Granulomatous lobular mastitis (GLM) is a rare, chronic, benign inflammatory breast disease that poses diagnostic and management challenges. This article aims to provide a comprehensive overview of GLM, including etiology, diagnosis, treatment, and the potential role of dietary modifications in managing the condition. It incorporates the latest research and expert consensus to offer evidence-based recommendations for healthcare professionals and patients alike.
Introduction to Granulomatous Lobular Mastitis (GLM)
Granulomatous lobular mastitis (GLM) is characterized pathologically by non-caseating granulomatous lesions with leukomonocytes, lymphocytes, neutrophils, and multinucleated giant cells located in the center of breast lobules. GLM tends to occur in child-bearing women with a prolonged and recurrent course. Although clinical findings and histopathological features are necessary in the diagnosis of GLM, currently, there are no international unified guidelines for GLM diagnosis and treatment.
Etiology and Predisposing Factors
Predisposing Factors
Lactation disorders resulting in milk stasis, hyperprolactinemia, and blunt trauma of the breast are considered predisposing factors for GLM. Milk stasis plays a key role, with breast tissue developing into a hypertrophic state subsequent to pregnancy, lactation, and hyperprolactinemia. Pituitary adenoma, antipsychotic drugs (such as potent D2 receptor antagonists, risperidone), and antidepressant drugs (such as selective serotonin reuptake inhibitors, fluoxetine) can lead to hyperprolactinemia. While the permeability of breast ducts increases, the immunogenic substance (retained milk) enters into lobular mesenchyme of the breast, causing T cell-mediated immune response and granuloma formation. Differences in race and region exist in the prevalence of GLM. GLM may be associated with dietary habits and genetic factors. GLM usually occurs in the Mediterranean region and developing Asian countries. This prevalence might be the reflection of under-diagnosis of tuberculosis mastitis. Sometimes routine histology studies are not sufficient to rule out the diagnosis of tuberculosis mastitis. Presence of atypical mycobacteria may also be involved in the pathogenesis of GLM which are difficult to isolate under routine culture conditions. This may also be related to poor habits of lactation and weaning in Mediterranean region that may lead to milk stasis (galactostasis) which is the most important predisposing factor for GLM. Some GLM patients depend on lactation from one breast only and neglect lactation from the other one which develops GLM due to milk stasis. Many patients neglect the routine breast massage and complete evacuation of both breasts after each time of lactation, and during the first weeks of weaning.
Pathogenesis of GLM
The most widely adopted theory considers GLM to be an immune reaction that involves both humoral and cell-mediated immunity stimulated by patients’ secretions such as retained milk. The pathogenesis of GLM may be due to increased permeability of breast duct caused by physical or chemical stimulation such as the infiltration of the lobular mesenchyme of breast with intraluminal secretions such as retained milk. This causes local inflammation in the mesenchyme which then induces the infiltration of immunocompetent cells to form delayed-type hypersensitivity. Finally, localized granulomas are formed
Relationship between GLM and Corynebacterium infection
The relationship between GLM and Corynebacterium infection is not yet definitive. If Corynebacteria are the causative factor in the development of GLM, the latter should be classified as infectious granulomatous mastitis. However, as a part of normal skin flora, the presence of Corynebacterium may be a colonization. Therefore, there are three hypotheses to explain the pathogenetic of GLM in relation with Corynebacterium. (1) Primary factor: As an independent immunogenic factor, Corynebacterium enters lobular mesenchyme of breast through increased permeability of breast ducts, inducing an autoimmune response. (2) Cofactor: Corynebacterium and immunogenic factors such as retained milk enter the lobular mesenchyme through increased permeability of breast ducts, and induce an autoimmune response. (3) Irrelevant factor: Corynebacteria does not participate in the process of autoimmune response.
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Diagnosis of GLM
Diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations, and pathology.
Clinical Presentation
The main clinical presentation is a palpable, painful breast lump with concomitant skin erythema, nipple retraction, sinus tract formation, cellulitis changes, and axillary adenopathy formation, and in severe cases, there are usually multiple coexisting focal abscesses with skin inflammation and ulceration. Patients often endure a long disease course, as well as changes in breast appearance caused by the disease, which has serious physical and psychological effects on patients. The most common finding was a palpable mass with pain; some patients had a breast abscess, many suffered from skin lesions, and approximately 5% had fistulas and erythema nodosum. Based on clinical symptoms, the disease was typed as the mass, abscess, and refractory types. Unilateral involvement was observed the most in patients.
Diagnostic Modalities
To diagnose IGM, ultrasound-guided core needle biopsy is the best option. However, in some cases, women with classic symptoms may not require a biopsy for diagnosis. The best way to diagnose GM is with imaging, usually a breast ultrasound, and an image-guided biopsy. The radiologist can often tell the subtle differences on ultrasound between the inflammatory phlegmon, a cancerous tumor, or a pocket of pus in the breast. The diagnosis is finalized by taking a sample of the tissue using a core needle biopsy gun. Pathologists then analyze this tissue in the lab with a microscope. Histopathological examination is a necessary and gold-standard method for the diagnosis of granulomatous mastitis, so a definitive diagnosis of GM was largely accomplished with core needle biopsy in this study.
Treatment Approaches
The approach to treatment of GLM should be applied according to the different clinical stages of GLM. Treatment aims to reduce inflammation, minimize symptoms, and lower the risk of recurrence rates over the long term, as there is no cure. Currently, the main treatments include observation, medication therapy (steroids, antibiotics, methotrexate (MTX), and anti-molecular bacilli) and/or operative interventions (abscess incision and drainage, simple mass excision, enlarged mammary mass excision, etc.), and medication therapy is the most commonly used treatment.
Medical Management
Medications taken by mouth, such as prednisone, Methotrexate, Celebrex, and doxycycline, can also reduce symptoms by targeting and reducing significant inflammation and possible infection. Topical diclofenac gel or triamcinolone may be prescribed to treat the affected areas. In some cases, steroids may also be injected into lesions. This can be quite helpful in improving symptoms.
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Low-dose steroid therapy has been recommended in idiopathic granulomatous mastitis (IGM) in various studies in the literature, but the therapeutic minimum dose has not been determined yet. Administration of steroids to patients with IGM is a generally accepted treatment method, and different doses of steroid treatment (0.4-0.8 mg/kg) are recommended in various studies.
Surgical Interventions
While some cases of IGM may resolve from a simple mass, many go on to form fluid collections that may drain on their own. These are mistakingly called “abscesses.” They are in fact just fluid collections of dead inflammatory cells.
In addition, according to clinical experience, surgical interventions should be avoided in patients with IGM, except for abscess drainage and excisional biopsy in localized small, non-healing masses.
Dietary Recommendations for Managing GLM
Given the inflammatory nature of GLM, dietary modifications may play a supportive role in managing symptoms and promoting overall well-being. While there is no specific "GLM diet," adopting an anti-inflammatory dietary approach may be beneficial.
Anti-Inflammatory Diet Principles
An anti-inflammatory diet aims to reduce chronic inflammation in the body by emphasizing foods that combat inflammation and minimizing those that promote it. Key components include:
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- Probiotic Foods: Incorporate foods like yogurt with live cultures, kefir, miso, and sauerkraut to support gut health.
- Prebiotic Foods: Consume foods such as steel-cut oats, bananas, ground flax seeds, vegetables, and legumes to nourish beneficial gut bacteria.
- Limit GI-Irritating Foods: Reduce or eliminate foods that can irritate the gastrointestinal tract, including those with a high lactose load (ice cream, whole milk, soft cheeses), wheat, refined sugar (sucrose), and corn.
It is important to note that not all dairy contains high lactose loads. Low-lactose dairy items include yogurt, hard cheeses, butter, and heavy cream.
Specific Dietary Considerations
- Vitamin D: Vitamin D deficiency has been observed in the pathophysiology of various inflammatory diseases. Vitamin D levels were evaluated in some IGM patients. Vitamin D replacement was performed in patients with serum 25-hydroxyvitamin D level below 30 ng/mL and prednisolone was given to all patients at a dose of 0.05-0.1 mg/kg/ day. Vitamin D replacement was given to some patients. Recovery time was shorter in patients receiving vitamin D replacement
The Role of Gut Health
Subclinical mastitis (SCM) is common, and while many IBCLCs have anecdotally recognized similarities between clients, a specific etiology is not well defined. Certainly, it may be possible that subclinical mastitis is associated with a chronic pro-inflammatory state. In one study, researchers found that treatment of mastitis with topical curcumin significantly improved mastitis symptoms when measuring with the inflammation severity index.
Additional Lifestyle Factors
Avoiding tobacco, losing weight and controlling diabetes can help. These treatments calm down the body’s overactive inflammation, starting with two to three over-the-counter ibuprofen tablets every six hours.
Case Management Model
Recently, one approach to managing care that has gained wide popularity is case management, which promote access to provide patients with regular and targeted disease monitoring and health guidance through follow-up visits and WeChat consultations in China (WeChat is a mobile chat software by the Chinese company Tencent, in which patients can quickly consult with medical staff by sending voice messages, videos, pictures and texts over the internet quickly). Nurse specialists are responsible for the overall coordination, management, and continuity of care for a specific treatment or intervention to meet the health needs of an individual, reduce health care costs and improve the quality of service. Currently, it is known that case management is widely applied for patients with breast disease, especially breast cancer, but it is rarely to applied for GM patients. Based on the characteristics of the disease, which is mostly treated and followed up in outpatients, a tailored model should be developed that it enables health providers monitor the condition changes of GM patients from outpatient to community to inpatient settings.
A hospital-to-community model of case management, which allows cases managers to track and manage the treatment of GM patients from hospital to community settings, was described by Lamb in 1992, and includes the following five basic activities of case management: (1) assessment, (2) planning, (3) linking, (4) monitoring, and (5) advocacy.
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