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Radiology Case Reports Nov 2020Infantile myofibromatosis, the most common fibrous tumor of infancy, is classified in 2 forms; as a solitary nodule or as numerous, widely-distributed multicentric...
Infantile myofibromatosis, the most common fibrous tumor of infancy, is classified in 2 forms; as a solitary nodule or as numerous, widely-distributed multicentric lesions with or without visceral involvement. Although benign, multicentric myofibromas are still associated with a high incidence of morbidity and mortality due to the infiltration of critical structures. Herein, we present a case of an infant with aggressive and mutation-negative myofibromas distributed throughout the vascular, respiratory, and gastrointestinal systems. The extensive disease resulted in pulmonary hypertension, respiratory failure and gastrointestinal obstruction refractory to chemotherapy and unamenable to surgical resection. Despite the presence of numerous highly invasive myofibromas, multiple imaging modalities largely underestimated, or even missed, tumors found at autopsy. This case demonstrates the limitations of radiographic imaging to assess disease burden in multicentric infantile myofibromatosis. The postmortem findings of extensive disease far exceeding what was demonstrated by multiple imaging modalities suggests that pediatricians should have a high index of suspicion for undetected tumors if clinical deterioration is otherwise unexplained.
PubMed: 33014229
DOI: 10.1016/j.radcr.2020.09.029 -
Familial Cancer Oct 2021Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue...
Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
Topics: Child; Child, Preschool; Genetic Testing; Humans; Imatinib Mesylate; Myofibromatosis; Receptor, Platelet-Derived Growth Factor beta
PubMed: 32888134
DOI: 10.1007/s10689-020-00204-2 -
BMC Medical Imaging Aug 2020The aim of this study was to characterize the radiological features of myofibroma on multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) and...
BACKGROUND
The aim of this study was to characterize the radiological features of myofibroma on multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) and correlate the imaging findings with pathologic features.
METHODS
The radiological findings of 24 patients with 29 myofibromas were retrospectively reviewed. All images were evaluated with emphasis on density, signal intensity, hypointense area, and enhancement, correlating these with pathologic findings.
RESULTS
On plain MDCT scan, 4(26.7%) tumors were homogeneous isodensity, 4(26.7%) tumors were heterogeneous hyperdensity, and 7(46.7%) tumors were heterogeneous hypodensity. On contrast-enhanced MDCT scan, all tumors (9/9) showed heterogeneous enhancement with moderate in 3(33.3%) and marked in 6(66.7%) tumors, and their enhancements were higher compared to adjacent skeletal muscle (P = 0.0001). On MRI, heterogeneous slight hyperintensity, homogeneous slight hyperintensity, and heterogeneous hypointensity on T1-weighted imaging (T1WI) were observed in 14(82.3%), 1(5.9%) and 2(11.8%) tumors, respectively. On T2-weighted imaging (T2WI) and fat-suppressed (FS) T2WI, all tumors demonstrated heterogeneous hyperintensity. All tumors showed heterogeneous marked enhancement on FS contrast-enhanced T1WI. On T1WI, T2WI, FS T2WI, and FS contrast-enhanced T1WI, irregular strip or/and patchy hypointensities were found in 16(94.1%), 12(100%), 17(100%) and 17(100%) tumors, respectively, and pseudocapsule was seen in 5(29.4%) tumors. The hypointensities and pseudocapsule on MRI were exactly corresponding to pathological interlacing collagen fibers and fibrosis. The age of the recurrent group was lower than that of the non-recurrent group (P = 0.001) and the tumors without pseudocapsule were more likely to recur than those with pseudocapsule (P = 0.034).
CONCLUSION
Myofibromas are characterized by heterogeneous density or signal intensity, with moderate or marked enhancement. The hypointensities and pseudocapsule on MRI may be helpful in diagnosis, and the absence of pseudocapsule and younger age may be risk factors for tumor recurrence.
Topics: Adolescent; Adult; Age Factors; Child; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multidetector Computed Tomography; Myofibroma; Myofibromatosis; Retrospective Studies; Young Adult
PubMed: 32847537
DOI: 10.1186/s12880-020-00498-9 -
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 -
International Journal of Clinical and... 2019To describe a rare case of aggressive fibromatosis of the stomach and discuss the differential diagnoses.
OBJECTIVES
To describe a rare case of aggressive fibromatosis of the stomach and discuss the differential diagnoses.
METHODS
A 47-year-old man presented with nonspecific abdominal pain. Gastroscopy revealed stomach wall swelling. An antral gastrectomy was performed. Histological examination revealed spindle-shaped cells and morphology typical of aggressive fibromatosis. We performed a literature search to identify conditions with features similar to those of aggressive fibromatosis.
RESULTS
Aggressive fibromatosis does not metastasize, but it is locally invasive and has a tendency to relapse; however, our patient has not had recurrence > 1 year after surgery. Aggressive fibromatosis of the stomach may be confused with an inflammatory fibroid polyp, a gastrointestinal stromal tumor, schwannoma, leiomyoma, inflammatory myofibroblastic tumor, scirrhous carcinoma of the stomach, follicular dendritic cell sarcoma, inflammatory malignant fibrous histiocytoma, myofibroma/myofibromatosis, and solitary fibrous tumor of the stomach.
CONCLUSIONS
Aggressive fibromatosis of the stomach is a rare spindle cell tumor that must be differentiated from a variety of conditions.
PubMed: 31933754
DOI: No ID Found -
Ultrasound in Obstetrics & Gynecology :... Nov 2020
Topics: Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Myofibromatosis; Pregnancy
PubMed: 31909539
DOI: 10.1002/uog.21964 -
Cold Spring Harbor Molecular Case... Oct 2019Infantile myofibromatosis (IM) is an aggressive neoplasm composed of myofibroblast-like cells in children. Although typically localized, it can also present as...
Infantile myofibromatosis (IM) is an aggressive neoplasm composed of myofibroblast-like cells in children. Although typically localized, it can also present as multifocal disease, which represents a challenge for effective treatment. IM has previously been linked to activating somatic and germline point mutations in the PDGFRβ tyrosine kinase encoded by the gene. Clinical panel-based targeted tumor sequencing of a tumor from a newborn with multifocal IM revealed a novel rearrangement, which was reported as being of unclear significance. Additional sequencing of cDNA from tumor and germline DNA confirmed a complex somatic/mosaic rearrangement with an apparent partial tandem duplication disrupting the juxtamembrane domain. Ectopic expression of cDNA encoding the mutant form of PDGFRB markedly enhanced cell proliferation of mouse embryo fibroblasts (MEFs) compared to wild-type PDGFRB and conferred tumor-forming capacity on nontumorigenic 10T1/2 fibroblasts. The mutated protein enhanced MAPK activation and retained sensitivity to the PDGFRβ inhibitor imatinib. Our findings reveal a new mechanism by which PDGFRB can be activated in IM, suggest that therapy with tyrosine kinase inhibitors including imatinib may be beneficial, and raise the possibility that this receptor tyrosine kinase might be altered in a similar fashion in additional cases that would similarly present annotation challenges in clinical DNA sequencing analysis pipelines.
Topics: Animals; Cell Line; Extracellular Signal-Regulated MAP Kinases; Female; Fibroblasts; Germ-Line Mutation; Humans; Imatinib Mesylate; Infant, Newborn; Mice; Myofibromatosis; Protein Kinase Inhibitors; Receptor, Platelet-Derived Growth Factor beta
PubMed: 31645346
DOI: 10.1101/mcs.a004440 -
Indian Journal of Ophthalmology Jul 2019Myofibroma is a rare benign mesenchymal tumor of uncertain histogenesis. A six-year-old boy presented with a unilateral lower eyelid mass of six weeks' duration. MRI...
Myofibroma is a rare benign mesenchymal tumor of uncertain histogenesis. A six-year-old boy presented with a unilateral lower eyelid mass of six weeks' duration. MRI revealed a circumscribed mass in the inferolateral orbit with bony erosion. A systemic examination was unremarkable. Excision with histopathology revealed a partially infiltrative spindle cell tumor with bland nuclear morphology expressing smooth muscle actin and muscle-specific actin, compatible with myofibroma. Solitary myofibroma is a rare childhood orbital tumor and may clinico-radiologically closely mimic a malignancy. Histopathology and immunohistochemistry can help reach a definitive diagnosis. Systemic evaluation and close follow up are crucial in such cases.
Topics: Biopsy; Child; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Myofibroma; Orbit; Orbital Neoplasms; Rare Diseases; Tomography, X-Ray Computed
PubMed: 31238482
DOI: 10.4103/ijo.IJO_1553_18 -
JAMA Dermatology Aug 2019Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease.
IMPORTANCE
Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease.
OBJECTIVE
To determine the frequency, spectrum, and clinical implications of mutations in the PDGFRB receptor tyrosine kinase found in sporadic myofibroma and myofibromatosis.
DESIGN, SETTING, AND PARTICIPANTS
In this retrospective study of 69 patients with sporadic myofibroma or myofibromatosis, 85 tumor samples were obtained and analyzed by targeted deep sequencing of PDGFRB. Mutations were confirmed by an alternative method of sequencing and were experimentally characterized to confirm gain of function and sensitivity to the tyrosine kinase inhibitor imatinib.
MAIN OUTCOMES AND MEASURES
Frequency of gain-of-function PDGFRB mutations in sporadic myofibroma and myofibromatosis. Sensitivity to imatinib, as assessed experimentally.
RESULTS
Of the 69 patients with tumor samples (mean [SD] age, 7.8 [12.7] years), 60 were children (87%; 29 girls [48%]) and 9 were adults (13%; 4 women [44%]). Gain-of-function PDGFRB mutations were found in samples from 25 children, with no mutation found in samples from adults. Mutations were particularly associated with severe multicentric disease (13 of 19 myofibromatosis cases [68%]). Although patients had no familial history, 3 of 25 mutations (12%) were likely to be germline, suggesting de novo heritable alterations. All of the PDGFRB mutations were associated with ligand-independent receptor activation, and all but one were sensitive to imatinib at clinically relevant concentrations.
CONCLUSIONS AND RELEVANCE
Gain-of-function mutations of PDGFRB in myofibromas may affect only children and be more frequent in the multicentric form of disease, albeit present in solitary pediatric myofibromas. These alterations may be sensitive to tyrosine kinase inhibitors. The PDGFRB sequencing appears to have a high value for diagnosis, prognosis, and therapy of soft-tissue tumors in children.
PubMed: 31017643
DOI: 10.1001/jamadermatol.2019.0114 -
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