Idiopathic Granulomatous Mastitis Associated with Corynebacterium Sp. Infection

Abstract

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast. The etiology and treatments options of IGM remain controversial. Previous case reports have suggested that Corynebacterium sp., a gram-positive bacillus endogenous to the skin, may be associated with IGM. In the present report, we describe the first case of IGM with a positive culture for Corynebacterium sp. reported in the United States.

Introduction

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast with unclear etiology and variable treatment options.^1–5 The usual presenting symptoms of breast mass, pain, and erythema suggest an inflammatory or neoplastic process.^6–8 However, mammography and ultrasound findings are nonspecific and histopathologic features, which include noncaseating granulomatous changes centered on lobules, are notable for a distinct absence of neoplastic changes.^1,3,5,6

While the etiology of this disease remains obscure, the majority of cases of IGM are aseptic, and an autoimmune pathogenesis of the disease has therefore been endorsed.^9–12 However, reports of coexistent organisms suggest that an initial pathogenic insult may be responsible for generating a subsequent autoimmune response.^13–15 In particular, it has been suggested that Corynebacterium species, a gram-positive bacillus endogenous to the skin, may be associated with IGM.^13,15–19 In the present report, we describe a case of IGM associated with a positive culture for Corynebacterium sp.

Case Report

A 33-year-old non-puerperal, gravida 6 para 4 woman initially presented to clinic with a 2-week history of erythema, edema, and tenderness in her left breast accompanied by subjective fevers and chills for 4 days. Her history was notable for uneventful breastfeeding of all her children, with no history of mastitis. On physical examination, the patient was afebrile, however she was noted to have 2 fluctuant lesions on the left breast, one lateral and the other periareolar. There was diffuse erythema and induration of the areola, with marked tenderness to palpation, however no fluid was expressed from the nipple. Ultrasound revealed ill-defined heterogenic and hypoechoic areas with no obvious abscess, consistent with mastitis. However, scant purulent fluid was obtained with fine needle aspiraet and sent for culture, and a presumptive diagnosis of spontaneous infectious mastitis was made. A prophylactic course of Bactrim was prescribed and the patient was sent home in stable condition. Wound cultures subsequently revealed pan-sensitive 4+ Corynebacterium sp.

Unfortunately, the patient returned 2 days later, having discontinued Bactrim due to intolerable nausea and vomiting, and again complained of persistent erythema and induration, and worsening tenderness in the left breast. Admission CBC was significant for a leukocytosis with bandemia. Repeat ultrasound indicated diffuse heterogenecity with increased echogenecity, and a small periareolar fluid collection was identified. The patient was admitted for failed outpatient therapy and was initiated on intravenous antibiotic therapy (penicillin G and vancomycin). An incision and drainage was performed at the bedside where a copious amount of non-foul smelling purulent material was expressed and sent for further analysis. Subsequent bacterial, KOH preparation, AFB, fungal, and yeast cultures and smears were negative. Over subsequent days, the patient's left breast continued to be tender, erythematous, and warm, and an OR incision and drainage with core needle biopsy was performed. Loculations and purulent material were drained from the periareaolar and lateral aspect of the breast. Biopsy results demonstrated granulation and giant cell formation with liquefactive necrosis, compatible with granulomatoid inflammation and abscess, with no evidence of malignancy (Figures 1–4). The patient was continued on empiric intravenous antibiotic therapy, and the patient was discharged in improved condition the following week with a course of oral doxycycline.

Figure 1.

Low power histopathology of breast tissue fat lobules with evidence of chronic inflammation.

Figure 2.

Low power histopathology image of breast tissue lobules with evidence of chronic inflammation and formation of granuloma (→).

Figure 3.

High power histopathology image of granuloma within breast tissue lobules.

Figure 4.

High power histopatholgy of breast lobule with evidence of giant cells (↑).

Discussion

The pathogenesis of granulomatous mastitis is unknown, although a progression from subclinical mastitis to mastitis, and finally to breast abscess with granuloma formation has been suggested.¹⁹ Competing theories regarding the etiology of granulomatous mastitis include autoimmune and hypersensitivity processes,^5,20–22 versus an infectious pathogenesis.^14,15,23,24 Although the majority of cases of IGM appear aseptic, case reports of documented coinfection with Corynebacterium sp. have been reported in the United Kingdom,¹⁶ France,^13,17–19 and Italy.¹⁷ However, the present case is the only published report of IGM associated with Corynebacterium sp. documented in the United States.

The limited number of case reports demonstrating an association between infection with Corynebacterium sp. and IGM may be due to underdetection in an already rare disease. Corynebacterium sp. are typically non-pathogenic in immunocompetent individuals and therefore may not always be routinely screened for in cases of IGM. Furthermore, culture of lipophilic Corynebacterium sp. requires a 72 hr incubation period on special media, further contributing to the possibility of false negative reports of infection.¹⁵ However, Corynebacterium sp. are routinely implicated in the development of mastitis in livestock,²⁵ and may be associated with infection at higher rates in humans than previously considered. While the role of Corynebacterium sp. in the pathogensis of IGM has not been definitively established, the strongest supporting evidence has been documented by Taylor et al.¹⁵ who demonstrated granulomatous disease in 27 of 34 patients with inflammatory mastitis and concomitant Corynebacterium infection.¹⁵

In the context of a possible infectious etiology, the present case in which Corynebacterium sp. were identified in the progression of IGM illustrates the controversial nature of an optimal treatment paradigm. Initially, alternative causes of mammary granulomas, such as tuberculosis and sarcoidosis, must be excluded. However, the results of this case report and the previous studies above support a recommendation of additionally screening for Corynebacterium sp. prior to accepting a diagnosis of aseptic IGM. While adequate response to immunosuppresion has been described with aseptic IGM (9–12), in the present case we relied on systemic antibiosis and surgical incision and drainage with positive results, thus avoiding a definitive mastectomy.