Nuclei count and diagnostic confidence in MDM2 FISH: findings from a departmental audit

Background: MDM2 amplification drives p53 degradation and is characteristic of atypical lipomatous tumour and liposarcoma, but not benign adipocytic lesions or other sarcomas. An MDM2:CEP12 ratio >2 on FISH is gold standard to define amplification, yet the required nuclei count varies widely (20–100). Our department historically counted 50 nuclei, based on Kashima (2012), 1 which reported 93% sensitivity for distinguishing ALT from benign adipocytic lesions. Taking inspiration from Gambella (2023), 2 we evaluated whether reducing the nuclei count to 20 would maintain diagnostic accuracy.