Granulomatous lobular mastitis (GLM) is a rare inflammatory disease of the breast that was first described in 1972 by Kessler and Wolloch. It most commonly affects women in the childbearing age group. 1 The etiology of GLM is still unknown. GLM has two forms: non-specific granulomatous lobular mastitis and specific granulomatous lobular mastitis. Specific GLM can be associated with chronic infections like tuberculosis, fungal infections, parasitic infections, corynebacterial infections, or complications of systemic inflammatory diseases like sarcoidosis, Wegener's granulomatosis, syphilis and foreign body reaction due to an implant. 2 It may mimic infective mastitis and malignancy based on clinical presentation and imaging findings, but diagnosis is usually made by histopathological examination. 3 To the best of our knowledge, there is a lack of extensive work on the imaging findings of GLM to characteristically differentiate it from other diagnoses.

The aim of this study is to review the imaging findings particularly mammographic and ultrasound features of granulomatous lobular mastitis and to identify specific imaging features to differentiate it from malignancy.

The present research is a single institute retrospective study approved by the institutional ethical and scientific committee. It was done between January 2019 and November 2022 in the Department of Radiology, Kovai Medical Center and Hospital, Coimbatore (Tertiary care hospital). Overall, 54 patients who were diagnosed with GLM by core needle biopsy in histopathology were included.

Out of the 54 patients, three patients were excluded from the study due to either association with tuberculosis or other infective organisms in the final culture analysis and hence were categorized as specific GLM. A total of 51 patients with the diagnosis of idiopathic or non-specific GLM were included. Imaging data of all 51 patients were reviewed retrospectively.

Mammograms (MG) with supplementary ultrasound were performed in all patients above the age of 40 years and in patients between 30-40 years of age, with a clinical suspicion of malignancy. Standard craniocaudal and mediolateral-oblique projections were performed with a Siemens (Mammomat Inspiration) or Hologic 3 Dimensions equipment. Additional views had been performed as per the patient's study requirements.

Ultrasound was performed in all patients who were less than 30 years of age and when there was no clinical suspicion of malignancy in patients between 30 and 40 years of age. Ultrasound examinations of both breasts were performed using a high-frequency transducer (5 -18 MHz) in a Supersonic Aixplorer Ultimate or Supersonic Mach 30 ultrasound equipment. A conclusive diagnosis was obtained by ultrasound guided core needle biopsy using 14G Bard core biopsy needle and a minimum of 3 cores per biopsy.

All the data were entered in excel and analyzed using SPSS version 22. Categorical variables are presented as frequency and percentages.

In this study, 51 patients who were diagnosed with GLM in biopsy with negative culture analysis belonged to the age group between 20-64 years. Overall, 10/51 (19.6%) patients belonged to < 30 years age group, 32/51 (62.7%) patients belonged to 31-40 (17.6%) years age group and 9 patients belonged to >40 years age group. Out of 51 patients, 32 patients underwent only ultrasound and 19 underwent digital mammograms with ultrasound.

The most common mammographic finding was focal or global asymmetry which was seen in 10/19 (52.6%) patients (Figures 1 & 2). Focal asymmetry with associated architectural distortion was found in 3 patients.

Other findings including irregular mass with indistinct margins, oval or round lesions with obscured margins, and associated skin thickening were also noted. None of the lesions showed calcifications. Table 1 shows the common and uncommon mammographic findings of idiopathic granulomatous mastitis.

Single or multiple collections with or without tracts were the most common morphological abnormality in ultrasound that was seen in 37 patients (72.5%). Other morphological abnormalities were irregular hypoechoic non-mass area, irregular hypoechoic mass and dilated ducts. The common associated abnormalities were, perilesional hyperechogenicity, increased peripheral vascularity, skin thickening and axillary adenopathy. Table 2 and Figures 1 to 3 show the common and uncommon sonographic findings in GLM.

Sinus tracts extending to the skin surface were seen in 8/51 (15.7%) patients.

Granulomatous lobular mastitis is characterized by granuloma and abscess formation. 4 Women commonly present with a unilateral breast mass that that may or may not be associated with pain, skin thickening and sinus formation. 5 Figure 1. A 40-year-old patient, presented with a palpable lump in left breast with spontaneous left white nipple discharge for 1 month. A&B: Left craniocaudal and mediolateral-oblique mammogram showed an oval high-density lesion with obscured margins. C to E: On ultrasound, a large hypoechoic collection with moving internal echoes within. Few ducts appear to be communicating with the collections. F: USG guided aspiration of the collection was done and biopsy was taken from the wall of the collection. Histopathology was suggestive of granulomatous lobular mastitis. The etiology has been uncertain, and it had been suggested that GLM results from a local autoimmune response to an initial insult to the ductal epithelial cells, which causes extravasation of luminal secretions into the lobular stroma, leading to inflammatory processes in stromal tissue with accumulation of lymphocytes, macrophages, and subsequent granuloma formation. 5 GLM is commonly associated with hyperprolactinemia and shows increased incidence in non-white women. 67 Several studies have found a strong association between IGM and a history of pregnancy and lactation, with most patients reporting having a pregnancy within 5 years before the diagnosis. 1478 All our patients who were < 40 years of age had a history of lactation within 10 years. Five of our patients were on antidepressants resulting in hyperprolactinemia.

Our study shows GLM is usually unilateral and predominantly involves peripheral location, with few of the cases showing bilateral as well as retroareolar and subareolar involvement. Similar findings were described by Oztekin PS et al. 9 , Memis et al. 10 , and Aghajanzadeh et al. 11 The most common findings in our study on mammography were focal or global asymmetry with or without architectural distortions. Oztekin PS et al. 9 , Memis et al. 10 , Yilmaz et al. 12 , and Fazzio et al. 13 also described 'focal asymmetric density' as the most frequent mammographic pattern. Han et al. 14 reported 'multiple small masses' or a 'large focal asymmetric density' as the most common finding.

Three of our patients showed oval lesions with obscured margins and three of the patients showed irregular masses with indistinct margins. Lee et al. 15 described an irregular ill-defined/obscured mass as the most common finding in their study.

Though mammographic findings are nonspecific, they are helpful in differentiating malignancies that mimic GLM by ruling out suspicious microcalcifications or masses and all our patients who underwent mammography did not show any suspicious microcalcifications.

Single or multiple collections with or without tracts were the most common morphological abnormality in ultrasound, similar to the studies by Memis et al. 10 and Gautier et al. 6 The second most common morphological abnormality was irregular hypoechoic non-mass area with tubular extensions and tracts. These findings were concordant with other studies reported by Han et al. 14 , Yilmaz et al. 12 , Lee et al. 15 , and Manogna et al. 16 . The tracts/tentacles explain the insinuating nature of IGM around the breast lobules. Seven patients had dilated ducts.

The common associated abnormality on ultrasound irrespective of morphological abnormality was perilesional hyperechogenicity and increased peripheral vascularity which were seen in 86.3% and 88.2% of patients, respectively.

Associated inflammatory changes such as skin thickening, sinus tracts and axillary lymphadenopathy were also observed. Whenever there was an abnormal axillary lymph-node, the nodes showed only diffuse cortical thickening with increased vascularity.

Additional findings such as heterogeneous breast parenchyma, a circumscribed hypoechoic mass and parenchymal distortion with acoustic shadowing but without a discrete mass were described by Hovanessian Larsen et al. 17 and Dursun et al. 18 Table 3 shows differentiating clinical and imaging features between infective mastitis and granulomatous lobular mastitis. The differentiation of IGM from aggressive malignancy such as inflammatory breast cancer is necessary, since these malignancies can have similar clinical profiles and imaging findings such as focal asymmetry, skin edema or thickening, and axillary lymphadenopathy. 19 Table 4 shows the differentiating features between granulomatous lobular mastitis and malignancy. In diagnostic evaluation, ultrasound is always performed either as an only modality or as a supplementary examination with mammogram and the characteristic ultrasound findings in GLM include hypoechoic tracts connecting the irregular collections and extending to the subcutaneous plane. On color Doppler, there is peripheral vascularity with surrounding inflammation (Figure 3). Thus, ultrasound remains the cornerstone modality to suspect granulomatous mastitis and guide further investigations and treatment.

In our study, we found ultrasound as the most useful imaging modality to diagnose GLM and to The treatment of GLM remains controversial and includes surveillance, medical management with oral, intralesional and topical steroids and surgery 202122232425 . The natural course of the disease is a relapsing and remitting course with eventual burn-out in 1 to 2 years. For incidentally detected lesions and patients with mild symptoms, we suggested conservative management with imaging surveillance. Patients who had significant symptoms were started on oral steroids for at least 3 months with monthly follow-up (Figure 4 and 5). Patients who had extensive disease, progressive disease on medical management were treated surgically. Figure 6 shows the approach to diagnosing granulomatous lobular mastitis. Our study has several limitations, including retrospective and descriptive parameters. The role of magnetic resonance imaging to characterize the GLM was not evaluated.

Though imaging cannot differentiate GLM from malignancy on all occasions, our study revealed certain specific ultrasound features of GLM. Mammography was not informative for the diagnosis of GLM except for ruling out microcalcifications which would point towards malignancy. When GLM presents as non-mass areas or ductal abnormalities, presence of perilesional hyperechogenicity, peripheral rather than central vascularity, absence of suspicious calcifications, presence of interconnecting tracts and benign enlargement of lymph-nodes help to differentiate it from malignancy.