A single center experience with a rare clinical entity of idiopathic granulomatous mastitis: Case series and review of the literature

Abstract

Introduction and importance

Idiopathic granulomatous mastitis (IGM), also called autoimmune mastitis or granulomatous lobular mastitis is a benign, rare disease of the breast lobules. It is characterized by chronic non-caseating granulomatous sterile inflammation of the breast lobules. It is a disease of middle-aged women.

Case series presentation

Herein we report six cases of IGM the General Surgery Department at Palestinian Medical Complex (PMC) with a good response to treatment and significant improvement. The patients were followed-up for an average of 4-month period.

Discussion

Pathophysiology is uncertain. It has a wide differential diagnosis and malignancy should be ruled out. Its diagnosis is highly challenging and is only made by biopsy. Treatment options include medical and surgical therapy. Patients are usually started with a low dose prednisolone, other options include immunosuppressive agents, antibiotics, NSAIDs, colchicine and minimally invasive surgery. IGM has a high recurrence rate up to 40 % and long term follow up is advised.

Conclusion

IGM is a rare breast pathology that evolves in an unpredictable manner over time. Clinical and radiological aspects vary and pose a diagnostic challenge, particularly in breast cancer. The pathological examination is still the most important component of certain diagnoses. The clinically correlated treatment is still debatable.

Highlights

• •Idiopathic Granulomatous Mastitis (IGM), a rare benign breast disease, features chronic inflammation in lobules. Predominantly affecting middle-aged women, its etiology remains uncertain.
• •IGM's uncertain pathophysiology necessitates ruling out malignancy. Diagnosis, challenging and biopsy-dependent, offers varied treatment options—prednisolone, immunosuppressants, antibiotics, NSAIDs, colchicine, or minimally invasive surgery.
• •Despite treatment success, IGM boasts a 40% recurrence rate, underscoring the need for long-term follow-up. The choice between medical and surgical therapies remains debatable, emphasizing the intricacies in managing this condition.

1. Introduction

Idiopathic granulomatous mastitis (IGM), also known as Lobular granulomatous mastitis (LGM), is a rare chronic breast disease that primarily affects young women. Regardless of its escalating prevalence in recent years, the etiopathogenesis of this disease remains unknown. Several arguments have been advanced in support of autoimmunity in the pathophysiologic process of IGM [[1], [2], [3]]. It continues to be a challenge in both diagnosis and treatment. Breast carcinoma is the most common differential diagnosis at a certain stage. Its imagery is general. Only histology can provide a definitive diagnosis by distinguishing between lobular necrosis and non-caseous granulomatous inflammation. The underlying etiology continues to largely influence treatment and evolution [1,3,4].

2. Methods

This case series include six cases of idiopathic granulomatous mastitis reported at the General Surgery Department at Palestinian Medical Complex (PMC). Table 1 shows a summary of each patient clinical scenario. This case series has been reported in line with PROCESS criteria [5].

Table 1.

summarizes the most important findings of the included patients.

Patient number	Age	Clinical presentation	Diagnostic findings	Treatment	Outco	Patient number
1	26	Left-sided breast pain and swelling, progressive, nipple discharge, fever, chills	Breast ultrasound: Soft tissue edema, fat stranding. Follow-up: Vascularized heterogeneous hypoechoic area, multilocular abscesses	Initial: Oral antibiotics, Follow-up: Prednisolone, True-cut biopsy, Second ER visit: Incision and drainage	Recurrent abscesses, Prednisolone tapered to 5 mg daily, Methotrexate added	6 months
2	40	Right-sided breast pain, swelling	Initial: Multiple cystic structures. Follow-up: Breast abscess	Initial: Oral antibiotics, Follow-up: Incision and drainage, Macroductectomy	Excellent response, Prednisolone tapered gradually	4 months
3	33	Left-sided breast painful swelling, sudden onset, throbbing	Breast ultrasound: Anechoic lesion, inflamed fat. Follow-up: Multiple abscesses	Aspiration, True-cut biopsy. Second ER visit: Incision and drainage, Second biopsy	Excellent response, Prednisolone tapered gradually	2 months
4	34	Left-sided breast pain, swelling, feverish sensation	Breast ultrasound: Ill-defined hypoechoic collection, sinuses, enlarged axillary lymph nodes	Incision and drainage, Methotrexate added	Minimal improvement, Recurrence, Methotrexate continued	5 months
5	25	Right-sided breast pain, swelling, skin changes, polyarthralgia, fever	Breast ultrasound: Heterogeneous suspicious parenchyma. Follow-up: Incision and drainage	Initial: Oral antibiotics, Follow-up: Incision and drainage, Prednisolone	Dramatic change, Mass size decreased, Complete resolution	9 months
6	36	Right-sided breast lump, induration, erythema, palpable lymph nodes	Breast ultrasound: Increased echogenicity, hypoechoic areas. Mammography: Multilobulated mass	Initial: Oral antibiotics, Follow-up: Incision and drainage, Prednisolone	Dramatic improvement, Tapered gradually	3 months

3. Results

3.1. patient 1

A 26-year-old female patient, married, Gravida 1- para 1, non-lactating, and non-smoker presented to our ER complaining of left-sided breast pain and swelling at the upper outer quadrant of five days duration.

The history of the patient dates back to two years ago when she started to complain of bilateral breast pain, increases with menses, and burning in nature, mainly on the left side. The pain became more progressive and increased in severity in the last few months followed by swelling of the left breast, nipple discharge, nausea, fever, and chills. The patient had free past medical and free past surgical history and denies any personal or family history of breast diseases, oral contraceptive (OCP) use or breast trauma. Age of menarche was at twelve years of age and the last pregnancy was in 2018. Upon her first presentation, the patient was fully awake, conscious, alert, and oriented. Breast examination revealed mild left breast erythema and tenderness, no palpable masses, no discharge per nipple and there is old history of left retracted nipple. Breast ultrasound showed left breast soft tissue edema with significant fat stranding, no evidence of definitive collection or cystic or solid masses, and no axillary lymphadenopathy, these findings suggest left breast mastitis. The patient was discharged home on oral antibiotics and advised to follow up in our out-patient clinic.

After two weeks after the first presentation, the patient came for a follow-up in the out-patient clinic, in which she had painful breast swelling with no improvement on oral antibiotics. She underwent a true-cut biopsy of the left breast which showed idiopathic granulomatous lobular mastitis with no evidence of malignancy and the patient started on prednisolone 20 mg tablet once daily.

One month later, the patient presented again to ER with a chief complaint of left breast painful swelling and skin redness. New breast ultrasound showed a left breast vascularized heterogeneous hypoechoic area with irregular borders and internal echogenic foci (air) measuring 6*2.5 cm surrounded by inflamed soft tissue and edematous thickened skin, no solid masses or duct dilatation identified and no axillary lymphadenopathy. These features suggest multilocular abscesses. Laboratory tests showed leukocytosis 17, neutrophils 82 % and CRP 17. The patient was admitted to the surgical ward and underwent incision and drainage of a left breast abscess in which swab culture showed no growth and the patient was discharged home on oral antibiotic and oral prednisolone 20 mg once daily. A few days later, the patient presented again to ER with the same complaint in which laboratory tests showed WBC of 16 and CRP of 33. Breast ultrasound showed well-defined heterogeneous non-vascularized collection 3*5 cm with multiple hyperechoic foci at the periareolar area from 12 o'clock extending to 6 o'clock, surrounded by fat inflamed fat stranding and edematous fat planes and no axillary lymph adenopathy. These findings suggest recurrent left breast abscesses. The patient underwent incision and drainage in which the second swab culture also showed no growth. The patient was discharged home on oral antibiotic and oral prednisolone 40 mg once daily which was tapered gradually up to 5 mg daily. The patient claims minimal clinical improvement and methotrexate 2.5 mg (seven tablets once a week) were added. The patient is followed up for 6 months at the outpatient clinic without any reported adverse events or complications.

3.2. Patient 2

A 40-year-old female patient, married, Gravida 11- para 4, non-lactating and non-smoker presented to our ER complaining of right-sided breast pain and swelling at the upper outer quadrant. The history of the patient dates back to two days prior to presentation when she started to complain of right sided breast pain, gradual in onset, progressive, and continuous with no history of nipple discharge, nausea, fever, or chills. The patient has a medical history of hypothyroidism for more than ten years, and a past surgical history of cesarean section. She denies any personal or family history of breast diseases, OCP use or history of breast trauma. Age of menarche is at fifteen years of age and her last pregnancy was in 2017. Upon her first presentation, the patient was fully awake, conscious, alert, and oriented. Breast examination revealed right sided breast swelling, solid with no signs of infection. Breast ultrasound was done, and showed right sided multiple variables sized well defined cystic structures with posterior enhancement, the largest one measures 1.7*1.8 cm with septations, evidence of well-defined hypoechoic nodule seen at 9 o'clock, no evidence of solid masses or collections, no axillary lymph node enlargement could be seen. The patient was discharged home on oral antibiotic and advised to follow up in outpatient clinic.

The patient states no improvement in her symptoms and returned with a complaint of right-sided breast painful swelling with hotness and redness. New breast ultrasound showed right sided breast abscess with no solid masses. Aspiration was done and the patient was discharged home on oral antibiotics. Mammogram was done with unremarkable result. The patient states recurrent visits due to the same complaint in which incision and drainage was done again. Last breast ultrasound showed BIRADs II, duct ectasia with focal collection in which the patient was discharged home on oral antibiotics and later underwent macroductectomy. Pathology showed granulomatous lobar mastitis with abscess formation, duct ectasia and fibrocystic changes and no evidence of malignancy. She started on oral prednisolone 20 mg tablet once a day and tapered gradually with excellent response. The patient is followed up for 4 months at the outpatient clinic without any reported adverse events or complications.

3.3. Patient 3

A 33-year-old female patient, married, Gravida-4, Para-3, pregnant 15 weeks+ and non-smoker, presented to our ER complaining of left-sided breast painful swelling at the inner upper quadrant of two days duration. The pain was sudden in onset, progressive and continuous, throbbing in nature with no history of fever, chills, nausea, vomiting or nipple discharge. The patient states free past medical and surgical histories and denies any personal or family histories of breast diseases, no history of OCP use and no history of breast trauma. Age of menarche was at nineteen years of age. Breast ultrasound showed well defined anechoic lesion measuring about 1.3*1.5 cm associated with echogenic inflamed fat suggestive of left breast abscess. No axillary lymph node enlargement could be seen. Aspiration of pus was done and the patient was discharged home on oral antibiotics to be followed in our out-patient clinic. Few days later, the patient returned to ER complaining of progressive swelling with hotness and redness. On physical examination there is a left sided breast swelling about 7*5 cm with fluctuation and skin changes, no nipple discharge. Laboratory tests showed wbc; 8.3, neut;88, and crp;33. Aspiration was done again and wound swab culture was taken and showed micrococcus species. The patient was discharged home on oral antibiotics according to the sensitivity with no improvement and recurrence of symptoms. So tru-cut biopsy was taken and showed no evidence of granulomatous inflammation, dysplasia, or malignancy and findings are keeping with breast abscess.

The patient has no improvement in her symptoms with multiple and recurrent visits with the same complaints. Last breast ultrasound showed left sided multiple well-defined collections containing hyperechoic foci, and surrounded by inflamed fat, seen diffused in the breast tissue and connected by tracts, the largest measures 3*2 cm at 9 o'clock, finding represent multiple abscesses, no axillary lymph node enlargement could be seen. The decision was to repeat true cut biopsy in which the second pathology showed granulomatous lobar mastitis with associated mixed inflammation, there is no evidence of dysplasia or malignancy. She started on oral Prednisolone 20 mg tablet once a day which was tapered gradually with excellent response. The patient is followed up for 2 months at the outpatient clinic without any reported adverse events or complications.

3.4. Patient 4

A 34-year-old female patient, married, Grvida-3, Para-3, non-lactating and non-smoker presented to our ER complaining of left sided breast pain and swelling at the upper outer quadrant of three days duration. The pain was gradual in onset, progressive and throbbing in nature, associated with feverish sensation and chills.

The history of the patient dates back to two months ago when she started to complain of left sided breast swelling, associated with amenorrhea since the last few months. The patient sought medical advice in the private sector, in which breast ultrasound was done showing extensive skin edema in the left breast with hyperemia, solid ovular lobulated lesion 2*0.8 cm in super-external quadrant, no axillary enlarged lymph nodes, otherwise both breasts are normal. The patient was discharged on oral antibiotics with no improvement. After few days she returned with a complaint of progressive swelling and pain in which aspiration was done and the patient continued on antibiotics. The patient had free past medical history and denies any personal or family histories of breast diseases, no history of OCP use and no history of breast trauma. Age of menarche was at thirteen years old and last pregnancy in 2019. Upon her first presentation, the patient was fully awake, conscious, alert and oriented. Breast examination revealed left-sided retro and periareolar induration extending to the lower surface of the breast with two well localized cystic lesions at 12 o'clock, oval in shape, the largest measures almost 4*2 cm and smallest one 2*1 cm, fluctuant with skin changes hotness, redness and tenderness. No nipple retraction discharge with palpable and tender left sided axillary lymph nodes. Laboratory tests showed HGB; 10.4 -, WBC18 and CRP;113. Breast ultrasound showed ill-defined hypoechoic collection with hyperechoic foci with air foci measuring 5*2.3 cm at the retro-areolar region at 12 o'clock, extending to periphery, with multiple sinuses measuring 8 cm and 2.9 cm connected to subcutaneous collection measuring 4.6*0.8 cm and another smaller collection measuring 1.1*2 cm at periphery at 3 o'clock, these collections are surrounded by significant fat stranding, and enlarged left axillary lymph nodes (short axis measuring 11 mm),with preserved fatty hilum reactionary to inflammatory process, right breast showed hypo-echoic lesion at 1 o 'clock, parallel to skin measuring 11*4 mm, with no calcification or posterior features, and at 9 o'clock another similar lesions measuring 8.5*7 and 8.5*14 mm, no enlarged right axillary lymph nodes. The patient underwent incision and drainage in which wound swab culture and tissue biopsy were taken and showed coagulase negative staphylococcus, and granulomatous mastitis respectively with no evidence of malignancy. The patient was discharged home on oral antibiotics and oral prednisolone 20 mg tablet once a day. On follow up, the patient states minimal improvement with recurrence of symptoms in which methotrexate 2.5 mg (seven tablets/once a week) was started. The patient is followed up for 5 months at the outpatient clinic without any reported adverse events or complications.

3.5. Patient 5

A 25-year-old female patient presented complaining of right-sided breast pain and swelling at the upper outer quadrant of one week duration. The history of the patient dates back to one month ago when she started to complain of right sided breast pain. The pain became more progressive and increased in severity in the last week followed by swelling of the right breast, associated with erythematous skin changes, polyarthralgia and feverish sensation. Upon her first presentation, the patient was fully awake, conscious, alert, and oriented. Breast examination revealed right breast erythema and in duration on 9 o'clock, no palpable masses, no discharge per nipple. Breast ultrasound showed 8–11 o'clock heterogeneous suspicious parenchyma. She underwent Tru-cut biopsy which showed severe chronic active inflammation with few foreign body giant cells and no evidence of malignancy. They reviewed the pathology for a second opinion which showed cystic neutrophilic granulomatous mastitis and no evidence of malignancy. The patient was discharged home on oral antibiotics and advised to be followed in our out-patient clinic.

One month after the first presentation, the patient came for a follow-up, in which she had painful breast swelling with no improvement on oral antibiotics. On physical examination there was a huge mass occupying the outer quadrant of the right breast, solid, with skin erythema and fluctuation. The patient underwent incision and drainage of a right breast abscess, PPD skin test was done showing negative result. The patient was discharged home on oral antibiotic and oral prednisolone 40 mg once a day, which was tapered gradually with slight decrease in the mass size but dramatic change of consistency from firm to soft, and complete resolution of inflammatory process. The patient is followed up for 9 months at the outpatient clinic without any reported adverse events or complications.

3.6. Patient 6

A 36-year-old female patient presented to ER complaining of right-sided breast lump of one month duration. The patient denies any personal or family histories of breast diseases, OCP use or breast trauma. Upon her first presentation, the patient was fully awake, conscious, alert, and oriented. On physical examination there was a mass occupying the upper and lower outer quadrants of the right breast, with induration and erythema of the overlying skin, with palpable right axillary lymph nodes. Breast ultrasound showed increased echogenicity of the right side, compared with the left, with multiple hypoechoic areas. Several enlarged axillary lymph nodes were seen. Mammography revealed multilobulated mass. Radiological examination showed a picture similar to that of an inflammatory breast carcinoma. FNA was done on the lump, and cytological findings were consistent with a granulomatous inflammatory lesion, no evidence of malignancy. The patient was discharged on oral antibiotics without improvement. The patient's symptoms were not improved in which she had recurrent right breast abscess and underwent incision and drainage twice. Swab cultures showed no growth. Skin test for TB was done and showed negative results. She started on high dose prednisolone tablet with dramatic improvement and tapered gradually. The patient is followed up for 3 months at the outpatient clinic without any reported adverse events or complications.

4. Discussion

Idiopathic granulomatous mastitis or autoimmune mastitis or granulomatous lobular mastitis is a benign, relatively rare breast disease of the young parous women. It is characterized by chronic idiopathic non-caseating necrotizing granulomatous sterile inflammation of the breast lobules [[6], [7], [8]].

The incidence of IGM is uncertain. It represents approximately 0.44 %–1.6 % of all breast and 24 % of all inflammatory breast histopathologies. It is a disease of childbearing middle-aged women (<50 years old with an average age of 36 years old). Usually unilateral with approximately 15 % presents with lymph node involvement [6,[8], [9], [10]].

IMG highly resembles other malignant (inflammatory breast CA) and infectious (for example: periductal mastitis, brucellosis, fungal infection, TB and sarcoidosis) breast diseases putting it in a highly challenging and difficult diagnosis. >50 % of IGM cases were initially reported as breast CA. It is diagnosed after exclusion of other causes of granulomatous inflammation (infectious or non-infectious) [7,10,11].

Usually, the etiology of IGM is unclear, based on the review of the literature, there are multiple theories for the pathophysiology of this disease. These include autoimmune reaction, chemical reaction (oral contraceptive pills), infective etiology and hormonal hypothesis (evidence of high prolactin serum levels in these patients). It is thought that any factor causing damage to ductal epithelium (trauma, local irritant or infection) will lead to local immune reaction and migration of immune cells (predominantly T-lymphocytes and microphages). Due to the rarity of this disease, none of these theories were based on scientific evidence [6,7,11,12].

Clinical presentation varies among patients. The most common symptom is painful unilateral breast mass. IGM can affect the breast at any quadrant (most commonly in the upper outer quadrant) except for the sub-areolar area. Other symptoms include unilateral mastodynia, lymphadenopathy (in 15 % of patients) and local skin changes such as erythema, hotness, swelling, ulceration and skin dimpling which mimic may mimic breast cancer. Complications of IGM include suppuration, multiple and recurrent abscess formation and open draining sinuses [[6], [7], [8], [9],11].

The differential diagnosis is a critical element in the evaluation of patients of IGM. These include TB, sarcoidosis, Wegener granulomatosis, the use of local irritants and chemicals, antipsychotic therapy and trauma. In cases of TB mastitis and sarcoidosis, granulomatous caseation necrosis and diffuse granulomas are identified respectively as compared to IGM which has limited granulomas to the involved breast lobule. IGM is a diagnosis of exclusion and is only by biopsy and histopathological assessment (gold standard for the differential diagnosis) because it has no specific clinical or radiological features [[13], [14], [15]].

Triple assessment of the patient is usually needed including physical examination, radiological and pathological assessment. There is no pathognomonic sign of IGM on either breast ultrasound, mammogram or MRI and they are usually used to exclude other causes. Ultrasonography may show single or multiple hypoechoic lesions, skin thickening, mass abscess chambers (one or more abscesses) and tubular structure with finger-like aspects (fistula-like), duct ectasias and axillary lymphadenopathy. Mammographic findings include asymmetrical ill-defined focal opacities, irregular mass, diffusely increased density, parenchymal distortion and retraction or microcalcifications that may be confused with malignancy. MRI may help in showing the potential malignancy of the lesion and its vascular nature, skin and tissue edema, abscesses, multicentric lesions and lymphadenopathy [7,8,12,16].

Diagnosis is usually made only by histopathology, which is the gold standard of diagnosis of IGM. Biopsy findings are consistent with lymphocytes, epithelioid histiocytes, plasma cells, granulomas and Langerhans-type giant cells induced by eosinophilic reactions centered on the breast lobule (typical features of chronic non-caseating granulomas with or without micro-abscess formation). Core biopsy, in addition to confirmation of diagnosis, it is used to rule out other infectious causes included in the differential diagnosis [12,15,16].

Based on the review of the literature, there is no ideal treatment modality for IGM, but the most common modality is local excision with or without steroid therapy. Combination therapy and minimally invasive approach is usually needed because it poses a less recurrence rate. Medical treatment options include steroids (intralesional injection or systemic), colchicine, immunosuppressive agents, NSAIDs and antibiotics. Surgical treatment options include wide local excision, incision and drainage or mastectomy and used in cases refractory or suboptimal response to medical treatment [11,14,17].

Steroids are often used starting with a low dose prednisone, 25 mg/day and 0.8 mg/kg/day or triamcinolone injections every 1–2 weeks (Mix 40 mg/ 1 mL triamcinolone with 3 mL 2 % lidocaine for a total volume of 4 mL) and is usually effective. Antibiotics are used according to the fluid cultures obtained with steroids or colchicine [11].

Immunosuppressive therapy is used in cases resistant to steroids. Methotrexate has limited use is lactation and azathioprine are more safe and ideal option in breastfeeding population [11,17]. Notably, four out of our included six patients experienced a significant response to immunosuppressive treatment.

The recurrence rate may reach up to 40 %, in cases with recurrent IGM, PCR test for TB is usually required prior to starting steroid therapy. After exclusion of any infectious process, oral prednisolone can be started and tapered until clinical response is achieved. If the patient developed recurrence or was resistant to steroids, methotrexate is started (10–15 mg/week with a low dose steroid for 12–24 months) [8,9,11].

In cases with failed medical and minimally invasive surgical treatment, mastectomy with reconstructive surgery is a good option. These patients need long term follow up since relapses are common and there is no role for long term low dose steroids in preventing recurrence [7,8].

5. Conclusion

IGM is a benign rare granulomatous inflammatory breast disease which has a significant clinical importance. Surgeons, pathologists and radiologists should be more familiar with this disease. Its cause is unknown. Malignancy should be excluded. Treatment is usually medical with oral corticosteroids.

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Ethical approval

This study is exempt from ethical approval in our institution “Al-Quds University Ethics Committee” as the patient consent was taken and authors have no conflict of interest.

Funding

The authors declare that writing and publishing this manuscript was not funded by any organization.

Author contribution

• ➢Writing the manuscript: Asil Musleh, Oadi N. Shrateh, Nima Ishtaya, Khaled Abbadi, Malvina Asbah
• ➢Reviewing & editing the manuscript: Sahar Ayyad

Guarantor

Khaled Abbadi

Research registration number

Not Applicable.

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this article.