Orbital Cellular Epithelioid Hemangioma.

Dear Editor, This letter is a follow-up to an article published in the Journal of Ocular Oncology and Pathology in 2019 entitled “Orbital Cellular Epithelioid Hemangioma” [1]. The publication detailed a case of a vascular orbital lesion in a 58-year-old woman in whom the distinction between a benign cellular epithelioid hemangioma (EH) and a malignant epithelioid hemangioendothelioma (EHE) was difficult to make on histologic features alone. The case was reviewed by Christopher Fletcher, MD, at Brigham and Women’s Hospital, who utilized FOSB and CAMTA1 immunostains to detect cytogenetic rearrangements that supplemented the histopathologic examination in diagnosis. The consensus diagnosis of the lesion was benign cellular EH based on the presence of multifocal nuclear positivity for FOSB and negativity for CAMTA1 as both of these findings have been considered reassuring features that support a diagnosis of benign cellular EH and argue against a diagnosis of malignant EHE [2]. A recent re-evaluation of this case by Dr. Fletcher included an immunostain for TFE3 which showed weak positivity, followed by FISH that revealed a TFE3 gene rearrangement. As such, this lesion is better interpreted as an example of the rare subset of EHE characterized by YAP1-TFE3 gene fusion [3]. Since the time the original articles demonstrating FOSC gene rearrangements in EHs with associated overexpression of FOSB protein by IHC were published, it has been shown that FOSB and FOS may be expressed in a variety of other vascular lesions in the absence of gene rearrangement. Therefore, the positive IHC result in this case was false positive. The treating clinician and patient have been informed of the reclassification of this tumor as a malignant EHE, rather than a benign orbital cellular EH. These lesions are thought to account for approximately 5% of all EHE, and it is now recognized that they fortunately have a much better prognosis than conventional EHE [4]. The patient in this case is alive, with no known recurrence or metastasis.