Distinguishing Second Primary Müllerian Cancer from Breast Cancer Recurrence: Immunohistochemical Pitfalls and a Proposed Diagnostic Algorithm: A Case Report and Literature Review

Fangjian Zhou,1,* Huihui Chen,2,3,* Jili Qiu,2,* Xi Guo,2,4 Haoying Liu,2,4 Licong Chen,2,4 Dan Li,2 Sifeng Tao,2 Fu Zhang11Department of General Surgery, The People’s Hospital of Yuhuan, The First Affiliated Hospital of Wenzhou Medical University (Yuhuan Branch), Taizhou, Zhejiang, People’s Republic of China; 2Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fu Zhang; Sifeng Tao, Email zfddt111@163.com; taosifeng@zju.edu.cn;Abstract: Distinguishing a second primary Müllerian high‑grade serous carcinoma (HGSC) from metastatic breast cancer in survivors is a diagnostic challenge, especially when peritoneal carcinomatosis occurs without an adnexal mass. We report a 48‑year‑old woman with prior luminal B breast cancer who presented with liver and abdominal wall nodules. Initially misdiagnosed as breast cancer recurrence based on limited immunohistochemistry (IHC), she received 12 months of ineffective therapy. Repeat biopsy with an extended panel (PAX8+, WT1+, p53 mutant‑type, GATA3 weak/partial, GCDFP‑15−) established primary HGSC. A literature review of comparative IHC studies identifies key pitfalls: TRPS1 is positive in 40– 47% of HGSCs in large cohorts, with some series reporting up to 70%; PAX8 with the MRQ50 clone is falsely positive in 40% of triple‑negative breast cancers (TNBC); and GATA3 shows weak/focal positivity in 6– 13% of HGSCs. A proposed six‑marker panel (PAX8, WT1, GATA3, p53, GCDFP‑15, TRPS1) is recommended to prevent misdiagnosis and expedite appropriate platinum‑based therapy and cytoreductive surgery.Keywords: breast cancer, Müllerian cancer, second primary malignancy, misdiagnosis, immunohistochemistry