Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors: A Common Genomic Abnormality in Vascular Malformation/Hemangioma and Simple Bone Cyst.

A simple bone cyst (SBC) is a cystic bone lesion predominantly affecting young males. The cyst is lined by a fibrous membrane and filled with serosanguinous fluid. EWSR1/FUS-NFATC2 rearrangements were recently identified in SBC. We here report exactly the same rearrangement in 3 lesions diagnosed as vascular malformations of 2 elderly patients. In total, through Archer FusionPlex, fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction the EWSR1-NFATC2 rearrangement was identified in 6 of 9 SBC, 3 of 12 benign vascular tumors, and none of 5 aneurysmal bone cyst lacking USP6 fusion. Using fluorescence in situ hybridization, it was apparent that amplification of the fusion, as seen in EWSR1-NFATC2 round cell sarcomas, was absent, and that in the vascular tumors the fusion was present both in the lining cells as well as in the surrounding spindle cells. Of note, not all of the spaces in the vascular malformations were lined by endothelial cells. Aggrecan was positive in all cases but was not specific. NKX2-2 and NKX3-1 staining were negative in all cases. Thus, even though the overlap between the 2 entities is limited to the presence of few thick-walled cysts lacking endothelial lining in the benign vascular malformations, the spectrum of benign tumors containing NFATC2 fusions should be expanded and contains not only SBC in the young, but also vascular malformation/hemangioma in elderly patients.

[Benign and malignant giant-cell rich lesions of bone: Pathological diagnosis with special emphasis on recent immunohistochemistry and molecular techniques]. / Diagnostic des lésions osseuses riches en cellules géantes : démarche diagnostique et intérêt des nouvelles techniques complémentaires immuno-histochimiques et moléculaires.

The infiltration by numerous osteoclastic giant cells is a frequent finding in bone tumors and pseudo-tumors. Pathologists must integrate clinical and radiological data to achieve a correct diagnosis in bone pathology. Benign giant-cell rich lesions of bone encompass giant cell tumor of bone, aneurysmal bone cyst, chondroblastoma, brown tumor and fibrous cortical defect/non-ossifying fibroma. Amongst malignant neoplasms, variants of conventional osteosarcoma, undifferentiated pleomorphic sarcoma, leiomyosarcoma and bone metastasis must be discussed. Recently, new diagnostic markers, antibodies for immuno-histochemistry and genetic markers, have been developed and are helpful to diagnose such lesions.

Aneurysmal bone cyst: its pathogenesis based on angiographic, immunohistochemical and electron microscopic studies.

Based on angiographic, immunohistochemical as well as electron microscopic findings, authors outline a hypothesis for the etiopathogenesis of aneurysmal bone cysts. No changes were found at the arterial site in 16 studied aneurysmal bone cysts, with no signs of an arteriovenous shunt. In certain cases, however, dilated and tortous efferent veins became visible in the late venous phase. Due to the impedance of venous flow, the intracystic pressure increases and the small veins become dilated causing formation of aneurysmal slits. This is supported by the immunohistochemical finding that S-actin shows concentric arrangement around the aneurysmal cavities. Endothelial lining and basal membrane remnants were detectable in places, though the aneurysmal slits were devoid of continuous endothelial lining and basal membrane. We suggested that the aneurysmal bone cyst corresponds to a hemodynamic disturbance and is due to primary or secondary venous malformation of the bones.