Molecularly Confirmed Pseudomyogenic Hemangioendothelioma with Unusual EGFL7::FOSB Fusion in the Head and Neck Region of an Older Patient

Abstract

Pseudomyogenic hemangioendothelioma (PMHE), a rare vascular neoplasm, was first described in 1992 asa fibroma-like variant of epithelioid sarcoma, and would be termed as epithelioid sarcoma-like hemangioendothelioma a decade later due to its significant histologic overlap with epithelioid sarcoma and diffuse cytokeratin expression. PHME is currently defined as a distinct, potentially intermediate malignant, rarely metastasizing neoplasm with vascular/endothelial differentiation. It is characterized by young age (typically less than 40 years old), extremity location (approximately ~80%), and t(7:19) SERPINE1::FOSB fusion as the most common molecular alteration. Herein, we report a case of a 59-year-old male presenting with multifocal lesions, including in the right temporalis muscle, right frontoparietal calvarium, right pterygoid muscles, and right mandibular condyle. Histologic examination of the right temporal lesion revealed a multinodular biphasic lesion composed of sheets and fascicles of elongated spindle and epithelioid cells infiltrating into the adjacent skeletal muscle. Admixed abundant neutrophilic infiltration is noted; however, areas of necrosis, increased mitosis, nuclear atypia, or rhabdomyoblast-like cells are absent. Immunohistochemical (IHC) staining showed that the tumor cells were diffusely and strongly positive for FOSB, pan-cytokeratin (AE1/AE3), CD31, and ERG. Molecular testing demonstrated a t(9:19) EGFL7::FOSB fusion mRNA. This constellation of morphological, IHC and molecular findings was consistent with a diagnosis of PMHE. This is the first reported case of multifocal PMHE with EGFL7::FOSB fusion in the head and neck area of a patient aged more than 50 years old. Since the differential diagnoses for PMHE includes high-grade malignancies with aggressive clinical behavior, coupled with the rare reports of PMHE in the head and neck region, awareness of this tumor in the head and neck region will avoid the misdiagnosis and overtreatment of this entity.