Next-Generation Sequencing: Key for Diagnosing Angiomyolipoma - A Case Report.

Introduction: Renal angiomyolipomas (AMLs) are rare tumors categorized within the perivascular epithelioid cell tumor (PEComa) family, most of which are benign, except for epithelioid AMLs (EAML) with malignant potential. EAML develops sporadically or as part of the tuberous sclerosis complex (TSC), where mutations of the TSC1/2 genes result in increased activation of the mammalian target of the rapamycin (mTOR) signaling pathway.

Case presentation: A 52-year-old female patient experienced dyspnea and abdominal pain, leading to the discovery of a retroperitoneal tumor confirmed by tomography. She was initially diagnosed with a retroperitoneal liposarcoma with lung metastasis. Following a first-line anthracycline-based chemotherapy, the patient achieved a complete clinical and tomographic response. Subsequent surgical resection of the primary tumor and a course of ifosfamide monotherapy yielded a 36-month progression-free survival to date. Comprehensive molecular profiling of the primary tumor by whole exome sequencing revealed pathogenic mutations in TSC2 and the absence of amplifications in MDM2 and CDK4, raising the need to consider a differential diagnosis in PEComas, and contemplate the potential use of AKT/Pi3K/mTOR pathway inhibitors. Pathological re-evaluation confirmed the diagnosis of a metastatic retroperitoneal AML with complete response and no evidence of disease.

Conclusion: This case underscores the invaluable role of next-generation sequencing testing in the differential diagnosis of retroperitoneal tumors, as well as the ability to identify precise therapeutic targets for the treatment of rare soft tissue cancer types within the realm of precision medicine.