病例報告-多重抗藥性之轉移性腎臟惡性血管週上皮樣細胞腫瘤

江衍諭¹、林嘉祥^1,2、吳俊賢^1,2

義大醫療財團法人義大醫院 外科部 泌尿科¹, 義守大學 醫學系²

Metastatic Renal Malignant PEComa Refractory to Multimodal Therapy: A Case Report

Yen-Yu Chiang¹, Victor C. Lin ^1,2, Chun-Hsien Wu ^1,2.

Divisions of Urology, Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan ¹, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan ²

Abstract

Background:

Malignant perivascular epithelioid cell tumors of the kidney (malignant renal PEComas) are ultra-rare, aggressive mesenchymal neoplasms with an estimated incidence of less than one per million and a strong female predilection. These tumors are typically driven by mTOR pathway hyperactivation. While National Comprehensive Cancer Network (NCCN) guidelines recommend targeted mTOR inhibitors as the primary systemic therapy for advanced disease, the clinical management of highly aggressive, mTOR-refractory cases remains a formidable challenge. Herein, we detail a uniquely challenging case of a multimodal-refractory renal PEComa that initially presented with a spontaneous rupture, underscoring the severe limitations of current standard-of-care salvage protocols.

Case Presentation:

A 49-year-old female presented with acute abdominal pain secondary to a spontaneous retroperitoneal hemorrhage, initially masquerading as a ruptured right renal cell carcinoma. (Figure 1) Following stabilizing transcatheter arterial embolization and a subsequent partial nephrectomy, histopathological and immunohistochemical analyses (focal positivity for SMA, HMB45, and Melan-A) confirmed a highly aggressive malignant renal PEComa.(Figure 2) The patient experienced rapid local recurrence and retroperitoneal metastasis, necessitating an open radical nephroureterectomy that confirmed Stage IV disease with paracaval lymph node and peritoneal involvement.(Figure 3)  Following surgical staging, targeted mTOR inhibition (everolimus) was initiated. After nine months of disease control, she developed a distant metastasis to the sigmoid mesocolon, which was managed with a radical colectomy. (Figure 4) Subsequent explosive multi-organ progression—involving the liver, peritoneum, and retroperitoneum—proved completely refractory to anthracycline-based cytotoxic chemotherapy (AIM regimen). As a salvage strategy, she transitioned to combined immunotherapy (pembrolizumab) and anti-angiogenic targeted therapy (pazopanib). This clinical course was ultimately complicated by severe gastrointestinal hemorrhage secondary to direct duodenal tumor invasion, prompting next-generation sequencing (NGS) to explore personalized therapeutic avenues.

Discussion:

The structurally dysplastic vasculature characteristic of these tumors frequently predisposes them to aneurysm formation and spontaneous rupture, clinically distinguishing hemorrhagic renal PEComas from typical clear cell renal cell carcinomas. The rapid exhaustion of guideline-directed targeted therapies and conventional chemotherapy in this case highlights the profound chemo-refractoriness of malignant renal PEComas. This provides a strong, mechanistic rationale for integrating comprehensive molecular profiling (NGS) early in the disease course to distinguish between TSC1/2 mutations (responsive to mTOR inhibition) and TFE3 fusions (potentially responsive to VEGFR-TKIs). Furthermore, it supports exploring immune checkpoint inhibitors alongside tyrosine kinase inhibitors to synergistically modulate the tumor microenvironment.

Conclusion:

This case emphasizes the diagnostic complexities of ruptured renal PEComas and the stark limitations of current therapeutic modalities upon acquired mTOR resistance. It illustrates the emergent, albeit high-risk, application of combined immunotherapy and anti-angiogenesis in the salvage setting, ultimately underscoring the critical need for advanced molecular profiling (NGS) to identify actionable targets and guide personalized interventions for intractable rare malignancies.