Psammomatoid Ossifying Fibroma Is Defined by SATB2 Rearrangement

Psammomatoid ossifying fibroma (PsOF), also known as juvenile PsOF, is a benign fibro-osseous neoplasm predominantly affecting the extragnathic bones, particularly the frontal and ethmoid bones, with a preference for adolescents and young adults. The clinical and morphologic features of PsOF may overlap with those of other fibro-osseous lesions, and additional molecular markers would help increase diagnostic accuracy. Because identical chromosomal breakpoints at bands Xq26 and 2q33 have been described in 3 cases of PsOF located in the orbita, we aimed to identify the exact genes involved in these chromosomal breakpoints and determine their frequency in PsOF using transcriptome sequencing and fluorescence in situ hybridization (FISH). We performed whole RNA transcriptome sequencing on frozen tissue in 2 PsOF index cases and identified a fusion transcript involving SATB2, located on chromosome 2q33.1, and AL513487.1, located on chromosome Xq26, in one of the cases. The fusion was validated using reverse transcription (RT)-PCR and SATB2 FISH. The fusion lead to a truncated protein product losing most of the functional domains. Subsequently, we analyzed an additional 24 juvenile PsOFs, 8 juvenile trabecular ossifying fibromas (JTOFs), and 11 cemento-ossifying fibromas (COFs) for SATB2 using FISH and found evidence of SATB2 gene rearrangements in 58% (7 of 12) of the evaluable PsOF cases but not in any of the evaluable JTOF (n = 7) and COF (n = 7) cases. A combination of SATB2 immunofluorescence and a 2-color SATB2 FISH in our index case revealed that most tumor cells harboring the rearrangement lacked SATB2 expression. Using immunohistochemistry, 65% of PsOF, 100% of JTOF, and 100% of COF cases showed moderate or strong staining for SATB2. In these cases, we observed a mosaic pattern of expression with >25% of the spindle cells in between the bone matrix, with osteoblasts and osteocytes being positive for SATB2. Interestingly, 35% (8 of 23) of PsOFs, in contrast to JTOFs and COFs, showed SATB2 expression in <5% of cells. To our knowledge, this is the first report that shows the involvement of SATB2 in the development of a neoplastic lesion. In this study, we have showed that SATB2 rearrangement is a recurrent molecular alteration that appears to be highly specific for PsOF. Our findings support that PsOF is not only morphologically and clinically but also genetically distinct from JTOF and COF

Thoracic outlet syndrome (TROTS) registry:A study protocol for the primary upper extremity deep venous thrombosis section

Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep venous thrombosis (pUEDVT). pUEDVT includes venous thoracic outlet syndrome related upper extremity deep venous thrombosis (UEDVT) and idiopathic UEDVT. Research on these conditions has been hampered by their rarity, lack of uniform diagnostic criteria, and heterogeneity in therapeutic strategies. To improve current research data collection using input of all various pUEDVT treating medical specialists, we initiated the ThoRacic OuTlet Syndrome (TROTS) registry. The aim of the TROTS registry is to a) collect extensive data on all pUEDVT patients through a predefined protocol, b) give insight in the long term outcome using patient reported outcome measures, c) create guidance in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future research. Methods and analysis The TROTS registry was designed as an international prospective longitudinal observational registry for data collection on pUEDVT patients. All pUEDVT patients, regardless of treatment received, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition, a survey containing general questions, a Health-related Quality of Life questionnaire (EQ-5D-5L), and Functional Disability questionnaire (Quick-DASH) will be sent periodically (at the time of inclusion, one and two years after inclusion, and every five years after inclusion) to the participant. The registry protocol was approved by the Medical Ethical Review Board and registered in the Netherlands Trial Register under Trial-ID NL9680. The data generated by the registry will be used for future research on pUEDVT and published in peer reviewed journals. Conclusion TROTS registry data will be used to further establish the optimal management of pUEDVT and lay the foundation for future research and guidelines

Thoracic outlet syndrome (TROTS) registry: A study protocol for the primary upper extremity deep venous thrombosis section

Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep venous thrombosis (pUEDVT). pUEDVT includes venous thoracic outlet syndrome related upper extremity deep venous thrombosis (UEDVT) and idiopathic UEDVT. Research on these conditions has been hampered by their rarity, lack of uniform diagnostic criteria, and heterogeneity in therapeutic strategies. To improve current research data collection using input of all various pUEDVT treating medical specialists, we initiated the ThoRacic OuTlet Syndrome (TROTS) registry. The aim of the TROTS registry is to a) collect extensive data on all pUEDVT patients through a predefined protocol, b) give insight in the long term outcome using patient reported outcome measures, c) create guidance in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future research. Methods and analysis The TROTS registry was designed as an international prospective longitudinal observational registry for data collection on pUEDVT patients. All pUEDVT patients, regardless of treatment received, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition, a survey containing general questions, a Health-related Quality of Life questionnaire (EQ-5D-5L), and Functional Disability questionnaire (Quick-DASH) will be sent periodically (at the time of inclusion, one and two years after inclusion, and every five years after inclusion) to the participant. The registry protocol was approved by the Medical Ethical Review Board and registered in the Netherlands Trial Register under Trial-ID NL9680. The data generated by the registry will be used for future research on pUEDVT and published in peer reviewed journals. Conclusion TROTS registry data will be used to further establish the optimal management of pUEDVT and lay the foundation for future research and guidelines