The Notch-Crossing Liposarcoma: A Rare MDM2/CDK4-Amplified Giant

Background: Retroperitoneal liposarcomas are rare malignant adipocytic neoplasms that may grow to massive sizes before detection due to the capacious nature of the retroperitoneal space. Dedifferentiated variants often show heterogeneous radiologic patterns and require combined clinicoradiologic, histopathologic, and immunohistochemical evaluation for accurate characterization. Overexpression of MDM2 and CDK4 is a key diagnostic feature, allowing reliable distinction from benign adipocytic lesions and other sarcomas. Case Presentation A 60-year-old male presented with a six-month history of progressive abdominal distension after incidentally noting a right iliac fossa mass while lying down. He had no abdominal pain, vomiting, altered bowel habits, weight loss, or constitutional symptoms. Examination revealed a firm, ill-defined, non-tender mass extending from the right iliac fossa toward the umbilical region, with no organomegaly or ascites. Contrast-enhanced CT demonstrated a large heterogeneous fat-attenuating retroperitoneal mass measuring 20.6 × 13.1 cm, abutting the aorta, inferior vena cava, and right psoas muscle, with displacement of bowel loops. A second similar lesion (11.6 × 6.5 cm) extended from the pelvis into the left gluteal region through the greater sciatic notch. No lymphadenopathy or visceral invasion was observed. Ultrasound-guided core biopsy revealed atypical spindle-cell proliferation within myxoid stroma. Immunohistochemistry showed strong nuclear positivity for MDM2 and CDK4, with a Ki-67 index of approximately 40%, favouring a diagnosis within the liposarcoma spectrum. The patient underwent open surgical excision, achieving en bloc removal of the mass. Postoperative recovery was stable, and he was discharged with plans for histologic subtyping and close oncologic follow-up. Conclusion This case highlights the silent but progressive nature of giant retroperitoneal liposarcomas and the pivotal role of multimodal evaluation—imaging, core biopsy, and molecula immunohistochemistry—in establishing diagnosis. Complete surgical excision remains the cornerstone of management, and vigilant postoperative surveillance is crucial due to the high risk of recurrence associated with dedifferentiated variants.