Malignant Perivascular Epithelioid Cell Tumor (PEComa) of the Uterus: A Rare Type of Mesenchymal Tumors and a Management Challenge

Abstract

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies.

Keywords: PEComa; mTOR; mesenchymal neoplasms; perivascular epithelioid cell neoplasm; tuberous sclerosis complex.

Figure 1

Axial and sagittal reformatted contrast-enhanced CT pelvic image of ruptured uterine PEComa with hemoperitoneum. Axial and sagittal reformatted contrast-enhanced CT pelvic images reveal a well-marginated mass arising exophytically from the uterine fundus (*), with hypoattenuating areas consistent with cystic/necrotic changes and solid components showing progressive heterogeneous enhancement during arterial ((1,3)) and venous ((2,4)) phases. A small amount of peritoneal fluid can also be noted (arrow).

Figure 2

Hematoxylin–eosin-stained section from a uterine PEComa. Epithelioid cells with clear to eosinophilic cytoplasm in a radial/perivascular distribution, with stromal hyalinization (20× magnification).

Figure 3

Immunostaining of HMB-45 in a uterine PEComa. Patchy granular cytoplasmic staining for HMB-45 (40× magnification).