Perinephric Myxoid Pseudotumor of Fat

Perinephric myxoid pseudotumor of fat (PMPTF) is a recently characterized lesion typically associated with non-neoplastic renal disease. Its pathogenesis is thought to result from chronic renal "irritation," either due to mass effect from renal carcinoma or inflammation related to benign renal conditions. Prompted by several cases arising in the absence of underlying renal pathology, we conducted a multi-institutional study of 29 mass-forming cases with detailed clinical, histologic, and molecular characterization. We also reviewed 79 published cases to place our findings in a broader context. Histologic slides were reviewed for morphologic and immunohistochemical features. Clinical and follow-up data were obtained through retrospective chart review. The mean age was 67 years (range: 35 to 82), with a strong male predominance (M:F=13.5:1). The average tumor size was 10.3 cm. Liposarcoma was the most common initial diagnosis (n=20). Twelve patients (42%) had non-neoplastic renal disease, 7 (24%) had both non-neoplastic disease and renal cell carcinoma, one (3%) had renal cell carcinoma only, and 9 (31%) had no renal pathology. Histologically, lesions showed mature fat with scattered bland spindle to stellate cells, chronic inflammation, lymphoid aggregates, myxoid change, fat necrosis, hemosiderin, and prominent vasculature; extramedullary hematopoiesis was rare. All tested 28 cases were negative for MDM2 amplification by FISH. Comprehensive targeted NGS (Oncomine) and whole transcriptome sequencing (n=4) did not reveal any pathogenic alterations. Follow-up (n=28; mean, 20 months) showed stable or no disease in 24 cases; 3 patients died of unrelated causes, and one from postoperative complications. PMPTF is a benign, mass-forming lesion that mimics malignancy, particularly well-differentiated liposarcoma. Its occurrence in patients without identifiable renal pathology suggests alternative etiologies. Lack of genomic alterations supports its non-neoplastic nature. Accurate recognition is critical to prevent overtreatment. PMPTF may represent an early-stage reactive process within a broader spectrum of adipose tissue remodeling that includes renal replacement lipomatosis.