-
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 -
Fibroblastic and myofibroblastic tumors of children: new genetic entities and new ancillary testing.F1000Research 2018Fibroblastic and myofibroblastic tumors comprise a morphologically diverse and biologically variable group of neoplasms that affect a wide age range. Specific entities... (Review)
Review
Fibroblastic and myofibroblastic tumors comprise a morphologically diverse and biologically variable group of neoplasms that affect a wide age range. Specific entities tend to occur most frequently in infants and young children. Recent years have witnessed a proliferation of information concerning the unique biology of these tumors. In this report, I will review recent findings that serve to further characterize this group of neoplasms. Included will be newer information on fibrous hamartoma of infancy, infantile myofibromatosis, lipofibromatosis, and infantile fibrosarcoma and tumors resembling it, including primitive myxoid mesenchymal tumor of infancy and new genetic entities. I will also discuss the differential diagnosis, which includes spindle cell rhabdomyosarcoma, dermatofibrosarcoma protuberans, and calcifying aponeurotic fibroma.
Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Fibroblasts; Humans; Neoplasms, Connective and Soft Tissue; Neoplasms, Fibrous Tissue
PubMed: 30613391
DOI: 10.12688/f1000research.16236.1 -
Korean Journal of Radiology Mar 2020Ultrasonography (US) is usually the first imaging examination performed to evaluate palpable or visible superficial soft tissue lesions that are common in children.... (Review)
Review
Ultrasonography (US) is usually the first imaging examination performed to evaluate palpable or visible superficial soft tissue lesions that are common in children. Although clinical assessments, such as age at presentation, clinical course, and overlying skin discoloration, are important for the differentiation of pediatric soft tissue lesions, US allows a specific diagnosis of some typical benign lesions and helps in guiding further investigation since it provides detailed information about the lesion location, characterization including solid versus cystic, vascularity, and compressibility. Therefore, sufficient knowledge of the normal anatomy, proper ultrasonographic techniques, and the imaging findings of common and uncommon soft tissue lesions in children are crucial for accurate assessment and management of patients. In this article, we review the techniques and imaging findings focusing on the ultrasonographic features of a variety of superficial soft tissue lesions detected in children.
Topics: Adolescent; Child; Child, Preschool; Fasciitis; Female; Hemangioendothelioma; Humans; Infant; Infant, Newborn; Kasabach-Merritt Syndrome; Lipoblastoma; Male; Myofibromatosis; Neurofibroma; Sarcoma, Kaposi; Soft Tissue Neoplasms; Ultrasonography; Vascular Malformations
PubMed: 32090527
DOI: 10.3348/kjr.2019.0343 -
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 -
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 -
Molecular and Cellular Pediatrics Jun 2021Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral...
BACKGROUND
Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM.
CASE PRESENTATION
We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy.
CONCLUSIONS
PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.
PubMed: 34132909
DOI: 10.1186/s40348-021-00117-9 -
Cureus Nov 2022Solitary infantile myofibroma is a benign fibrous tumor occurring in early childhood. Although rare, it is the most common benign fibrous tumor of infancy. The clinical...
Solitary infantile myofibroma is a benign fibrous tumor occurring in early childhood. Although rare, it is the most common benign fibrous tumor of infancy. The clinical course of the disease is almost uniformly good since most tumors regress spontaneously. When indicated, conservative surgical excision is the treatment of choice, with a low recurrence rate. We present a case of solitary infantile myofibroma that recurred after three attempts of surgical excision, questioning the reported recurrence rate and the standard of care in recurrent solitary infantile myofibroma.
PubMed: 36514628
DOI: 10.7759/cureus.31300