A rare metastatic mesenteric malignant PEComa with TSC2 mutation treated with palliative surgical resection and nab-sirolimus: a case report

Abstract

Background: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas.

Case presentation: Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient's excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease.

Conclusions: This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.

Keywords: Malignant PEComa; Nab-sirolimus; TP53; TSC2; mTOR.

Fig. 1

Gross, light microscopic, and IHC findings. A Intra-operative gross photo of the tumor. B Representative section of tumor consisting of fleshy surfaces with extensive necrosis and hemorrhage. H&E stain showing sheets of malignant epithelioid cells with granular eosinophilic cytoplasm, marked nuclear atypia, and prominent nucleoli, 4x (C) and 20x (D). Tumor cells show patchy positive staining for Melan-A (E), HMB-45 (F), desmin (G), and CD117 (H)

Fig. 2

Radiographic image findings. A Sagittal and coronal CT abdominal images on initial presentation showing a large abdominopelvic mass. White arrows in coronal view highlight metastatic disease in the abdomen. B Coronal CT abdominal post-surgical interventions showing absence of the main mass and the LAMS stent. C Coronal and sagittal PET CT images one month post initiation of nab-sirolimus showing stable residual disease in the abdomen as highlighted by the white arrows