Bilateral idiopathic granulomatous mastitis

Abstract

A 35-year-old woman presented to the surgery outpatient department with a lump in her right breast for 2 months and pain for 1 month. After clinical examination and relevant investigations, we kept a working diagnosis of antibioma. The lump was excised under local anaesthesia and biopsy was sent. However, histopathological examination reported multiple non-caseating granulomas without acid-fast bacilli. Two months later, she developed a sinus with serous discharge at the scar site. At the same time, she developed pain in the left upper breast, which subsequently progressed to an abscess. Incision and drainage of the abscess was done, but the wound did not heal, and a discharging sinus appeared at the site. Finally, a diagnosis of idiopathic granulomatous mastitis was made, after excluding all other causes, and the patient was prescribed oral steroids. She recovered fully after 8 months and there is no recurrence till date.

Background

Mastitis is a common disease in women, which sometimes becomes difficult to cure by the treating surgeon owing to its varied aetiology, diagnostic difficulty and limited therapeutic options. Idiopathic granulomatous mastitis (IGM), as the name suggests, is an idiopathic benign disease of the breasts, which is associated with chronic inflammation of the affected breast parenchyma. Five cases of this rare disease were described for the first time by Kessler and Wolloch in their landmark article in 1972.¹ Even though the disease is rare, cases have been reported from world over, mostly in young Hispanic and Asian women. Due to the rarity of the disease, exact prevalence is still not known. According to a retrospective research study, only 20 patients were diagnosed with IGM based on histopathological findings, out of the 1106 patients of benign breast disease.² As an outcome, clinicians or surgeons may find it difficult in reaching a correct diagnosis of IGM. Furthermore, the lack of characteristic radiological features adds to the confusion. Most patients of IGM present with the complaint of a lump in one of the breasts, with or without the involvement of skin. Examination of the axilla may also reveal the presence of lymph nodes. These findings are similar to those seen in breast carcinoma.¹ Owing to this similarity, the surgeon might be tempted to keep malignancy on top of the differential diagnosis list. The available treatment options include active surveillance, immunosuppressive drugs or steroids, and surgical excision whenever indicated. In this report, we intend to discuss a patient with bilateral IGM, who was managed with multiple surgical procedures and steroid therapy. The patient had provided a written and informed consent for this report.

Case presentation

A 35-year-old woman presented to the surgical outpatient department (OPD) with a lump in her right breast for 2 months and pain in the lump for 1 month. She did not give any history of nipple discharge, trauma to the breast or any previous breast swelling. There was no history of tuberculosis (TB) infection in the past. She attained menarche at the age of 13 years, and menstrual cycles had been regular since then. She had her first pregnancy 3 years ago and breast fed her child for 1.5 years. There was no history or family history of any chronic illness. None of the first-degree or second-degree relatives of the patient had breast malignancy and there were no malignancy-related deaths in the family. General physical examination showed no abnormality. Localised erythema was present on the upper outer quadrant of the right breast. A well-defined, 4×4 cm tender lump was palpable underneath the erythematous skin. The lump was firm in consistency and was not fixed with the overlying skin, the underlying Pectoralis major muscle and chest wall. The nipple areola complex was normal, and the right breast showed no distortion of size or shape. Ipsilateral axilla, contralateral breast and axilla were normal. No supraclavicular lymph nodes were palpable.

Bilateral mammography of the patient showed dense breast parenchyma on the affected right side (figure 1). An ultrasonography of the right breast reported ill-defined heterogeneous echoes in the subareolar region. Hence, a provisional diagnosis of antibioma was made. The breast mass was then excised under local anaesthesia and the postoperative period was uneventful. Histopathology report showed multiple non-caseating granulomas and the absence of acid-fast bacilli (AFB) (figures 2 and 3). Cultures for aerobic and anaerobic bacteria, fungi and mycobacteria were negative. PCR test for TB from the mass was also negative.

Figure 1.

Bilateral mammography of the patient showed dense breast parenchyma on the affected right side.

Figure 2.

Microphotograph of histopathology specimen H&E (low power) showing multiple noncaseating granulomas (black arrows) and absence of Acid-Fast Bacilli.

Figure 3.

Microphotograph of histopathology specimen (H&E; high power) showing giant cells (red arrows) and granuloma with lymphocytic infiltrates (black arrow).

The patient was then followed up in the OPD on regular basis. Two months into the follow-up period, she developed a sinus at the scar margin, which was discharging serous contents. The cytology smear of the discharge showed epithelioid histiocytes. The sinus was managed with serial dressings. Meanwhile, the patient started to feel pain in her left breast. Examination revealed no lump, and the left breast and axilla were normal (figure 4). She was prescribed non-steroidal anti-inflammatory drugs for the pain, and an MRI scan of the breasts was planned. The MRI (T2 weighted image) showed a normal left breast parenchyma and multiple small left axillary lymph nodes. The right breast showed a scar with a sinus tract. There was focal deformity of the breast contour with parenchymal distortion and margins in the region of the scar were spiculated. Multiple cystic areas in the rest of the breast parenchyma and multiple small lymph nodes in right axilla were also observed. No deformity of ribs, pectoralis major and intercostals muscles was noted (figure 5). However, pain in the left breast became more severe. Swelling and redness appeared at the site of pain during the next 2 weeks. Ultrasonography of the left breast showed focal mastitis between 12 and 1 o’ clock position. This progressed to an abscess, which needed to be surgically drained.

Figure 4.

Clinical photograph of bilateral breasts showing eschar with scars.

Figure 5.

MRI of the bilateral breasts, T2 weighted image. Right breast showed a scar with a sinus tract with focal deformity of breast contour and parenchymal distortion (white arrow).

Investigations

Mammography films may show focal or regional asymmetry, a solitary mass or multiple masses, skin thickening, skin and nipple retraction and axillary lymphadenopathy.^3–10 Microcalcifications are not uniformly reported in all cases. The diseased breast may just appear larger in size than the other breast in many of the mediolateral oblique view mammograms. However, mammography may occasionally fail to identify any pathology, due to the presence of dense breast parenchyma. The resemblance of IGM lesions with invasive or inflammatory breast cancer on mammogram warrants further investigation using advanced imaging modalities.¹¹

IGM lesions may appear as masses, architectural distortion, parenchymal oedema, fluid collections, skin thickening or axillary lymph nodes on sonography.^{3–10 12} However, the most common finding on sonography remains the visualisation of a mixed echogenicity with predominance of a hypoechoic mass with angular, irregular or indistinct margins, which may be associated with sinus tracts. There are variable degrees of posterior acoustic enhancement and shadowing.^{4 5 13}

MRI is often required to be done in patients with an advanced, aggressive or refractory disease. It gives the most accurate assessment of the disease extent and status of the contralateral breast.¹¹ MRI cannot differentiate active inflammatory process from tumorous process but may have a role in determining disease regression over time and may be useful for assessing resolution.¹⁴ MRI findings vary with the extent of inflammation associated with IGM. Heterogeneous, ill-defined masses and non-mass enhancement associated with mixed kinetics are usually seen. The pathological parenchyma shows intense enhancement as compared with the normal tissue.¹¹

Fine Needle Aspiration Cytology (FNAC) may not always distinguish between IGM and other granulomatous diseases of the breast. Histopathological samples, negative microbiological investigations and clinical correlation are essential for an accurate diagnosis of IGM. Adequate tissue specimens are, therefore, required to differentiate IGM from other entities. The presence of lobular non-caseating granulomas, epithelioid histiocytes and Langhans giant cells in a background of inflammatory cells, mostly neutrophils and lymphocytes with no necrosis, are the typical features of IGM on histopathology. Fat necrosis and microabscesses may also be observed. Furthermore, non-caseating granulomas are a variable finding and may not occur in every case. However, the presence of epithelioid histiocytes is a constant feature observed in all histopathological slides of IGM. It is important to ensure that acid-fast stains are performed in every case because some mycobacteria can be variably gram positive. Negative microbiological investigations further cement the diagnosis of IGM.^{2 15}

Differential diagnosis

The causes of granulomatous disease of the breast can be broadly categorised into infectious, autoimmune, local breast-related, systemic and idiopathic. Mycobacterium tuberculosis and Corynebacterium are the prime bacterial organisms, which may cause granulomatous mastitis. Fungal infections such as blastomycosis, histoplasmosis, cryptococcosis and actinomycosis have been described as causative factors. Filarial infection may also lead to the development of granulomatous mastitis. Autoimmune diseases include granulomatosis with polyangiitis, giant cell arteritis and foreign body reaction. Duct ectasia, plasma cell mastitis, subareolar granuloma, periductal mastitis and fat necrosis are the local breast-related causative factors. Other systemic diseases, like diabetes mellitus and sarcoidosis may also contribute in the development of granulomatous mastitis.¹⁶ TB is an important differential diagnosis to rule out, since it is endemic in India. The presence of caseous necrosis and the presence of AFB are confirmatory of TB. Bilateral tuberculous mastitis is an extremely rare entity and the number of reported cases is very few.^17–20 However, differentiating IGM from TB is of extreme importance, since the latter can be cured with antitubercular treatment. As discussed earlier, clinical presentation and mammography findings are not of much help in differentiating IGM from breast carcinoma and diagnosis is confirmed only on histopathological examination. A granulomatous reaction occurring in carcinoma is probably the most important differential diagnosis that needs to be excluded. The rarity of the disease and lack of adequate experience of surgeons in treating it, together contribute in delaying the establishment of correct diagnosis by approximately 7–12 months.²¹

Treatment

Incision and drainage of the left breast abscess was done under local anaesthesia, and the patient withstood the procedure well. Abscess wall biopsy showed granulomas without AFB. After excluding all other diagnosis, we kept a working diagnosis of bilateral IGM (figure 4) and started her on tablet methylprednisolone 60 mg/day for 8 weeks. The drug was tapered off during the next 6 weeks. The wounds were managed with serial dressings.

Outcome and follow-up

The patient was followed up on OPD basis every 2 weeks. She developed a sinus through the wound in the left breast. Again, this was managed by serial dressings. The sinus in the right breast stopped discharging after 4 months and healed after 6 months of lumpectomy. The sinus in the left breast stopped discharging after 6 months and healed completely after 2 more months. At the time of writing this report, which is after 16 months of OPD follow-up, the patient has had no recurrence, or any new symptoms and surgical sites show healthy scars.

Discussion

Women belonging to the childbearing age group are mostly affected by IGM. However, young adolescents and elderly women developing IGM have also been reported in the literature. In most cases, a preceding history of childbirth and breastfeeding within 5 years of the development of IGM was observed.²² The disease can occur in any quadrant of the breast but not in the subareolar region.²² The most common presentation of the disease, as was mentioned earlier, was a progressively increasing painful breast mass, which may be associated with skin changes or lymph node involvement. Fifteen per cent of the cases had associated regional lymph nodes.¹⁶ Nipple retraction or peau d’orange may also complicate the presentation of IGM. This makes it difficult to distinguish the disease from breast carcinoma, especially when regional lymph nodes are enlarged. Chronic IGM manifests in the form of fistulae and sterile abscesses.²³

Causative factors involved in the pathogenesis of IGM include use of oral contraceptive pills, autoimmune reaction, trauma, infections and a limited local immunological reaction in response to extravasated secretions from the lobules.^{1 23–26} It is thought that the inciting event is an injury to the ductular epithelium, which results in extravasation of luminal contents into the lobular connective tissue. The extravasated secretion propagates a granulomatous inflammation, which damages the nearby lobular tissue.²⁷ Pregnancy, breastfeeding, breast trauma, hyperprolactinaemia with galactorrhoea and alpha-1-antitrypsin deficiency have also been suggested to be risk factors for developing IGM.^28–31

Most cases of IGM can be treated successfully by an active follow-up, use of immunosuppressive therapy and an appropriate surgical intervention. Lai et al³² observed in their research that half of their enrolled patients of IGM showed spontaneous recovery without any treatment within 2–24 months (mean 14.5 months). The authors concluded that antibiotics are not required in the treatment of IGM. A few decades ago, DeHertogh et al proposed that complete resection or open biopsy with 60 mg/kg/day prednisolone therapy was adequate for treatment of granulomatous mastitis.³³ It is advisable that once steroids are initiated at a dose of 1 mg/kg/day, they should be tapered off gradually after assessing the clinical response.³⁴ However, approximately half of the cases relapse after cessation or reduction in the dose of steroids.^{34 35} Addition of steroid sparing agents such as methotrexate or azathioprine may help in the tapering of steroids.^{35 36}

Earlier, IGM had been treated by surgical excision of the mass alone. However, this was associated with a significantly higher recurrence rate when compared with steroid treatment.^{29 37 38} To reduce the probability of recurrence, wide excision with negative margins is performed.^{15 39} However, surgical procedures are more likely to give rise to local complications during the postoperative period. These include fistula formation, poor wound healing and disfigurement.³² According to an extensive retrospective review, resolution of the disease occurs in about 6–12 months’ time, regardless of the type of therapy used.³¹ Some patients may respond very well to steroids, while others with extensive and resistant disease may only be cured by radical procedures like bilateral mastectomy.²² Available literature shows that surgical excision alone or with steroid therapy is the most commonly adopted approach for the treatment of IGM. However, some authors still argue that once the diagnosis of IGM has been confirmed, a non-operative approach should be pursued, reserving drainage of abscesses with small incisions only when deemed necessary.¹⁴ Our patient required surgical procedures like drainage and excision of lump, and oral steroid therapy lasting several months for the control of the disease.

Very few cases of bilateral IGM have been reported in the literature.^{40 41} A 10-year retrospective review identified 41 patients of IGM, out of which, only 2 patients had bilateral disease.⁴² In another retrospective study, the authors reported bilateral disease in only 1 patient out of the 22 patients of IGM studied.⁴³ The largest series of 10 cases of bilateral IGM was reported by Velidedeoglu et al.⁴⁴ Owing to the scarcity of reported cases of bilateral IGM, the prevalence of the entity cannot be determined.

Learning points.

• It is extremely important to differentiate idiopathic granulomatous mastitis (IGM) from breast malignancy or abscess.

• Most young surgeons have limited experience in the diagnosis and management of IGM; therefore, advise and help of senior consultants or specialists should be sought early.

• IGM is a diagnosis of exclusion and all relevant investigations must be done to ascertain the aetiology.

• A long-term follow-up is recommended to monitor the patient’s progress.

• Bilateral IGM is a rare presentation.