Identification ofEWSR1–NFATC2fusion in simple bone cysts
Autor: | G. Petur Nielsen, Julio A. Diaz-Perez, Yin P Hung, Jochen K. Lennerz, Kevin A. Raskin, Miriam A. Bredella, A. John Iafrate, Valentina Nardi, Adam S. Fisch, Andrew E. Rosenberg, Santiago A. Lozano-Calderon |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Histology Adolescent Biology Malignancy Pathology and Forensic Medicine law.invention Intramedullary rod Young Adult 03 medical and health sciences 0302 clinical medicine law Pathognomonic medicine Bone Cysts Humans Femur Humerus Tibia Fibula Homeodomain Proteins NFATC Transcription Factors Simple Bone Cyst High-Throughput Nucleotide Sequencing Nuclear Proteins General Medicine medicine.disease Homeobox Protein Nkx-2.2 030104 developmental biology medicine.anatomical_structure Child Preschool 030220 oncology & carcinogenesis Female Gene Fusion RNA-Binding Protein EWS Transcription Factors |
Zdroj: | Histopathology. 78:849-856 |
ISSN: | 1365-2559 0309-0167 |
Popis: | Aims Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1-NFATC2 or FUS-NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. Methods and results Using RNA-based next-generation sequencing and/or fluorescence in-situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3-23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1-NFATC2 fusion (showing identical breakpoints to those in EWSR1-NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1-NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. Conclusions More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy. |
Databáze: | OpenAIRE |
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