Immune pathogenesis of idiopathic granulomatous mastitis: from etiology toward therapeutic approaches.

Idiopathic granulomatous mastitis (IGM) is a noncancerous, chronic inflammatory disorder of breast with unknown causes, posing significant challenges to the quality of life due to its high refractoriness and local aggressiveness. The typical symptoms of this disease involve skin redness, a firm and tender breast mass and mastalgia; others may include swelling, fistula, abscess (often without fever), nipple retraction, and peau d'orange appearance. IGM often mimics breast abscesses or malignancies, particularly inflammatory breast cancer, and is characterized by absent standardized treatment options, inconsistent patient response and unknown mechanism. Definite diagnosis of this disease relies on core needle biopsy and histopathological examination. The prevailing etiological theory suggests that IGM is an autoimmune disease, as some patients respond well to steroid treatment. Additionally, the presence of concurrent erythema nodosum or other autoimmune conditions supports the autoimmune nature of the disease. Based on current knowledge, this review aims to elucidate the autoimmune-favored features of IGM and explore its potential etiologies. Furthermore, we discuss the immune-mediated pathogenesis of IGM using existing research and propose immunotherapeutic strategies for managing this condition.

Cytokines the Etiology of Idiopathic Granulomatous Mastitis.

OBJECTIVE: To investigate the roles of cytokines in the etiopathogenesis of idiopathic granulomatous mastitis (IGM). DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Istanbul Training and Research Hospital, Istanbul, Turkey, from September 2020 to January 2021. METHODOLOGY: Idiopathic Granulomatous Mastitis patients in active or remission who were admitted to the breast diseases outpatient clinic and healthy volunteers were included prospectively in the present study. The IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23 and IL-33 values were measured with Flow Cytometry. The blood samples were taken before the treatment in the active IGM group. The ages, physical examination findings, menopausal and smoking conditions, and treatment methods were also evaluated. RESULTS: A total of 32 patients including 19 patients with active and 13 in remission, and 18 controls, were inducted making up a total of 50 subjects. The mean age was 37.18±7.15. The IL-1ß, TNF-α, IL-10, and IL-18 values were lower in patients with IGM than in the control group. Granulomatous Mastitis patients smoked more than the healthy participants. When the active patients, remission patients, and control group were evaluated together, no significant differences were detected in cytokine levels. CONCLUSION: The autoimmune and granulomatous reactions may not play a role in the etiopathogenesis of IGM because of the low levels of Th1 and Th17-related cytokines. However, some to baseline reference ranges were established. KEY WORDS: Idiopathic granulomatous mastitis, Cytokine, Autoimmunity, Smoking.

Idiopathic Granulomatous Mastitis: Etiology, Clinical Manifestation, Diagnosis and Treatment.

Idiopathic granulomatous mastitis (IGM) is a rare form of chronic inflammatory breast disease. Although it is a benign breast lesion, it may be sometimes difficult to distinguish from breast cancer. The cause of IGM is unknown, but may be associated with autoimmunity, abnormal hormone levels and infection. While the clinical manifestations of IGM involve various manifestations of inflammation, the diagnosis is principally established by histopathology, characterized by non-caseating granulomas and microabscess formation centered on the breast lobules. Therapeutic options for IGM range from observation to various medical treatments, such as steroids, immunosuppressants, and antibiotics, to surgical intervention, particularly if secondarily infected. Given that the controversy on etiology and treatment choices, we accomplished the present review through reviewing IGM-related literature published in 'Pubmed' and 'Web of science' databases during 1997 to 2020, aiming to provide the basis for rational clinical diagnosis and treatment.

New Findings on Autoimmune Etiology of Idiopathic Granulomatous Mastitis: Serum IL-17, IL-22 and IL-23 Levels of Patients.

BACKGROUND: Idiopathic Granulomatous Mastitis (IGM) is a benign chronic inflammatory breast disease that mimics breast cancer, and the etiopathogenesis has not yet been fully evaluated. Autoimmunity has received the most focus as a possible etiology. Our aim in this prospective clinical study was to investigate the possible association between the cytokines, interleukin IL-17, IL-22, IL-23 and IGM. MATERIALS AND METHODS: The current study was conducted in 26 women with histopathologically diagnosed IGM, and 15 control women of reproductive age having no breast disease history. Blood samples were collected, and serum concentrations of IL-17, IL-22, and IL-23 were determined. RESULTS: In the analysis of variables, the patients with IGM and the control group had statistically significant differences between serum IL-22 titers (p = 0.0378) and IL-23 titers (p = 0.0469. No statistically significant difference was found between IGM patients and the control group in serum IL-17 titers (p = 0.9724). CONCLUSION: The results of the current study, especially pertaining to serum IL-22 and IL-23 levels, support the etiopathogenesis of IGM in favor of the autoinflammatory thesis. Nevertheless, this thesis should be supported by a large case number and prospective clinical studies.

Management of Granulomatous Mastitis Following Aesthetic Breast Surgery.

BACKGROUND: Granulomatous mastitis (GM) is not among the well-known diseases in the field of aesthetic breast surgery (ABS). The clinical presentation of GM resembles infectious diseases or malignancies, but the management of these diseases is quite different. In this study, we aimed to present the management of GM in patients who underwent ABS. METHODS: In this study, patients with GM (n = 65) and patients who underwent ABS (n = 531) were evaluated. A total of six GM patients with a history of ABS were included in the study between January 1, 2010, and January 1, 2019. The data were collected retrospectively. The quantitative variables are shown as medians (minimum-maximum), and categorical variables are shown as numbers and percentages (%). RESULTS: Median duration of disease onset after the ABS was 16 (8-38) months. After the diagnosis of GM was obtained, all patients received steroid treatment. Median steroid treatment duration was 10 (8-20) weeks. Methotrexate was administered in two patients due to persistent breast mass and steroid side effect. Surgical excision was performed in three patients with wide excision. No patient needed further surgery such as mastectomy. Median follow-up period was 37.5 (18-70) months. CONCLUSION: This is the first study to declare GM in patients who underwent ABS. Atypical clinical presentation such as breast abscess, mass or fistula after ABS should alert the surgeon about GM. Unlike other mastitis, the primary treatment of this rare disease is steroid and immunosuppressive treatment. Insufficient knowledge about GM can lead to unnecessary surgeries or breast loss. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette-Guerin treatment.

Idiopathic granulomatous mastitis (IGM) is a benign chronic inflammatory disorder of the breast tissue, with unknown etiology. IGM is extremely rare among male gender. In this case report, we present a male patient with superficial high grade bladder cancer, who was complaining of a palpable mass in his right breast for two weeks following intravesical Bacillus Calmette-Guerin (BCG) treatment. There was an assymetrical, mass-like density without distinct contours in retroareolar area of the right breast. US guided core-needle biopsy was performed. Histopathology confirmed the diagnosis of IGM. To our knowledge, this is the first case of IGM following intravesical BCG administration.

Diagnostic techniques and multidisciplinary approach in idiopathic granulomatous mastitis: a revision of the literature.

Idiopathic granulomatous mastitis (IGM) is a chronic benign inflammatory disease of the breast that may mimic breast cancer. It is most common in parous young fertile women, although it can occur in nulliparous women and in men. IGM is an idiopathic disease due to the influence of some environmental factors in genetically predisposed subjects. Several pathogenic hypothesis have been proposed in the last years (autoimmune, hormonal, infective genesis). IGM presents as a painful palpable mass located in one of the two udders. The skin is usually normal but could present signs of inflammation with or without lymph nodes involvement. Ultrasonography, mammography, magnetic resonance can be diagnosed an IGM, but pathognomonic radiological signs has not yet reported in literature. Biopsy findings show granulomatous lesion centered on the breast lobule, as in granulomatous mastitis induced by tuberculosis or sarcoidosis. The aim of this review of literature is to verify the development of new advanced diagnostic techniques and multidisciplinary approach for this condition. In the last years innovative approaches have modified IGM diagnosis and therapy, avoiding surgery in most of cases, introducing a more conservative medical approach based on recent etiopathological hypothesis.

Idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis (IGM) is a rare, poorly understood condition that presents as inflammatory nodules of the breast. It is often initially misdiagnosed as furunculosis or cellulitis. Despite the painful, scarring, and debilitating nature of the disease, patients often have a delay in accurate diagnosis and treatment. Even when IGM is considered as a diagnosis, it is one of exclusion, with the differential diagnosis including serious conditions such as breast cancer, sarcoidosis, and cutaneous tuberculosis. Therefore, appropriate workup is important. Given that IGM is a disease of the skin, it is important for dermatologists to be familiar with its presentation. We describe 3 cases of young women with this condition and demonstrate that identification of triggers or methotrexate treatment is highly successful in sparing patients the drastic surgical alternative of mastectomy.

Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4-Related Disease.

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.

Idiopathic granulomatous mastitis: Long-discussed but yet-to-be-known.

Idiopathic granulomatous mastitis (IGM) is a chronic benign inflammatory disease of the breast with unknown etiology. It is an important diagnostic and therapeutic challenge, as most patients were initially misdiagnosed by their primary care physicians, leading to diagnostic confusion and heightened anxiety. Although several triggers have been proposed for development of IGM, the etiologic association of neither of them has been documented. Three main hypotheses about the possible causes of IGM have been suggested, including autoimmune response, infectious disease, and hormonal disruption. Here, we discuss a hypothetical perspective of IGM to explain the possible role of autoinflammation in the pathogenesis of the disease. We also reviewed the previously published literature on pathogenesis of IGM.

Association between Hyperprolactinemia and Granulomatous Mastitis.

Granulomatous mastitis (GM) is a relatively uncommon inflammatory breast lesion with multiple suggested etiologies. Although most GM cases show association with lactation and pregnancy, a minority of cases have been linked to hyperprolactinemia caused by either dopamine antagonist medications or with intracranial lesions, such as pituitary adenoma. The goal of this study is to review the GM cases reported in the literature with a specific emphasis on those cases associated with hyperprolactinemia and prolactinomas and to identify cases of GM seen at the Cleveland Clinic Florida which demonstrate co-occurrences of GM and intracranial lesions. CoPath and Epic data bases at Cleveland Clinic Florida were searched for cases describing inflammatory breast lesions in patients with pituitary pathology. Chart reviews were conducted and pertinent medical history was extracted for case reports. H&E-stained paraffin-embedded sections retrieved from Cleveland Clinic Florida pathology storage were evaluated by light microscopy. Four cases showing a co-occurrence of GM and hyperprolactinemia were consequently identified. A prolactin-secreting pituitary adenoma was present in two of the three GM cases. The third case demonstrated a concomitant craniopharyngioma, which was also associated with a rise in serum prolactin. This phenomenon was presumably attributable to compression, resulting in compromised transport of dopamine to the adenohypophysis and subsequent disinhibition of prolactin secretion by lactotrophs. The fourth patient with GM had a similar history of elevated prolactin. Classical histopathological features of GM were found in all four cases, including noncaseating granulomas, multinucleated giant cells, epithelioid histiocytes, and chronic inflammation. Intriguingly, complete resolution of inflammatory breast lesions along with normalization of prolactin levels occurred following the surgical excision of the craniopharyngioma, suggesting that intracranial lesion-induced hyperprolactinemia might be directly causal in GM. Therefore, the authors would suggest screening for pituitary tumors and evaluate prolactin levels in the workup of GM patients without a recent history of lactation and pregnancy and no other identified etiology.

Two Cases of Granulomatous Mastitis Caused by Corynebacterium kroppenstedtii Infection in Nulliparous Young Women with Hyperprolactinemia.

Recently, an association between granulomatous mastitis and local infection with Corynebacterium (C.) kroppenstedtii has been suggested. We herein report two cases of granulomatous mastitis resulting from C. kroppenstedtii infection in nulliparous young women with hyperprolactinemia. Both cases involved nulliparous patients with drug-induced hyperprolactinemia, and both individuals received incision and drainage, after which the pus was sent to our laboratory. Corynebacterium spp. grew on blood agar, and 16S rRNA gene sequencing identified the pathogen as C. kroppenstedtii. In conclusion, lactational changes caused by drug-induced hyperprolactinemia may increase the risk of granulomatous mastitis after C. kroppenstedtii infection.

[Breast cancer treated by antibiotherapy? Granulomatous mastitis with Corynebacterium]. / Cancer du sein traité par antibiotherapie ? Mastite granulomateuse à corynébactérie.

Granulomatous mastitis is a rare disease, often associated with Corynebacterium infection. It raises the problem of diagnosis of breast tumor with a fast evolution and inflammatory character. We report two cases of granulomatous mastitis with Corynebacterium. It concerns the clinical and radiological description, followed by the therapeutic alternatives and future of the patients. The clinical presentation is variable. The treatment consists in a surgical procedure of resection. The medical treatment based of corticosteroids also proves efficient. The association between Corynebacterium presence and this pathology seems frequent and needs a specific bacteriological search.

An SLE patient with prolactinoma and recurrent granulomatous mastitis successfully treated with hydroxychloroquine and bromocriptine.

Granulomatous mastitis (GM) is a rare benign mammary lesion in which autoimmunity and hyperprolactinemia are considered possible etiological factors. GM has a high frequency of relapse and may lead to chronic ulceration and fistula if not treated properly. Here we report a case of a 22-year-old systemic lupus erythematosus (SLE) patient with three years' disease duration, stable on prednisone and hydroxychloroquine, who was found to have prolactinoma and recurrent GM after she discontinued medication on her own accord. The patient subsequently recovered and remained free of GM relapse under treatment of prednisone, hydroxychloroquine and bromocriptine. Though autoimmune disorders and prolactinoma were reported in GM, a coexisting condition of SLE, prolactinoma, and granulomatous mastitis has rarely been observed in one patient. We suggest our case as an illustrative example of the complex interaction between autoimmunity, neuroendocrine dysfunction, and manifestations in the breast: Immunological disturbances in the background of SLE, coupled with elevated prolactin levels secondary to a prolactinoma, may have predisposed the patient to the development of GM. The mammary lesion recovered and maintained free of relapse under immunosuppressive and antiprolactinemic therapy.

First report of granulomatous mastitis associated with Sjögren's syndrome.

Granulomatous mastitis is a rare and often considered as idiopathic disease. However, clinical examination and thorough diagnostic investigations have to be carried out in order to identify cases that are secondary to infections or systemic diseases since these forms may be cured with appropriate etiologic treatment. To the best of our knowledge, this report is the first to describe the association of granulomatous mastitis with Sjögren's syndrome. We discuss the clinical, pathological and therapeutic implications of this association.

[Idiopathic granulomatous mastitis]. / La mastite granulomateuse idiopathique.

Idiopathic granulomatous mastitis (IGM) is a rare localized granulomatosis of unknown aetiology that usually affects women of childbearing age. It often mimics breast carcinoma or abscess. Histopathologic evaluation and elimination of the others aetiologies of granuloma play a crucial role in the diagnosis. Its etiopathogeny remains poorly understood, but Corynebacteria might be involved. The disease course is usually protracted, with a significant impact on quality of life. The management of IGM remains controversial, but corticosteroids are usually the first-line treatment.

Borderline-lepromatous leprosy manifesting as granulomatous mastitis.

Leprosy is characterised by a chronic granulomatous inflammation of the skin and peripheral nerves. Dissemination of the lepra bacilli may cause involvement of other tissues as well. We describe an unusual case of the granulomatous involvement of the nipple-areola complex in a 35-year-old male consequent to borderline-lepromatous leprosy.