Idiopathic granulomatous mastitis (IGM), first reported by Kessler and Wolloch in 1972, presents a significant treatment challenge. IGM is an uncommon, recurrent inflammatory breast disease with a benign prognosis and an elusive pathogenesis.^1,2 Although prevalence data for this rare condition in women remains scarce, it has been reported as 0.37%, equivalent to 37 cases per 10,000 women in the USA and 0.24%, or 24 cases per 10,000 women, in Europe.^3,4 The disease typically peaks around age 30 and is more common in women with a history of breastfeeding and pregnancy. Interestingly, non-breastfeeding cases have been linked to antidepressant use, leading to hyperprolactinemia.⁵ Clinically, IGM often mimics breast carcinoma, complicating diagnosis and occasionally resulting in incorrect treatment. Recent findings suggest a racial association, with most reported cases originating from the Middle East and Mediterranean regions.^3,5

The etiology of IGM remains unclear due to its rarity and complex presentation. Various hypotheses have been proposed, including autoimmune reactions, infectious agents—particularly bacterial species—and hormonal dysregulation.⁶ While IGM predominantly affects women around the age of 30, the precise mechanisms underlying its development continue to be explored. Some studies suggest an association with bacterial infections, including Corynebacterium kroppenstedtii.⁷ Bacterial involvement appears to differ by region, with studies highlighting the prevalence of specific bacterial strains in different populations.⁸ Additionally, prolonged breastfeeding duration and hyperprolactinemia remain significant hormonal factors associated with disease onset.⁹ While antibiotic therapy has been explored as a potential treatment for IGM, its effectiveness remains inconsistent. Recent studies indicate that certain antibiotics may be effective, particularly in cases with an identified bacterial component, but results vary based on the pathogen involved and the patient's immune response.^10–12 In this study, we focused on identifying the etiologic agent and detecting bacterial genes in clinical samples.

A comprehensive analysis was conducted which provides valuable insights into the demographic, reproductive, and clinical characteristics of IGM patients. The demographic data underscores the role of reproductive history, particularly pregnancy and breastfeeding, while the presence of Escherichia coli in 21 out of 22 cases (95.5%) supports the hypothesis of bacterial involvement. Additionally, hormonal factors, such as prolonged breastfeeding and contraceptive use, may influence disease susceptibility. Clinically, the predominance of deep collections and erythema aligns with inflammatory processes commonly associated with bacterial infections. Collectively, these findings highlight the significance of the presented data in understanding IGM's complex etiology, addressing concerns about its relevance.

Our study provides new insights into the role of bacterial involvement in IGM by highlighting the predominance of E. coli in biopsy samples. These findings challenge previous assumptions that bacterial involvement in IGM is rare or predominantly associated with C. kroppenstedtii.^6,14 While E. coli has historically been recognized as a cause of mastitis in bovine populations, its consistent detection in human IGM tissues, as observed in our study, suggests a potential pathogenetic role that warrants further investigation. This discovery may have therapeutic implications, particularly for antibiotic selection and resistance patterns.¹⁵

The demographic patterns observed in our cohort further support the existing literature on IGM. The mean age of 35.23 years aligns with previous reports that identify IGM as a condition typically affecting women of reproductive age.¹⁶ Our findings also emphasize the role of hormonal factors, as evidenced by the mean breastfeeding duration of 39 months and the fact that 27.3% of patients reported contraceptive use. This reinforces the hypothesis that prolonged exposure to hormonal stimuli, including hyperprolactinemia, may contribute to the disease process.¹⁷ This aligns with observations from Metanat et al., who reported similar hormonal patterns in their cohort.³ Additionally, the high frequency of bilateral breast involvement in nearly half of the cases (45.5%) aligns with reports indicating the symmetrical nature of IGM in hormonally active women.⁶

The predominance of inflammatory symptoms, particularly erythema (observed in 36.4% of patients), underscores the inflammatory nature of the disease. The prevalence of deep collections (45.5%) and superficial skin destruction (18.2%) aligns with findings by Co et al., who also reported significant tissue involvement in chronic mastitis cases.¹⁸ The co-occurrence of these symptoms with bacterial DNA presence suggests an inflammatory process potentially driven by bacterial dysbiosis rather than sterile granulomatous inflammation alone.¹⁹ This insight challenges traditional perspectives that consider IGM a primarily autoimmune condition.²⁰ Furthermore, recent studies suggest that inflammatory processes may also be exacerbated by genetic predispositions, such as polymorphisms affecting immune response genes.²¹

Our findings also raise questions about potential regional and environmental factors influencing bacterial profiles in IGM. The near-exclusive detection of E. coli may reflect specific environmental exposures or population-specific microbiota patterns, as suggested by Krawczyk et al., who reported regional variations in bacterial profiles of granulomatous mastitis.²² Further research incorporating multi-center data could elucidate whether such bacterial patterns are unique to our study region or part of a broader epidemiological trend. Additionally, the regional distribution of IGM cases, with a higher prevalence in the Middle East, further supports the need for region-specific diagnostic and therapeutic protocols.^3,8

A key limitation of our study is the absence of control tissue samples from healthy breast tissue. Recent research has highlighted the presence of a normal breast microbiome, which may influence inflammatory processes.²³ Without comparative data from normal tissue, distinguishing pathogenic bacterial involvement from commensal microbiota is challenging. Future studies should incorporate control samples to accurately assess bacterial contributions to idiopathic granulomatous mastitis and distinguish between microbial colonization and true infection.

Although current evidence does not conclusively establish the link between E. coli and IGM, this hypothesis can pave the way for further research. Detailed investigations and clinical studies can help clarify the role of this bacterium in the onset and exacerbation of IGM. While this study demonstrates the presence of E. coli in the majority of IGM biopsy samples, further research is necessary to investigate the potential role of bacterial involvement in the disease's pathogenesis and its implications for future therapeutic approaches.

The study was approved by the Ethics Committee of Kurdistan University of Medical Sciences.

Data related to this study are presented in the article.