Mastitis in Autoimmune Diseases: Review of the Literature, Diagnostic Pathway, and Pathophysiological Key Players

Abstract

Mastitis frequently affects women of childbearing age. Of all the pathological breast conditions requiring specific management, autoimmune mastitis is in the third position after infection and breast cancer. The aim of this literature review was to make a comprehensive description of autoimmune diseases targeting the mammary gland. Four main histological patterns of autoimmune mastitis are described: (i) lymphocytic infiltrates; (ii) ductal ectasia; (iii) granulomatous mastitis; and (iv) vasculitis. Our literature search found that all types of autoimmune disease may target the mammary gland: organ-specific diseases (diabetes, thyroiditis); connective tissue diseases (such as systemic erythematosus lupus or Sjögren's syndrome); vasculitides (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, polyarteritis nodosa, Behçet's disease); granulomatous diseases (sarcoidosis, Crohn's disease); and IgG4-related disease. Cases of breast-specific autoimmune diseases have also been reported, including idiopathic granulomatous mastitis. These breast-limited inflammatory diseases are sometimes the first symptom of a systemic autoimmune disease. Although autoimmune mastitis is rare, it is probably underdiagnosed or misdiagnosed. Early diagnosis may allow us to detect systemic diseases at an earlier stage, which could help to initiate a prompt, appropriate therapeutic strategy. In case of suspected autoimmune mastitis, we hereby propose a diagnostic pathway and discuss the potential pathophysiological pathways leading to autoimmune breast damage.

Keywords: IgG4-related disease; breast lymphocytic infiltrates; granulomatous mastitis; mammary duct ectasia; mastitis; vasculitis.

Figure 1

Lymphocytic infiltrates of the breast. (A) Dense, pseudonodular, lymphocytic infiltrates associated with a diagnosis of Sjögren’s syndrome mastitis; (B) Dense keloid-like fibrosis with perivascular lymphocyte infiltrates and prominent myofibroblasts in keloid stroma (arrow) associated with a diagnosis of diabetic mastopathy (Hematoxylin and eosin staining, magnification × 100).

Figure 2

Mammary duct ectasia. Ductal ectasia (asterisks). Periductal lymphocytic infiltrates (arrow) (Hematoxylin and eosin staining, magnification × 100).

Figure 3

Different histological patterns of granulomatous mastitis. (A) Granulomatous mastitis leading to a diagnosis of idiopathic granulomatous mastitis with polymorphonuclear neutrophil micro abscess; (B) Non-necrotizing epithelioid and gigantocellular granulomas involving a lobule with lymphoplasmacytic reaction and fibrosis, leading to a diagnosis of breast sarcoidosis; (C) Granulomatous mastitis with caseous necrosis leading to a diagnosis of tuberculous mastitis; (D) Granulomatous mastitis with neutrophils micro abscess in a 34-year-old patient with a granulomatous with polyangiitis vasculitis with lung and skin involvement (Hematoxylin and eosin staining, magnification × 100).

Figure 4

Breast biopsy histological patterns and corresponding defined auto-immune diseases. As described, IgG4-related breast disease, Sjögren’s syndrome-associated mastitis, breast GPA and EGPA, or Behçet’s disease can share several histological patterns. GPA, granulomatosis with polyangiitis; EGPA, Eosinophilic Granulomatosis with Polyangiitis; PAN, polyarteritis nodosa; GCA, Giant Cell Arteritis; IgG4, immunoglobulin type 4.

Figure 5

Proposed strategy for dealing with suspected inflammatory diseases of the breast. CBC, complete blood count; CRP, C-reactive protein; SPE, serum protein electrophoresis; HIV, human deficiency virus; HBV, hepatitis B virus; ANCA, Anti-neutrophil cytoplasm antibodies; ANA, antinuclear antibodies; ENA, extractable nuclear antigens; SSa, anti-Sjögren’s syndrome related antigen A antibody; ACE, angiotensin-converting enzyme.