Supplementary Material for: The Conundrum of Papillary Breast Lesions within the C3 Category

<b><i>Objectives:</i></b> To identify features that could define papillary ductal cell proliferation within the C3 category and to subcategorise papillary lesions into benign papillomas which can be managed conservatively and atypical/malignant papillary neoplasms which require surgical intervention. <b><i>Study Design:</i></b> A blind microscopic rescreen of all C3 cases was conducted. The corresponding histological outcome was compared with the cytology. Statistical analysis was performed using papillary versus non-papillary outcomes and benign versus atypical/malignant papillary lesions. In addition, macropapillary lesions (papilloma and encysted papillary carcinoma) were plotted against micropapillary ductal carcinoma in situ. <b><i>Results:</i></b> Two hundred thirty FNA cases reported as C3 included 72 papillary neoplasms (52 benign papillomas and 20 atypical/malignant papillary lesions). Features specific to papillary lesions within C3 include macropapillary fragments, complex sheets, palisading strips, cystic background, cohesion and a decreased nuclear-to-cytoplasmic ratio. Features favouring atypical/malignant papillary lesions include decreased numbers of bare bipolar nuclei, discohesion and a non-cystic background. These features are common to most breast malignancies; however, identification of papillary features often results in a downgraded diagnosis from C5. <b><i>Conclusions:</i></b> This study supports the ability to reliably identify papillary ductal cell proliferation within C3. Certain features can distinguish papillary lesions from other C3 pathologies. This separation is likely to be clinically useful as papillary lesions may require a different management approach.

<b><i>研究目的：</i></b> 旨在明确可定义C3类别下乳头状导管细胞增殖的特征，并将乳头状病变进一步划分为可保守治疗的良性乳头状瘤与需手术干预的非典型/恶性乳头状肿瘤。<b><i>研究设计：</i></b> 对所有C3病例开展盲法显微镜复筛，将对应组织学结局与细胞学结果进行比对。采用乳头状与非乳头状结局、良性与非典型/恶性乳头状病变开展统计学分析；此外，将大乳头状病变（乳头状瘤及囊性乳头状癌）与微乳头状导管原位癌进行对比分析。<b><i>研究结果：</i></b> 230例被诊断为C3的细针抽吸活检（Fine Needle Aspiration, FNA）病例中，共包含72例乳头状肿瘤（52例良性乳头状瘤与20例非典型/恶性乳头状病变）。C3类别下乳头状病变的特异性特征包括大乳头状碎片、复杂细胞团、栅栏状条索、囊性背景、细胞黏附性及降低的核质比。有助于确诊非典型/恶性乳头状病变的特征包括裸露双核细胞数量减少、细胞去黏附性及非囊性背景。上述特征多见于多数乳腺恶性肿瘤；但乳头状特征的识别通常可使诊断从C5降级。<b><i>研究结论：</i></b> 本研究证实可在C3类别下可靠识别乳头状导管细胞增殖。部分特征可区分乳头状病变与其他C3类病理改变。该分类方法具备临床应用价值，因乳头状病变可能需要差异化的诊疗策略。