Morphology-Guided Diagnosis of Triple-Negative Breast Carcinoma: From Histopathological Evaluation to Molecular Testing

Abstract

Background: Triple-negative breast carcinoma (TNBC) comprises several histological entities with different molecular alterations and clinical behaviour. Recognising these entities is important for accurate classification and for choosing appropriate immunohistochemical and molecular tests. Methods: We conducted a narrative review of English-language literature identified through PubMed/MEDLINE, Scopus, Web of Science Core Collection, citation searching and a Scopus publication list. Journal publications available through 24 August 2026 were eligible. Current reporting and regulatory guidance was obtained from official websites. Findings were synthesised qualitatively, without statistical pooling. Results: The review included 93 journal publications and two official documents. Secretory carcinoma, adenoid cystic carcinoma, tall cell carcinoma with reversed polarity and metaplastic carcinoma require a different diagnostic approach from conventional high-grade invasive breast carcinoma of no special type. Architectural, cytological and stromal findings guide the differential diagnosis and the selection of immunohistochemical stains and molecular assays. Limited sampling, tumour heterogeneity and treatment-related changes can affect tissue selection and interpretation. Conclusions: Pathology reports should specify the histological type and clearly state any remaining diagnostic uncertainty. Morphology should guide diagnostic testing, while validated predictive biomarkers and clinical criteria determine treatment eligibility.