DOI: 10.1148/rg.252045077
RadioGraphics 2005;25:411-424
© RSNA, 2005
Radiologic Evaluation of Uncommon Inflammatory and Reactive Breast Disorders1
Josep M. Sabaté, MD,
Montse Clotet, MD,
Antonio Gómez, MD,
Pilar De las Heras, MD,
Sofia Torrubia, MD and
Teresa Salinas, MD
1 From the Unit of Breast Imaging, Department of Diagnostic Radiology, Hospital de Sant Pau, Avda Sant Antoni Maria Claret 167, Barcelona 08025, Spain (J.M.S., M.C., A.G., S.T., T.S.); and the Departments of Breast Imaging (J.M.S., A.G.) and Breast Pathology (P.D.l.H.), CEDIMMA, Barcelona, Spain. Presented as an education exhibit at the 2003 RSNA Scientific Assembly. Received April 19, 2004; revision requested June 16 and received July 30; accepted August 5. All authors have no financial relationships to disclose.
Address correspondence to J.M.S. (e-mail: jsabate{at}hsp.santpau.es).
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Abstract
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The radiologic features of breast lesions caused by immunologic, reactive, and noncurrent infectious diseases often mimic those of malignancy, frequently constituting a diagnostic challenge even if the underlying disease is known. Churg-Strauss syndrome mimics carcinomatous mastitis. Amyloidosis usually manifests as a suspicious mass, often accompanied by microcalcifications. Wegener granulomatosis and sarcoidosis often manifest as irregular masses, although sarcoidosis can also manifest as round, well-defined masses reflecting intramammary node involvement. Diabetic mastopathy is a rare but well-known entity in patients with long-standing insulin-dependent diabetes. Breast involvement by necrobiotic xanthogranulomatosis is rare and manifests as multiple bilateral asymmetric lesions. Multiple clustered hypoechoic tubular structures in a large hypoechoic mass seen after pregnancy can be suggestive of granulomatous mastitis. Mammary tuberculosis can manifest with a nodular, diffuse, or sclerosing pattern. A granulomatous inflammatory reaction must be carefully evaluated because it constitutes the major feature of a diverse group of diseases that includes vasculitis, granulomatous mastitis, tuberculosis, and carcinoma-associated sarcoidlike reactions. Core biopsy can play a major role in developing a differential diagnosis for these rare immunologic, inflammatory, or infectious disorders affecting the breast, and knowledge of these entities can, in the appropriate clinical setting, help the radiologist narrow the differential diagnosis, although cancer must be excluded definitively.
© RSNA, 2005
Abbreviations: FNA = fine-needle aspiration, H-E = hematoxylin-eosin
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Identify uncommon breast disorders that can simulate breast carcinoma and lead to misdiagnosis.
- Describe the most diagnostically relevant clinicopathologic features of these disorders.
- Discuss the most common radiologic manifestations of each disorder and the value of different diagnostic procedures.
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Introduction
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Breast involvement by inflammatory or noncurrent infectious diseases is rare. The breast lesions caused by these disorders often clinically resemble a carcinoma; therefore, they constitute a diagnostic dilemma and usually require biopsy (1,2). In this article, we present the radiologic features and briefly describe the most relevant clinical and pathologic features of several of these uncommon diseases. Knowledge of these rare entities may be helpful in diagnosis and clinical management, pointing toward the simplest and most precise diagnostic techniques.
We classified these entities into four groups according to their respective causes (Table). The first group is composed of disorders with a clear, recognized immunologic status such as Churg-Strauss syndrome, amyloidosis, Wegener granulomatosis, sarcoidosis, and diabetic mastopathy. The second group includes necrobiotic xanthogranulomatosis and granulomatous mastitis, inflammatory entities in which an immunologic cause is suspected but has not been confirmed. The third group consists of radiologic manifestations of those infections that rarely involve the breast; we focus on M tuberculosis. The fourth group consists of vascular disorders; we focus on thrombophlebitis of the subcutaneous mammary veins, also known as Mondor disease.
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Immunologic Diseases
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Churg-Strauss Syndrome
Churg-Strauss syndrome is a very uncommon condition characterized by asthma, pulmonary disease, eosinophilia, and necrotizing vasculitis. The cause of Churg-Strauss syndrome remains unknown, although the disease has classically been considered an immunoallergic disorder. Churg-Strauss syndrome almost invariably affects asthmatic patients. According to the first reported series, the disease was characterized by three major histologic criteria: vasculitis, tissue infiltration of eosinophils, and extravascular granulomas (3). However, more recent series have shown that these components do not always coexist (4,5).
The lung is the most commonly involved organ, followed by the skin and the nervous system. Approximately 70% of affected patients have abnormal chest radiographic findings, usually consisting of transient, patchy airspace consolidations with predominance at the periphery. The heart and the gastrointestinal tract are often involved. Lymphadenopathy has also been described (4–7).
In the present case—to our knowledge, the very first reported case—mammographic findings consisted of a diffuse increase in parenchymal density with skin thickening (Fig 1). However, these findings are nonspecific because they can also be seen in numerous other common disorders such as current mastitis, edema, lymphoma, and inflammatory carcinoma. It is of interest that fine-needle aspiration (FNA) cytologic analysis was diagnostic, demonstrating large numbers of eosinophils and ductal cellularity. The dramatic response to steroids was documented with mammography, which showed complete resolution of the earlier radiologic findings (7).
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Figure 1a. Churg-Strauss syndrome in a 32-year-old woman with clinically suspected bilateral mastitis. The diagnosis of Churg-Strauss syndrome had been established 19 years earlier on the basis of asthma, fever, purpuric cutaneous disease, tachycardia, lung disease, blood eosinophilia, and findings at transbronchial biopsy. (a) Right mediolateral mammogram shows a diffuse increase in parenchymal density. (b) Photomicrograph (original magnification, x400; hematoxylin-eosin [H-E] stain) reveals an inflammation-rich eosinophilic process (arrows) with extensive ductal cellularity (*). (c) Right mediolateral mammogram obtained after corticosteroid therapy demonstrates almost complete resolution of breast involvement.
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Figure 1b. Churg-Strauss syndrome in a 32-year-old woman with clinically suspected bilateral mastitis. The diagnosis of Churg-Strauss syndrome had been established 19 years earlier on the basis of asthma, fever, purpuric cutaneous disease, tachycardia, lung disease, blood eosinophilia, and findings at transbronchial biopsy. (a) Right mediolateral mammogram shows a diffuse increase in parenchymal density. (b) Photomicrograph (original magnification, x400; hematoxylin-eosin [H-E] stain) reveals an inflammation-rich eosinophilic process (arrows) with extensive ductal cellularity (*). (c) Right mediolateral mammogram obtained after corticosteroid therapy demonstrates almost complete resolution of breast involvement.
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Figure 1c. Churg-Strauss syndrome in a 32-year-old woman with clinically suspected bilateral mastitis. The diagnosis of Churg-Strauss syndrome had been established 19 years earlier on the basis of asthma, fever, purpuric cutaneous disease, tachycardia, lung disease, blood eosinophilia, and findings at transbronchial biopsy. (a) Right mediolateral mammogram shows a diffuse increase in parenchymal density. (b) Photomicrograph (original magnification, x400; hematoxylin-eosin [H-E] stain) reveals an inflammation-rich eosinophilic process (arrows) with extensive ductal cellularity (*). (c) Right mediolateral mammogram obtained after corticosteroid therapy demonstrates almost complete resolution of breast involvement.
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Amyloidosis
Amyloidosis can be classified into systemic and localized forms as well as into different types, including primary, secondary, heredofamilial, endocrine, and senile amyloidosis (1,8). Breast involvement is rare and is usually a late manifestation of a previously diagnosed underlying disease in patients in whom diffuse visceral amyloid depositions are known (1). Localized amyloidosis of the breast is a very rare manifestation (8–10).
At pathologic analysis, amyloid deposition is found around ducts and blood vessels and within lobules, leading to atrophy and obliteration of these glandular components. It is easily demonstrated with Congo red stain. Amyloid deposits may lead to focal calcification or a foreign body–like reaction with multinucleate giant cells. FNA cytologic analysis may be useful in the preliminary diagnosis of the disease, although histologic analysis is mandatory. Interestingly, given that amyloid has been detected in the stroma of breast carcinoma, malignancy must be adequately ruled out (1,8).
Breast involvement usually manifests clinically in elderly women as a suspicious solitary firm or hard tumor, although multiple and bilateral lesions have also been described. The most common mammographic findings are irregular or spiculated masses, often accompanied by irregular or amorphous microcalcifications, leading to the radiologic diagnosis of carcinoma (Fig 2) (9). In addition, two other rare manifestations have been reported: a suspicious focus of clustered microcalcifications at routine screening mammography (10,11), and diffuse infiltration of the mammary gland mimicking an inflammatory carcinoma with skin thickening (12). The coexistence of mammary amyloidosis and breast cancer has also been described (12).
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Figure 2a. Amyloidosis of the breast. (a) Mammogram shows an ill-defined lobular mass with microcalcifications and large calcifications. The patient underwent needle localization and surgical excision. (b) Photomicrograph (original magnification, x10; H-E stain) shows diffuse deposits of dense amorphous material (*) surrounding ductal structures (arrows).
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Figure 2b. Amyloidosis of the breast. (a) Mammogram shows an ill-defined lobular mass with microcalcifications and large calcifications. The patient underwent needle localization and surgical excision. (b) Photomicrograph (original magnification, x10; H-E stain) shows diffuse deposits of dense amorphous material (*) surrounding ductal structures (arrows).
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Wegener Granulomatosis
Wegener granulomatosis is a necrotizing granulomatous vasculitis that characteristically affects the upper and lower respiratory tracts and kidneys. The skin, joints and muscles, eyes, and peripheral nervous system are also often involved (13,14). Breast involvement by this uncommon disease is rare, with very few cases having been described. Wegener granulomatosis is usually found in patients with well-known systemic manifestations; thus, primary breast involvement can be considered exceptional (13).
Clinical manifestations usually mimic carcinoma, although most tumors are described as tender (13–16). Mammographic findings have been reported as ill-defined or irregular masses that are suspicious for carcinoma (Fig 3) (16). Findings at FNA cytologic analysis can suggest the diagnosis in the appropriate setting, although biopsy is required to demonstrate the particular pathologic findings. Mammography clearly helps evaluate tumor response after appropriate treatment with steroids and immunosuppressive drugs (16).
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Figure 3a. Wegener granulomatosis in a post-menopausal woman with well-known systemic disease. The diagnosis was confirmed at subsequent core-needle biopsy. (a) Mammogram shows a suspicious focal asymmetric density (arrowheads). (b) Ultrasonographic (US) image demonstrates an irregular hypoechoic mass. (c) Photomicrograph (original magnification, x400; H-E stain) reveals a severe inflammatory reaction with numerous eosinophils and a prominent granulomatous component.
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Figure 3b. Wegener granulomatosis in a post-menopausal woman with well-known systemic disease. The diagnosis was confirmed at subsequent core-needle biopsy. (a) Mammogram shows a suspicious focal asymmetric density (arrowheads). (b) Ultrasonographic (US) image demonstrates an irregular hypoechoic mass. (c) Photomicrograph (original magnification, x400; H-E stain) reveals a severe inflammatory reaction with numerous eosinophils and a prominent granulomatous component.
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Figure 3c. Wegener granulomatosis in a post-menopausal woman with well-known systemic disease. The diagnosis was confirmed at subsequent core-needle biopsy. (a) Mammogram shows a suspicious focal asymmetric density (arrowheads). (b) Ultrasonographic (US) image demonstrates an irregular hypoechoic mass. (c) Photomicrograph (original magnification, x400; H-E stain) reveals a severe inflammatory reaction with numerous eosinophils and a prominent granulomatous component.
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Sarcoidosis
Sarcoidosis is an immunologic disease that may affect the lungs, lymph nodes, skin, spleen, and liver. Breast involvement is very rare, accounting for less than 1% of cases, and generally occurs in patients with well-known systemic involvement (17,18). Primary breast involvement can be considered exceptional (19). Sarcoidosis of the breast, like that involving other anatomic structures, generally manifests in women in the 3rd and 4th decades of life. Sarcoidosis manifests clinically as firm to hard masses, often mimicking carcinoma (17,18).
Breast involvement may result from intrinsic parenchymal involvement by the granulomatous inflammatory process or from lymph node enlargement. The inflammatory process is characterized by epithelioid granulomas that form nodules among lobules and ducts. Multinucleate Langhans giant cells may form Schaumann bodies. Caseous necrosis, calcifications, and fat necrosis are not found (19,20). Nonnecrotizing sarcoidlike granulomatous inflammation accompanying carcinoma and certain specific infections such as tuberculosis must be adequately excluded (21).
At mammography, breast sarcoidosis has been described as irregular or ill-defined, often spiculated masses that are suspicious for carcinoma, although small, well-defined round masses have also been described (Fig 4). The latter finding may in some cases represent intramammary lymph node involvement. Calcifications are absent. US findings are also indicative of malignancy, with irregular hypoechoic masses being the most common. Variable appearances, both benign and malignant, have also been described at magnetic resonance (MR) imaging (17,18,22).
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Figure 4a. Sarcoidosis in a 47-year-old woman who presented with a palpable mass. Systemic disease had been diagnosed 5 years earlier. (a) Mammogram of the right breast shows a round mass with well-circumscribed margins in the upper outer quadrant. (b) Photomicrograph (original magnification, x600; H-E stain) shows nonnecrotizing granulomatous inflammation involving a lobule.
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Figure 4b. Sarcoidosis in a 47-year-old woman who presented with a palpable mass. Systemic disease had been diagnosed 5 years earlier. (a) Mammogram of the right breast shows a round mass with well-circumscribed margins in the upper outer quadrant. (b) Photomicrograph (original magnification, x600; H-E stain) shows nonnecrotizing granulomatous inflammation involving a lobule.
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Diabetic Mastopathy
Earlier studies have described diabetic mastopathy as being characterized by the presence of benign breast masses in women with long-standing insulin-dependent diabetes (23,24). Although diabetic mastopathy is a rare disease, it has been found in up to 13% of these patients (25). It has also been reported in men (26).
At pathologic analysis, diabetic mastopathy is characterized by a perilobar and perivascular lymphocytic infiltrate of mature B cells accompanied by intense keloidal fibrosis of the stroma with lobular atrophy and characteristic myofibroblastic epithelioid cells (23,24). These pathologic changes appear to be relatively specific for insulin-dependent diabetes mellitus but may also be seen in nondiabetic patients. For this reason, the pathologic features of diabetic mastopathy can be included in a more general pathologic entity called lymphocytic mastopathy that has been described in association with certain immunologic diseases such as Hashimoto thyroiditis, Sjögren syndrome, and lupus erythematosus (27,28).
Diabetic mastopathy manifests clinically as a large, painless, hard breast mass that is usually indistinguishable from breast cancer. Multicentric or bilateral involvement is a relatively frequent phenomenon, often occurring in late stages of the disease (25,29).
The most common mammographic findings are ill-defined masses or asymmetric densities. Such lesions are often masked by dense glandular tissue, making mammographic evaluation difficult. US often reveals the most characteristic imaging findings of the disease: irregular hypoechoic masses with marked posterior acoustic shadowing (Fig 5) (25,26,30–32). Less typical manifestations include well-circumscribed masses and slightly hypoechoic masses without acoustic shadowing (33). These less common manifestations are often seen in the initial stages of the disease, when the pathologic degree of fibrosis is usually lower; in contrast, previous studies have described fibrosis as being dominant in more advanced stages (27). Reported MR imaging findings are variable, ranging from decreased diffuse contrast material enhancement to rapid, intense enhancement that is indistinguishable from breast carcinoma (29,31).
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Figure 5a. Diabetic mastopathy in a 26-year-old woman with long-standing insulin-dependent type 1 diabetes mellitus who presented with a palpable mass. (a) Craniocaudal mammogram of the left breast shows subtle foci of asymmetric density in the outer quadrant at the location of the palpable mass (arrows). (b) US image reveals an irregular hypoechoic mass with ill-defined margins and discrete acoustic shadowing. (c) Photomicrographs (original magnification, x400 [left] and x200 [right]; H-E stain) reveal extensive collagenous stromal fibrosis (*) accompanied by the characteristic perivascular (left) and periductal (right) lymphocytic inflammatory infiltration.
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Figure 5b. Diabetic mastopathy in a 26-year-old woman with long-standing insulin-dependent type 1 diabetes mellitus who presented with a palpable mass. (a) Craniocaudal mammogram of the left breast shows subtle foci of asymmetric density in the outer quadrant at the location of the palpable mass (arrows). (b) US image reveals an irregular hypoechoic mass with ill-defined margins and discrete acoustic shadowing. (c) Photomicrographs (original magnification, x400 [left] and x200 [right]; H-E stain) reveal extensive collagenous stromal fibrosis (*) accompanied by the characteristic perivascular (left) and periductal (right) lymphocytic inflammatory infiltration.
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Figure 5c. Diabetic mastopathy in a 26-year-old woman with long-standing insulin-dependent type 1 diabetes mellitus who presented with a palpable mass. (a) Craniocaudal mammogram of the left breast shows subtle foci of asymmetric density in the outer quadrant at the location of the palpable mass (arrows). (b) US image reveals an irregular hypoechoic mass with ill-defined margins and discrete acoustic shadowing. (c) Photomicrographs (original magnification, x400 [left] and x200 [right]; H-E stain) reveal extensive collagenous stromal fibrosis (*) accompanied by the characteristic perivascular (left) and periductal (right) lymphocytic inflammatory infiltration.
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FNA cytologic analysis does not often help in the diagnosis of diabetic mastopathy because (a) it usually does not provide sufficient cellular material for evaluation and (b) it is characteristically difficult to perform due to the firmness of the masses and the resistance to the back-and-forth motion required for appropriate aspiration (25,29,30).
Although surgical excision was usually performed in the past to exclude malignancy, core biopsy is currently accepted as adequate for the diagnosis of this disease. In fact, core biopsy is a reliable method for establishing the diagnosis in the proper clinical setting and can eliminate the need for more aggressive procedures such as surgical biopsy. Furthermore, it has recently been reported that surgery may increase the number and extent of recurrences (29).
Diabetic mastopathy is usually a self-limited disease that does not require treatment, although recurrences are common (25,29). Despite the pathologic similarities with other lymphoepithelial lesions involving other glands (eg, Sjögren syndrome, Hashimoto thyroiditis), to our knowledge, no increased prevalence of breast lymphoma has been reported to date (28).
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Inflammatory Diseases of Unknown Origin
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Necrobiotic Xanthogranulomatosis
Necrobiotic xanthogranulomatosis is a very rare disorder. It was first described in 1980 (34) and was included in the heterogeneous group of diseases known as histiocytic infiltrates or "non-X histiocytoses." At pathologic analysis, the disease is characterized by the presence of extensive areas of necrobiosis and granulomatous foci composed of histiocytes, foam and xanthic cells, and multi-nucleate giant cells of both the Touton and foreign-body type (35).
Necrobiotic xanthogranulomatosis is characterized by multiple sharply demarcated nodules and large indurated plaques that are often associated with hard nodules in the subcutaneous fascia elsewhere in the body. There is a predilection for the periorbital area, but other areas of the face, as well as the trunk and limbs, are often involved. Visceral involvement can develop, and the most frequent complications are hematologic and ophthalmic in nature. Paraproteinemia is almost always present (35).
To our knowledge, our case is the only reported case of breast involvement that manifested as multiple and bilateral asymmetric densities at mammography and as hypoechogenic foci with a "teardrop" or wavelike configuration at US (Fig 6).
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Figure 6a. Necrobiotic xanthogranulomatosis diagnosed with screening mammography in a 68-year-old woman. (a) Bilateral mammograms show multiple ill-defined asymmetric densities involving both breasts (arrows). (b) Bilateral US images demonstrate multiple solid hypoechoic masses with a teardrop or wavelike configuration. (c) Photomicrographs (original magnification, x400 [left, upper right] and x200 [lower right]; H-E stain) show an extensive area of central necrosis (*) surrounded by an inflammatory process with xanthic cells (arrows) and giant Touton cells (arrowhead).
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Figure 6b. Necrobiotic xanthogranulomatosis diagnosed with screening mammography in a 68-year-old woman. (a) Bilateral mammograms show multiple ill-defined asymmetric densities involving both breasts (arrows). (b) Bilateral US images demonstrate multiple solid hypoechoic masses with a teardrop or wavelike configuration. (c) Photomicrographs (original magnification, x400 [left, upper right] and x200 [lower right]; H-E stain) show an extensive area of central necrosis (*) surrounded by an inflammatory process with xanthic cells (arrows) and giant Touton cells (arrowhead).
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Figure 6c. Necrobiotic xanthogranulomatosis diagnosed with screening mammography in a 68-year-old woman. (a) Bilateral mammograms show multiple ill-defined asymmetric densities involving both breasts (arrows). (b) Bilateral US images demonstrate multiple solid hypoechoic masses with a teardrop or wavelike configuration. (c) Photomicrographs (original magnification, x400 [left, upper right] and x200 [lower right]; H-E stain) show an extensive area of central necrosis (*) surrounded by an inflammatory process with xanthic cells (arrows) and giant Touton cells (arrowhead).
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Granulomatous Mastitis
Granulomatous mastitis is a very rare inflammatory disease of unknown origin that can clinically mimic carcinoma (36–38). Immunologic factors have been postulated as possible causes; however, the absence of vasculitis or of a prominent lymphocytic component in pathologic specimens mitigates against this hypothesis (39,40).
The diagnosis of granulomatous mastitis is based on exclusion, since it depends on the demonstration of a particular histologic pattern combined with the exclusion of other granulomatous reactions such as sarcoidosis, Wegener granulomatosis, and especially tuberculosis, fungal infections, and those other benign inflammatory disorders found in association with carcinomas (1,39,40). At pathologic analysis, granulomatous mastitis manifests as a noncaseating, nonvasculitic granulomatous inflammatory reaction centered on lobules. Fat necrosis, abscess formation, and fibrosis are commonly associated end-stage features that can disrupt the normal lobular anatomy (1,39,40).
Granulomatous mastitis generally manifests as a distinct, firm to hard mass that may involve any part of the breast but tends to spare the subareolar regions. The relationship of granulomatous mastitis to pregnancy or lactation has been strongly emphasized because this disease entity typically affects younger women, usually within 6 years of pregnancy (36,41). Reactive lymphadenopathy may be present in up to 15% of patients (37,39,41).
The mammographic features are variable, ranging from normal findings in patients with dense breasts to masses with benign or malignant features and focal asymmetric density, the most frequently described abnormality. The US appearance of multiple clustered, often contiguous hypoechoic tubular lesions is sometimes associated with a large, hypoechoic mass and has been considered suggestive of the disease, although the latter feature is not always found (Fig 7) (36–39).
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Figure 7a. Granulomatous mastitis in a 35-year-old woman 2 years after pregnancy. (a) Mammogram of the left breast shows a subtle asymmetric density in the upper outer quadrant at the location of the palpable mass (arrows). (b) US image reveals a heterogeneously hypoechoic tubular mass with ill-defined margins surrounded by hyperechoic boundaries. (c) Photomicrograph (original magnification, x200; H-E stain) shows lobular lymphocytic inflammatory infiltrate with abundant multinucleate histiocytes centrally.
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Figure 7b. Granulomatous mastitis in a 35-year-old woman 2 years after pregnancy. (a) Mammogram of the left breast shows a subtle asymmetric density in the upper outer quadrant at the location of the palpable mass (arrows). (b) US image reveals a heterogeneously hypoechoic tubular mass with ill-defined margins surrounded by hyperechoic boundaries. (c) Photomicrograph (original magnification, x200; H-E stain) shows lobular lymphocytic inflammatory infiltrate with abundant multinucleate histiocytes centrally.
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Figure 7c. Granulomatous mastitis in a 35-year-old woman 2 years after pregnancy. (a) Mammogram of the left breast shows a subtle asymmetric density in the upper outer quadrant at the location of the palpable mass (arrows). (b) US image reveals a heterogeneously hypoechoic tubular mass with ill-defined margins surrounded by hyperechoic boundaries. (c) Photomicrograph (original magnification, x200; H-E stain) shows lobular lymphocytic inflammatory infiltrate with abundant multinucleate histiocytes centrally.
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The prognosis is good, although local recurrence has been reported. Primary treatment consists of excisional biopsy. Corticosteroid therapy has also proved effective (36–38).
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Specific Infections
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Mycobacterial, fungal, and parasitic infections, although rare, can affect the breast, inducing an inflammatory, commonly granulomatous reaction that can be observed both clinically and radiologically.
Among parasitic infections, filariasis has been described as serpiginous calcifications associated with a mass (42), schistosomiasis as calcifications with mild architectural distortion (43), sparganosis as a lobulated mass with irregular contours (44), and echinococcosis as a dense, well-circumscribed mass at mammography with a heterogeneous, complex cystic appearance at US (45,46).
Among fungal infections, actinomycosis has been described as a lobulated mass with irregular borders with skin thickening closely mimicking malignancy (47). Blastomycosis manifests as a partially circumscribed subcutaneous mass or bilateral masses with well-defined contours at mammography and a complex cystic structure at US (48,49).
M tuberculosis infections are a serious clinical problem in undeveloped countries (50). In Western countries, socioeconomic and medical progress has led to a dramatic decline in the prevalence of these infections, although at the beginning of the past decade there was a slight increase in disease prevalence in association with immunodepression, especially in patients infected with human immunodeficiency virus (51).
Tuberculous mastitis as the primary manifestation of the disease is rare. It is considered likely that breast infection is secondary in most patients, although the primary focus can remain clinically unapparent. The most frequent mode of infection is retrograde spread from axillary nodes, followed by direct extension from contiguous structures such as the chest wall. Retrograde spread from cervical or internal mammary lymph nodes is possible. Hematogenous dissemination is another cause of infection and has been observed in acquired immunodeficiency syndrome patients with miliary breast involvement. Direct inoculation of the nipple via the lactiferous ducts may account for some pregnancy-related infections (51,52).
Most patients present with a hard, painless lump in the breast that is often indistinguishable from carcinoma. Up to 50% of patients have axillary node enlargement. Premenopausal women are often affected, and there may be a predilection for women who are lactating (52,53). Male involvement is rare (53).
The radiologic manifestations of mammary tuberculosis can be classified into three distinct patterns: nodular, diffuse, and sclerosing. Tuberculosis of the nodular type manifests as an ill-defined or irregular mass that closely resembles carcinoma (Fig 8). Skin bulging and one or more sinus tracts are considered to be suggestive of the disease. Findings of a diffuse type simulate inflammatory carcinoma with skin thickening (Fig 9). The sclerosing type, which usually affects elderly women, manifests as dense breast tissue, sometimes associated with areas of architectural distortion (Fig 10) (52,53,55,56). US can be useful in the evaluation of the internal cystic, solid, or complex structure of the masses and can help identify a fistula or sinus tract (55,57). Large, dense, calcified axillary nodes can be demonstrated with appropriate axillary views and are considered to be suggestive of the disease (Fig 9b). CT and MR imaging can better depict direct or contiguous involvement of adjacent anatomic regions such as the chest wall (52,57). The coexistence of mammary tuberculosis and breast carcinoma has been described (Fig 11).
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Figure 8a. M tuberculosis of the breast (nodular type) in a 45-year-old woman with a previous history of pulmonary tuberculosis. (a) Mammogram of the left breast shows a lobular mass with indistinct margins (although the mass is partially well defined) in the inner quadrant. The patient underwent surgical biopsy. (b) Photomicrograph (original magnification, x200; H-E stain) shows extensive granulomatous inflammation with epithelioid and Langhans giant cells. Foci of necrosis are seen in one of these granulomas (*).
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Figure 8b. M tuberculosis of the breast (nodular type) in a 45-year-old woman with a previous history of pulmonary tuberculosis. (a) Mammogram of the left breast shows a lobular mass with indistinct margins (although the mass is partially well defined) in the inner quadrant. The patient underwent surgical biopsy. (b) Photomicrograph (original magnification, x200; H-E stain) shows extensive granulomatous inflammation with epithelioid and Langhans giant cells. Foci of necrosis are seen in one of these granulomas (*).
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Figure 9a. M tuberculosis of the breast (diffuse type) in a 47-year-old woman with a 9-year history of systemic tuberculous disease. (a) Mammogram shows a diffuse lymphatic pattern, with thickening of the Cooper ligaments and superficial fascia. (b) Axillary mammogram demonstrates calcified nodes, a finding that is highly suggestive of tuberculosis in the appropriate clinical setting (as in this case).
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Figure 9b. M tuberculosis of the breast (diffuse type) in a 47-year-old woman with a 9-year history of systemic tuberculous disease. (a) Mammogram shows a diffuse lymphatic pattern, with thickening of the Cooper ligaments and superficial fascia. (b) Axillary mammogram demonstrates calcified nodes, a finding that is highly suggestive of tuberculosis in the appropriate clinical setting (as in this case).
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Figure 10. M tuberculosis of the breast (sclerosing type) in a 64-year-old woman with a previous history of pulmonary tuberculosis. The patient presented with a palpable, painful mass, with marked glandular and cutaneous retraction. Mammogram shows a central asymmetric mass with architectural distortion and secondary nipple and cutaneous retraction.
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Figure 11. Mammary and chest wall tuberculosis and breast carcinoma in a 64-year-old woman. Mammogram of the left breast reveals a mass involving the posterior region of the breast secondary to chest wall tuberculosis. FNA cytologic analysis was performed (arrow indicates needle) and helped confirm that the mass was a result of chest wall tuberculosis. In addition, a small focus of architectural distortion was found in the outer quadrant (circle) that corresponded to an invasive ductal carcinoma. Square outlines a magnified view of the area of architectural distortion.
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The diagnosis of mammary tuberculosis is often difficult and is usually based on inflammatory and granulomatous findings at FNA cytologic analysis or biopsy. Acid-fast bacteria are not detected in most cases; in addition, cultures develop slowly and are not always demonstrative (1,51, 52).
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Vascular Disorders (Mondor Disease)
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Mondor disease is a rare, usually self-limited thrombophlebitis of the subcutaneous veins of the breast. It has commonly been related to trauma, physical exertion, and surgery (58), and up to 12% of cases are associated with carcinoma (59). About 25% of cases involve men (58). Antibiotic and anticoagulant therapy are rarely necessary, and there is occasionally evidence of associated deep venous thrombosis (58).
Diagnosis is usually established clinically on the basis of the presence of a characteristic painful, tender, palpable cordlike structure, generally located on the lateral aspect of the breast (58,60). At mammography, the thrombosed vein may appear to be linear, ropelike, or tubular. Rarely, the vein calcifies. Tangential views demonstrate the superficial position of the involved vein. At US, the vein appears as a superficial tubular structure filled with low-level internal echoes, a finding that reflects the thrombotic phenomenon (Fig 12) (60,61).
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Figure 12a. Mondor disease in a 35-year-old woman who presented with the characteristic clinical finding of a palpable, painful cordlike structure on the lateral aspect of the breast. (a) Mammogram of the left breast shows a superficial linear density in the outer quadrants (arrows) corresponding to the cordlike area seen at clinical examination. (b) US image reveals an echogenic tubular structure corresponding to the thrombophlebitic vein.
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Figure 12b. Mondor disease in a 35-year-old woman who presented with the characteristic clinical finding of a palpable, painful cordlike structure on the lateral aspect of the breast. (a) Mammogram of the left breast shows a superficial linear density in the outer quadrants (arrows) corresponding to the cordlike area seen at clinical examination. (b) US image reveals an echogenic tubular structure corresponding to the thrombophlebitic vein.
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Conclusions
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The breast may occasionally be involved by certain immunologic or inflammatory diseases or by specific infections that usually manifest with radiologic features resembling malignancy. Knowledge of these entities can, in the appropriate clinical setting, lead the radiologist to consider these entities as possible diagnoses, but cancer must be excluded. Core biopsy can play a major role in the diagnostic process, helping obviate more invasive procedures such as surgical biopsy.
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Acknowledgments
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The authors wish to thank our nurses, Maria Valls and Montserrat Valdearcos, for their expert assistance in daily clinical practice, and Carolyn Newey for her editorial support.
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Abstract
LEARNING OBJECTIVES
