Background Granulomatous mastitis (GM) is a rare benign inflammatory breast disease that may mimic carcinoma. Etiology remains unclear, but emerging evidence suggests a role for both breast and gut microbiota. Methods Between June 2022 and June 2024, 32 women with histopathology-confirmed GM and 44 non-GM controls (benign and non-granulomatous inflammatory conditions) were enrolled. Granulomatous tissue, adjacent normal breast tissue, and stool samples were collected. Microbiota composition was analyzed using 16S rRNA sequencing. Clinical variables were documented. Diversity analyses and receiver operating characteristic (ROC) curves assessed microbial differences and diagnostic potential. Results The GM cohort had a mean age of 36.8 years and BMI of 27.6 ± 3.9 kg/m2; 86.2% were postpartum, with no autoimmune or malignant conditions. GM lesions showed enrichment of Corynebacterium (notably C. kroppenstedtii), Staphylococcus, and Microbacterium, whereas Lactobacillus and Bifidobacterium were higher in normal tissue. Fecal samples exhibited reduced microbial diversity in GM compared with controls but did not replicate breast microbial profiles. ROC analysis indicated that Corynebacterium discriminated GM from controls with excellent accuracy (AUC = 0.87), while Staphylococcus was moderate (AUC = 0.78) and Lactobacillus inversely associated (AUC = 0.11). Conclusions GM demonstrates distinct microbial signatures, including pro-inflammatory taxa enrichment and protective commensal depletion, along with systemic dysbiosis. These findings support a microbiota-driven pathogenesis and highlight the potential of microbial biomarkers and therapeutic modulation.

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition of unknown aetiology. It is a diagnosis of exclusion with a wide differential diagnosis. To date, no diagnostic guidelines exist for IGM in the UK. This scoping review aims to evaluate histopathological and microbiological approaches for the diagnosis of IGM. A scoping review was performed by conducting a search of MEDLINE, Embase and Cochrane databases from 2003 to 2023. Studies involving human participants with histopathologically confirmed IGM were included. Data on histopathological and microbiological investigations were extracted and analysed. Out of 3208 search results, 225 studies involving 13 062 participants were included. Histological assessment was performed in 72.5% of participants, predominantly via core or excision biopsy. Microbiological investigations were inconsistently applied; only 47% of studies reporting the use of microscopy and culture. Only 24.9% of studies tested for tuberculosis using methods beyond histochemical Ziehl-Neelsen staining, and just 14 studies including 5% of participants described performing mycobacterial culture, despite this being the gold standard for diagnosis. Corynebacterium kroppenstedtii was identified in several studies using advanced molecular techniques, suggesting possible misclassification of cystic neutrophilic granulomatous mastitis as IGM. Substantial heterogeneity exists in the diagnostic workup for IGM, particularly in excluding infectious and systemic causes. Histopathology alone is insufficient for definitive diagnosis. A comprehensive, standardised diagnostic framework that incorporates clinical, microbiological and epidemiological factors is needed to improve diagnostic accuracy and ensure appropriate management, particularly in the context of possible immunosuppressive therapy.

The diagnostic dilemma of idiopathic granulomatous mastitis with an emphasis on histopathologic findings.

Background: Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast disease with poorly understood etiology. Current wound management lacks standardized protocols, highlighting the need for evidence synthesis to inform clinical decision-making.Objectives: To comprehensively search the relevant literature on wound treatment and nursing in patients with granulomatous lobular mastitis at home and abroad, to sort out and analyze the included literature, and to extract, sort out and integrate the items of wound-related interventions, so as to provide a framework and basis for the construction of breast wound care programs for patients with granulomatous lobular mastitis.Methods: We conducted a systematic review following the 6S evidence pyramid model (Jan 2023 version). Twelve databases were searched from inception to January 2025, including: BMJ Best Practice, Up to Date, The Journal of the American Medical Association (JAMA), Scottish Intercollegiate Guidelines Network (SIGN), CNKI, Wan fang, CBM. Inclusion criteria covered clinical studies and guidelines addressing GLM wound care. Two reviewers independently performed quality assessment using AMSTAR-2 (for reviews) and JBI tools (for primary studies), with evidence graded (Level 1-5) and recommendations categorized (Grade A/B).Results: From 1,333 screened records, 19 studies met inclusion criteria:3 systematic reviews,3 consensus guidelines,6 RCTs,6 quasi-experimental studies,1 cohort study. Key findings were synthesized into 38 evidence statements across four domains: Assessment (8 items): Recommended use of GMDAI for inflammatory activity monitoring, Wound care (20 items): Strong evidence (Grade A) for TCM patching in chronic phases. Education (5 items): Structured self-care programs reduced recurrence by 30%. Follow-up (5 items): Combined digital and clinic follow-ups improved compliance.Conclusion: This study summarized the evidence of wound care for GLM patients through evidence-based nursing methods, and provided evidence support for the clinical formulation of breast wound care programs for GLM patients. Healthcare professionals can apply evidence to the clinic based on the clinical context to improve breast wounds and quality of life.

Granulomatous mastitis (GM) is a refractory chronic inflammatory breast disease. Current first-line treatments, such as intralesional triamcinolone acetonide (TA) injections, are limited by short duration of efficacy, systemic side effects, and poor patient compliance. This study aimed to develop a novel chitosan (CS)-based TA-loaded polyvinyl alcohol (PVA) microneedle delivery system (MNs@TA-CS) for localized and sustained transdermal therapy. TA-CS nanoparticles were prepared using ionic gelation and subsequently incorporated into PVA microneedles. The resulting MNs@TA-CS was characterized for morphology, mechanical strength, and drug release profile. A rat GM model was induced by hyperprolactinemia and tissue homogenate-Freund's adjuvant. Therapeutic efficacy was evaluated through lesion size measurement, cytokine analysis, histopathological examination, and macrophage polarization assessment. The MNs@TA-CS exhibited excellent mechanical properties and a biphasic drug release profile. In the GM rat model, MNs@TA-CS demonstrated comparable therapeutic efficacy to conventional TA injections, significantly reducing lesion area (82.7% reduction), downregulating pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and modulating macrophage polarization. Histopathological and immunohistochemical analyses confirmed marked reduction in granulomatous inflammation and fibrosis. Notably, the MNs@TA-CS showed good biocompatibility with no signs of liver or kidney toxicity. The MNs@TA-CS achieves comparable efficacy to traditional injections while offering sustained drug release and minimized systemic exposure. Its biphasic release mode provides both rapid onset and prolonged therapeutic effect, making it a promising minimally invasive, patient-friendly alternative for GM treatment.

Introduction Recently, neutralizing autoantibodies against different cytokines have been found to explain susceptibility to infections. Because the clinical pictures mimic innate immune disorders (IIDs), they have been defined as phenocopies of IIDs. Autoantibodies against GM-CSF have recently been associated with disseminated cryptococcosis and alveolar proteinosis. Clinical Case The patient was a 17-year-old female with no family or personal history of disease. She presented with clinical symptoms for one year, characterized by fainting episodes, headaches, and vomiting. She underwent multiple medical evaluations, but no diagnostic conclusions were reached. Over time, the headache intensity increased and was associated with fever, asthenia, refusal of food, and subcutaneous lesions on the abdomen and chest that appeared to be lipomas. Ultimately, her condition was associated with mastitis, a solid nodule, and inflamed lymph nodes in the axillary regions. The biopsy revealed chronic granulomatous mastitis with Langhans giant cells and structures consistent with Cryptococcus spp. The cytochemical study of the cerebrospinal fluid showed hyperproteinorrhea and hypoglycorrhachia. The brain MRI revealed a lesion in the right basal ganglia related to cryptococcosis. Disseminated cryptococcosis was confirmed, and she completed six weeks of amphotericin B. It was suspended due to kidney damage and changed to fluconazole, which remains on to date. The immunological approach included a complete blood count, immunoglobulins, and lymphocyte subpopulations with normal values for her age. The autoimmunity approach and HIV test were negative. Antibodies against cytokines were requested, with identification of anti–GM-CSF autoantibodies. Discussion In all patients with disseminated cryptococcosis, we must look for immunological abnormalities. If no monogenic defects are found, we must look for autoantibodies against GM-CSF. In Mexico, we have implemented this search in the immunodeficiency laboratory. Patients may develop alveolar proteinosis, so they should be followed up by a pneumologist. Autoantibodies are compatible with autoimmunity, so treatment is immunosuppressive and immunomodulatory.

BackgroundGranulomatous lobular mastitis (GLM) is a nonspecific chronic inflammatory breast disorder with an obscure etiology and pathogenesis. Neutrophil extracellular traps (NETs), which are extracellular web-like structures composed of decondensed chromatin and granular proteins released by activated neutrophils, disrupt normal tissue architecture and perpetuate inflammatory responses. The aim of the present study was to explore the role of NETs in GLM and the underlying regulatory mechanisms.MethodsNeutrophils were isolated from the blood of GLM patients and healthy controls (HCs) to assess NET formation. The presence of NETs in GLM tissues was detected using Western blot, immunohistochemistry, and immunofluorescence analyses. A mouse model of GLM was established to determine whether the inhibition of NET production, which is dependent on S100A8/S100A9, alleviates mammary gland inflammation. The potential mechanisms and therapeutic implications were further explored through in vitro and in vivo assays.ResultsNETs were significantly increased in GLM tissues, as characterized by elevated levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO). S100A8/S100A9 was highly expressed in GLM and demonstrated significant diagnostic value alongside NET markers. Mechanistically, S100A8/S100A9 promoted NETosis through interactions with peptidylarginine deiminase 4 (PAD4). Both paquinimod (an S100A8/S100A9 inhibitor) and Cl-amidine (a PAD4 inhibitor) effectively suppressed NET formation in vitro. In the GLM mouse model, both inhibitors reduced mammary gland inflammation, NET accumulation, and tissue damage.ConclusionsThe present findings indicated that NETs contribute to the pathogenesis of GLM. S100A8/S100A9 plays a critical role in promoting NET formation via PAD4 activation. Targeting this axis with paquinimod effectively inhibits NETosis and alleviates GLM, suggesting a promising therapeutic strategy for GLM and other inflammatory diseases.

BackgroundGranulomatous lobular mastitis (GLM) frequently mimics ductal carcinoma in situ (DCIS) in clinical presentation and imaging characteristics, leading to misdiagnosis and unnecessary aggressive interventions. This study aimed to develop and validate a practical nomogram for differentiating GLM from DCIS.MethodsWe conducted a retrospective study at Quanzhou First Hospital from January 2020 to April 2025, including 290 patients with histopathologically confirmed GLM (n=128) or DCIS (n=162). Patients were randomly divided into training (n=203) and validation (n=87) sets. Clinical, laboratory, and ultrasound features were analyzed using univariate and multivariate logistic regression to identify independent predictors. A nomogram was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis.ResultsSix independent predictors were incorporated into the final nomogram: age, lesion size, margin characteristics, microcalcifications, posterior acoustic enhancement, and peri-lesional flow. The nomogram demonstrated excellent discriminative performance with areas under the ROC curve of 0.95 (95% CI: 0.92-0.98) in the training set and 0.93 (95% CI: 0.88-0.98) in the validation set. At optimal thresholds, the model achieved sensitivity of 92% and specificity of 89% in the training set, and 89% and 79% respectively in the validation set. Calibration plots confirmed high predictive accuracy, and decision curve analysis demonstrated substantial clinical benefit across clinically relevant threshold probabilities.ConclusionsThis novel nomogram represents a diagnostic tool specifically designed for GLM versus DCIS differentiation. Its reliance on widely available clinical and ultrasound parameters makes it particularly valuable for resource-limited settings, potentially reducing unnecessary biopsies and associated patient morbidity.

Background/Objectives: Segmental non-mass enhancement (NME) is the breast MRI distribution pattern with the highest positive predictive value (PPV) for malignancy. Despite its diagnostic relevance, its imaging characteristics have rarely been examined in isolation, leaving uncertainty in clinical practice. This multicenter retrospective cohort study aimed to evaluate multiparametric MRI features—including internal enhancement pattern, dynamic contrast-enhanced (DCE) kinetics, and diffusion restriction—in segmental NME to identify malignancy predictors. Methods: This retrospective cohort review included 14,834 breast MRI reports from five institutions (September 2017–February 2024), identifying 103 women (mean age, 44.4 ± 9.9 years) with segmental NME (70 malignant, 33 benign). MRI was performed at 1.5 T or 3 T using standardized protocols. Two breast radiologists, blinded to pathology, assessed internal enhancement, DCE kinetics, diffusion restriction, and short tau inversion recovery (STIR) features according to BI-RADS. Statistical analyses included chi-square/Fisher’s tests and logistic regression. Results: Clustered ring enhancement (CRE) was significantly associated with malignancy (p = 0.004). Fast initial-phase enhancement (p < 0.001) and delayed-phase washout (p = 0.011) also correlated with malignancy. On multivariate analysis, fast initial-phase enhancement remained an independent predictor (odds ratio [OR] = 5.133, p = 0.031), whereas slow enhancement predicted benignity (OR = 0.194, p = 0.020). Histologies included ductal carcinoma in situ, invasive ductal carcinoma, granulomatous mastitis, and benign hyperplastic lesions. Conclusions: This study, focusing exclusively on segmental NME, identifies CRE, fast initial-phase enhancement, and washout kinetics as reliable imaging biomarkers. Incorporating these features into breast MRI interpretation may improve diagnostic accuracy, risk stratification, and management decisions.

Granulomatous mastitis—a retrospective observational cohort analysis of treatment outcomes in over 600 patients

Granulomatous mastitis: A 5-year single-center case series from North Africa

Clinical outcome of Granulomatous Mastitis amongst women in West Sweden between 2003-2023: a retrospective cohort study

BackgroundIdiopathic granulomatous mastitis (IGM) is a chronic inflammatory breast disorder with unclear etiology. Isthmin‐1 (ISM1), a secreted protein with anti‐inflammatory properties, has not been previously studied in IGM.ObjectiveThis study aimed to compare serum and tissue ISM1 levels between IGM patients and healthy controls, and to assess its diagnostic potential.MethodsThis case–control study included 30 women with histopathologically confirmed IGM and 30 age‐matched controls undergoing breast reduction surgery. Serum and tissue ISM1 levels were measured using ELISA. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of serum ISM1.ResultsISM1 concentrations were significantly lower in IGM patients compared to controls in both serum (541.42 ± 191.01 vs. 1139.19 ± 698.43 pg/mL; p = 0.019) and tissue (511.07 ± 188.16 vs. 778.24 ± 261.98 pg/mL; p < 0.001). ROC analysis demonstrated moderate diagnostic accuracy (area under the curve [AUC]: 0.768, 95% CI: 0.651–0.885; optimal cutoff: 676.13 pg/mL; sensitivity: 66.7%; specificity: 83.7%). Standard inflammatory markers showed no significant differences between groups.ConclusionsReduced ISM1 levels in IGM patients suggest potential involvement in disease pathogenesis. While serum ISM1 shows promise as a supportive biomarker, larger studies, including other inflammatory breast conditions, are needed to confirm specificity and clinical utility.

The Role of Imaging Methods in the Diagnosis and Treatment of Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease affecting women aged 20-40, and it can mimic infectious or neoplastic mastitis. This retrospective study at Saint-Louis Hospital (2010-2023) analyzed 19 histologically confirmed cases to refine clinicopathological features and evaluate treatments. Clinically, 89% of patients presented with one or more erythematous breast masses, often associated with abscesses, adenopathy, nipple retraction, edema, or fistulas. Histology showed large peri-lobular granulomas with polymorphic inflammation. Among 18 treated patients, NSAIDs achieved complete remission (CR) in 50% (6/12), corticosteroids in 40% (2/5), and surveillance alone in 60% of minimally symptomatic cases (5/8). Antibiotics led to partial remission (PR) in 23% but no CR. Surgery was not recommended due to its aesthetic impact. The median time to CR was six months, with three relapses. NSAIDs appear as an effective first-line treatment, while antibiotics showed limited efficacy. Further research is needed to standardize therapeutic protocols.

Granulomatous mastitis is a rare, uncommon chronic inflammatory condition of the breast. The condition is a well-known mimicker of malignancy, both clinically and radiographically. Diagnostic dilemmas arise frequently in such cases, which delay the treatment. In the present study, we studied the cytomorphological features in cases of granulomatous mastitis diagnosed by fine needle aspiration cytology (FNAC) to attribute the clinical and radiological findings to each case. A total of 13 cases with cytological diagnoses of granulomatous mastitis were reviewed and studied. Fine needle aspiration was performed on these patients, and smears were examined. In this study, the cytomorphological features were studied in depth and correlated with clinical and radiological findings. Ziehl-Neelsen stain and/or Truenat were performed in all 13 cases. Clinical examination revealed a lump in the breast in all the patients and a lump with pus discharge in two patients. Ultrasonographic examination suggested an inflammatory pathology in most of the cases. The smear examination showed diverse cytomorphological features, ranging from epithelioid cell granuloma to a vague collection of histiocytes, multinucleated giant cells, neutrophils, plasma cells, and a few lymphocytes. In four cases, there was prominent emperipolesis of neutrophils. Additionally, granulomatous mastitis was diagnosed in accessory axillary breasts in one of the cases. Based on cytomorphological features and after excluding commonly encountered granulomatous infective pathology, a diagnosis of granulomatous mastitis was made. In addition, the cytological diagnosis rests on finding histiocytes with neutrophils, giant cells, and epithelioid cell granulomas with or without necrosis and excluding other common differential diagnoses like tuberculosis, fungal infection, and Rosai-Dorfman disease. It is important to keep a possibility of granulomatous mastitis in women presenting with painful nodular breast lumps. Aggressive management of other specific etiological causes of granulomatous mastitis can be avoided with an accurate cytological diagnosis of idiopathic granulomatous mastitis.

Abstract Introduction/Objective In this case report, we present a 20-year-old female with a well-circumscribed left breast mass, which was biopsied and later excised. The diagnostic workup revealed this lesion to be a fibroepithelial lesion with multinucleated giant cells. The patient eventually returned for a complete re-excision, submitted entirely, and determined to be a fibroepithelial lesion with multinucleated giant cells. This case report aims to show a practical approach to the workup and diagnosis of a lesion in the “grey zone” when classifying it as a benign, borderline, or malignant lesion. Generally, benign fibroepithelial lesions of the breast can range from benign to malignancy, the classification of which is based on the cellularity and pleomorphism of the stroma. The most common of these is fibroadenoma and phyllodes tumors. Previous cases have highlighted the presence of multinucleated giant cells in the presence of fibroadenomas, sarcoid, and granulomatous mastitis, all of which were absent in this patient’s case. The latest publication similar to the concept of this case was a case series published in 1994, which highlights scattered giant cells in fibroepithelial lesions in only 11 cases observed. Methods/Case Report Case report Results N/A Conclusion This case report aims to show this infrequent, benign entity’s diagnostic approach and findings from the biopsy and the surgical excision. Highlighting the differences between this entity and other benign fibroepithelial lesions will shed light on establishing a proper diagnosis and establishment of appropriate nomenclature. Presenting this case report will demonstrate our approach to ruling out the most common entities (phyllodes and fibroadenomas) and malignant entities and establishing a descriptive diagnosis. Many of the fibroepithelial lesions in the “grey zone” are usually descriptive diagnoses; however, an evaluation of the complete excision of the tumor could indicate further investigation into the re-classification of this entity.

Rare breast tumors

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast disease of unknown etiology, predominantly affecting women of reproductive age. Its variable clinical presentation and unpredictable course make it a persistent diagnostic and therapeutic challenge. Case presentation: We report the case of a 41-year-old woman presenting with a painful, erythematous nodule in the left breast, complicated by cutaneous fistulization and purulent discharge. Microbiological cultures were sterile. Breast ultrasound revealed a 20 × 18 mm hypoechoic lesion with multiple perilesional abscesses (BIRADS 4A). Core needle biopsy demonstrated granulomatous inflammation without caseous necrosis or malignancy. A comprehensive etiologic workup was unremarkable. The diagnosis of IGM was established, and oral corticosteroid therapy (60 mg/day) was initiated, leading to marked clinical improvement. The dose was gradually tapered, with no recurrence observed after 15 months of follow-up. Discussion and conclusion: IGM should be considered in reproductive-age women presenting with inflammatory breast masses after exclusion of infectious and autoimmune causes. Histopathology remains essential for diagnosis. While management is still debated, corticosteroid therapy is the preferred first-line approach. Surgery should be reserved for complicated or refractory cases. A conservative,

Idiopathic granulomatous mastitis (IGM) is rare globally and infrequent in some middle-east regions. Sex-hormonal factors have been mentioned as predisposing factors for IGM, recent large-sale studies indicate a 7.5-fold increased risk in women who have breastfed. This study investigates BF-related factors that contribute to IGM development. We conducted a multicenter case–control study and recorder BF-related events in 730 IGM patients and healthy 760 controls. The mean age of participants was 36.63 ± 6.49 in the Case and 36.96 ± 6.11 years in the Control Group (p = 0.31). IGM occurred more frequently in the contralateral breast in one-sided BF (p < 0.001), with discordance between the affected side and BF side in 68.3% of cases (p = 0.005). Multivariate analysis revealed significant associations between IGM and one-sided BF (OR = 4.21), post-weaning breast engorgement (OR = 3.06), lactational mastitis (OR = 1.93), and oral medication use for infants (OR = 2.59). The study achieved 100% statistical power for both primary and secondary objectives, with narrow confidence intervals indicating high precision. This study provides robust evidence supporting the milk stasis hypothesis, demonstrating that BF-related issues leading to milk stasis are strongly associated with IGM development. Preventive strategies to minimize milk stasis and encourage bilateral BF may help reduce IGM risk.