El Sheikh Soha, Mansour Mohamed A, Provenzano Elena, Shaaban Abeer, Lee Andrew, Mir Yasmeen, McMillan-Slater Rebecca, Carder Pauline, Di Palma Silvana, Boyd Clinton, Makhija Purnima, Warren Madhuri, Pritchard Susan, Deb Rahul, Ellis Ian, Rakha Emad, Quinn Cecily, Pinder Sarah
Research Department of Pathology, University College London (UCL) Cancer Institute, London, UK.
Department of Histopathology, Royal Free London Foundation Trust, London, UK.
Histopathology. 2025 May;86(6):953-966. doi: 10.1111/his.15402. Epub 2024 Dec 20.
Atypical ductal hyperplasia and flat epithelial atypia (FEA) have defined diagnostic criteria, yet there is variation in the interpretation of these criteria, particularly when the atypia is present in a background of columnar cell lesions (CCLs). This study focuses upon cases which are especially challenging or difficult to classify reproducibly according to existing criteria.
Thirteen breast pathology experts were asked to classify 10 challenging cases with CLLs as atypical or non-atypical. Interobserver agreement was calculated. After two consensus meetings, which explored the morphological features underlying the decision, the cases were reassessed. Finally, a photomontage was compiled as a visual aid for practising pathologists representing a range of straightforward cases and others where subjective interpretation causes disagreement within current diagnostic criteria. Overall interobserver agreement and pairwise pathologist agreement coefficients were both in the fair range (κ = 0.22 and κ = 0.3-0.4, respectively). This improved to moderate or substantial agreement (κ = 0.6-0.8) after two consensus meetings. The most controversial cases were atypical cases that lacked the regular rounded nuclei of FEA, and non-atypical cases that had florid architectural changes bordering on architectural atypia.
Among expert breast pathologists, interobserver agreement in the diagnosis of atypia in CCLs was higher in cases with classical features of FEA. Consensus was difficult to achieve if nuclear or architectural atypia fell outside the classical definition of FEA, suggesting that this category does not encompass the range of low-grade cytological atypia in CLLs. This study provides rationale for expanding the definition of atypia in CCLs other than FEA.
非典型导管增生和扁平上皮异型增生（FEA）有明确的诊断标准，但对这些标准的解读存在差异，尤其是当异型增生出现在柱状细胞病变（CCL）背景中时。本研究聚焦于根据现有标准特别具有挑战性或难以进行可重复性分类的病例。
邀请13位乳腺病理专家将10例伴有CCL的具有挑战性的病例分类为非典型或典型。计算观察者间的一致性。在两次共识会议探讨了诊断决策背后的形态学特征后，对病例进行重新评估。最后，编制了一组拼接照片作为视觉辅助工具，供执业病理学家参考，其中包括一系列简单病例以及其他在当前诊断标准下因主观解读而导致分歧的病例。观察者间总体一致性和病理学家两两之间的一致性系数均处于一般范围（分别为κ = 0.22和κ = 0.3 - 0.4） 。经过两次共识会议后，一致性提高到中等或高度一致（κ = 0.6 - 0.8）。最具争议的病例是缺乏FEA典型圆形核的非典型病例，以及具有接近非典型结构改变的显著结构变化的典型病例。
在乳腺病理专家中，对于具有FEA典型特征的CCL病例异型增生的诊断，观察者间一致性更高。如果核异型或结构异型超出FEA的经典定义，则难以达成共识；这表明该类别并未涵盖CCL中低度细胞学异型增生的范围。本研究为扩大FEA以外的CCL异型增生定义提供了理论依据。
