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Der Hautarzt; Zeitschrift Fur... Mar 2022We present the case of a patient with a discreet acne and multiple keloids in the area of the upper trunk, histologically showing an unusual myofibroblastic...
We present the case of a patient with a discreet acne and multiple keloids in the area of the upper trunk, histologically showing an unusual myofibroblastic differentiation. So far, the clinical course shows a poor response to the treatment, including cryotherapy, intralesional corticosteroid injections, occlusive silicone dressings and dye laser.
Topics: Acne Vulgaris; Adrenal Cortex Hormones; Cicatrix, Hypertrophic; Cryotherapy; Humans; Injections, Intralesional; Keloid
PubMed: 33904964
DOI: 10.1007/s00105-021-04815-3 -
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 -
American Journal of Medical Genetics.... May 2021Activating variants in the platelet-derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and...
Activating variants in the platelet-derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next-generation sequencing-based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB-activating variants through literature search. The conditions caused by PDGFRB-activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant-related phenotypes are present. Whole-body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6- to 12-month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.
Topics: Adult; Aging, Premature; Aneurysm; Child; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Growth Disorders; High-Throughput Nucleotide Sequencing; Humans; Infant; Intracranial Aneurysm; Male; Middle Aged; Mosaicism; Phenotype; Receptor, Platelet-Derived Growth Factor beta; Skin Abnormalities; Young Adult
PubMed: 33683022
DOI: 10.1002/ajmg.a.62126 -
Familial Cancer Oct 2021In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique...
In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique mutation/methylation signatures may indicate the presence of an underlying cancer predisposition syndrome (CPS). The proportion of children with a cancer type suggesting a CPS among all children with cancer is unknown. To determine the proportion of children with cancer types suggesting an underlying CPS among children with cancer. We evaluated the number of children with cancer types strongly associated with CPS diagnosed in Germany between 2007 and 2016. Data were obtained from various sources including two national pediatric pathology reference laboratories for brain and solid tumors, respectively, various childhood cancer trial offices as well as the German Childhood Cancer Registry. Among 21,127 children diagnosed with cancer between 2007 and 2016, 2554 (12.1%) had a cancer type strongly associated with a CPS. The most common diagnoses were myelodysplastic syndrome and juvenile myelomonocytic leukemia, retinoblastoma, malignant peripheral nerve sheath tumor, infantile myofibromatosis, medulloblastoma, rhabdoid tumor as well as atypical teratoid/rhabdoid tumor. Based on cancer type only, 12.1% of all children with cancer have an indication for a genetic evaluation. Pediatric oncology patients require access to genetic counselling and testing.
Topics: Cerebellar Neoplasms; Child; Genetic Counseling; Humans; Medulloblastoma; Neurofibrosarcoma; Rhabdoid Tumor
PubMed: 33634344
DOI: 10.1007/s10689-021-00234-4 -
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 -
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 -
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 -
Pediatric Dermatology Jan 2021The initial clinical presentation of infantile myofibromatosis can vary from subtle skin changes to large tumors. Here, we describe a case of congenital generalized...
The initial clinical presentation of infantile myofibromatosis can vary from subtle skin changes to large tumors. Here, we describe a case of congenital generalized infantile myofibromatosis which presented with diffuse hypopigmented macules, some with subtle atrophy and telangiectasia. Further workup revealed visceral involvement which led to treatment with systemic chemotherapy. Awareness of this rare clinical presentation is crucial to expedite workup and treatment given the poor prognosis in infants with visceral involvement.
Topics: Humans; Infant; Infant, Newborn; Myofibromatosis
PubMed: 33222239
DOI: 10.1111/pde.14456 -
Cardiology in the Young Feb 2021Cardiac tumours are relatively uncommon, particularly in children. Myofibroma is an extremely rare variety of cardiac tumour, which nearly always arises in the context...
Cardiac tumours are relatively uncommon, particularly in children. Myofibroma is an extremely rare variety of cardiac tumour, which nearly always arises in the context of infantile myofibromatosis. Herein, we present a case of a solitary cardiac myofibroma causing right ventricular outflow tract obstruction in a 2-month-old male infant.
Topics: Child; Heart Defects, Congenital; Heart Neoplasms; Humans; Infant; Male; Myofibroma; Myofibromatosis; Skin Neoplasms; Ventricular Outflow Obstruction
PubMed: 33103641
DOI: 10.1017/S1047951120003583 -
American Journal of Ophthalmology Case... Dec 2020Myofibromas are benign soft tissue tumors commonly encountered in infancy and childhood. Developing usually within the first two years of life, they can be multicentric...
PURPOSE
Myofibromas are benign soft tissue tumors commonly encountered in infancy and childhood. Developing usually within the first two years of life, they can be multicentric and involve deep visceral organs.
OBSERVATIONS
We present the rare occurrence of a solitary orbital myofibroma in an adult patient. The clinical, histopathologic and immunohistochemical findings of the tumor are documented.
CONCLUSIONS
A comprehensive review of pediatric and adult orbital and periocular involvement by myofibroma is presented. Its characteristic pathologic and molecular findings are reviewed.
IMPORTANCE
Myofibromas are uncommon but important tumors that can occur in the head and neck region, including the orbit. Seen more often in children, they can rarely be encountered in adult patients. Diagnosis is possible with a panel of immunostains and molecular analysis can be further confirmatory.
PubMed: 33089011
DOI: 10.1016/j.ajoc.2020.100955