Morphology-Guided Diagnosis of Triple-Negative Breast Carcinoma: From Histopathological Evaluation to Molecular Testing
6 affiliations
- 1Department of Human Pathology of Adults and Developmental Age “Gaetano Barresi”, Division of Pathology, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy
- 2Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy
- 3Istituto Clinico Polispecialistico C.O.T. Cure Ortopediche Traumatologiche S.p.A., Via Ducezio 1, 98124 Messina, Italy
- 4Applied Biology and Experimental Medicine, Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
- 5BIOMORF Department, Oncologic Imaging Division, University Hospital Policlinico G. Martino, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy
- 6Medical Oncology Unit, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy
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.
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BibTeX
@article{zuccala2026morphologyguided,
title = {{Morphology-Guided Diagnosis of Triple-Negative Breast Carcinoma: From Histopathological Evaluation to Molecular Testing}},
author = {Valeria Zuccalà and Ida Rizzuto and Ludovica Pepe and Teresa Maria Martorana and Vincenzo Fiorentino and Pietro Tralongo and Gabriele Ricciardi and Giuliana Ciappina and Francesco Marcello Aricò and Maria Adele Marino and Massimiliano Berretta and Maurizio Martini and Guido Fadda and Giovanni Tuccari and Antonio Ieni},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15208197},
url = {https://www.mdpi.com/2077-0383/15/20/8197},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Morphology-Guided Diagnosis of Triple-Negative Breast Carcinoma: From Histopathological Evaluation to Molecular Testing
AU - Valeria Zuccalà
AU - Ida Rizzuto
AU - Ludovica Pepe
AU - Teresa Maria Martorana
AU - Vincenzo Fiorentino
AU - Pietro Tralongo
AU - Gabriele Ricciardi
AU - Giuliana Ciappina
AU - Francesco Marcello Aricò
AU - Maria Adele Marino
AU - Massimiliano Berretta
AU - Maurizio Martini
AU - Guido Fadda
AU - Giovanni Tuccari
AU - Antonio Ieni
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15208197
UR - https://www.mdpi.com/2077-0383/15/20/8197
AB - 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.
SN - 2077-0383
ER -