BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor of endothelial origin with variable clinical behavior, posing significant diagnostic and therapeutic challenges. Due to its nonspecific presentation and diverse imaging features, it is frequently misdiagnosed. We present a unique case of HEHE with recurrent liver involvement and distant metastases over a 14-year period, emphasizing diagnostic markers, treatment strategies, and the prognostic value of serial biomarker assessment.

CASE REPORT: A 48-year-old woman underwent right partial hepatectomy in 2011 after a routine health check-up incidentally revealed a liver lesion. Histological examination revealed characteristic epithelioid and dendritic tumor cells, confirmed by immunohistochemistry (CD31+, CD34+, Ki-67 5%). Postoperative surveillance detected tumor recurrence 7 years later in the left lobe, necessitating laparoscopic left partial hepatectomy. In 2020, further progression to the caudate lobe and regional lymph nodes prompted complex resection, with Ki-67 rising to 15%. Serial Ki-67 assessments across sequential specimens demonstrated a progressive increase in proliferative activity: 5% (2011), 15% (2020), and ultimately 40% in a pleural metastasis biopsy (2024), correlating closely with clinical progression. The patient received repeated surgical resections and adjuvant interferon alpha-2b, with palliative nab-paclitaxel attempted during the terminal stage but proving ineffective. The patient died in August 2025, approximately 14 years after initial diagnosis.

CONCLUSIONS: This case highlights the importance of the Ki-67 index as a dynamic biomarker for monitoring tumor evolution and guiding treatment decisions in recurrent HEHE. Regular long-term follow-up and a multidisciplinary approach are crucial for managing this unpredictable neoplasm, given its potential for late recurrence and metastasis.

Keywords: Hemangioendothelioma, Epithelioid, Recurrence