The Pathological Characteristics Of Mammary Ductectasia And Its Correlation With IL-1?

BACKGROUNDNon breast-puerperal mastitis(NPM)is a kind of benign breast inflammatory disease.which diagnosis and treatment are very difficult.Its etiology is uncertain.Because of the long term attack,and the high morbidity of its recurrence,many women have to accept the pain.At present,NPM can be divided into two types,they are mammary ductectasia(MDE.sometimes is called periductal mastitis,PDM)and granulomatous lobular mastitis(GLM).MDE always occurs in adult women,mainly characterized by recurrent episodes of aperiodic breast pain,nipple discharge,nipple retraction,breast lumps,abscesses subareolar or periareola.with or without inflammation and fever.Seriously abscess,burst.even fistula.etc.appear.Its recognized as a refractory benign breast disease.In recent years,the frenquncy arised.This kind of disease was first mentioned by Bloodgood in 1923.At the first time.the term of mammary ductectasia(MDE)was summarized by Haagensen in 1951.according to the clinical manifestations of disease.The disease with the same characteristics like these.is also known as occlusive mastitis,varicose veins tumors,plasma cell mastitis,mastitis.periductal mastitis and secretory disease of the breast,etc.Dixon.1983 considered that periductal mastitis occured before the dilation of breast duct by retrospectively analysis and it is the first manifestation of the disease,so the product considered that PDM is forward of MDE,and this may reflect that they were the different stages in the process of the same kind of disease.Then some scholars agreed with this point of view.Thus,breast experts usually call MDE as PDM,though a few scholars believed that they were different independent diseases.Now,many exports still follow the most people's point of view.Now,it is lack of a unified specific standard about MDE.As early as 1951 when Haagensen proposed this concept,he divided MDE into different clinical stages.And he considered that there were different pathology characteristics during different period,and there may be different periods coexist in the same organization.In 1969,AbramsonDJ agreed with Haagensen.He pointed out that the the disease developed in different stages,and he described the clinical manifestations and histopathological features of different periods in details.At present.domestic and foreign scholars use two ways to devide the clinical stages.One kind is divided them into three periods:acute,subacute and chronic phase.More scholars tend to divide them into four periods,which names sometimes are inconsistent but the standard is similar:the hidden period(also called ductal dilation),mass(also known as inflammation block)stage,abscess and fistula(also called fistula period).The pathological diagnosis is the gold standard of the disease.But it is lack of unified specific consensus.As early as 1952.Frantz and his team found that in the early period of MDE.the terminal ducts below the nipple and areola area are obviusly expansive,which consist of lipid and cell debris.The ductal epithelium is still neat with no obvious inflammation occuring.AbramsonDJ described the pathological characteristics in detail,and considered that hyperplasia of the duct epithelium occuring during the progress of the disease.But his pathologic description caused many disputes.For example.Haangensen thought that it was not the hyperplasia but the expansion of ductal epithelium.Tedeschi believed that atrophy is the basic change of epithelium,but epithelial hyperplasia might happen during the process when it secreted.While Frantz found the presence of colostrum sample cells and foam cells in patients with MDE,and the epithelium hyperplasia or top secret were present.The expansive duct contained nucleus lens,amorphous debris and debris.Contentious debates still exist now.The clinical symptoms of granulomatous lobular mastitis(GLM)are similar to those of MDE.And it is easily confused between the two diseases through clinical physical examination and imaging examination.Then,some experts put forward that it needs wide public concern about the diagnosis of lactation mastitis and non-lactation mastitis.But because of the absence of knowledge in some medical institutions,many cases of MDE were confused with GLM.Different diagnosis need different treatment,while misdiagnosis lead to great pain.Specific pathological diagnosis becomes a problem to be solved at present.It is not yet clear about MDE.Since 1951,Haagenson defined the disease with the term MDE,he has described the dynamic characteristics of this disease:the collecting tube expanded under the areola,content accumulated,during the progress of the disease,the expansive duct further dilated,eventually triggered a fracture of the duct,the contents.involving multiple ducts,caused inflammation of suround,even abscess.This is the so-called "block hypothesis".Haagensen emphasized the main cause was that the clogging lead to the stop of the ductal epithelium hyperplasia,and the hyperkeratosis of the epithelium occured,then ducts expanded and became thin and flat.Then many scholars have proposed vary opinions.Many hypothesis arised at different historic moment.Some summarezed that MDE may be associated with endogenous or exogenous mechanical factors,such as the deformation of nipple,congenital nipple or breast dysplasia,vessel endothelial proliferation,ductal epithelial tumor or cyst,etc.Others reported that there may be some factors leading to the discharge obstruction of the intraductal secretion.Some researchers believe that may be due to hormonal disorders,but it is lack of the in-depth inquiry.Rodman and Ingleby thought that this disease may because of the degradation of colostrum structures by the enzyme with the help of some mechanism in non-lactating women.Tedechi thought MDE is related to some chemical stimulation,etc.And the mechanism about the secretion secreted into surrounding tissues may be related to the epithelial cells of storage,including focal infection or local trauma surgical trauma.some said.So many hypothesis,but so little about the"blocking".Even no one to study in-depth.Until 1983,Dixon proposed the opposite views against Haagensen,he thought that MDE began with PDM,duct dilation is the result.In 1989,Dixon considered that bacteria,especially the anaerobic bacteria playing a role at the early stage of inflammation.but the exact reason is unclear.It is still controversial about whether the disease comes from bacteria invasion or exogenous infection.For recent 30 years.professors have proposed there may be correlation between hyperprolactimia and this disease.Some reports hypothesized that smoking is a risk factor,and some put forward that the disease may be associated with autoimmunity.Now more and more inclined to find the basic pathological changes,and thought there may be joint actions of variety of other factors,which show different pathological lesions,and biological changes in different stages.We need to investigate further cause of disease.Researchers generally believe that the pathogenesis of this disease will be accompanied with a series of changes in and surroud the duct:duct expansion,and then rupture,inflammation,the final formation of granuloma,fibrosis around the duct and so on.In this process,the perception,production and the release of proinflammatory cells build the important step of the host defense.The cytokines of IL-1 family not only induce inflammation,but also regulate the reaction of T lymphocytes,maintaining the balance of internal stability and metabolism.IL-la and IL-1? act as important inflammatory factors to activate the occurrence of inflammatory response.Some studies suggested that the occurrence of acne is derived from the expansion of hair follicle sebaceous gland epithelium,accumulation of the contents,resulting in cell hyperkeratosis and local inflammation.The level of IL-1? in skin epithelial cells of patients with early acne was significantly increased,and it was concluded that IL-1? might promote the early hyperkeratosis of epithelium and inflammation.In vicew of the similar mechanisms between mammary duct ectasia and acne.it is needed to explore the mechanism of immunity factors in the process of epithelial hyperkeratosis and inflammation around the duct in future.Based on the background above.we divided the disease into four stages according to the current application of MDE.Our study summarizes the pathological characteristics in different clinical stages of' MDE.and the result also summarizes the different expressions of IL-1? in different clinical stages of MDE,in order to finds out the pathological characteristics of MDE and the application value of the relationship between IL-1? and the etiology of MDE.which can provide some reference for the follow-up diagnosis and treatment.PurposeThis study was performed on patients who were pathologically diagnosed as MDE.We aim to 1.Summarize the different pathological characteristics of different clinical stages;2.Investigate the correlation between IL-1? and the etiology of MDE;3.Investigate the correlation between IL-la and prolactin by measuring the expressions of IL-1? in different clinical stages of MDE.Participants and methods1.ParticipantsThis study includes 155 patients with non-lactating mastitis in our hospital between April 2011 to November 2016.124 patients of these cases were diagnosed as MDE,and 31 cases were GLM.By reviewing medical records and pathological section,physical examination,auxiliary examination,we divided the MDE cases into four stages which are hidden stage(21 cases),mass stage(36 cases),abscess stage(47 cases),fistula stage(20 cases),and GLM(31 cases).The age from 16 years old to 62 years old.This study is conducted using internal controls.2.Data collectionReview HE pathological sections and carry out clinical staging.Review and summarize all the pathological sections under the guidance of pathologist,conclude the different pathological manifestations of different clinical stages and pathological types.3.The expression of IL-1? was measured by immunohistochemistry.4.The stained slides were reviewed and scored independently and blindly by two pathologists.Summarize the results of immunohistochemistry according to different clinical stages.and analyze the different expressions of IL-1? in different clinical stages of MDE.5.Application of Roche electrochemical luminescence detection system is used to detect prolactin levels in plasma of 30 patients with MDE.6.Statistical analysisSpss17.0 software package was used for statistical data processing.The different expressions of IL-la in different clinical stages of MDE were statistically analyzed by chi-square test and regression analysis,all results are bilateral,P<0.05 was considered statistic difference,P<0.01 was considered to be statistically significant difference.Results1.Clinical and pathological characteristics of MDEHidden stageClinical presentation:In this period,some have no obvious inflammation and clinical symptoms.some have a slight inflammation,with nipple discharge,breast tenderness,or mild tenderness,sometimes accompanied by cystic masses less than 2.0 cm in diameter.We can touch enlargement of the tube under the nipple,and the "cheese" or"acne" sample material can be extruded from the nipple,which can be yellow,thick liquid or with blood.Pathological characteristics:Breast ducts are significantly expanded,contents of the ducts are visible,there are foam cells or cholesterol crystals,as well as cell debris and so on;the arrangement of epithelial cells begins to disorder or even missing;mild inflammation may occur around the duct,a small amount of lymphocytes can also be found.Massive stageClinical presentation:In this period,obvious inflammation occurs,nipple retraction,breast lumps.or skin irritation,can be found mostly around the areola.Mostly mass is more than 2.0 cm in diameter.Pathological characteristics:Most of the ductal ducts disappear,even if ducts exist.their walls are destroyed.A large number of lymphocytes,plasma cells and tissue cells appear.Macrophages are significantly increased,neutrophils are sparse.eosinophils are occasionally founded,interstitial elastic fibers increase.Abscess stageClinical presentation:This is a period of acute inflammation secondary after the mass stage.In this period,skin redness,fluctuations of bump can be touched around areola,bump is often more than 2.0 cm in diameter with local tenderness.and the ipsilateral axillary lymph nodes can be swollen.Pathological characteristics:Ducts disappear.Abscess is visible,lymphocytes are comparable to massive stage,broken neutrophils and tissue cells increased significantly.Plasma cells decreased slightly than massive stage,eosinophils slightly increased than massive stage.Interstitial elastic fibrous layer was thickened.Sinus stageClinical presentation:After burst or after surgical drainage of the abscess,fistula occurs,which delays a long time.Pathological characteristics:Abscess area disappear,the number of broken neutrophils and tissue cells is similar to the abscess stage,and they are no longer gathered,but gradually dispersed,plasma cells and eosinophils decreased.2.The clinical presentation and pathological characteristics of GLM Clinical presentation:Similar to the massive stage and the abscess stage.Pathological characteristics:Ducts and acini are visible in lobular when light inflammation occurs.The terminal ducts expand,the cavity is empty or contains necrotic material and even abscess forms.Numerous inflammatory cells gathered arround,such as lymphoid cells,macrophages,neutrophils and multicore macrophages.The ducts and acini epithelium can shrink.If the Inflammation is severe,the epithelium is damaged or disappears.Lesions in the fusion,lobular structures disappear,suppurative inflammation granulomatous appear,and abscess form.Some ductal epithelium is hyperplasia,inflammatory cells infiltrate,especially the lymphocytes,numerous neutrophils,monocytes,epithelioid cell nucleus multinucleated giant cells,multinucleated giant cell such as langerhans,and some eosinophils.Most abscess becomes vacuoles,fat necrosis,but no caseous necrosis.Within the stroma,fibrous tissue hyperplasia,sometimes with MDE.3.Immunohistochemistry of IL-la expressionHidden stage:Large number of ducts ectasia are visible,epithelial cells of dilated duct were positive performance,contents in the dilated ducts were also stained positively.Sporadic positive stained macrophages are visible in the stroma.Massive stage:Most of the ducts disappear,a large number of positive-stained macrophages and multinucleated macrophages are scattered in the field of view.A large number of plasma cells showed positive performance.Remaining ducts are occasionally seen,with positive staining of epithelial cells,inferring that some areas are still in hidden stage.Abscess stage:Residual ductal epithelial cells showed positive expression.Most plasma cells,macrophages are positive performance,considering the possibility of coexistence of three stages.Sinus stage:Positive expression of ductal epithelial cells are rare.Positive expression of plasma cells and macrophages is significantly reduced.Inferring that the peak of inflammation has passed.Granulomatous lobular mastitis:Ductal epithelium was significantly destroyed,the residual epithelial cells showed positive expression,and plasma cells and macrophages were positive expression.4.Pathology scores of Immunohistochemical stainingTwo pathologists evaluated the specific staining results of IL-1?immunohistochemistry according to the modified Harvey score independently and blindly.The result showed that with the progression of the disease from the occult stage to the sinus period,the expression of IL-la in ductal epithelial cells showed decreasing trend(P<0.001),while the expression of IL-la in macrophages showed an increasing trend(P<0.05).The results of the above studies showed that IL-1? is associated with MDE and may be involved in the development and progression of the disease.30 patients with mammary duct ectasia accepted plasma prolactin level detection,it can be divided into two groups(normal group of 19 people,abnormal group of 11).The result is that although there is no statistical difference about expression of IL-1?in two groups of patients(P = 0.327 epithelial cells and macrophages in P = 0.417.P = 1)in plasma cells,but the proportion of the positive expression of IL-1?in the epithelial cells in the abnormal group(90.9%)was obviously higher than the normal group(26.3%).Conclusions1.Pathological characteristics of MDE are different according to the clinical stages.Pathological characteristics are different between MDE and GLM.2.Expression of IL-1? differs in different stages of MDE.The positive expression rate of IL-1? in dilated ductal epithelial cells was higher at the initial stage of disease,and the expression of IL-1? was decreased in the epithelial cells as the disease progressed.The expression of IL-1? in macrophages was positively correlated with clinical stage,and the expression of IL-la was increased in macrophages as the disease progressed.3.IL-la may be associated with the hyperkeratosis of the epithelium,and may be associated with the development and progression of MDE.4.IL-1? may be associated with prolactin,and hyperprolactinemia may be correlated with MDE.