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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 -
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 -
A Unique Presentation of Multicentric Myofibromatosis in the Masseter Muscle of a Pediatric Patient.Ear, Nose, & Throat Journal Sep 2022A 12-year-old female with a history of multicentric infantile myofibromatosis (IM) presented with a tender, enlarging cheek mass and trismus. Imaging identified an...
A 12-year-old female with a history of multicentric infantile myofibromatosis (IM) presented with a tender, enlarging cheek mass and trismus. Imaging identified an intramasseteric tumor. Given the unknown etiology of the tumor and her bothersome symptoms, the mass was excised using a transoral approach with concurrent facial nerve monitoring. Her pathology report confirmed the diagnosis of a myofibromatosis lesion embedded within the masseter muscle. While IM can often present with lesions in the head and neck region, the intramasseteric location is rare and presents unique considerations for surgical approach. Myofibromatosis lesions typically occur before two years of age, although there are some rare documented cases of multicentric myofibromatosis lesions presenting at older ages. Furthermore, this patient's family history of similar lesions suggests a familial variant, which may have implications for disease behavior and need for further work-up, monitoring, and management. Overall, this was an unusual presentation of IM given the patient's age, prevalent family history, and the location of the mass. This case report adds to the literature and discusses the clinical differential of a pediatric cheek mass, the surgical considerations for an intramasseteric tumor, and the natural history of infantile myofibromatosis.
PubMed: 36085035
DOI: 10.1177/01455613221125933 -
Journal of Cellular and Molecular... Jul 2022Penttinen syndrome is a rare progeroid disorder caused by mutations in platelet-derived growth factor (PDGF) receptor beta (encoded by the PDGFRB proto-oncogene) and...
Penttinen syndrome is a rare progeroid disorder caused by mutations in platelet-derived growth factor (PDGF) receptor beta (encoded by the PDGFRB proto-oncogene) and characterized by a prematurely aged appearance with lipoatrophy, skin lesions, thin hair and acro-osteolysis. Activating mutations in PDGFRB have been associated with other human diseases, including Kosaki overgrowth syndrome, infantile myofibromatosis, fusiform aneurysms, acute lymphoblastic leukaemia and myeloproliferative neoplasms associated with eosinophilia. The goal of the present study was to characterize the PDGFRB p.Val665Ala variant associated with Penttinen syndrome at the molecular level. This substitution is located in a conserved loop of the receptor tyrosine kinase domain. We observed that the mutant receptor was expressed at a lower level but showed constitutive activity. In the absence of ligand, the mutant activated STAT1 and elicited an interferon-like transcriptional response. Phosphorylation of STAT3, STAT5, AKT and phospholipase Cγ was weak or undetectable. It was devoid of oncogenic activity in two cell proliferation assays, contrasting with classical PDGF receptor oncogenic mutants. STAT1 activation was not sensitive to ruxolitinib and did not rely on interferon-JAK2 signalling. Another tyrosine kinase inhibitor, imatinib, blocked signalling by the p.Val665Ala variant at a higher concentration compared with the wild-type receptor. Importantly, this concentration remained in the therapeutic range. Dasatinib, nilotinib and ponatinib also inhibited the mutant receptor. In conclusion, the p.Val665Ala variant confers unique features to PDGF receptor β compared with other characterized gain-of-function mutants, which may in part explain the particular set of symptoms associated with Penttinen syndrome.
Topics: Acro-Osteolysis; Aged; Humans; Interferons; Limb Deformities, Congenital; Myofibromatosis; Progeria; Receptor, Platelet-Derived Growth Factor beta; STAT1 Transcription Factor
PubMed: 35689379
DOI: 10.1111/jcmm.17427 -
Clinical Case Reports Feb 2022Describe a novel use for a kinase inhibitor, imatinib, in young children with a known activated somatic mutation in PDGFR-beta. Two patients with infantile...
Describe a novel use for a kinase inhibitor, imatinib, in young children with a known activated somatic mutation in PDGFR-beta. Two patients with infantile myofibromatosis treated with imatinib. Case description of evaluation, diagnosis and treatment decisions for infantile myfibromatosis of the head and neck. Description of medical therapy for infantile myofibromatosis in these patients. For function threatening myofibromas of a known genotype, in infants, targeted medical therapy is a treatment option.
PubMed: 35154723
DOI: 10.1002/ccr3.5382 -
Children (Basel, Switzerland) Jan 2022Infantile myofibromatosis (IM) is a rare condition with a variable clinical presentation that characteristically affects young children. Most frequently it presents as...
Infantile myofibromatosis (IM) is a rare condition with a variable clinical presentation that characteristically affects young children. Most frequently it presents as one or more benign nodules of the skin, bones, soft tissues, or, rarely, visceral organs. According to the location and number of lesions, there are three different forms: solitary, multicentric without visceral involvement, and multicentric with visceral involvement (generalised), with the latter having the least favourable prognosis. We present a unique case of severe congenital generalised IM in a new-born male who required intubation and mechanical ventilation immediately after the birth due to respiratory distress. A chest radiograph showed numerous tumours involving the entire lung, resembling a metastatic lung disease. Additionally, the neonate had multiple, bluish, papular skin nodules and a biopsy of a skin nodule ultimately led to the diagnosis of IM. Diffuse lung involvement prevented adequate ventilation which resulted in multiorgan failure and death before targeted treatment could have been initiated. The presented case is unique, as such atypical extensive involvement of the lung and leptomeninges in IM has not been reported before. In this brief report, we present the findings of radiographic and ultrasonographic examinations in correlation with autopsy and histopathology.
PubMed: 35053678
DOI: 10.3390/children9010053 -
Medicine Dec 2021The purpose of this study was to investigate the upper trapezius muscle thickness (UTMT) in congenital muscular torticollis (CMT) patients and determine the correlation... (Observational Study)
Observational Study
The purpose of this study was to investigate the upper trapezius muscle thickness (UTMT) in congenital muscular torticollis (CMT) patients and determine the correlation among sternocleidomastoid muscle thickness (SCMT), accessory nerve (AN) cross-sectional area (CSA), and UTMT in CMT.This retrospective study consisted of 2 participant groups: Group 1 (SCM mass CMT, n = 20) and Group 2 (Postural CMT, n = 22). For both groups, B-mode ultrasound was performed by a physiatrist to measure the SCMT and UTMT and calculate the CSA of the AN. The correlation among SCMT, CSA of the AN, and UTMT in both groups was evaluated.The between-group comparison revealed that Group 1 had significantly greater SCMT, UTMT, and CSA of the AN on the affected side than Group 2 (P < .05). The intragroup comparison between the affected and unaffected sides also revealed that, in Group 1, the SCMT, UTMT, and CSA of the AN were significantly higher on the affected side than on the unaffected side (P < .05), whereas no significant differences were observed in Group 2. In Group 1, a positive correlation (r = 0.55) was observed between the UTMT and CSA of the AN on the affected side, but not observed between the SCMT and CSA of the AN.The findings of the study indicate that sternocleidomastoid muscle size may impact the thickness of the upper trapezius muscle via the accessory nerve in patients with congenital torticollis.
Topics: Adult; Female; Fibroma; Humans; Male; Middle Aged; Myofibromatosis; Neck Muscles; Retrospective Studies; Superficial Back Muscles; Torticollis; Ultrasonography
PubMed: 34967390
DOI: 10.1097/MD.0000000000028466 -
Diagnostics (Basel, Switzerland) Dec 2021Infantile myofibromatosis (IM) is a soft tissue disease with solitary or multiple benign tumors, and an etiology still unknown. IM is a mesenchymal disorder of early...
BACKGROUND
Infantile myofibromatosis (IM) is a soft tissue disease with solitary or multiple benign tumors, and an etiology still unknown. IM is a mesenchymal disorder of early infancy and is more frequent in males. IM may present as a solitary lesion of the skin, bone, muscle, subcutaneous tissue, located at the head, neck, and trunk, with good prognosis; or, as a multicentric form, with or without visceral involvement (heart, lung, gastrointestinal tract, kidney), with a poor prognosis. The definitive diagnosis of IM is confirmed by pathology. Treatment may be conservative, surgical, or chemotherapeutical.
CASE PRESENTATION
A two months old female patient, prenatally diagnosed at 30 weeks, presenting with a tumor on the antero-internal aspect of the left thigh. She was admitted due to rapid postnatal evolution, and the patient required surgery for tumor resection. Previously, clinically, biological and imaging investigations were performed, but the final diagnosis was histological and by immunostaining. The patient had a favorable postoperative outcome.
CONCLUSIONS
Despite its low frequency, IM should be considered in the differential diagnosis of soft tissue masses at an early age. The clinical form (solitary or multicentric), location, and visceral involvement will dictate the treatment and prognosis.
PubMed: 34943624
DOI: 10.3390/diagnostics11122389 -
Asian Journal of Surgery Jan 2022
Topics: Diagnostic Imaging; Humans; Leiomyoma; Magnetic Resonance Imaging; Myofibroma; Myofibromatosis
PubMed: 34848146
DOI: 10.1016/j.asjsur.2021.10.024