Differences In Clinicopathological Features Of Periductal Mastitis And Granulomatous Lobular Mastitis

BackgroundNon-puerperal mastitis(NPM)is a group of benign diseases that occur in women during non-lactation,mainly including periductal mastitis(Periductal mastitis,NPM).PDM)and granulomatous lobular mastitis(GLM),also known as mammary duct ectasia(MDE)or plasma cell mastitis(PCM).In recent years,the incidence of NPM has been increasing year by year,with a long course of disease and a tendency to relapse.In particular,inappropriate treatment leads to repeated conditions,so that breast resection not only affects the beauty of patients’ breasts,but also has a great impact on their physical and mental health.At present,the pathogenesis of NPM is still unclear.Possible causes of PDM include congenital nipple invagination,bacterial infection,etc.,among which the most widely recognized is the theory of "duct obstruction".Haagensen believes that in periductal mastitis,ductal epithelial cells secrete lipid substances,resulting in ductal dilation and flattening of ductal epithelial cells.Finally,the catheter ruptures and causes inflammation around the catheter.The possible pathogenic factors of GLM include bacterial infection,immune system disorders,sex hormone secretion disorders,smoking,α1-antitrypsin deficiency,long-term oral contraceptives,etc.Ogura et al.found a large number of IgG4+plasma cells and CD4+or CD8+ infiltration in 2 cases of GLM.High IgG4 levels were detected in serum of 1 GLM patient,suggesting that GLM may be associated with autoimmune diseases.PDM and GLM have similar clinical manifestations and are difficult to distinguish,but their treatment methods are different,their prognosis is different,and their classification diagnosis is not clear.Therefore,the differential diagnosis of GLM and PDM is in urgent need of research.Both PDM and GLM can present as breast mass,breast abscess,sinus tract or ulcer.Imaging examination of both PDM and GLM is similar to that of breast cancer,and it is difficult to distinguish them.Pathological examination is the key to differential diagnosis.PDM is generally characterized by ductal dilatation and the formation of secretions in the ducts.GLM is mainly manifested by the formation of granulomatous lobular inflammation centered on the breast,with or without microabscesses.However,both diseases have a large number of lymphocytes,neutrophils,and plasma cells,and few systematic studies have been conducted on the differences between the two diseases.GLM and PDM lack a unified classification and diagnostic criteria.This study intends to summarize the clinicopathological characteristics of GLM and PDM and analyze their differences,so as to further identify the two diseases and provide some references for their pathogenesis and treatment.AimsThis study was designed to summarize the case characteristics,review pathological slides and conduct relevant immunohistochemical studies:1.The clinicopathological characteristics of PDM and GLM were summarized and analyzed.2.The differences in the distribution proportion of infiltrating lymphocyte subsets in PDM and GLM lesions were compared,and the changes in the continuity of myoepithelial cells in PDM were observed,so as to preliminarily explore the etiological differences between PDM and GLM.Methods1.Subjects:Retrospective analysis was performed on 178 cases diagnosed as non-lactation mastitis in the Department of Breast Surgery of the Second Hospital of Shandong University from January 2011 to October 2020,among which 121 cases were pathologically diagnosed as periductal mastitis and 57 cases were granulomatous lobular mastitis.This study has been approved by the Medical Ethics Committee of the Second Hospital of Shandong University.2.The collecting of subjects:The clinical information and auxiliary examination data of the patients were collected,and the HE sections were re-checked by 2 pathologists in our hospital.The pathological feature description questionnaire designed by ourselves was filled in,and the inflammatory cell count was carried out using ImageJ software,and the data were input and checked to ensure accuracy.3.Immunohistochemical stainingThe distribution ratio of CD3,CD4,CD8,CD20,CD 138 and Calponin cells was evaluated by immunohistochemical staining.The results were evaluated by pathologists in a "back-to-back" manner.Calponin staining results were used to observe the continuity of myoepithelial cells in PDM tissue samples.4.Statistical analysisSPSS26.0 software package was used for statistical processing of the data,descriptive analysis and binary Logistic regression were used to analyze the clinicopathological characteristics of periductal mastitis and granulomatous lobular inflammation,and t test was used to statistically analyze the differences in CD3,CD4,CD8,CD20 and CD138 expressions.All results were bilateral.P<0.05 was considered statistically significant,while P<0.01 was considered statistically significant.Result1.Clinicopathological characteristics and differences of PDM and GLMThe clinical characteristics of PDM and GLM were similar,but the onset age of PDM was wider than that of GLM.The mean onset age of PDM was 37.9±10.4 years old,and the mean onset age of GLM was 32±6 years old.The age difference between the two groups was statistically significant(P<0.001).The time from the onset of PDM to the last pregnancy was longer than that of GLM,and the difference was statistically significant(P<0.001).There were no significant differences between the two groups in pregnancy history,breastfeeding history,smoking history,secondhand smoke exposure history,contraceptive use history,history of hyperprolactinemia and pituitary microadenoma.PDM patients mostly occurred in the areola region(n=68,56.2%),while GLM patients mostly occurred in the peripheral quadrant of the breast(n=43,79.6%)(χ2=21.2,P<0.001).GLM was significantly larger than PDM(P<0.001),but PDM was often associated with breast skin redness and swelling(χ2=15.0,P<0.001).In PDM,the lesions were mainly peri-duct(χ2=109.3,P<0.001),while in GLM,the lesions were lobule-centered(χ2=118.7,P<0.001).PDM showed more ductal dilatation,rupture,peri-duct fibrosis and wall thickening than GLM(P<0.001).There were more secretions in the lumen of the catheter(χ2=23.0,P<0.001).The most significant feature of GLM was increased granulomatous structure formation(χ2=116.5,P<0.001),including more epithelioid cells,multinucleated giant cells and fibroblasts surrounding GLM than PDM,the difference was statistically significant(P<0.001).The formation of lipid vacuoles and microabscesses was significantly higher in GLM than in PDM(x2=26.4,x2=23.0,P<0.001).2.Observation of the phenomenon of "catheter rupture"When the catheter ruptures,the epithelial cells around the ruptured catheter become flattened,the proliferative fibrous connective tissue around the catheter ruptures and necrotic,and a large number of inflammatory cells infiltrate around the catheter.Loss of myoepithelial cell continuity was observed in 30 cases of PDM(n=30,62.5%).3.The proportion of lymphocyte subsets in PDM and GLMBoth PDM and GLM were dominated by lymphocyte infiltration and CD20+B lymphocytes.The average proportion of CD20+cells in PDM was 45.4%,and the average proportion of CD20+cells in GLM was 41.6%(P=0.015).The proportion of CD 138+cells in GLM group was significantly higher than that in PDM group(P<0.001).The number of multinucleated giant cells、neutrophils and CD8+T cell in GLM was higher than that in PDM.Conclusion1.PDM and GLM are two types of diseases with similar clinical manifestations caused by different etiologies,and pathological diagnosis is still the "gold standard" for their differential diagnosis.The identification points of the two diseases are summarized as follows:Diagnostic features of PDM:(1)The onset of PDM can occur at all ages,most of which occur 4 years after childbirth.(2)Unilateral areolar mass is the clinical manifestation of initial diagnosis.The acute stage of redness,swelling,heat and pain has a long course of disease,which may be accompanied by nipple discharge,nipple invagion,breast pain or abscess formation;(3)The main pathological manifestations were catheter dilatation,powdery lipid secretions and cholesterol crystallizations in the catheter,disorderly arrangement of duct epithelial cells,loss of continuity in the late stage of the lesion,outflow of duct contents,formation of foam cells inside and outside the catheter,rare granulomatous structure,and rarely accompanied by microabscess formation in the granuloma;Periductal fibrosis,abscess area formation,surrounding a large number of lymphocytes,plasma cells,neutrophils,and eosinophils infiltration.Diagnostic features of GLM:(1)The age of GLM is usually 30-40 years old,and the onset of GLM occurs within 4 years after birth.(2)Unilateral peripheral breast mass with large diameter,some of which may be accompanied by breast abscess or sinus tract formation;(3)The main pathological manifestations were noncaseous granuloma with lobules as the center,accompanied by or without microabscess.The center of the microabscess was mostly filled with lipid vacuoles,surrounded by a large number of neutrophils,and surrounded by a large number of inflammatory cells such as lymphocytes and plasma cells.2.Catheter occlusion hypothesis may be one of the etiology of PDM;PDM and GLM are related to immune system disorders,among which PDM may be related to the humoral immune response assisted by Th2/TFH,Th1/Th17 involved in cellular immune response and cytotoxic effect of CTL may mediate the occurrence and development of GLM.