Pseudomyogenic hemangioendothelioma: A series of 13 patients, highlighting unusual cardiac locations, novel gene fusions, and malignant behavior

Abstract

Pseudomyogenic hemangioendothelioma (PHE) is a rare vascular tumor of intermediate biologic behavior. It typically occurs in the lower extremities of young adults, and is molecularly characterized by FOSB gene rearrangements, most commonly with SERPINE1 or ACTB fusion partners. Multifocality and local recurrence are common, but distant metastasis is rare. In this retrospective study, we collected 13 cases of PHEs and described their clinicopathologic features and available molecular findings. The patients ranged from 4 to 78 years of age, and had a male predilection (male: female=3.3: 1). The tumors involved the lower extremities (n = 4), upper extremities (n = 4), trunk (n = 3), and most extraordinarily, the heart (n = 2). Most cases showed typical histologic features with eosinophilic plump spindle cells, frequent inflammatory infiltrate, and immunoreactivity to cytokeratin (9/9), ERG (8/8), CD31(5/9), FOSB (7/7), and rarely CD34 (1/6). One exceptional case showed an extensive myxoid stroma and spindle to epithelioid cytomorphology. Molecular findings were available in 4 cases, with SERPINE1::FOSB, ACTB::FOSB, MAPK1IP1L::FOSB, and NPIPA7::NIPBL fusions in one case each. The novel MAPK1IP1L::FOSB and NPIPA7::NIPBL fusions were both detected in cardiac tumors. In total, 4 patients had metastatic diseases, which affected the bones (n = 3), lungs (n = 2), skin (n = 1), brain (n = 1), and lymph nodes (n = 1). Two patients died of diseases, both with pulmonary metastasis at initial presentation. In conclusion, our cohort expands the clinicopathologic spectrum of PHE, with a wide range of age, cases with unusual cardiac locations, novel MAPK1IP1L::FOSB and NPIPA7::NIPBL fusions, and uncommon malignant behavior.