囊性中性粒细胞性肉芽肿性乳腺炎：优势菌感染与组织学特征的关联研究

doi:10.16150/j.1671-2870.2025.01.009

摘要/Abstract

摘要：

目的观察囊性中性粒细胞性肉芽肿性乳腺炎（cystic neutrophilic granulomatous mastitis，CNGM）样本中的细菌类型，分析CNGM优势菌感染与组织学表现的关联强度。方法采用计算机随机抽样方法，从2017年1月至2020年12月31日期间在上海中医药大学附属曙光医院东院手术的术前诊断为乳腺炎及纤维腺瘤的连续病例中，随机抽取20例乳腺炎患者和10例纤维腺瘤患者。采用16S rRNA基因测序和生物信息学技术，对其中12例有CNGM图像的病例（实验组）和5例病理确诊乳腺纤维腺瘤的病例（对照组）样本进行细菌鉴定和分析。将上述17例病变组织制备石蜡切片，分别进行HE染色、革兰氏染色、抗酸染色和PAS染色，在光镜下观察，分析细菌类型与病理特征之间的关联。结果差异效应大小分析显示，与对照组比较，实验组在丰度上有显著差异的物种依次为棒状杆菌目、棒状杆菌科、棒状杆菌属、中慢生根瘤菌属、未培养细菌、慢生根瘤菌属、SHA_109菌属及硝化杆菌属。进一步分析发现，实验组9例（9/12）检测出柯氏棒状杆菌（Corynebacterium kroppenstedtii），而对照组均未检测出柯氏棒状杆菌（0/5），差异有统计学意义（P<0.05）。观察组织切片，检出柯氏棒状杆菌的9例CNGM中，有6例（6/9）在肉芽肿中央的脂质空泡内查见革兰阳性杆菌，抗酸染色和PAS染色均阴性。对照组切片中未发现革兰阳性细菌。结论在CNGM病变中，柯氏棒状杆菌的检出率为75%，且其在脂质空泡内的定位与周围形成的化脓性肉芽肿密切相关。在脂质空泡内存在革兰阳性杆菌，结合组织切片中的典型肉芽肿病变，提示柯氏棒状杆菌可能在CNGM的发生、发展中发挥了重要作用。

关键词: 囊性中性粒细胞性肉芽肿性乳腺炎, 肉芽肿性小叶乳腺炎, 柯氏棒状杆菌

Abstract:

Objective To observe the bacterial types in cystic neutrophilic granulomatous mastitis (CNGM) samples and analyze the association between the dominant bacterial infections and the histological features in CNGM. Methods Using 16S rRNA gene sequencing and bioinformatics technology, bacterial identification and analysis were conducted on 12 CNGM samples (experimental group) and 5 breast fibroadenoma samples (control group). Paraffin sections were prepared from the 17 lesion tissues and stained with hematoxylin and eosin (HE), Gram staining, acid-fast staining, and PAS staining, followed by observation under light microscopy. The association between bacterial types and pathological features was assessed by combining molecular biology techniques with histological observations. Results Linear discriminant analysis effect size revealed significant differences in abundance between the experimental and control groups, with notable species including Corynebacteriales, Corynebacteriaceae, Corynebacterium, Mesorhizobium, uncultured bacterium, Bradyrhizobium, SHA_109, and Nitrobacter. Further analyses revealed that Corynebacterium kroppenstedtii was detected in 9 cases (9/12) of the experimental group, while none of the control group samples (0/5) showed its presence. This difference was statistically significant (P<0.05). Upon examination of histological sections, among 9 CNGM cases positive for Corynebacterium kroppenstedtii, 6 cases (6/9) showed Gram-positive rods within lipid vacuoles at the center of the granulomas. Both acid-fast staining and PAS staining were negative. No Gram-positive bacteria were found in the tissue samples of the control group. Conclusions Corynebacterium kroppenstedtii was detected in 75% of CNGM lesions, and its localization within lipid vacuoles was closely associated with the formation of surrounding pyogenic granulomas. The presence of Gram-positive rods within lipid vacuoles, combined with the typical granulomatous lesions observed in tissue sections, suggests that Corynebacterium kroppenstedtii may play an important role in the occurrence and development of CNGM.

Key words: Cystic neutrophilic granulomatous mastitis, Granulomatous lobular mastitis, Corynebacterium kroppens-tedtii, 16S rRNA

中图分类号:

R655.8

王子元, 陈永其, 房振, 吴丽莉. 囊性中性粒细胞性肉芽肿性乳腺炎：优势菌感染与组织学特征的关联研究[J]. 诊断学理论与实践, 2025, 24(01): 59-64.

WANG Ziyuan, CHEN Yongqi, FANG Zhen, WU Lili. Cystic neutrophilic granulomatous mastitis: a study on association between dominant bacterial infection and histological characteristics[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(01): 59-64.

图/表 3

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