Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.

AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.

Novel MEAF6-SUZ12 fusion in ossifying fibromyxoid tumor with unusual features.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non-specific immunoprofile harboring a novel MEAF6-SUZ12 fusion. A 34-year-old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan-white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next-generation sequencing studies (sarcoma gene fusion next-generation sequencing panel with subsequent Sanger confirmation) performed on formalin-fixed paraffin-embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.

Superficial malignant ossifying fibromyxoid tumors harboring the rare and recently described ZC3H7B-BCOR and PHF1-TFE3 fusions.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation and intermediate biologic potential. Up to 85% of OFMTs, including benign, atypical, and malignant forms, harbor fusion genes. Most commonly, the PHF1 gene localized to 6p21 is fused with EP400, but other fusion partners, such as MEAF6, EPC1, and JAZF1 have also been described. Herein, we present two rare cases of superficial OFMTs with ZC3H7B-BCOR and the very recently described PHF1-TFE3 fusions. The latter also exhibited moderate to strong diffuse immunoreactivity for TFE3. Reciprocally, this finding expands the entities with TFE3 rearrangements. Accumulation of additional data is necessary to determine if OFMTs harboring these rare fusions feature any reproducible clinicopathologic findings or carry prognostic and/or predictive implications.

Primary malignant ossifying fibromyxoid tumour of the bone. A clinicopathologic and molecular report of two cases.

OBJECTIVE: To report the exceptional occurrence of ossifying fibromyxoid tumour (OFMT) as a primary bone lesion. OFMT is a rare soft tissue tumour of uncertain differentiation and variable malignant potential, that occurs in adults with a slight male predominance. It is typically located in the subcutis or in the skeletal muscles of the extremities, followed by trunk or head and neck. METHODS: Two cases of OFMT proven to arise from bone are presented. The first is a 65-year old female with a history of rib "osteosarcoma", presenting with an inferior lobe left lung mass. The second is a man with a lytic lesion of the 5th cervical vertebra that recurred shortly after resection. Following H&E and immunohistochemical examination, tumour samples were analysed by NGS and by break-apart FISH to detect rearrangement of the PHF1 and TFE3 genes. RESULTS: PHF1 gene-rearrangement was identified by FISH on both the primary and the metastatic lesion of first patient. NGS identified a PHF1(intron1) and EPC1 (exon 10) fusion transcript later confirmed by positive PHF1 rearrangement on FISH in the second case. CONCLUSIONS: The demonstration of PHF1 gene rearrangements represents a fundamental ancillary diagnostic test when presented with challenging examples of OFMT.

A potential conundrum in dermatopathology: molecularly confirmed superficial ossifying fibromyxoid tumors with unusual histomorphologic findings and a novel fusion.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain histogenesis, primarily arising in subcutaneous tissues of the extremities, head and neck, or trunk. Most cases present as well-circumscribed masses with a characteristic morphologic appearance, comprising cytologically bland ovoid cells with fibromyxoid stroma, a peripheral rim of metaplastic bone, and lobulated architecture. Nevertheless, tumors displaying unusual morphologic characteristics pose significant diagnostic challenges, requiring the detection of a pathogenic fusion for a definitive diagnosis. The majority of OFMTs exhibits PHF1 gene rearrangements. Herein, we present six cases of molecularly confirmed OFMTs with uncommon histomorphologic features, including the absence of myxoid stroma, extensive chondroid differentiation, prominent clear cell morphology, collagen entrapment, interdigitating fibrocollagenous and fibromyxoid stromal elements, and conspicuous red blood cell extravasation. One case harbored a novel fusion (EPC1::SUZ12). This study emphasizes the broad range of morphologic manifestations that can be encountered in OFMT and the crucial role of molecular testing in establishing a conclusive diagnosis in such cases.

Face memory and face perception in autism.

LAY ABSTRACT: It is well known that some people with autism have difficulties recognizing faces. It is generally thought that this is not because autistic individuals cannot perceive faces, but because autistic individuals have greater problems than people without autism in remembering faces. Here, we worked with a group of autistic adults and a group of non-autistic adults to test their ability to perceive and remember faces. We also asked each person to report any difficulties that they have with recognizing faces in everyday life. We find that, as a group, people with autism have difficulties with both remembering and perceiving faces, and report more problems recognizing faces in everyday life. However, it is worth noting that we observed a wide range of scores in the group of people with autism, with some autistic participants scoring as well as the group of people without autism.

Two-stream fusion model using 3D-CNN and 2D-CNN via video-frames and optical flow motion templates for hand gesture recognition.

Hand gestures are useful tools for many applications in the human-computer interaction community. Here, the objective is to track the movement of the hand irrespective of the shape, size and color of the hand. And, for this, a motion template guided by optical flow (OFMT) is proposed. OFMT is a compact representation of the motion information of a gesture encoded into a single image. Recently, deep networks have shown impressive improvements as compared to conventional hand-crafted feature-based techniques. Moreover, it is seen that the use of different streams with informative input data helps to increase the recognition performance. This work basically proposes a two-stream fusion model for hand gesture recognition. The two-stream network consists of two layers-a 3D convolutional neural network (C3D) that takes gesture videos as input and a 2D-CNN that takes OFMT images as input. C3D has shown its efficiency in capturing spatiotemporal information of a video, whereas OFMT helps to eliminate irrelevant gestures providing additional motion information. Though each stream can work independently, they are combined with a fusion scheme to boost the recognition results. We have shown the efficiency of the proposed two-stream network on two databases.

Ossifying Fibromyxoid Tumor: A Rare Subcutaneous Tumor.

Description The following case study demonstrates a 26-year-old male that presented to the dermatology clinic with an enlarging, raised skin nodule located on the left inferior lateral lower back. The patient reported it had persisted for two years, and he had not received prior treatment. He noted a family history of nonmelanoma skin cancer but had no other dermatological issues in the past. Physical examination revealed a pink, firm and well-circumscribed subcutaneous mass with a prominent follicular pore. It was assumed the lesion was an epidermal inclusion cyst, and surgical excision was performed. Histopathology revealed lobules of epithelioid cells with indistinct cytoplasm in a fibromyxoid hyalinized matrix surrounded by lamellar bone and a collagenous pseudocapsule. Immunohistochemical staining showed moderate desmin immunoreactivity and negative immunoreactivity for CD34, S-100, EMA, actin and pancytokeratin. Based on the findings, a diagnosis of ossifying fibromyxoid tumor was made. Given the uncertain biological potential of this lesion, re-excision was performed. No residual tumor was identified on repeat pathological evaluation. The patient was scheduled for close follow-up to survey for recurrence or possible metastasis.

Malignant ossifying fibromyxoid tumor of the calvaria: illustrative case.

BACKGROUND: Ossifying fibromyxoid tumor (OFMT) is a rare entity of soft tissue tumor that most commonly occurs in the subcutaneous tissues of trunk or extremities with occasional cases involving the head and neck; however, primary involvement of the skull has not been reported. While historically considered slow-growing benign to intermediate malignant, few cases of atypical or malignant features have been described. OBSERVATIONS: Herein, the authors present a case of malignant OFMT with primary skull and transcranial extension. The tumor caused lytic calvarial destruction with intra- and extracranial soft tissue components. Gross total resection was performed, and histopathology revealed malignant OFMT with 40 mitoses per 50 high-power fields and moderate nuclear atypia. LESSONS: OFMT can rarely occur in the head and neck and, as reported herein, may involve the skull with intracranial extension. While no uniformly recognized histological criteria for malignancy exist, a three-tiered classification has been proposed: typical, atypical, and malignant, based on features such as hypercellularity, mitotic activity, infiltrative growth, and/or nuclear atypia. Malignant variants should be considered along the high-grade sarcoma spectrum with elevated risk for recurrence or metastatic spread. Routine adjuvant radiotherapy is not typically recommended; however, surveillance imaging is advised.

A rare case report of a typical variant ossifying fibromyxoid tumor (OFMT), located in the retroauricular perimastoid region.

INTRODUCTION: Ossifying fibromixoid tumor of soft parts (OFMT) is a rare soft tissue and bone tumor. In its classic form, is considered benign, nevertheless aggressive clinical behaviour tumors with a different cytoarchitectural features of a malignant variant, have been described.The classification contains "typical", "atypical" and "malignant" variants. METHODS: A CT ear scan without contrast enhancement was carried out (October 2015), with coronal, sagittal and 3D reconstructions. It was decided the removal of the neoformation with a simple dissection. RESULTS: In this report, we present a case of a typical variant OFMT localized in the retroauricular perimastoid region, with mastoid bone cortex not involved. CONCLUSIONS: Considering the extreme rarity of this "enigmatic" tumor which displays an uncertain line of differentiation, renders the differential diagnosis a true challenge.

Soft Tissue Tumors of Uncertain Histogenesis: A Review for Dermatopathologists.

The mesenchymal tumors discussed herein represent a heterogeneous group of neoplasms with distinctive morphologic, immunophenotypic, and molecular genetic features. These uncommon tumors often arise in the dermis and subcutis and can pose a major diagnostic challenge to dermatopathologists because they closely mimic melanoma, carcinoma, fibrous histiocytoma, schwannoma, or granulomatous inflammation. This article reviews the clinical presentation, histopathology, differential diagnosis, and diagnostic pitfalls of epithelioid sarcoma, clear cell sarcoma, perivascular epithelioid cell tumor, ossifying fibromyxoid tumor, pleomorphic hyalinizing angiectatic tumor, and hemosiderotic fibrolipomatous tumor. Associated molecular genetic findings are also briefly reviewed with an emphasis on their diagnostic usefulness.