Review examines diagnostic challenges of flat epithelial atypia in breast lesions, suggesting a context-integrated framework for improved diagnosis.
Flat epithelial atypia (FEA) is a diagnostically challenging lesion within the spectrum of columnar cell alterations of the breast, occupying a borderline position between benign columnar cell change and flat type intermediate nuclear grade ductal carcinoma in situ (DCIS). Despite extensive study and incorporation into classification systems, its definition remains largely dependent on subjective morphological thresholds rather than outcome-driven or genomic criteria, contributing to persistent diagnostic variability. This review examines the diagnostic framework of FEA, emphasising the primacy of morphological assessment integrated with clinical and radiological context. We propose a pragmatic, context-based approach to diagnosis and highlight key cytological and architectural features, alongside practical tips to distinguish FEA from lesions with overlapping features, including apocrine proliferations and FEA within other breast lesions. FEA forms part of a morphological and biological continuum within the low nuclear grade neoplasia pathway. FEA shares recurrent molecular alterations, particularly chromosome 16q loss, 1q gain, with low nuclear grade DCIS; however, these are not diagnostically specific. Reproducibility remains limited, particularly at the interface with benign columnar cell lesions and flat low/intermediate-grade DCIS. Evidence indicates that clinical significance is context-dependent, with low upgrade rates in adequately sampled 'pure' lesions, supporting selective conservative management. Accurate diagnosis of FEA requires integration of reproducible morphological criteria with clinical context. This work proposes a pragmatic, context-integrated diagnostic framework addressing key sources of interobserver variability, which may improve concordance, reduce overdiagnosis, and support risk-adapted patient management.
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Emad A. Rakha (2026) studied this question.
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