不同分期肉芽肿性小叶性乳腺炎的临床病理观察及CD4^(+)/CD8^(+)比值的变化

Clinicopathological features and the change of CD4^(+)/CD8^(+) ratio in granulomatous lobular mastitis with different stages

目的分析不同分期肉芽肿性小叶性乳腺炎(GLM)的临床病理学形态以及CD4^(+)、CD8^(+)的表达及CD4^(+)/CD8^(+)比值,以探讨疾病发展过程中的形态学变化及相关机制。方法收集山东中医药大学附属医院乳甲外科53例手术确诊肉芽肿性小叶性乳腺炎患者病例,根据GLM临床特点分为肿块期(n=14)、脓肿期(n=23)、溃后期(n=16),各组手术切除标本行石蜡制作、HE染色及免疫组织化学染色,观察组织形态学特点,计算各期CD4^(+)、CD8^(+)的表达及CD4^(+)/CD8^(+)比值;同时检测其外周血CD4^(+)/CD8^(+)的比值。结果53例GLM患者发病中位年龄33岁,左侧38例,右侧15例,22例伴有催乳素升高,患者多以乳腺肿块为首发症状,病程1~12个月。GLM镜下表现为非干酪样肉芽肿性炎,肿块期仍可见小叶结构,而脓肿期小叶逐渐融合,溃后期小叶融合成片,多无法辨清小叶结构并伴大量中性粒细胞浸润。免疫组织化学表达结果:53例GLM患者共有44例病灶处CD4^(+)/CD8^(+)的比值小于1.5,且CD4^(+)/CD8^(+)<1.5病例数在溃后期明显低于肿块期与脓肿期(P<0.05),肿块期与脓肿期差异不明显。53例患者的外周血中有33例CD4^(+)/CD8^(+)比值小于1.5,CD4^(+)/CD8^(+)<1.5病例数在溃后期明显低于肿块期与脓肿期(P<0.05),肿块期与脓肿期差异不明显。结论病理诊断是肉芽肿性小叶性乳腺炎的金标准,应该注重病理诊断;肉芽肿性小叶性乳腺炎溃后期相对于肿块期及脓肿期,病灶处及外周血CD4^(+)/CD8^(+)比值降低的病例数明显减少,提示CD4^(+)/CD8^(+)比值降低可以作为GLM严重程度的指标,为揭示肉芽肿性小叶性乳腺炎发生发展的机制及提供治疗手段有重要意义。

Objective To analyze the clinicopathological morphology of granulomatous lobular mastitis(GLM)with different stages,as well as the expression of CD4^(+),CD8^(+)and the ratio of CD4^(+)/CD8^(+),so as to explore the morphological changes and related mechanisms during the development of GLM.Methods Surgical pathologic specimens of GLM were collected from 53 patients admitted to Affiliated Hospital of Shandong University of Traditional Chinese Medicine.Based on the clinical characteristics of GLM,the tissues were divided into mass stage(n=14),abscess stage(n=23),and late ulceration stage(n=16).Paraffin wax production,HE staining and immunohistochemical staining were carried out to see morphological characteristics,the expression of CD4^(+),CD8^(+)and CD4^(+)/CD8^(+)ratio;meanwhile,the ratio of CD4^(+)/CD8^(+)in peripheral blood was also detected.Results The median age of onset of the 53 patients with GLM was 33 years,38 cases occurred on the left side,15 cases occurred on the right side;22 cases happened with elevated prolactin,and the first symptom was a breast mass in most of the patients.The course of disease was from 1 month to 12 months.Microscopically,GLM presented as non-caseous granulomatous inflammation,with lobular structures still noted at mass stage,gradually fused lobules at abscess stage,and fused lobules at late ulceration stage in which lobular structures were indistinguishable.Immunohistochemical staining result showed that 44 of the 53 patients with GLM had CD4^(+)/CD8^(+)ratio less than 1.5,and the proportion of cases with CD4^(+)/CD8^(+)<1.5 in the late ulceration stage was significantly lower than that in the mass stage and the abscess stage(P<0.05),and there was no significant difference between the mass stage and the abscess stage.In the peripheral blood of 53 patients,CD4^(+)/CD8^(+)ratio was less than 1.5 in 33 cases,and the proportion of cases with CD4^(+)/CD8^(+)<1.5 in the late ulceration stage was significantly lower than that in the mass stage and the abscess stage(P<0.05),but there was no significant difference between the mass stage and the abscess stage.Conclusion Pathological diagnosis is the gold standard in the diagnosis of granulomatous mastitis,and attention should be paid to pathological diagnosis;compared with mass stage and abscess stage,the proportion of cases with reduced CD4^(+)/CD8^(+)ratio in lesions and peripheral blood is significantly lower in the late ulcerative stage,which suggests that the reduced CD4^(+)/CD8^(+)ratio could be used as an indicator of the severity of GLM and it may help reveal the mechanism of the occurrence and development of GLM and thus provide treatment options.