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Identification of EWSR1–NFATC2 fusion in simple bone cysts
Author(s) -
Hung Yin P,
Fisch Adam S,
DiazPerez Julio A,
Iafrate A John,
Lennerz Jochen K,
Nardi Valentina,
Bredella Miriam A,
Raskin Kevin A,
LozanoCalderon Santiago A,
Rosenberg Andrew E,
Nielsen G Petur
Publication year - 2021
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14314
Subject(s) - pathognomonic , pathology , biology , tibia , femur , intramedullary rod , immunohistochemistry , humerus , long bone , anatomy , medicine , paleontology , disease
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.