Clinicopathological features of myofibromas and myofibromatosis affecting the oral and maxillofacial region: A systematic review.

BACKGROUND: Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report. RESULTS: A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases. CONCLUSION: MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.

Isolated infantile myofibroma of the calvarium: Report of a case with a literature review.

OBJECTIVE: Infantile myofibromatosis is a rare entity of childhood characterized by benign myofibroblastic tumors in the soft tissues, the bones, and occasionally the viscera. Solitary skeletal lesions are relatively uncommon. Calvarial involvement should be distinguished from more aggressive tumors for appropriate treatment. METHODS: We reviewed solitary infantile myofibroma of the calvarium and discussed the relevant computed tomography and magnetic resonance imaging findings along with differential diagnosis. A case study of the frontal bone in a 5-month-old girl was also presented. RESULTS: Fourteen cases were reviewed, including the current case. Of the 13 cases with known sex, eight were male and five female. The mean age was 3.03 with an age range of 0.41-9 years. Nine of the 14 tumors were in the frontal bone. The lesions were intradiploic with tabula interna and/or externa of the calvaria involvement. The mean largest diameter was 22.3 mm. Upon computed tomography, all the lesions were expansile and lytic, and hypoattenuated, isoattenuated or occasionally hyperatenuated. Calcification was not seen. On magnetic resonance imaging, most neoplasms were hypointense on T1-weighted and T2-weighted images. Neoplasms showed hypointense signal on diffusion-weighted imaging and hyperintense on apparent diffusion coefficient, without restricted diffusion in three cases. All lesions were intensely enhanced after gadolinium administration. Treatment was total surgical resection and recurrence was not observed during follow-up. CONCLUSIONS: Infantile myofibromas are rare, typically intradiploic expansile lytic lesions with tabula interna and/or externa involvement. Distinctive imaging features include the presence of hipointense signals on T2-weighted magnetic resonance images without restricted diffusion on diffusion-weighted imaging. A slow-growing, firm, painless, and nontender mass with supportive imaging findings should raise suspicion of the disease.

Intraosseous myofibroma mimicking an odontogenic lesion: case report, literature review, and differential diagnosis.

BACKGROUND: Intraosseous myofibroma of the jaw is a rare neoplasm of mesenchymal origin with limited comprehensive understanding. It typically affects patients in the first two decades of life with a male predilection. CASE PRESENTATION: This study presents a rare case of myofibroma mimicking an odontogenic lesion in a 2-year-old boy. The patient presented with an incidental finding of a painless swelling of the right mandibular ramus of unknown etiology. Imaging analysis revealed a solid, expansile lesion adjacent to the germinal zone of the right mandibular first molar. Histopathologic analysis and immunohistochemistry after incisional biopsy suggested a possible central odontogenic fibroma, and the patient underwent total enucleation, leading to the final diagnosis of intraosseous myofibroma. Follow-up examinations showed no evidence of recurrence. CONCLUSIONS: This report contributes to the understanding of myofibroma in pediatric patients and underscores the critical role of meticulous histopathologic examination for effective surgical planning and optimal patient outcomes.

Unresectable infantile myofibroma discovered in utero.

The authors present a case of a proliferative nodule located beneath an infant's lower lip that was initially discovered on prenatal ultrasound and fetal magnetic resonance imaging (MRI). Biopsy revealed a smooth muscle actin-positive spindled cell proliferation with hemangiopericytoma-like vessels consistent with infantile myofibromatosis (IM). Since the location prevented surgical management, the clinicians opted to observe the lesion. Ultimately, the lesion fully regressed on its own confirming conservative management is an option for isolated IM.

Solitary intraosseous myofibroma: a rare case diagnosed from mandibular fracture.

Intraosseous myofibroma is a rare tumor of benign nature, slow growth, and low morbidity. The aim of this article is to report a case of pathologic fracture associated with the incidental diagnosis of myofibroma in the mandible of an adolescent. A 15-year-old girl reported that she experienced a physical assault resulting in facial injuries 1 month previously and had since experienced severe pain, malocclusion, and chewing difficulty. The cone beam computed tomographic examination revealed multiple features suggestive of pathologic fracture associated with a hypodense lesion with lobulated limits, as well as expansion and thinning of the cortical bone in the left mandible. The histopathologic diagnosis of the lesion indicated myofibroma. Treatment consisted of enucleation and curettage of the lesion with reduction and internal fixation of the fracture. After 18 months, the osteosynthesis plates and an impacted mandibular third molar were removed. Curettage of the lesion in association with treatment of the mandibular fracture proved to be effective for both bone consolidation and absence of recurrence while restoring mandibular functionality.

Uterine tumours with myogenic differentiation harbouring SRF::RELA fusions.

AIMS: In 2017, a subset of cellular variants of myofibroma and myopericytoma with a smooth muscle-like immunophenotype and harbouring recurrent SRF::RELA gene fusions was reported. Although the anatomical distribution was found to be quite broad, no tumours with these gene fusions in the female reproductive system have been illustrated to date. METHODS AND RESULTS: Herein, we report the histological and immunophenotypical features of three uterine tumours with SRF::RELA gene fusions. Microscopically, all three tumours were composed of cellular oval to spindle cells arranged in intersecting fascicles with variable amounts of collagen and a rich capillary network. Mitotic figures were scant. Regarding immunohistochemistry, diffuse staining for desmin, oestrogen receptor and progesterone receptor was observed in all three cases. The first case exhibited focal staining for h-caldesmon, whereas the latter two cases had diffuse staining. Furthermore, SRF::RELA rearrangement was observed in all three cases by using next-generation sequencing (NGS). Follow-up, ranging from 11 to 15 months, was available for these three patients, all of whom were well without evidence of disease. CONCLUSIONS: In conclusion, we reported a special group of uterine neoplasms with myogenic differentiation harbouring SRF::RELA rearrangement. Although the follow-up time was limited, morphological characteristics and other studies with follow-up data supported that this type of uterine neoplasm appeared to behave in a benign manner. Further studies with longer follow-up are needed to clarify the biological nature of this particular type of uterine tumour.

Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series.

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.

Solitary cutaneous infantile myofibroma as a hallmark of myofibromatosis: Two cases and review of the literature.

Infantile myofibroma (IM) commonly presents as a benign cutaneous fibrous tumor in infancy. Although the majority of solitary IM regress without any morbidity, some cases have underlying bone or visceral involvement that can lead to both morbidity and mortality. In this report with review of the literature, we present two cases of solitary cutaneous IM with internal involvement and discuss screening cases of solitary IM with full body imaging.

A rare low-grade myofibroblastic sarcoma in lower jaw with the resemblance to benign lesions.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a rare solid infiltrative soft tissue tumor with a predilection for the head and neck region. CASE PRESENTATION: We report the diagnostic steps of a fast-growing lesion of the lower left jaw in a 45-year-old otherwise healthy woman. A first biopsy and subsequent histopathological examination showed potential differentials of a benign myofibroma, benign nodular fasciitis or an LGMS. This diagnostic overlap was a challenge for the decision of the further treatment approach. The treatment consisted of a segmental en bloc resection of the mandible including the second premolar, first and second molar. Histopathological examination of the resected tumor confirmed an LGMS. CONCLUSION: The histopathologic resemblance of LGMS to a range of benign and reactive tumors may lead to misdiagnosis and mistreatment. The rarity of LGMS explains the lack of established treatment protocols. This case shows the importance of adequate clinical decisions, expertise in the histopathology of rare tumors and interdisciplinary exchange to achieve state-of-the-art patient management.

Epibulbar solitary myofibroma in an elderly patient: a case report.

A 93-year-old male patient presented with abrupt expansion of an old epibulbar mass at the temporal area of the left eye. He had a medical history of previously treated laryngeal cancer with surgery and radiotherapy. The tumor, despite being firmly attached to the underlying sclera, was excised completely and histopathological examinations revealed a solitary myofibroma. The patient had a 4-month uneventful follow-up with excellent wound healing. Solitary myofibroma may be a differential diagnosis for epibulbar masses in elderly patients.

Infantile Myofibroma: A Series of 2 Cases with Special Reference to Cytological Features.

BackgroundInfantile myofibromas (IM) are benign soft tissue lesions of childhood and represent a significant portion of the benign spectrum of fibroblastic-myofibroblastic tumors. Cytological diagnosis of these tumors can be challenging because of overlapping morphology and limited case report descriptions. We describe the cytological features and the cytological differential diagnoses.Case reportWe describe cytological features of two IMs. The main features were the presence of loose clusters and dispersed bland myofibroblasts in varying stages of maturation with traversing blood vessels and myxoid stroma. The cells typically lacked features of atypia, mitoses and significant pleomorphism.ConclusionDiagnosis of IM on the basis of cytology alone can be tricky and definitive diagnosis should be made only after correlating the cytological features with histology. However, bland morphology of differentiating myofibroblasts can aid in cytological diagnosis and help to exclude other malignant spindle cells neoplasms needing preoperative chemotherapy.

Infantile Fibrosarcoma and Other Spindle Cell Neoplasms of Infancy. A Review of Morphologically Overlapping yet Molecularly Distinctive Entities.

BACKGROUND: Regardless of age at presentation, many soft tissue neoplasms have overlapping histopathologic and immunophenotypic features to serve as a diagnostic challenge. CASE REPORT: We reported a case of a spindle cell neoplasm in an infant, which was initially considered a vascular anomaly clinically and an eventual biopsy revealed marked inflammation with a spindle cell component that was resolved as an infantile fibrosarcoma with an ETV6 break-apart. CONCLUSION: The context of this case lead to a further consideration of various other spindle cell neoplasms arising predominantly in the soft tissues during the infancy period as defined by the first two years of age. Though sharing similar morphologic features, these tumors can be categorized into several molecular genetic groups, which have provided both diagnostic and pathogenetic insights as well as treatment options in some cases.

Infantile Myofibroma: A Report of Two Cases with Differential Diagnoses.

Infantile myofibromas (IMs) are benign soft-tissue tumors of children. They are of fibroblastic-myofibroblastic origin and show considerable morphological overlap with other spindle cell neoplasms. Here, we present two cases of solitary myofibromas, one in a neonate and one in a 2-year-old girl. A 2-day-old girl presented with severe respiratory distress and died during intubation. At autopsy, a myofibroma involving the oropharynx with extension up to the larynx was noted. Second case was a 2-year-girl with a myofibroma in the hard palate. IM must be differentiated from other benign and malignant spindle cell tumors of infancy and childhood. Oropharyngeal myofibroma should be considered in the differentials of neonatal respiratory distress.

Novel COL4A1-VEGFD gene fusion in myofibroma.

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.

An unusual case of a solitary cardiac myofibroma causing severe right ventricular outflow tract obstruction in an infant.

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.

Solitary myofibroma preceding the development of multicentric myofibromatosis: A report of two cases with surveillance recommendations.

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.

Odontogenic myxomas lack PDGFRB mutations reported in myofibromas.

BACKGROUND: The molecular pathogenesis of odontogenic myxoma has not been established yet. Considering that odontogenic myxoma may show myofibroblastic differentiation and myxoid areas can be observed in intra-osseous myofibromas, we tested the hypothesis whether both tumors share a common molecular profile. As recent studies have reported PDGFRB recurrent driver mutations in myofibroma, we evaluated PDGFRB mutations in odontogenic myxomas. METHODS: A convenience sample of 15 odontogenic myxomas cases was selected. We direct sequenced PDGFRB exons 12 and 14, where p.R561C (c.1681C>T) and p.N666K (c.1998C>G) hotspot mutations have been reported among others in single and/or multiple myofibromas. RESULTS: All 15 odontogenic myxoma samples were successfully sequenced, and all 15 had wild-type sequences for the PDGFRB mutations investigated. CONCLUSION: Our findings suggest that PDGFRB mutations do not play a role in odontogenic myxoma pathogenesis, which might be helpful in the differential diagnosis of challenging cases.

Myofibroma/myofibromatosis: MDCT and MR imaging findings in 24 patients with radiological-pathological correlation.

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.

Kosaki overgrowth syndrome: A newly identified entity caused by pathogenic variants in platelet-derived growth factor receptor-beta.

Specific classes of de novo heterozygous gain-of-function pathogenic variants of the PDGFRB (platelet-derived growth factor receptor-beta) cause a distinctive overgrowth syndrome, named the Kosaki overgrowth syndrome (KOGS) (OMIM #616592). Until now, six patients with this condition have been reported in the literature. In addition to skeletal overgrowth, these patients exhibit hyperelastic, translucent, and fragile skin, scoliosis, progressive loss of subcutaneous adipose tissue, skull deformity, infantile myofibromas, neuropsychiatric symptoms, and arachnoid cysts in the posterior fossa and periventricular white matter signal abnormalities on neuroimaging. This constellation of phenotypes clearly distinguishes KOGS from other PDGFRB-related disorders, including idiopathic basal ganglia calcification, infantile myofibroma, and Penttinen-type premature aging syndrome. From a molecular standpoint, PDGFRB is a dimeric receptor tyrosine kinase that plays critical roles in cell growth and tumorigenesis. The two known types of pathogenic variants (p.(Pro584Arg) and p.(Trp566Arg)) of the PDGFRB that cause KOGS are exclusively located in the juxtaglomerular domain that regulates autoactivation/inhibition of PDGFRB. In-vitro evidence suggests that p.(Pro584Arg) represents a gain-of-function pathogenic variant. Inhibition of PDGFRB activity using multi-kinase inhibitors appears to be a potentially promising therapeutic approach. Investigation of the molecular mechanisms underlying the pathogenesis of this disease using induced pluripotent stem cells is under way. Presence of skeletal overgrowth, distinctive facial features, characteristic hyperelastic and fragile skin, and cerebral white matter lesions with neuropsychiatric symptoms should prompt genetic analysis of the PDGFRB.

Infantile Myofibromatosis With Intracranial Extradural Involvement and PDGFRB Mutation: A Case Report and Review of the Literature.

Infantile myofibroma is a rare benign mesenchymal tumor that presents as solitary or multiple lesions (myofibromatosis) in the skin, soft tissue, bone, or internal organs. It most commonly affects the head and neck of infants and young children, but it can also affect adults. Intracranial involvement is reported to be extremely rare, and its clinical picture has been poorly characterized. Recently, it has been demonstrated that germline and somatic mutations in the platelet-derived growth factor receptor beta (PDGFRB) are associated with familial infantile myofibromatosis. We report a case of infantile myofibromatosis with predominant posterior fossa extradural involvement in a 14-year-old adolescent girl with a confirmed mutation in the PDGFRB gene.