早期乳腺癌术中快速冰冻切片病理学检查延迟诊断率分析：一项真实世界的回顾性研究

doi:10.19401/j.cnki.1007-3639.2025.04.008

摘要/Abstract

摘要：

背景与目的：对于少数空芯针穿刺未能明确诊断的早期乳腺癌，冰冻切片病理学检查的延迟诊断率尚不清楚。本回顾性队列研究旨在探讨术中快速冰冻切片病理学检查在这种情况下的临床应用价值。方法：回顾性分析2006年5月1日—2019年12月31日在复旦大学附属肿瘤医院就诊的乳腺癌患者的临床资料。收集患者的临床特征、影像资料和病理学资料。采用logistic回归分析方法探索患者的临床特征与术中快速冰冻切片病理学检查延迟诊断的相关性，并构建预测延迟诊断率的诺模图。本研究获得复旦大学附属肿瘤医院伦理委员会批准（伦理批号：050432-4-2108*）。结果：共876例患者符合入组标准而纳入本研究。对空芯针穿刺未能明确诊断的乳腺癌的术中快速冰冻切片病理学检查诊断率为67.7%，延迟诊断率为32.3%。多因素分析中，空芯针标本伴有非典型增生的乳头状病变[比值比（odds ratio，OR）=4.251，95% CI: 2.804~6.492，P<0.001]和硬化性腺病（OR=3.727，95% CI: 1.897~7.376，P<0.001）是导致冰冻切片延迟诊断的正相关因素，乳房X线摄影见簇状微钙化（OR=0.345，95% CI: 0.216~0.543，P<0.001）和超声诊断结果依据乳腺影像报告和数据系统（Breast Imaging Reporting and Data System，BI-RADS）分类为4C~5类（OR=0.250，95% CI: 0.081~0.777，P=0.016）是术中诊断率高的正相关因素。通过这些因素构建的诺模图能较好地预测术中快速冰冻切片病理学检查的延迟诊断率，从而更好地筛选出适合术中快速冰冻切片病理学检查的病例。结论：术中快速冰冻切片病理学检查对空芯针穿刺未能明确诊断的乳腺癌有一定的延迟诊断率，通过模型预测的方法可有效地筛除延迟诊断的病例，避免一些不必要的术中快速冰冻切片病理学检查。

关键词: 冰冻切片, 乳腺癌, 延迟诊断, 预测模型, 空芯针穿刺

Abstract:

Background and purpose: For few of early-stage breast cancers who are undiagnosed by core needle biopsy, the delayed diagnosis rate of intraoperative rapid frozen section pathological examination is unclear. The purpose of this retrospective cohort study was to investigate the clinical application value of frozen sections in this situation. Methods: This study reviewed data of 876 breast cancer patients that were undiagnosed by core needle biopsy in Fudan University Shanghai Cancer Center from May 1, 2006 to December 31, 2019. Clinical characteristics and image data and pathological data of patients were collected. The correlation between clinical features and delayed diagnosis rate (DDR) of frozen section was explored using logistic regression analysis, then a nomogram was constructed to predict the probability of delayed diagnosis. This study was approved by Ethics Committee of Fudan University Shanghai Cancer Center (No.: 050432-4-2108*). Results: A total of 876 patients met the inclusion standards. The intraoperative diagnosis rate of frozen section for breast cancers that were undiagnosed by core needle biopsy was 67.7%, and the DDR was 32.3%. In multivariate analysis, papillary lesion [odds ratio (OR)=4.251, 95% CI: 2.804-6.492; P<0.001) and sclerosing adenosis (OR=3.727; 95% CI: 1.897-7.376; P<0.001) accompanied by atypical epithelial hyperplasia on core needle biopsy (CNB) were positive correlation factors of delayed diagnosis, while clustered microcalcifications on mammography (OR=0.345; 95% CI: 0.216-0.543; P<0.001) and ultrasonic category 4C-5 according to Breast Imaging Reporting and Data System (BI-RADS) (OR=0.250; 95% CI: 0.081-0.777; P=0.016) were positive correlation factors of intraoperative diagnosis. The nomogram constructed by these factors could better predict the delayed diagnosis rate of frozen section and screen out low delayed diagnosis population. Conclusion: Frozen section has a certain delayed diagnosis rate for breast cancer that is not clearly diagnosed by core needle biopsy. The method of model prediction can effectively eliminate the delayed diagnosis cases and avoid some unnecessary frozen sections.

Key words: Frozen section, Breast cancer, Delayed diagnosis, Prediction model, Core needle biopsy

薛佳磊, 李剑伟, 龚悦, 柳光宇, 刘哲斌. 早期乳腺癌术中快速冰冻切片病理学检查延迟诊断率分析：一项真实世界的回顾性研究[J]. 中国癌症杂志, 2025, 35(4): 404-411.

XUE Jialei, LI Jianwei, GONG Yue, LIU Guangyu, LIU Zhebin. Predicting delayed diagnosis rate of intraoperative rapid frozen section pathological examination for early-stage breast cancer: a real-world retrospective study[J]. China Oncology, 2025, 35(4): 404-411.

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Item	Total (n=876)	Training set (n=613)	Testing set (n=263)
Age/year
Median age	53 (28-86)	54 (30-86)	51 (28-83)
<45	183 (20.9)	127 (20.7)	56 (21.3)
45-59	410 (46.8)	286 (46.6)	124 (47.1)
≥60	283 (32.3)	200 (32.6)	83 (31.6)
Ultrasonographic features
Echo type
Mixed echo	82 (9.4)	55 (9.0)	27 (10.3)
Low echo	764 (87.2)	538 (87.8)	226 (85.9)
Medium echo	30 (3.4)	20 (2.2)	10 (3.8)
Maximum diameter D/mm
≤10	111 (12.7)	75 (12.2)	36 (13.7)
>10	765 (87.3)	538 (87.8)	227 (86.3)
Dense punctate strong echo
Yes	298 (34.0)	201 (32.8)	97 (36.9)
No	578 (66.0)	412 (67.2)	166 (63.1)
BI-RADS
1-3	29 (3.3)	18 (2.9)	11 (4.2)
4A or 0	192 (21.9)	136 (22.2)	56 (21.3)
4B	344 (39.3)	240 (39.2)	104 (39.5)
4C or 5	311 (35.5)	219 (35.7)	92 (35.0)
Mammographic features
Microcalcifications
Yes	420 (47.9)	297 (48.5)	123 (46.8)
No	456 (52.1)	316 (51.5)	140 (53.2)
BI-RADS
1-3	71 (8.1)	45 (7.3)	26 (9.9)
4A or 0	269 (30.7)	182 (29.7)	87 (33.1)
4B	247 (28.2)	171 (27.9)	76 (28.9)
4C or 5	289 (33.0)	215 (35.1)	74 (28.1)
Physical examination symptoms
Palpable mass
Yes	812 (92.7)	571 (93.1)	241 (91.6)
No	64 (7.3)	42 (6.9)	22 (8.4)
Nipple discharge
Yes	96 (11.0)	69 (11.3)	27 (10.3)
No	780 (89.0)	544 (88.7)	236 (89.7)
Pathological features
Papillary lesions
Yes	252 (28.8)	174 (28.4)	78 (29.7)
No	624 (71.2)	439 (71.6)	185 (70.3)
Sclerosing adenosis
Yes	61 (7.0)	45 (7.3)	16 (6.1)
No	815 (93.0)	568 (92.7)	247 (93.9)
Frozen section
False negative	283 (32.3)	203 (33.1)	80 (30.4)
Ture positive	593 (67.7)	410 (66.9)	183 (69.6)

Variables	No. of patients (delayed diagnosis/total)	DDR/%	OR	95% CI	P value
Dense punctate strong echo
No	176/412	42.7	1.000	-	-
Yes	27/201	13.4	0.595	0.335-1.044	0.073
US-BI-RADS
1-3	9/18	50.0	1.000	-	-
0 or 4A	61/136	44.9	0.601	0.195-1.861	0.372
4B	88/240	36.7	0.434	0.143-1.321	0.137
4C-5	45/219	20.5	0.250	0.081-0.777	0.016
Microcalcifications on MG
No	155/316	49.1	1.000	-	-
Yes	48/297	16.2	0.345	0.216-0.543	<0.001
Papillary lesions
No	98/439	22.3	1.000	-	-
Yes	105/174	60.3	4.251	2.804-6.492	<0.001
Sclerosing adenosis
No	180/568	31.7	1.000	-	-
Yes	23/45	51.1	3.727	1.897-7.376	<0.001

Cut-off value		No. of patients n		Real DDR/%
Total score	Predicted DDR/%	Total	Delayed diagnosis	Real DDR/%
≤40	≤10	220	22	10.0
≤76	≤15	246	25	10.2
≥190	≥50	235	152	64.7
≥220	≥60	159	114	71.7
≥251	≥70	60	44	73.3
≥288	≥80	8	7	87.5