Resolving Morphological Ambiguity in Molar Pregnancy: The Diagnostic Role of p57 Immunohistochemistry

To evaluate the diagnostic utility of p57 immunohistochemistry (IHC) in differentiating complete and partial hydatidiform mole (PHM) from non-molar pregnancies, with emphasis on resolving morphologically ambiguous cases.

This hospital-based cross-sectional study was conducted in a tertiary referral centre from March 2024 to October 2025. A total of 60 histopathologically diagnosed cases of complete hydatidiform mole (CHM), PHM, and non-molar pregnancies were included. Tissue sections were examined on H&E staining for morphological features, followed by p57 IHC on paraffin-embedded sections. Nuclear staining in villous cytotrophoblasts and stromal cells was evaluated. Statistical analysis was performed using appropriate tests, with p < 0.05 considered significant.

Of 60 cases, 30 were non-molar and 30 molar pregnancies (12 complete, 14 partial, four unclassified on H&E). All non-molar cases showed positive p57 expression. Among CHMs, 91.7% were p57 negative, while 78.6% of PHMs were positive. Notably, 21.4% of cases initially diagnosed as PHMs lacked p57 expression and were subsequently categorised as CHMs based on combined histomorphological evaluation and immunohistochemical findings. Overall, p57 IHC led to reclassification in 13.3% of cases, mainly involving unclassified and PHMs. A significant association was observed between diagnosis and p57 expression (p < 0.001), driven by non-molar positivity and CHM negativity.

p57 IHC is a valuable adjunct to routine histopathology for differentiating CHM from PHM. Its use significantly improves diagnostic accuracy, particularly in early gestation and morphologically ambiguous cases, thereby facilitating appropriate clinical management, follow-up, and patient counselling.