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.

Infantile Myofibromatosis of the Femoral Neck: A Case Report.

CASE: A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in the left femoral neck. The patient was avoiding weight-bearing on the affected extremity; thus, stabilization of the femoral neck was performed using a proximal femur locking plate. Postoperatively, he achieved all gross motor developmental milestones. CONCLUSION: This report is the first to describe a solitary infantile myofibroma in the femoral neck and demonstrates the utility of operative stabilization of these lesions.

Post-surgical thyroid bed myofibroma simulating a recurrent papillary thyroid carcinoma: A case report and review of the literature.

RATIONALE: Myofibromas are rare benign spindle cell tumors of the soft tissue, bone, or internal organs that occur at any age. Here, we report a post-surgical thyroid bed myofibroma that mimicked a papillary thyroid carcinoma. PATIENT CONCERNS: A 56-year-old male presented with a mass in the thyroid surgical bed, detected 3 years post thyroidectomy following papillary carcinoma. DIAGNOSIS: Thyroid ultrasonography revealed a well-defined, lobulated, hypoechoic, solid nodule, with large rod-like echogenic foci in the thyroid surgical bed. The development of a postoperative suture granuloma was considered. However, ultrasonography performed 12 months later showed a marked increase in the lesion size. Two fine needle aspiration cytology yielded nondiagnostic results. INTERVENTION: Considering the possibility of local tumor recurrence, surgical resection was performed. OUTCOME: The diagnosis of a myofibroma was confirmed, and no additional treatment was administered. LESSONS: It is challenging to differentiate lesions occurring on the thyroid surgical bed after surgery, from recurrent thyroid cancer. A lesion measuring 6 mm, with a degree of punctate echogenicity, suggests tumor recurrence. Moreover, myofibromas are extremely rare. This case highlights that it is advisable to perform a core needle biopsy in cases of nondiagnostic fine needle aspiration results.

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.

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.

Cellular myofibromas with SRF fusions: clinicopathological and molecular study of 3 cases of a rare entity and a potential mimic of sarcoma.

Cellular myofibromas/myopericytomas harboring recurring SRF fusions are recently characterized as rare and diagnostically challenging entities, which can mimic myogenic sarcomas. These tumors belong to the pericytic/perivascular myoid tumor family, which comprises a group of genetically heterogenous and sometimes morphologically overlapping entities. In this series, we describe 3 cases of SRF-rearranged cellular myofibromas/perivascular myoid tumors with a smooth muscle-like phenotype in children. The children ranged from 7 to 16 years of age, and all presented with a painless mass in the extremities, 2 of which were deep-seated. Histologically, the tumors demonstrated a smooth muscle-like morphology and immunophenotype with mild atypia and low-level mitotic activity. Prominent dense collagen deposition and coarse calcification was observed in 2 tumors. RNA sequencing revealed SRF fusions in all cases, with each tumor showing a different 3' partner gene, RELA, NFKBIE, and NCOA3. Of these, NCOA3 has not been reported previously, and this expands the molecular spectrum by identifying a novel fusion partner for SRF. Given that histological features can be worrisome for a myogenic sarcoma, wider awareness of this emerging tumor is valuable to avoid potential misclassification.

[Pediatric myofibroma/myofibromatosis of the soft tissue and bone: a clinicopathological analysis of 28 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myofibroma/myofibromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.

Myofibroma mimicking peripheral nerve sheath tumour with ulnar nerve compression symptoms.

We report a case of myofibroma encasing the ulnar nerve on the medial aspect of the left arm with motor and sensory deficit secondary to compression. Initially, the tumour appeared to be a benign peripheral nerve sheath tumour based on preoperative imaging, with clinical examination positive for left hand clawing and a positive Wartenberg's and Froment's sign. However, intraoperative dissection demonstrated that the mass did not originate from the ulnar nerve proper, lowering suspicion for a peripheral nerve sheath tumour. Histopathological analysis showed spindle cell neoplasm, consistent with myofibroma. The patient underwent hand occupational therapy subsequently, with improvement of grip strength from 5 lb to 12 lb by 4 months postoperatively and resolution of clawing of the hand postoperatively. We discuss differentiating features for this rare occurrence of solitary adult myofibroma, where the final diagnosis was only made after formal histopathological analysis.

PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors.

Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.

A rare case of solitary palatal myofibroma in a young pediatric patient.

Myofibroma (MF) is a benign spindle cell neoplasm rarely found in the oral cavity. It is common in males than females (2:1) and mostly seen to develop before 2 years of age with few cases reported in adults. This article reports a rare case of solitary MF of the hard palate in an 8-year-old female child; highlighting the clinical features, histopathology, differential diagnosis while emphasizing the importance of immunohistochemistry in establishing an accurate diagnosis and management of the same. The objective should be to differentiate benign versus malignant spindle cell lesions of smooth muscle, nerve tissue, fibrocytic, and histiocytic origin. Rapid growth of the lesion often raises suspicion of malignancy and may lead to misdiagnosis and inappropriate management.

Pediatric Subcutaneous Scalp Mass: A Case Report and Review.

Infantile myofibroma is a unique fibrous tumor encountered in the head and neck. Although the majority of cases are solitary nodules that require only conservative management, awareness of the possibility of multicentric disease is important considering its substantial morbidity. A 3-month-old girl presenting with an enlarging 2.5-cm firm, mobile, nontender subcutaneous scalp mass was evaluated with magnetic resonance imaging and biopsy, revealing a diagnosis of infantile myofibroma. The literature was reviewed for supporting evidence of recommended management in a disease with no official treatment guidelines. Histological, genetic, and imaging characteristics are reviewed. Although biopsy is mandatory, conservative management can be employed for cases without multicentric involvement. Although there are no official guidelines for the evaluation of visceral involvement, skeletal radiograph and abdominal ultrasound are recommended. Infantile myofibroma is a distinct clinical entity with predilection for the head and neck. Its unique immunohistopathology and clinical course should be well understood and should be included in the differential diagnosis of infantile skin and subcutaneous masses.

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.

Identification and functional characterization of transcriptional activators in human cells.

Transcription is orchestrated by thousands of transcription factors (TFs) and chromatin-associated proteins, but how these are causally connected to transcriptional activation is poorly understood. Here, we conduct an unbiased proteome-scale screen to systematically uncover human proteins that activate transcription in a natural chromatin context. By combining interaction proteomics and chemical inhibitors, we delineate the preference of these transcriptional activators for specific co-activators, highlighting how even closely related TFs can function via distinct cofactors. We also identify potent transactivation domains among the hits and use AlphaFold2 to predict and experimentally validate interaction interfaces of two activation domains with BRD4. Finally, we show that many novel activators are partners in fusion events in tumors and functionally characterize a myofibroma-associated fusion between SRF and C3orf62, a potent p300-dependent activator. Our work provides a functional catalog of potent transactivators in the human proteome and a platform for discovering transcriptional regulators at genome scale.