 2017Solitary infantile myofibromatosis (IM) of bone is a rare benign osseous tumor of childhood with low rate of recurrence. Well documented within the multicenter form, its...
INTRODUCTION
Solitary infantile myofibromatosis (IM) of bone is a rare benign osseous tumor of childhood with low rate of recurrence. Well documented within the multicenter form, its solitary intraosseous location is less well described.
CASE REPORT
We present a rare case of intraosseous myofibromatosis arising the iliac bone of a 11-year-old girl, who was operated at 2 months of life for a retroauricular subcutaneous MF with unbalanced translocation t(9;16). She presented with a limping associated to a stiffness of the hip without pain. Imaging disclosed a 4×4×1cm intraosseous, lytic and heterogeneous mass with a soft tissue component on the medial cortical of the left iliac bone. Open biopsy was performed. Histology revealed proliferation of fusiform cells with eosinophil cytoplasm embedded in a myxoid and fibrous stroma without mitotic figures. On immunohistochemistry, cells were positive for actin, PS100, KL1, focally positive for EMA, CD34, P63, rarely CD31, which indicated diagnosis of new localization of IM. Cytogenetic analysis revealed absence of translocation t(9;16), which was found in the first tumor. Subsequent total resection was performed. The patient recovered normal function without recurrence of tumor at 3 years follow-up.
CONCLUSION
To our knowledge, this is the first case of solitary IM of the iliac bone, occurring 12 years after the first localization. Total resection resulted in excellent outcome. However recurrence can happen even long time after the first resection and new localization is possible, as in our case. This suggests close follow-up and clear information about the risk of recurrence.
PubMed: 29263742
DOI: 10.11138/ccmbm/2017.14.1.241 -
Human Molecular Genetics May 2017Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor...
Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma. Two patients had the same mutation in multiple separated lesions. By contrast, a third patient had three different PDGFRB mutations in the three nodules analyzed. Mutations were located in the transmembrane, juxtamembrane and kinase domains of the receptor. We showed that these mutations activated receptor signaling in the absence of ligand and transformed fibroblasts. In one case, a weakly-activating germline variant was associated with a stronger somatic mutation, suggesting a two-hit model for familial myofibromatosis. Furthermore, the mutant receptors were sensitive to the tyrosine kinase inhibitor imatinib, except D850V, which was inhibited by dasatinib and ponatinib, suggesting a targeted therapy for severe myofibromatosis. In conclusion, we identified gain-of-function PDGFRB mutations in the majority of multifocal infantile myofibromatosis cases, shedding light on the mechanism of disease development, which is reminiscent of multifocal venous malformations induced by TIE2 mutations. Our results provide a genetic test to facilitate diagnosis, and preclinical data for development of molecular therapies.
Topics: Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Mutation; Myofibromatosis; Receptor, Platelet-Derived Growth Factor beta; Receptor, TIE-2
PubMed: 28334876
DOI: 10.1093/hmg/ddx081