Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Mod Pathol. 2017 Sep;30(9):1273-1286. doi: 10.1038/modpathol.2017.51. Epub 2017 Jun 30.
Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.
在胆管刷检中诊断恶性肿瘤极具挑战性。七位具有不同背景和参与程度的审阅者对 60 个标本进行了盲法审阅（30 个恶性标本经组织学证实，30 个良性标本（15 个支架置入）有切除或≥18 个月无不良随访），检测了 14 种恶性特征的效用。11 种特征与恶性肿瘤显著相关，包括三维簇（恶性为 63%，良性为 3%，优势比 50，P=0.0003）、多形性（62 比 3，优势比 48，P=0.0004）、2 细胞群（60%比 3，优势比 44，P=0.0005）、染色质模式（低/高嗜碱性）改变（70%比 7%，优势比 33，P<0.0001）、核浆比升高（48 比 3%，优势比 27，P=0.0023）、细胞质空泡（43 比 3%，优势比 22，P=0.0042）、核不规则性（70 比 10%，优势比 21，P<0.0001）、细胞分离（38 比 3%，优势比 18，P=0.0082）、细胞密集（23%比 0%）、核塑型（20%比 0%）和明显核仁（21%比 0%）。坏死和浸润性炎症对识别恶性肿瘤没有帮助（“中性粒细胞自噬”在 43%的恶性刷片中可见）；30 个恶性刷片中 21 个（70%）有≥3 个恶性特征，而 30 个良性刷片中 23 个（77%）没有任何特征。在 20 个有≥4 个特征的刷片中，有 1 个（5%）被证实为良性，表现为刷片中恶性肿瘤的密切类似物-脱落异型性。识别 3 个特征可最大程度地提高联合敏感性（70%）、特异性（97%）和准确性（83%），但随着特征数量的增加，敏感性会下降。识别 3/11 个特征（三维簇、多形性、核浆比升高、核不规则性、细胞密集、分离、染色质改变、空泡、明显核仁、塑型和 2 细胞群）可极大地提高病理学家的整体表现。
