Immunohistochemistry in gynecologic carcinomas: Practical update with diagnostic and clinical considerations based on the 2020 WHO classification of tumors

This review provides an update on immunohistochemistry applications-diagnostic, prognostic, and predictive-in the pathology evaluation of gynecologic carcinomas. The 5th edition of the WHO Classification of Female Genital Tumors introduced important changes in the diagnostic classification of lower genital tract, endometrial, and ovarian carcinomas, with major influence on the routine pathology practice. Lower genital tract carcinomas and their precursor lesions are now classified based on their human papillomavirus (HPV)-associated and HPV-independent pathogenesis, reflecting the clinically significant prognostic differences and impacting the therapeutic decision-making. Immunohistochemical markers have an increasing role in the pathology evaluation of endometrial carcinomas: in addition to their traditional use in the differential diagnosis and histologic subtyping, they have also been recently advocated for prognostic classification as surrogates for the TCGA (The Cancer Genome Atlas) molecular groups. New entities - mesonephric-like adenocarcinoma and gastric (gastrointestinal)-type mucinous adenocarcinoma of the endometrium - have also been added and often require immunostains for diagnostic confirmation. Ovarian carcinomas frequently show overlapping morphologic patterns and heterogeneous appearance within the same tumor, necessitating immunohistochemical work-up. Beyond diagnostic applications, there is increasing clinical demand for screening of inherited cancer syndromes, prediction of prognosis and guiding targeted therapy. Practical issues and pitfalls related to mismatch repair protein immunohistochemistry, HER2, and PD-L1 testing are also discussed.