Genetic variant of SRF-rearranged myofibroma with a misleading nuclear expression of STAT6 and STAT6 involvement as 3' fusion partner.

Pediatric neoplasms with a myofibroblastic differentiation are frequent in children, in particular myofibroma. Recently, a novel deep soft tissue myofibroblastic neoplasm has been described with high cellularity, a smooth muscle phenotype and SRF-RELA fusion. We report the case of a 15-year-old boy who presented with a tumor of the deep soft tissue of the arm, with overlapping histological features with the recently described SRF-RELA group of myofibromas but differing by the presence of calcifications, a novel SRF-STAT6 fusion transcript and nuclear expression of STAT6. No local recurrence nor distant metastasis was detected at the current follow-up of 29 months. The clinical relevance of this novel fusion requires further investigations.

Putative Intravascular Myofibroma Mimicking a Vascular Malformation With Phleboliths.

Myofibroma is a rare, benign myofibroblastic tumor that commonly presents at birth or in early infancy, usually as a painless, slow-growing, solitary, nodular mass. We present a case of a 40-year-old woman with a painful, solitary, myofibroma on the right elbow. The unique features of this case include age and gender of the patient, site, pain on presentation, tumor morphology, and putative intravascular nature of the tumor.

Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.

Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery. One chest wall soft tissue tumor in a 3-month-old girl case showed a SRF-C3orf62 fusion, while the other, a forearm lesion in an 8-year-old girl, showed a SRF-RELA fusion. Further screening of 42 cellular examples of myofibroma/myopericytoma by fluorescence in situ hybridization identified additional 8 cases with recurrent SRF gene rearrangements, 6 of them showing identical SRF-RELA fusions. The cohort was composed of 7 females and 3 males, with a wide age range of 3 months to 63 years (mean=17). All tumors showed a densely packed growth of oval to spindle cells with fibrillary eosinophilic cytoplasm, arranged either in intersecting fascicles or with a distinct nested pattern around a rich vascular network. Despite the dense cellularity and variable mitotic activity none of the lesions displayed nuclear pleomorphism or necrosis. All tumors showed coexpression for SMA and desmin, in most cases with a strong and diffuse pattern of staining, while myogenin was consistently negative. No distant metastases were seen in the few cases with follow-up information. A control group of 34 well-characterized myofibroblastic and perivascular tumors, including 10 typical myofibromas and 3 myopericytomas, were also investigated for SRF gene abnormalities by fluorescence in situ hybridization and were negative. In summary, we report a subset of cellular variants of myofibroma and myopericytoma showing a smooth muscle-like immunophenotype and harboring recurrent SRF-RELA gene fusions, which mimic sarcomas with myogenic differentiation.

Phenotypic characterization of perivascular myoid cell neoplasms, using myosin 1B, a newly identified human pericyte marker.

Our aims were to identify pericyte-specific markers for the analysis of formalin-fixed, paraffin-embedded human tissue samples, and to characterize perivascular myoid cell neoplasms phenotypically. Previously identified pericyte markers failed to distinguish pericytes from other cellular types, such as vascular smooth muscle cells (vSMCs) and fibroblasts, in immunohistochemistry analysis. However, we compared gene expression profiles between pericytes, vSMCs, and fibroblasts, and performed human skin vasculature immunohistochemistry analysis, which led to the identification of myosin 1B (MYO1B) as a novel pericyte marker. Afterward, we investigated the expression levels of MYO1B and h-caldesmon (h-CD) in perivascular myoid cell neoplasms, angioleiomyomas (n=28), glomus tumors (n=23), and myopericytomas (n=3). Angioleiomyomas were shown to contain MYO1B-negative and h-CD-positive (MYO1B-hCD+) tumor cells, with vSMC features. Glomus tumors were predominantly composed of the MYO1B+hCD+ tumor cells, with the intermediate features between pericytes and vSMCs, whereas MYO1B+hCD- tumor cells with pericytic features and/or the MYO1B-hCD+ tumor cells with vSMC features were frequently found in these tumors. The perivascular concentric pattern of 2 myopericytoma cases was composed of MYO1B+hCD+ tumor cells, whereas that of one myopericytoma contained MYO1B-hCD+ tumor cells. These results indicate that the ability to distinguish between these cell types may allow us to understand the differentiation and origin of perivascular myoid cell neoplasms. This is the first study to identify cell properties of perivascular myoid cell neoplasms by using a pericyte-specific marker with considerably lower expression in vSMCs and fibroblasts.

A case of congenital myofibroma of the orbit presenting at birth.

PURPOSE: The purpose of this report is to highlight a rare cause of congenital proptosis. METHODS: This is a case report. RESULTS: We present a case of a baby girl born with a large myofibroma in the right retrobulbar space. This case is unusual because it presented from birth and was in a critical location. A prenatal ultrasound performed two days prior to birth did not reveal this mass to the technician or obstetrician. At birth, the tumor induced severe proptosis, with the eyelids unable to close around the globe. Deterioration of the ocular surface secondary to exposure was evident immediately after birth. One week after birth, the mass was excised by the Oculoplastics service in conjunction with a Neurosurgical team using a transcranial approach. The tumor was diagnosed by histopathology and immunologic staining as a myofibroma, a rare condition. CONCLUSIONS: Orbital myofibroma is a rare cause of congenital proptosis presenting at birth.

Myofibroma of the conjunctiva invading the cornea in infancy.

The authors report a novel case of solitary infantile myofibroma originating from the conjunctiva and encroaching over the limbus. This is an observational case report with clinicopathologic correlation. Immunostaining of the lesion was positive for vimentin and smooth muscle actin, and negative for pancytokeratin, desmin, myogenin, EMA, myoglobin, HMB45, and MelanA. To the authors' knowledge, this is the first reported case of myofibroma originating from the conjunctiva and this case highlights the importance of considering myofibromatosis in the differential diagnosis of unusual conjunctival lesions.

Oral myofibromas: report of two cases and review of clinical and histopathologic differential diagnosis.

Myofibroma is a benign mesenchymal neoplasm composed of myofibroblasts which has been described with different synonyms since the first report in 1951. It may show clinical and histologic features that may be misinterpreted as a malignancy. We describe 2 cases of oral myofibromas affecting infants; the first one showed a rapid growth with teeth displacement and ulceration; the second one presented a relatively slow growth with an indolent course. Differential diagnosis included benign and malignant mesenchymal neoplasms, salivary gland tumors, and reactive processes. Microscopic analysis of both lesions revealed a spindle cell tumor with immunoreactivity for vimentin, muscle-specific actin, and specific smooth muscle isoform alpha-actin, rendering the diagnoses of myofibroma. The patients were treated with surgical excision, and both are in follow-up without any signs of recurrence. Myofibroma presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessary aggressive therapy.

Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases.

BACKGROUND: Myopericytoma (MPC) is a generic denomination to describe tumors showing differentiation toward perivascular myoid cells /myopericytes. It has been suggested that MPC forms a morphologic continuum with glomus tumor (GT), solitary myofibroma (SMF), and angioleiomyoma (ALM). This proposed relationship has not yet been assessed in the oral region. METHODS: We reviewed our 28-year experience with 35 oral tumors, originally diagnosed as ALM (n = 28), SMF (n = 4), GT (n = 2), and MPC (n = 1) to analyze their overlapping microscopic features, with the assistance of immunohistochemistry. RESULTS: Myopericytoma showed a wide range of growth patterns; concentric perivascular whorls, hemangiopericytomatous areas, glomangiopericytoma (GPC)-type vessels and leiomyomatous foci. Intravascular growth was also seen. Among 28 cases studied, three ALM were reclassified as MPC (n = 2) and SMF (n = 1), based on the present diagnostic criteria. Additional MPC-type components, at varying degrees, were similarly found in four ALM and three SMF, at least focally. One GT featured intravascular whorls of spindle cells. These four interrelated groups of tumors had in common GPC-type vasculature and intraluminal cellular proliferation was nearly ubiquitously present. Diffuse immunoreactivity for alpha-smooth muscle actin and less staining intensity of muscle-specific actin were observed in all tumors. Only ALM displayed desmin positivity of variable extent. Neither case tested expressed CD34. CONCLUSIONS: Our data matches with the recent results in extraoral sites that MPC, GT, SMF, and ALM exhibit histologic and immunohistochemical overlap with each other. A common perivascular myoid differentiation between these tumor types is further reinforced by the present oral series.

[Pediatric mandibular myofibromatosis]. / Myofibromatose infantile de la mandibule.

INTRODUCTION: Pediatric myofibromatosis is a rare tumor in neonates and children. Two forms are described, solitary and multicentric, the solitary type is more common and is localized mainly on the head and the neck, mandible involvement is rare. The aim of this article was to report the anatomoclinical and therapeutic features of this pediatric tumor in a case as well as its follow-up. CASE REPORT: A 10-year-old girl was brought to consultation for a lower left gingival swelling 5 cm in diameter, forming a unit with the mandibular bone. The volume had gradually increased over the last 12 months. Imagery revealed the presence of an osteolytic tumor benign in aspect, but locally aggressive. Conservative surgery was performed. The diagnosis of pediatric myofibromatosis was confirmed. Evolution was excellent and after three years of follow-up, there was no evidence of relapse. DISCUSSION: Pediatric myofibromatosis often presents as a painless, well-circumscribed, solid nodule. Imagery is very useful to assess lesion extension and for the therapeutic follow-up. The diagnosis is made on anatomopathological findings and immunohistochemical assessment. The treatment of the solitary myofibromatosis is primarily surgical and its prognosis is excellent contrary to the multicentric form.

Plexiform angiomyxoid myofibroblastic tumor of the stomach.

We report 2 cases of plexiform angiomyxoid myofibroblastic tumor of the stomach, a tumor entity that has not been described previously. The patients were a 50-year-old man (case 1) and a 68-year-old man (case 2). In case 1, the patient presented with acute abdominal pain. The tumor in case 2 was incidentally found at laparoscopic cholecystectomy. Grossly, the tumors were 4.0 cm (case 1) and 4.5 cm (case 2) in their greatest dimension, and they were recognized as submucosal tumors. The tumor caused gastric perforation in case 1. Histologically, the tumors extended from the serosa to the submucosa of the gastric wall, showing a plexiform growth pattern. Bland spindle tumor cells were observed, and they were separated by abundant intercellular myxoid matrix. The stroma was rich in small vessels. Immunohistochemically, the tumor cells were positive for alpha-smooth muscle actin and muscle actin, and negative for KIT, CD34, and S-100 protein. Electron microscopic findings were consistent with the myofibroblastic nature of the tumor cells. No mutations were found in the c-kit and platelet-derived growth factor receptor alpha genes. Although clinical follow-up data were insufficient, the histologic appearances suggested the benign nature of the tumors. However, the tumor in case 1 caused gastric perforation and necessitated an emergency operation.

Angioleiomyoma: a clinicopathologic and immunohistochemical reappraisal with special reference to the correlation with myopericytoma.

In spite of the histologic overlap, the relationship between angioleiomyoma and myopericytoma has not yet been fully evaluated. One hundred thirty lesions originally diagnosed as angioleiomyoma and 4 tumors identified as myopericytoma were reassessed both histologically and immunohistochemically. One hundred twenty-two tumors were thus reclassified as angioleiomyoma (74 solid, 37 venous, and 11 cavernous types) and 12 as myopericytoma based on the predominant histologic pattern. In 1 patient, 1 myopericytoma and 1 venous-type angioleiomyoma were synchronously present. The perivascular concentric arrangement of cells, which is a salient feature of myopericytoma, was also focally recognized in 19 angioleiomyomas (12 venous, 4 solid, and 3 cavernous types). An angioleiomyoma-like fascicular pattern of elongated myoid cells was partially present in 7 myopericytomas, 4 of which resembled the feature of the cavernous subtype and 3 the venous one. Immunohistochemically, most tumor cells of all cases of both angioleiomyomas and myopericytomas were diffusely positive for actins (alpha-smooth muscle actin and HHF35) and calponin, and all cases, except for 1 myopericytoma, were also diffusely or focally positive for h-caldesmon. Desmin was diffusely positive in 75.7% of solid-type angioleiomyomas, 51.4% of venous type, and 18% of cavernous type, whereas most of the myopericytomas were negative for desmin, even though desmin-positive cells were only partially seen in 3 myopericytomas. The concentric structures of myoid cells in angioleiomyomas were, however, consistently negative for desmin. Our data further support the close kinship between angioleiomyoma and myopericytoma that has been recently suggested.

[Congenital myofibroma. A true hemangiopericytoma. A neonatal case with immunohistochemical and ultrastructural studies]. / Miofibroma congénito. Un hemangiopericitoma verdadero. Un caso neonatal con estudio inmunohistoquímico y ultraestructural.

We report the case of a male newborn infant with a pedunculated dermic tumor, located in the right malar region; who underwent a complete surgical resection of the tumor and had a satisfactory postoperative evolution. The histopathologic findings disclosed a subcutaneous tumor with a nodular aspect and a subendothelial intravascular growth, constituted by a dual population of small cells and spindle-shaped cells, distributed in a biphasic pattern. All tumor cells showed a strong pericellular reaction for PAS. The immunohistochemical studies revealed: diffuse cytoplasmic positivity for CD34 and Vimentin in all tumor cells, and only spindle-shaped tumor cells and less differentiated isolated neoplastic cells, presented cytoplasmic positivity for the smooth muscle alpha-actin. The electronic microscopy demonstrated a layer of basal membrane and in the citoplasm, numerous intermediate filaments with focal condensations. Based on all these findings, we conclude that this is a myofibroma, a "true hemangiopericytoma" with myofibroblastic differentiation. For this reason, we propose the term myofibropericytoma, in order to highlight its pericytic origin and its myofibroblastic differentiation. We emphasize the need to recognize this entity, in view of its low frequency and the possibility of a diagnostic mistake with other soft tissues tumors that display haemangiopericytoma-like features.

Solitary testicular myofibroma: a case report and review of the literature.

Myofibromas are benign mesenchymal neoplasms of myofibroblastic origin. Most present as solitary lesions at any age, but the presentation of multiple lesions in newborns and infants is known as infantile myofibromatosis. Multicentric lesions commonly involve soft tissues and bone and may involve internal organs, where they are associated with an unfavorable prognosis. Solitary lesions involving the viscera are rare. We report a case of a 3-month-old male infant with a left testicular mass detected during an evaluation for suspected torsion. The patient underwent orchiectomy, revealing a nodular mass with grossly evident foci of necrosis. Histologically, the lesion exhibited small fascicles of plump eosinophilic, smooth muscle actin-positive spindle cells, alternating with larger areas of primitive cells with vesicular nuclei and scant cytoplasm arranged around a hemangiopericytoma-like vasculature. To our knowledge, this is the first report of a myofibroma localized within the testis.

Urachal inflammatory myofibroblastic tumor with ALK gene rearrangement: a study of urachal remnants.

OBJECTIVES: Abnormalities of the urachus are rare among children and include a patent tract and cyst formation. These structures can also be affected by infection and abscess development. They are usually diagnosed during infancy and treated by surgical resection. Involvement of this remnant by either benign or malignant tumors is very infrequent. A few cases of mesenchymal tumors, such as desmoid tumor and leiomyoma, involving the urachus have been described in published reports. METHODS: We studied an inflammatory myofibroblastic tumor arising from the urachus in a 10-year-old boy. In addition, we reviewed 101 cases of urachal remnants retrieved from the surgical pathology and autopsy files in the Department of Pathology at the Children's Hospital Boston diagnosed in the past 82 years. RESULTS: The urachal inflammatory myofibroblastic tumor showed anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and fluorescence in situ hybridization techniques. No other neoplasms were diagnosed in the analyzed population. CONCLUSIONS: We describe an example of inflammatory myofibroblastic tumor involving the urachus. Involvement of the urachus by tumors is rare, but these should be considered in the differential diagnosis of urachal lesions.