Inflammatory breast disease: A pictorial essay with radiological-pathological correlation

Introduction

Inflammatory breast diseases are an uncommon group of diseases with clinical and radiological features that may resemble breast carcinoma.1 This may lead to a diagnostic conundrum necessitating histological confirmation. This pictorial essay illustrates a number of unusual inflammatory breast conditions encountered in a busy multidisciplinary breast service.

Non-puerperal subareolar breast abscess

Non-puerperal subareolar breast abscess accounts for 1–2% of all symptomatic breast conditions. It is a recurring disease with a strong link to obesity, diabetes and cigarette smoking.1 This is also known as squamous metaplasia of lactiferous ducts (SMOLD).2 It begins with squamous metaplasia of the cuboidal epithelium lining the main duct, leading to keratin plug formation and subsequent blockage. The ducts can then rupture, with secretions spilling out into the breast parenchyma and inciting an inflammatory reaction.3 On mammography, skin thickening and a mass beneath the nipple is expected. Ultrasound will demonstrate a mixed echogenic mass with central cystic components. Marked Doppler colour flow is seen at the periphery, indicative of increased vascularity (Fig. 1).

Mammary duct ectasia

Mammary duct ectasia, also known as plasma cell mastitis is usually seen in elderly women who present with nipple retraction, discharge and, on occasion, a palpable mass.4 Ultrasound shows dilated ducts (>2 mm in diameter) containing echogenic debris with increased colour Doppler flow in the periductal breast tissue.1 This can be an incidental finding on mammography, demonstrating characteristic dense, uniform needle-like calcifications, arranged in lines radiating from the nipple, due to calcified inspissated contents within the duct (Fig. 2). Histologically, ducts are ectatic with denuded epithelium, numerous foam cells or granular debris in the lumen with large calcified particles in the thickened, sclerotic duct wall (Fig. 3). Inflammation surrounding ducts varies with the stage of the disease and whether the duct has ruptured, but may be prominent early in the disease and minimal in the late stage. The end stage is obliterative mastopathy, where the ducts are entirely replaced by fibrosis.

Granulomatous mastitis

Granulomatous mastitis (GM) is a rare inflammatory condition seen in young women. It can be idiopathic or secondary to an extensive array of conditions including infections (caused by bacteria, parasites or fungi), connective tissue disorders and sarcoidosis.1 In dense breast of young patients, mammography may show an asymmetry while in fatty breasts a discrete mass may be noted. On ultrasound, GM is described in its early stages as being ill-defined with heterogeneous masses associated with acoustic shadowing.5 Later, interconnecting abscesses may develop. On histology, GM is characterized by the presence of granulomata with macrophages, multinucleated giant cells and variable numbers of lymphocytes, plasma cells and neutrophils. Necrotizing granulomata are common in infections, rare in idiopathic GM and not present in non-infectious granulomatous diseases.6

Idiopathic granulomatous mastitis

A diagnosis of Idiopathic GM is made when the typical radiological and histological features are identified and secondary causes of GM are excluded. Histopathology shows well-formed non-caseating granulomata with epithelioid macrophages and Langhans-type multinucleated giant cells (Fig. 4). Epithelioid macrophages often associated with plasma cells, lymphocytes and neutrophils, can occur around lobules and ducts without well-formed granulomata. Fibrosis is not prominent while necrosis is rare.6

Infectious granulomatous mastitis

Tuberculous (TB) mastitis is a rare extra-pulmonary manifestation caused by Mycobacterium tuberculosis. The gold standard for diagnosing TB mastitis is the visualization of acid-fast bacilli with a Ziehl-Neelsen stain or by culture. Due to the low diagnostic yield of microscopy and culture, some authors indicate that the diagnosis can be made when a high level of clinical suspicion is backed by a combination of immunological testing as polymerase chain reaction (PCR) and characteristic histopathology.7

Tuberculous mastitis is described in three forms as nodular, disseminated or sclerosing. Biopsies show well-formed necrotizing or non-necrotizing granulomata with epithelioid macrophages and Langhans-type multinucleated giant cells occurring more often around ducts than lobules and often associated with lymphocytes and eosinophils with few plasma cells (Fig. 5). Fibrosis may be prominent.6

Another form of infectious granulomatous mastitis is caused by gram-positive bacilli of the Corynebacterium species. According to Paviour,8 the most commonly associated species is Corynebacterium kroppenstedtii. The bacilli are noted within cystic vacuoles but may not be found in cultures due to their fastidious nature.1 (Fig. 6).

Granulomatosis with polyangitis (Wegener's Granulomatosis)

Granulomatosis with polyangitis is a systemic inflammatory disease predominantly with lung and kidney involvement. Rarely can it manifest in the breast (Fig. 7). The diagnosis is dependent on the presence of systemic disease and/or positive serological (p-ANCA, c-ANCA/PR3-ANCA) tests and histological features.6 Histopathology of the breast may show numerous multinucleated giant cells with foamy cytoplasm, plasma cells and lymphocytes and scattered neutrophils and eosinophils surrounding lobules and ducts and small blood vessels. Multiple foci of necrosis are usually seen within the stroma.

Diabetic mastopathy

Diabetic mastopathy (DM) is seen in women with long-standing type 1 or type 2 diabetes.9 On mammography DM presents as an asymmetric parenchymal density while on ultrasound the lesions are noted to have strong to variable degrees of acoustic shadowing mimicking a malignant lesion (Fig. 8).10 The histology shows ill-defined dense collagenous interlobular fibrosis sometimes with keloidal features and with prominent fibroblasts and often with epitheloid myofibroblasts. Perivascular intralobular and periductal lymphocytic infiltrates are common. Lobules are atrophic with intralobular fibrosis.11 If a core biopsy shows the characteristic histological features, these lesions can be managed with imaging follow-up to minimize excision biopsies.

Lymphocytic mastitis

Lymphocytic mastitis is similar to diabetic mastopathy and is found in non-diabetic patients who may have other autoimmune diseases (Figs 9,10).12

Fat necrosis

Fat necrosis of the breast accounts for 2.75% of all benign breast lesions and is associated with minor trauma, breast surgery and radiotherapy.13 Clinical presentation can vary from an asymptomatic screen-detected lesion to a palpable mass, with overlying skin and nipple changes. Similarly, mammographic and ultrasound features of fat necrosis form a spectrum of completely benign to highly suspicious lesions. Only the suspicious lesions should have pathological confirmation of fat necrosis (Fig. 11). Histopathology shows necrotic fat cells interspersed with foamy histiocytes and multinucleated giant cells with variable numbers of lymphocytes and plasma cells. Peripheral fibrosis may develop and replace the necrotic fat and is often associated with calcification and persisting oil cysts.1 The degree of resultant fibrosis determines the radiological appearance (Fig. 12).14

In conclusion, inflammatory breast diseases can mimic breast cancer clinically and radiologically, and therefore require a core needle biopsy and histological diagnosis. It is important that radiologists are aware of the spectrum of radiological and histopathological findings, to facilitate radiological-pathological concordance. It will help to avoid unnecessary surgery in this group of benign breast diseases, which are neither pre-malignant nor borderline for breast carcinoma.