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Pediatric Blood & Cancer Oct 2020Infantile myofibroma is the most common fibrous tumor of infancy. Despite the frequency of these tumors, the natural history is incompletely understood. We present two...
Infantile myofibroma is the most common fibrous tumor of infancy. Despite the frequency of these tumors, the natural history is incompletely understood. We present two cases with a unique pattern of disease: solitary myofibromas with subsequent progression to diffuse myofibromatosis. Given the variable spectrum of disease and the corresponding difference in morbidity and potential mortality based on the extent of disease, we propose surveillance recommendations.
Topics: Disease Progression; Female; Humans; Infant, Newborn; Male; Myofibroma; Myofibromatosis; Prognosis
PubMed: 32618426
DOI: 10.1002/pbc.28266 -
Journal of Molecular Neuroscience : MN Dec 2020The platelet-derived growth factor receptor beta (PDGFRB) gene is involved in proliferative and developmental processes in mammals. Variations in this gene lead to... (Meta-Analysis)
Meta-Analysis
The platelet-derived growth factor receptor beta (PDGFRB) gene is involved in proliferative and developmental processes in mammals. Variations in this gene lead to several different syndromic conditions, such as infantile myofibromatosis I, sporadic port-wine stain, primary familial brain calcification, and the Penttinen and overgrowth syndromes. Our objective was to investigate PDGFRB's genetic relationship to clinical conditions and evaluate the protein interactions using GeneNetwork, GeneMANIA, and STRING network databases. We have evidenced the gene's pleiotropy through its many connections and its link to syndromic conditions. Therefore, PDGFRB may be an important therapeutic target for treating such conditions.
Topics: Acro-Osteolysis; Binding Sites; Calcinosis; Genetic Pleiotropy; Genetic Predisposition to Disease; Growth Disorders; Humans; Limb Deformities, Congenital; Myofibromatosis; Port-Wine Stain; Progeria; Protein Interaction Maps; Receptor, Platelet-Derived Growth Factor beta
PubMed: 32613555
DOI: 10.1007/s12031-020-01618-4 -
Archives of Disease in Childhood Jun 2020
PubMed: 32576562
DOI: 10.1136/archdischild-2020-319229 -
Clinical Imaging Nov 2020Myofibroma is a benign, soft tissue neoplasm that predominantly affects infants and young children. Most occur in the skin or subcutaneous tissues, with a predilection...
Myofibroma is a benign, soft tissue neoplasm that predominantly affects infants and young children. Most occur in the skin or subcutaneous tissues, with a predilection for the head and neck regions. We describe the magnetic resonance (MR) imaging and histophathologic findings of a rare case of intramuscular myofibroma of the right deltoid in a healthy 30-year-old male. MR imaging revealed a well-circumscribed intramuscular mass, with isointense signal on T1-weighted images, hyperintense signal on T2-weighed images, and a "target-sign" with peripheral rim enhancement after gadolinium administration. The lesion was surgically excised with no complications, and the histopathologic analysis revealed the typical morphologic and histochemical markers of a myofibroma. We conclude that, although rare, myofibroma can be considered in the differential diagnosis of adults with lesions the above signal characteristics.
Topics: Adult; Diagnosis, Differential; Gadolinium; Head; Humans; Leiomyoma; Magnetic Resonance Imaging; Male; Myofibroma; Myofibromatosis; Neck; Soft Tissue Neoplasms
PubMed: 32531695
DOI: 10.1016/j.clinimag.2020.05.027 -
American Journal of Medical Genetics.... Jul 2020More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary...
More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late-onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB. Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.
Topics: Adolescent; Adult; Aneurysm; Child; Female; Genetic Association Studies; Humans; Imatinib Mesylate; Infant; Leukoencephalopathies; Male; Myofibromatosis; Pedigree; Protein Kinase Inhibitors; Receptor, Platelet-Derived Growth Factor beta
PubMed: 32500973
DOI: 10.1002/ajmg.a.61615 -
Pediatric Blood & Cancer Jun 2020Infantile myofibromatosis (IM) is characterized by solitary musculoskeletal nodules presenting during infancy but can manifest as multiple lesions with visceral...
Infantile myofibromatosis (IM) is characterized by solitary musculoskeletal nodules presenting during infancy but can manifest as multiple lesions with visceral involvement. Multicentric IM with visceral involvement carries a high risk of mortality and there is no consensus on treatment. We present a case of a patient with multicentric IM and pulmonary involvement who progressed on several chemotherapeutic regimens and subsequently had a complete response to sorafenib and later imatinib. This report describes the novel use of sorafenib and imatinib to treat generalized IM and the role of continued tyrosine kinase inhibitor therapy to maintain remission.
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Imatinib Mesylate; Infant; Myofibromatosis; Prognosis; Sorafenib
PubMed: 32307894
DOI: 10.1002/pbc.28288 -
Clinical Genetics Jul 2020Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen...
Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long-term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS-like disorders and suggest vascular imaging is indicated in these patients.
Topics: Adult; Cerebrovascular Disorders; Genetic Variation; Growth Disorders; Humans; Male; Middle Aged; Phenotype; Receptor, Platelet-Derived Growth Factor beta
PubMed: 32291752
DOI: 10.1111/cge.13752 -
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 -
Klinicka Onkologie : Casopis Ceske a... 2020The Connective Tissue Oncology Group Annual Meeting 2018 (CTOS 2018) took place in Rome from 4 to 17 November 2018, and the 39th Plenary Meeting of the Scandinavian...
The Connective Tissue Oncology Group Annual Meeting 2018 (CTOS 2018) took place in Rome from 4 to 17 November 2018, and the 39th Plenary Meeting of the Scandinavian Sarcoma Group (SSGM 2019) was held in Bergen from 8 to 10 May 2019. These two large international conferences brought together an overwhelming majority of molecular and clinical specialists in the sarcoma field, especially those working on soft tissue sarcoma. Topics discussed on the conferences included, among others, sarcoma genetics, clinical and molecular subclassification, targeted therapy, clinical prognostication, and new experimental sarcoma models. A large ongoing international study on germinal sarcoma genetics was presented, the interim results of which revealed the extremely complex nature of genetic disposition to sarcoma, and, surprisingly, a rather prominent place among predisposing genes for those coding for structural telomere constituents. Fusion oncogenes dominate somatic sarcoma genetics, especially because of their origin and impact on sarcoma clinical behaviour, and are especially relevant for karyotypically simple paediatric sarcomas. A crucial issue in karyotypically complex sarcomas are the efforts being made to obtain a subclassification of sarcoma, other than those based on pathology, using either the clinical characteristics of sarcomas (uterine leiomyosarcoma vs. soft tissue leiomyosarcoma) or specific gene expression profiles (molecular subtypes in undifferentiated pleiomorphic sarcoma), which showed that molecular characterization can open the way for subtype specific therapies. Other examples of where this type of strategy can be applied include gastrointestinal stromal tumours, infantile fibrosarcoma, and inflammatory myofibroblastic tumours, where targeted therapy could be conceived based on the actionable mutations identified. Attempts in this direction have been made also for clear cell sarcoma and dedifferentiated liposarcoma, albeit the effectiveness of molecular-targeted treatments for these sarcomas is still poor, and progress in the treatment of osteosarcoma is still rather slow. Actually, the platelet-derived growth factor signalling system holds a prominent position in searches for targeted therapies, not only against rare sarcoma types, where are activated by mutations (some gastrointestinal stromal tumours, infantile hereditary myofibromatosis, and dermatofibrosarcoma protuberans), but also against other more usual sarcoma types, where the blocking anti-PDGFRα-antibody olaratumab has been successfully integrated into combinatorial chemotherapeutic regimens. In the field of clinical prognostication, remarkable progress in sarcoma nomograms was reported. Interesting results were also presented in the area of new experimental sarcoma models. Participation on both scientifi c conferences and all the experimental work leading to the presented sarcoma models were supported by the Czech Science Foundation project No. 17-17636S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 20. 9. 2019 Accepted: 6. 11. 2019.
Topics: Humans; Molecular Targeted Therapy; Sarcoma; Soft Tissue Neoplasms
PubMed: 32075391
DOI: 10.14735/amko202066 -
Advances in Experimental Medicine and... 2020The evolutionary highly conserved Notch pathway governs many cellular core processes including cell fate decisions. Although it is characterized by a simple molecular... (Review)
Review
The evolutionary highly conserved Notch pathway governs many cellular core processes including cell fate decisions. Although it is characterized by a simple molecular design, Notch signaling, which first developed in metazoans, represents one of the most important pathways that govern embryonic development. Consequently, a broad variety of independent inherited diseases linked to defective Notch signaling has now been identified, including Alagille, Adams-Oliver, and Hajdu-Cheney syndromes, CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), early-onset arteriopathy with cavitating leukodystrophy, lateral meningocele syndrome, and infantile myofibromatosis. In this review, we give a brief overview on molecular pathology and clinical findings in congenital diseases linked to the Notch pathway. Moreover, we discuss future developments in basic science and clinical practice that may emerge from recent progress in our understanding of the role of Notch in health and disease.
Topics: Cell Differentiation; Genetic Diseases, Inborn; Humans; Receptors, Notch; Signal Transduction
PubMed: 32060876
DOI: 10.1007/978-3-030-34436-8_9