-
Cellular and Molecular Life Sciences :... Apr 2021PDGFRA and PDGFRB are classical proto-oncogenes that encode receptor tyrosine kinases responding to platelet-derived growth factor (PDGF). PDGFRA mutations are found in... (Review)
Review
PDGFRA and PDGFRB are classical proto-oncogenes that encode receptor tyrosine kinases responding to platelet-derived growth factor (PDGF). PDGFRA mutations are found in gastrointestinal stromal tumors (GISTs), inflammatory fibroid polyps and gliomas, and PDGFRB mutations drive myofibroma development. In addition, chromosomal rearrangement of either gene causes myeloid neoplasms associated with hypereosinophilia. Recently, mutations in PDGFRB were linked to several noncancerous diseases. Germline heterozygous variants that reduce receptor activity have been identified in primary familial brain calcification, whereas gain-of-function mutants are present in patients with fusiform aneurysms, Kosaki overgrowth syndrome or Penttinen premature aging syndrome. Functional analysis of these variants has led to the preclinical validation of tyrosine kinase inhibitors targeting PDGF receptors, such as imatinib, as a treatment for some of these conditions. This review summarizes the rapidly expanding knowledge in this field.
Topics: Animals; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Intestinal Polyps; Mutation; Myofibromatosis; Receptors, Platelet-Derived Growth Factor
PubMed: 33449152
DOI: 10.1007/s00018-020-03753-y -
Anais Brasileiros de Dermatologia 2017Infantile myofibromatosis is a mesenchymal disorder characterized by the fibrous proliferation of the skin, bone, muscle and viscera. It is the most common fibrous tumor...
Infantile myofibromatosis is a mesenchymal disorder characterized by the fibrous proliferation of the skin, bone, muscle and viscera. It is the most common fibrous tumor in childhood. We present a newborn with skin and bone disease without visceral involvement, who showed good response to vinblastine and methotrexate. Clinical features, etiology, diagnosis, and treatment are reviewed.
Topics: Dermatologic Agents; Humans; Immunohistochemistry; Infant, Newborn; Male; Methotrexate; Myofibromatosis; Treatment Outcome; Vinblastine
PubMed: 29364448
DOI: 10.1590/abd1806-4841.20175001 -
The Medical Journal of Malaysia Dec 2001Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with...
Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with widespread visceral involvement. It is characterised by its unique ability to spontaneously regress and has a typical histological appearance of actin-positive fibroblasts arranged in whorls or fascicles and vessels in a pericytomatous pattern. A male infant with multiple lesions involving the subcutaneous tissue and bone from birth is described and followed-up for two years. Treatment of IMF is dependent on the location of the tumour/s with surgery or chemotherapy reserved for rapidly progressive or symptomatic disease. However, due to the low rate of recurrence and the possibility of spontaneous tumoral regression, therapeutic abstention, as practised in our patient, is justified.
Topics: Humans; Infant; Infant, Newborn; Male; Myofibromatosis
PubMed: 12014771
DOI: No ID Found -
Modern Pathology : An Official Journal... May 2023PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented...
PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented in sarcomas with myogenic differentiation. Driven by occasional sarcomas harboring PDGFRB mutations, we investigated their prevalence and clinicopathologic and genomic features in a large cohort of sarcomas. An institutional targeted DNA next-generation sequencing database was searched for sarcomas with myogenic differentiation harboring hotspot PDGFRB gene alterations. Among 3300 patients with sarcomas, 21 (0.6%) patients were identified (17 women, 4 men) with an age range of 35 to 88 years. The site distribution included 13 gynecologic tract (12 uteri, 1 vagina), 4 bone and soft tissue, and 4 viscera. All except 1 were high grade. Most patients were diagnosed as sarcomas with myogenic differentiation based on partial staining for 1 or more muscle markers, whereas 6 were labeled as leiomyosarcoma (LMS). Most tumors showed monomorphic spindle morphology, with either heterogeneous features of myofibroblastic and smooth muscle differentiation or an undifferentiated phenotype. Hormone receptors were negative in all uterine cases. PDGFRB immunostaining in all cases tested was strong and diffuse, whereas PDGFRA was negative/focal. The most frequent PDGFRB mutations were exon 12 (43%), exon 14 (N666K/S/T) (38%), and exon 18 (D850Y/H/V or insertion/deletion) (19%). The most frequent co-existing genetic alterations (26% to 37%) occurred in CDKN2A/B, TP53, TERT, and MED12. Moreover, PDGFRB-mutant sarcomas had an overall distinct genomic landscape compared with both uterine and soft tissue LMS control groups. These tumors were associated with a highly aggressive clinical course, with frequent distant metastases (81%) and death (76%), regardless of anatomic location, and worse overall survival compared with the 2 LMS control groups. This is the first study documenting recurrent hotspot PDGFRB alterations in high-grade sarcomas, which show a predilection for uterine location and myogenic differentiation that fall short of the diagnostic criteria for LMS. Further studies are needed to investigate the therapeutic potential of kinase inhibitors in this group of tumors.
Topics: Humans; Female; Receptor, Platelet-Derived Growth Factor beta; Sarcoma; Leiomyosarcoma; Mutation; Soft Tissue Neoplasms
PubMed: 36788091
DOI: 10.1016/j.modpat.2023.100104 -
Pediatric Radiology Apr 2005Infantile myofibromatosis is the most common fibrous tumor of infancy. It can involve the skin, muscle, bone, and viscera. This uncommon entity is subdivided into...
BACKGROUND
Infantile myofibromatosis is the most common fibrous tumor of infancy. It can involve the skin, muscle, bone, and viscera. This uncommon entity is subdivided into solitary and multicentric forms, with or without visceral involvement.
OBJECTIVE
To describe the imaging characteristics of extracranial myofibromatosis.
MATERIALS AND METHODS
Six infants, aged 1 day-1 week, were evaluated by imaging. All six patients had evaluation of one of the masses by US; four patients had CT evaluation of at least one of the masses; and five patients had evaluation by MRI.
RESULTS
The US appearance of the myofibromas included a mass with a purely anechoic center with a thick wall, a mass with a partially anechoic center, and a mass without anechoic components. On enhanced CT, the masses had lower or similar attenuation compared to adjacent muscle, with some masses exhibiting peripheral enhancement. The MR appearance consisted of low signal on T1-weighted imaging. On T2-weighted imaging, two had low signal of the center and the other three had high signal. All masses showed peripheral enhancement after gadolinium administration.
CONCLUSIONS
Myofibromas have variable appearance on US, with a mass with an anechoic center being the most common feature. On CT, the mass can exhibit peripheral enhancement, calcifications, and erosion of adjacent bone. The MR appearance consisted of low signal on T1-weighted imaging and high or low signal of the center on T2-weighted imaging. All masses showed peripheral enhancement after gadolinium administration.
Topics: Back; Contrast Media; Diagnostic Imaging; Female; Gadolinium; Humans; Image Enhancement; Infant, Newborn; Magnetic Resonance Imaging; Male; Muscle Neoplasms; Myofibromatosis; Neck Muscles; Psoas Muscles; Radiographic Image Enhancement; Shoulder; Soft Tissue Neoplasms; Thigh; Thoracic Wall; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color
PubMed: 15558270
DOI: 10.1007/s00247-004-1357-7 -
Journal of Otolaryngology - Head & Neck... Mar 2019Infantile myofibromatosis is the most common benign fibrous tumor in infants. Three different types have been reported in the literature. The most commonly affected...
BACKGROUND
Infantile myofibromatosis is the most common benign fibrous tumor in infants. Three different types have been reported in the literature. The most commonly affected areas are the head, the neck and the trunk. Our patient showed a very high level of mandibular destruction resistant to all mandibular sparing treatment strategies requiring segmental mandibulectomy and complex reconstruction.
CASE PRESENTATION
We describe a rare case of multicentric infantile myofibromatosis with mandibular bone destruction. The treatment required a succession of chemotherapy, a subtotal transoral resection and a hemi-mandibulectomy. The mandibular reconstruction was staged with initial bridging titanium plate with a submental flap, followed later by a fibula free flap.
CONCLUSION
Mandibular involvement by myofibromatosis is rare, and the extend of bone destruction and reconstruction make this case unique. To our knowledge, this is the only reported case of fibula free flap mandibular reconstruction in a patient with infantile myofibromatosis , as well as one of the youngest reported submental island flaps for any pathology. We describe the clinical presentation and management, including relevant imaging, histopathology, medical and surgical treatment as well as a review of relevant literature.
Topics: Free Tissue Flaps; Humans; Infant; Male; Mandibular Osteotomy; Mandibular Reconstruction; Myofibromatosis; Plastic Surgery Procedures
PubMed: 30871614
DOI: 10.1186/s40463-019-0333-z -
Yonsei Medical Journal Dec 1989We report a case of infantile myofibromatosis in a male infant with involvement of the lungs and subcutaneous tissue. We studied our case by light microscopy,...
We report a case of infantile myofibromatosis in a male infant with involvement of the lungs and subcutaneous tissue. We studied our case by light microscopy, immunohistochemistry and electron microscopy. The results reveal that this entity is of a myofibroblastic nature. We reviewed 165 cases including our case. We believe this is the first report in Korea of infantile myofibromatosis with pulmonary involvement.
Topics: Humans; Infant, Newborn; Leiomyoma; Lung Neoplasms; Male; Microscopy, Electron; Prognosis; Skin Neoplasms
PubMed: 2626841
DOI: 10.3349/ymj.1989.30.4.376 -
Journal of Cellular and Molecular... May 2021Myofibroma is a benign pericytic tumour affecting young children. The presence of multicentric myofibromas defines infantile myofibromatosis (IMF), which is a...
Myofibroma is a benign pericytic tumour affecting young children. The presence of multicentric myofibromas defines infantile myofibromatosis (IMF), which is a life-threatening condition when associated with visceral involvement. The disease pathophysiology remains poorly characterized. In this study, we performed deep RNA sequencing on eight myofibroma samples, including two from patients with IMF. We identified five different in-frame gene fusions in six patients, including three previously described fusion transcripts, SRF-CITED1, SRF-ICA1L and MTCH2-FNBP4, and a fusion of unknown significance, FN1-TIMP1. We found a novel COL4A1-VEGFD gene fusion in two cases, one of which also carried a PDGFRB mutation. We observed a robust expression of VEGFD by immunofluorescence on the corresponding tumour sections. Finally, we showed that the COL4A1-VEGFD chimeric protein was processed to mature VEGFD growth factor by proteases, such as the FURIN proprotein convertase. In conclusion, our results unravel a new recurrent gene fusion that leads to VEGFD production under the control of the COL4A1 gene promoter in myofibroma. This fusion is highly reminiscent of the COL1A1-PDGFB oncogene associated with dermatofibrosarcoma protuberans. This work has implications for the diagnosis and, possibly, the treatment of a subset of myofibromas.
Topics: Biomarkers, Tumor; Collagen Type IV; Gene Expression Regulation, Neoplastic; Gene Fusion; Humans; Myofibroma; Prognosis; Vascular Endothelial Growth Factor D
PubMed: 33830670
DOI: 10.1111/jcmm.16502