Pulmonary epithelioid hemangioendothelioma with pleural dissemination: a case report of prolonged diagnostic delay and the role of surgical biopsy

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor with low incidence and nonspecific clinical and radiological features, frequently leading to misdiagnosis and delayed diagnosis. We report a 32-year-old man with bilateral pulmonary nodules that were followed for 6 years before the development of a new left lower lobe mass, pleuritic chest pain, dyspnea, and massive pleural effusion in 2025. Initial imaging revealed diffuse miliary nodules that remained relatively indolent for several years. Two transbronchial lung biopsies (TBLB) and repeated pleural fluid cytology failed to establish a diagnosis. Definitive diagnosis was achieved only after video-assisted thoracoscopic surgery (VATS), with immunohistochemical support for endothelial differentiation and molecular confirmation of the WWTR1–CAMTA1 fusion gene. The patient underwent surgery, systemic therapy, and intrapleural treatment, followed by maintenance sirolimus. Disease remained clinically and radiologically stable during 6 months of follow-up. PEH presents substantial diagnostic challenges because of its indolent course and nonspecific clinical and radiological features. For patients with unexplained multiple pulmonary nodules and pleural involvement, especially when minimally invasive investigations remain repeatedly nondiagnostic, early surgical biopsy combined with endothelial immunophenotyping, and molecular testing is essential for timely diagnosis and optimal management.