An Update on Granulomatous Lobular Mastitis: It is Time to Tell the Untold

Objective To investigate the value of color Doppler ultrasonography in differential diagnosis of granulomatous lobular mastitis (GLM) and breast cancer. Methods Preoperative sonograms of 45 GLM, 115 invasive ductal carcinoma (IDC) and 90 ductal carcinoma in situ (DCIS) patients were retrospectively analyzed and further confirmed by histopathology. Results The average age of patients in GLM group was obviously younger than those in IDC and DCIS groups(P<0.001). The size of mass lesion in GLM group was significantly larger than those in IDC and DCIS groups(P<0.001). Compared to IDC group, GLM group showed higher detection rate of liquidity area and mammary ductal ectasia (P<0.01), while less lesions with irregular shape, large A/T ratios (≥0.7), calcification, spiculate margin, peripheral hyperechoic zone or posterior echo attenuation (P<0.05). There were more lesions with spiculate margin, liquidity area or axillary lymph node enlargement found in GLM group than in DCIS group (P<0.01), but less calcification (P<0.001). The accordance rate of ultrasonic diagnosis and postoperative histopathology results in 45 GLM patients was 33.3%(15/45). Conclusions GLM shows the characteristic sonographic findings. In addition, there are some differences between GLM and both IDC & DCIS, such as spiculate margin, peripheral hyperechoic zone, blood flow richness and axillary lymph node enlargement. Combined with the clinical data, understanding the sonographic features of GLM is beneficial to its differential diagnosis with breast cancer. Key words: Ultrasonography; Granulomatous mastitis; Diagnosis, differential

Background: Granulomatous lobular mastitis (GLM) is a rare inflammatory disease of the breast. Its clinical features and imaging findings often mimic malignancy. The aim of this study is to review the mammographic and ultrasound features of granulomatous lobular mastitis to help differentiate it from other diagnoses. Methods: In our study, imaging data of 51 patients were reviewed retrospectively, who were diagnosed with granulomatous lobular mastitis by core needle biopsy and culture analysis. Results: The mammographic findings of granulomatous lobular mastitis observed in our study group were focal or global asymmetry (52.6%), oval or round lesions with obscured margins (15.7%), irregular mass with indistinct margins (15.7%) and associated skin thickening (26.3%) with no specific pointers to differentiate from malignancy.The most common morphological abnormality on ultrasound was single or multiple collections with or without tracts (72.5%). Other morphological abnormalities were non-mass areas with tracts (25.5%), dilated ducts with debris (13.7%) and mass (3.9%). The common associated abnormalities were perilesional increased echogenicity (86.3%), increased peripheral vascularity (88.2%), intercommunicating tracts (76.5%) and axillary adenopathy (68.6%) and these ultrasound features were pointers to differentiate granulomatous mastitis from malignancy. Conclusion: Granulomatous lobular mastitis has non-specific clinical and imaging features. Imaging, especially ultrasound as in our study, is found to be indispensable in diagnosing GLM and excluding other causes such as infective mastitis and malignancy.

Granulomatous lobular mastitis is a rare chronic breast disease, firstly described by Kessler and Wolloch in 1972. In this article we present a 35-year-old patient with granulomatous lobular mastitis and in situ ductal carcinoma and discuss clinicopathological characteristics of the disease with literature data. A 35-year-old female patient admitted to the outpatient clinic with a complaint of swelling in right breast ongoing since March 2017. On the basis of physical examination and radiological examinations, antibiotic therapy was initiated considering the inflammatory breast disease and the patient was referred to our general surgery clinic because she did not benefit from treatment. On the recommendation of histopathological correlation, trucut biopsy was performed and reported as granulomatous mastitis. In the histopathological examination of the prepared sections, we found lobule-restricted, non-caseous granulomas and neoplastic epithelial cell proliferation in 4 different foci, the largest being 0.7×0.4 cm in diameter, limited to the ductal lobular system. The case was diagnosed as granulomatous lobular mastitis and in situ ductal carcinoma. This lesion, which clinically and radiologically can be confused with carcinoma, rarely coexists with breast carcinoma. Our case demonstrates the coexistence of granulomatous lobular mastitis and in situ ductal carcinoma.

Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing their clinicopathological features. The aim of the present study was to investigate the etiology, clinicopathological characteristics and diagnosis of GLM and MDE. The clinical information and treatment of 118 female patients with pathologically-proven GLM or MDE were retrospectively analyzed in the present study. A total of 29 cases had GLM, 77 had MDE and 12 had GLM accompanied by MDE. GLM tends to occur in patients who have had their last birth within 5 years and are usually <40 years of age. GLM masses were usually larger than MDE masses and suppurated or ulcerated more easily. Histopathologically, GLM was characterized by a significant granulomatous inflammatory reaction centered on lobules. Compared with MDE, GLM had a higher incidence of granuloma and microabscess formation within the lobules and surrounding tissue. More multinucleated giant cells within granuloma were observed in patients with GLM than in those with MDE, while MDE was characterized by significant dilatation of the duct terminals and inflammatory changes in the duct wall and periductal tissues. When compared with patients with GLM, foam cells within the duct epithelium or surrounding stroma were more common in patients with MDE. The present study demonstrated that GLM and MDE had distinct clinicopathological characteristics. Further research is required in order to identify more appropriate treatment strategies for these specific types of breast inflammation.

We report a case of a rare inflammatory disease, granulomatous lobular mastitis. Two weeks prior to admission the patient, a 43 year-old woman, (gravida 1, para 1) had noticed a left breast mass associated with tenderness. Palpation, gross inspection, and clinical examination, as well as the rapid growth of the mass lesion led us to believe that it was highly suspicious of malignant neoplasm. Mammography, ultrasonography, and computed tomography did not differentiate it from a malignant neoplasm. Aspiration cytology revealed an inflammatory lesion with a few clusters of epithelial cells it was diagnosed as borderline malignancy(class III) by a prudent pathologist, and thus mastectomy was performed. However, the final histologi-cal diagnosis was granulomatous lobular mastitis with no evidence of malignancy. As the clinical manifestations of granulomatous mastitis are similar to those of mammary carcinoma and, as it is an inflammatory lesion of uncertain etiology and pathogenesis, it has often been mistaken clinically for carcinoma and treated as such. Our review of the literature indicated that granulomatous mastitis most often occurs in young patients with a history of childbirth or oral contraceptive usage. Recurrence was documented in 38% of patients, and, accordingly long-term follow-up by aspiration cytology, complete resection, and adequate drug treatment with corticosteroids are recommended.

Granulomatous lobular mastitis is a rare inflammatory disease of the breast of unknown etiology. Most present as breast masses in women of child-bearing age. A 29-year-old female presented with a swollen, firm and tender right breast, initially misdiagnosed as mastitis. Core needle biopsy revealed findings consistent with granulomatous lobular mastitis, and cultures were all negative for an infectious etiology. She was started on steroid therapy to which she initially responded well. A few weeks later she deteriorated and was found to have multiple breast abscesses. She underwent operative drainage and cultures grew Mycobacterium fortuitum. Granulomatous lobular mastitis is a rare inflammatory disease of the breast. The definitive diagnose entails a biopsy. Other causes of chronic or granulomatous mastitis should be ruled out, including atypical or rare bacteria such as Mycobacterium fortuitum. This is the first reported case of granulomatous mastitis secondary to Mycobacterium fortuitum. With pathologic confirmation of granulomatous mastitis, an infectious etiology must be ruled out. Atypical bacteria such as Mycobacterium fortuitum may not readily grow on cultures, as with our case. Medical management is appropriate, with surgical excision reserved for refractory cases or for drainage of abscesses.

Objective To investigate the effect of the ultrasonography-guided abscess puncture aspiration or drainage combined with local application of triamcinolone acetonide in the treatment of granulomatous lobular mastitis (GLM) . Methods The clinical data of forty-six severe GLM patients from February 2015 to February 2017 were analyzed. Twenty-three patients were treated with the ultrasonography-guided abscess puncture aspiration and irrigation (control group), and the other 23 patients were treated with triamcinolone acetonide injection 40 mg from the pinpoint or a drainage tube into the abscess cavity, pressure dressing, 2 times a week after the routine abscess puncture aspiration and irrigation treatment (observation group). The recovery rate, onset time, hospitalization days and patient satisfaction were compared between two groups, and hormone related adverse reaction of observation group was observed. Results There were 17 cases with effective treatment and 1 cured case in the observation group, while 10 cases with effective treatment, no cured case and 1 case lost in control group, with statistical difference (χ2=5.15, P=0.023). Compared with the control group, the observation group had faster onset time, fewer days of hospitalization, and higher satisfaction of the patients (t=5.81, 5.80, χ2=8.09, P<0.01, <0.01, 0.004). The observation group had no obvious hormone-related adverse reactions, whereas 6 patients in the control group had side effects, which gradually disappeared after the cessation of treatment. Conclusion The ultrasonography-guided percutaneous aspiration and drainage combined with local application of triamcinolone acetonide is a choice for clinical treatment of severe GLM. Key words: Granulomatous mastitis; Carcinoma, lobular; Paracentesis; Triamcinolone acetonide

Sometimes, mastitis needs to be differentiated from carcinoma because of its association with induration and with ultrasound findings (such as low-echo lesions) that resemble those in carcinoma. The aim was to define this type of mastitis and to examine 18 cases to clarify its clinicopathological features. All cases were categorized into three types: non-specific mastitis with neutrophilic infiltration (n = 7); non-specific mastitis with lymphoplasmacytic infiltration (n = 9); and granulomatous lobular mastitis (n = 2). The three types of mastitis presented similar ultrasound findings and shared certain histological features including fibrosis and diffuse or lobulocentric inflammation. Granulomatous lobular mastitis showed specific clinicopathological features including lobulocentric inflammation with giant cells, diffuse IgG4+ plasma cells, and also a high level of serum IgG4. Granulomatous lobular mastitis could be categorized into IgG4-related and non-IgG4-related granulomatous lobular mastitis. IgG4 immunohistochemistry serum IgG4 might be useful for diagnosis of IgG4-related granulomatous lobular mastitis and could help to avoid overtreatment such as wide excision.

The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain largely elusive and the expression levels and regulatory roles of microRNAs (miRNAs or miRs) in GLM have remained mostly undetermined. In the present study, the miRNAs that were differentially expressed in breast biopsy samples from patients with GLM and normal tissue adjacent to fibroadenoma were analyzed, a comprehensive differential expression profile of miRNAs was provided and potential biomarkers were screened out. The expression profile of miRNAs was determined by high-throughput sequencing in the tissues of patients with GLM and healthy controls. Significantly differentially expressed miRNAs were screened by threshold setting and cluster analysis and their target genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, circulating differentially expressed miRNAs between the GLM and control groups were further analyzed by reverse transcription-quantitative PCR (RT-qPCR). A total of 31,077 miRNAs were detected by high-throughput sequencing. By using the cutoff criteria of |log2 fold change|>2.5 and q<0.001, 13 miRNAs that were indicated to be GLM biomarkers were screened out. The expression levels of these 13 miRNAs in the GLM group were higher than those in the control group. GO and KEGG enrichment analyses suggested that the occurrence and development of GLM may be associated with autoimmune inflammation, metabolism and pathogenic organisms. miR-451a and miR-5571-3p were confirmed to be significantly increased in the serum of patients with GLM compared with their levels in the serum of healthy volunteers, which suggests that they may be used as biomarkers of GLM. To the best of our knowledge, the present study was the first report detailing genome-wide miRNA profiling of patients with GLM compared with controls. The possible targets and pathways of GLM were evaluated by bioinformatics analysis. The present study identified 13 differentially expressed miRNAs with important theoretical significance and potential application. Furthermore, miR-451a and miR-5571-3p were verified by RT-qPCR as possible biomarkers of GLM.

The exact etiology and pathogenesis of granulomatous lobular mastitis (GLM) are yet to be illuminated. This study aimed to investigate CD68, CD163-positive M2 macrophages, CD57-positive natural killer (NK) cells, and IgG4 in GLM lesion tissue to explore their correlation with the occurrence and clinical features of GLM. Surgical pathologic specimens of GLM were collected from patients admitted to Hunan Provincial People's Hospital between October, 2014 and October 2015. Based on the postoperative pathological diagnosis, the tissues were divided into 3 groups: the experimental group (GLM, n=36), control group 1 (plasma cell mastitis, PCM, n=17), and control group 2 (breast cystic hyperplasia, n=10). Immunohistochemical staining was carried out using Elivision super testing to detect CD68, CD163, CD57, and IgG4 expression in the pathological tissue samples. The relationship between clinical parameters, including age, reproductive condition, nipple retraction, and tumor size, and the expressions of CD68, CD163, CD57, and IgG4 was analyzed. There was no obvious difference in the levels of CD68, CD163, and CD57 expression between the GLM group and the PCM group, although both groups had higher expression levels of expression than the breast cystic hyperplasia group (P<0.05). In the GLM group, the expression level of CD57 at 2 weeks-3 months was significantly higher than at ≤2 weeks (P<0.05). The expression level of CD57 in PCM patients >2 years after lactation was significantly higher than in patients ≤2 years after lactation (P<0.05). The level of IgG4 expression in GLM patients with nipple retraction was significantly higher than in those without nipple retraction (P<0.05). Inflammatory cells are closely linked to the occurrence of GLM and PCM. In our study, both the GLM and PCM groups had low expression of IgG4, but the expression level of IgG4 in GLM patients with inverted nipples was significantly higher than that in patients without inverted nipples. This suggests that there may be two different clinical subtypes of GLM. Furthermore, our research also found that NK cells can provide a basis for GLM clinical staging.

It is unclear whether the mechanism of the interleukin (IL)-6 signaling pathway is similar between granulomatous lobular mastitis (GLM) and benign breast tumors. This study aimed to explore the differences and significance of peripheral blood IL-6 and related cytokines, routine blood test results, and C-reactive protein (CRP) levels between patients with GLM and benign breast tumors. Seventy-three inpatients with GLM who underwent surgery and 60 patients with benign breast tumors diagnosed based on pathological findings between November 2022 and May 2023 were included. The white blood cell (WBC) and neutrophil (NEU) counts were determined using an automatic blood cell analyzer, the CRP level was determined by an immunoturbidimetric assay, and serum IL-6 and related cytokine levels were determined by an enzyme-linked immunosorbent assay. The WBC, NEU, and CRP values in patients with GLM were significantly higher than those in patients with benign breast tumors (P < 0.01). Serum IL-6 levels were significantly higher in patients with GLM than in those with benign breast tumors (P < 0.01). There were no significant differences in the serum concentrations of IL-1β, IL-7, and interferon (IFN)-γ between patients with GLM and those with benign breast tumors (P > 0.05), but the tumor necrosis factor (TNF)-α level was higher in patients with GLM than in those with benign breast tumors (P < 0.01). In patients with GLM, the Pearson correlation analysis showed that the IL-6 level was positively correlated with NEU, NEU%, CRP, IL-17, and TNF-α values (P < 0.01). Additionally, the IL-6 level was weakly positively correlated with WBC and IFN-γ values. Conversely, in patients with benign breast tumors, the IL-6 level was not significantly correlated with the aforementioned indicators in routine blood tests but was positively correlated with IL-17, IFN-γ, and TNF-α values (P < 0.01). IL-6, NEU, NEU%, and CRP values were significantly elevated in patients with GLM compared to those with benign breast tumors, indicating that IL-6 plays an important role in the development and onset of GLM. The correlation between these cytokines and the development and progression of benign breast tumors needs to be further explored, as cytokines such as IL-6 may provide effective markers for the treatment of GLM.

Granulomatous lobular mastitis (GLM), also known as idiopathic granulomatous mastitis (IGM), is a chronic inflammatory lesion of the breast. The incidence of GLM has been increasing in recent years, especially among young women. The etiologies of GLM have not been fully elucidated but are associated with autoimmunity and bacterial infection. Bacteria, especially Corynebacterium species, play important roles in GLM. In this article, we review research progress regarding the bacteriology of GLM attained with the application of several new high-throughput detection techniques. Accurate detection might be important for deepening our understanding of the pathogenesis of GLM and hold promise for personalized GLM therapy.

Objective To investigate the effectiveness of glucocorticoids in the treatment of granulomatous lobular mastitis (GLM), and to discuss the optimal stage to add glucocorticoids during the treatment. Methods Twenty-four patients having received the core needle biopsy were involved. Ten cases with the explicit pathological diagnosis received the glucocorticoids therapy following the subtotal excision after remission. Pathological diagnoses of the rest 14 patients were undefined. For these 14 patients, simple partial excisions were given and the postoperative pathological diagnoses were presented as the GLM. Of all the 14 patients who accepted the surgical treatment firstly, 8 patients received the postoperative glucocorticoids adjuvant therapy. For the rest 6 patients, steroid hormone therapy was not used after surgery, and they were followed up postoperatively. All patients' clinical and pathological information were collected and analyzed. Results All patients were followed up for 6-36 months (average 18) by the outpatient service. Of all the 10 patients who received the glucocorticoids therapy before surgery, only 1 patient of them got the GLM recurrence. For the 8 patients who received the postoperative glucocorticoids treatment, only 1 patient got the recurrence. For the 6 patients who received simple partial excision, the recurrence of the GLM may be up to 3. There was no statistical difference between the two groups who both received the glucocorticoids therapy preoperatively and postoperatively (P>0.05). But compared with the pure surgery treatment, the difference was obviously (P<0.05). Conclusions The clinical presentation and imaging performance of GLM are unspecific, so the diagnosis of the GLM is difficult. There is no consensus regarding the optimal treatment for GLM. The glucocorticoids therapy may be necessary preoperatively or postoperatively. For the patient with clear preoperative biopsy diagnosis, preoperative glucocorticoids adjuvant chemotherapy followed by the wide excision may be an effective method. Key words: Granulomatous lobular mastitis; Diagnosis; Glucocorticoids; Operation

Background: Granulomatous lobular mastitis (GM) is a rare inflammatory breast disease. Reports focusing on GM caused by antipsychotic-induced hyperprolactinemia (HPRL) are very rare. Aim: To report a study of GM associated with antipsychotic-induced HPRL and discuss the mechanism and management. Materials and Methods: A retrospective review of patients with GM and psychiatric disorders were carried out. The clinical characteristics, management and outcome were collected and analyzed. The relationship between antipsychotics and GM was evaluated using the Naranjo Adverse Drug Reaction Probability Scale (Naranjo scale). Results: Nineteen female GM patients with psychiatric diseases, aged 21-39 years, who had received antipsychotics for 0.5-10.2 years were included. Most patients took multiple antipsychotics, and 10 (52.6%) took risperidone-containing regimens. Increased prolactin (PRL) was detected in all patients (range 35.15-200 ng/mL). The scores of Naranjo scale were 7-8, indicated the antipsychotics probably induced GM. All patients received systemic therapy, and were prescribed bromocriptine. Seven patients (36.8%) decreased the dose of antipsychotics, six (31.6%) switched antipsychotics, three (15.8%) continued the primary antipsychotics, and three (15.8%) discontinued antipsychotics. In addition, 14 patients (73.7%) received corticosteroid, 4 (21.1%) received antimycobacterials. PRL decreased to normal in 1 month. Seven patients (36.8%) received excisional surgery. After 12 months' follow-up (range 9-56 months), only three patients (15.8%) had a recurrence. Conclusion: Long-term use of antipsychotics may increase PRL levels, and lead to GM. It is vital to assess PRL level and reduce PRL to normal in patients with GM.

Granulomatous lobular mastitis (GLM) is an idiopathic inflammatory breast disease that tends to recur on the same side. With the accumulation of clinical cases, it has been observed that GLM can also occur contralaterally. Currently, most studies on GLM focus on treatment methods and risk factors for ipsilateral recurrence, and there are few reports on bilateral GLM. The study aimed to summarize the clinical characteristics of patients with bilateral GLM by reviewing their clinical data, and to discuss the risk factors affecting the occurrence of bilateral GLM. A retrospective study of the medical records database of patients with GLM admitted between May 2019 and August 2022 was performed. Patients were divided into bilateral GLM group (bilateral GLM group) and unilateral GLM patients (unilateral GLM group). Demographic and clinical characteristics, treatment, and follow-up were collected and analyzed. In this study, by reviewing the clinical data of 59 cases of bilateral GLM, we found that the median time between the onset of bilateral GLM on both sides was 6.63 (0-18) months. Additionally, because of the simultaneous or interval onset on both sides, the duration of the disease was longer compared to unilateral cases. Regarding the history of external hospital treatment, it was found that about 57.63% of patients with bilateral GLM received 2 or more treatment modalities, with a higher involvement of herbal medicine. Meanwhile, by counting the clinical data of the 2 groups of patients with bilateral GLM and unilateral GLM, it was shown by univariate analysis that fertility, nipple development, absolute CD4 value, and CD4/CD8 ratio were associated with contralateral onset of GLM in both groups, with inverted nipple being an independent risk factor.