Benign Inflammatory Conditions of the Breast

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Case Presentation

A 54-year-old African-American woman presented with a history of a persistent palpable lump, pain, and intermittent generalized swelling of the left breast for approximately 7 months. She had not noticed nipple discharge or nipple inversion, and there was no history of previous biopsy. She had no personal or family history of breast cancer. Pertinent obstetrical history included one prior pregnancy with a year of breast feeding. She had no significant past medical history. Upon presentation, work-up included bilateral mammogram and ultrasound (Figures 1-3). An aspirate was obtained, demonstrating no growth after 5 days. Ultimately, an ultrasound-guided biopsy was performed followed by bilateral breast MRI (Figure 4).

Key Clinical Findings

Unilateral or bilateral breast pain and erythema often with an associated palpable lump

Key Imaging Findings

Nonspecific mammographic findings, irregular masses or fluid collections on ultrasound, and masses, nonmass enhancement, sinus tracts, and fluid collections on MRI

Differential Diagnosis

Idiopathic granulomatous mastitis

Abscess

Diabetic mastopathy

Postsurgical fat necrosis

Lupus mastitis

Sarcoid

Mondor’s

Discussion

Inflammatory conditions of the breast include a wide array of causes, which are broadly divided into 3 categories: infectious mastitis, noninfectious inflammatory mastitis and inflammation secondary to underlying breast cancer (inflammatory breast cancer, IBC). There is significant overlap of the clinical and radiologic features of benign mastitis with IBC, which often delays diagnosis and treatment. 

Mastitis refers to inflammation of the breast parenchyma. The most common clinical presentation of mastitis includes pain, redness, warmth, subcutaneous edema and skin thickening. The radiologic features are often nonspecific and can mimic those of IBC. The focus of this paper is benign inflammatory conditions of the breast.

Differential Diagnosis

Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis (IGM) or granulomatous lobular mastitis is an uncommon, benign chronic inflammatory condition, first described in literature by Kessler and Wolloch in 1972.1 The definitive cause is unknown, but an autoimmune reaction is the most postulated etiology, possibly resulting from initial insult to the ductal epithelial cells with leakage of luminal protein secretions into the lobular breast stroma.2 IGM is a diagnosis of exclusion since certain types of breast cancer are included in the malignant differential. IGM usually presents with a recurrent or persistent disease course, resulting in significant patient morbidity. It most commonly affects parous premenopausal women of reproductive age with a history lactation. There is data suggesting a clinical association with hyperprolactinemia.2 It is mostly unilateral and commonly involves the periphery of the breast.

Imaging of IGM is variable with a focal asymmetry as the typical mammographic finding.3 Other less common mammographic findings include an irregular mass and global asymmetry. Skin and trabecular thickening can also be seen. On ultrasound, the most common presentation is an irregular hypoechoic mass with associated duct changes. Occasionally, the sonographic features of IGM may mimic an intraductal papilloma, especially if located in a retroareolar region. MRI findings of IGM most often include clustered ring enhancement and clumped nonmass enhancement (NME). The second most described finding is an enhancing mass with the most common enhancement pattern being rim enhancement. Additional associated features of architectural distortion, focal skin enhancement, skin thickening, sinus tracts, skin ulceration, nipple retraction and axillary lymphadenopathy have also been reported.4

Definitive diagnosis is usually made by histopathology as the clinical and imaging features are nonspecific. Ultrasound-guided core biopsy has higher diagnostic efficacy compared to fine-needle aspiration (FNA), especially in cases of abscess and fat necrosis. On histopathology, IGM is characterized by the presence of noncaseating granulomas with varying degrees of fibrosis around the breast lobules.

There is no definitive treatment for IGM; therefore, treatment should be tailored to each patient’s clinical presentation. The treatment options include conservative measures such as close clinical and imaging surveillance, medication therapy with antibiotics, corticosteroids and/or immunosuppressants such as methotrexate. The more aggressive surgical approach is wide local excision.

Abscess (Puerperal, Nonpuerperal)

One common cause of a tender breast lump is an infected fluid collection or abscess. Most breast abscesses are complications of infectious mastitis. They usually occur in the first 3 months postpartum or at weaning; thus, named puerperal abscesses.5 They are caused by bacteria, most commonly Staphylococcus aureus, that enter through small skin lacerations into stagnant lactiferous ducts. Although less common, nonpuerperal breast abscesses occur from lactiferous stagnation due to ductal obstruction by keratin plugs. Risk factors for the development of nonpuerperal breast abscesses, particularly those in the central breast, include Black race, obesity, and tobacco smoking. Peripheral abscesses are associated with chronic medical conditions, steroids, or recent breast interventions.5 Ultrasound and mammography are typically performed in the evaluation of patients over age 30; however, ultrasound is usually the first-line modality as patients are often in pain. The typical sonographic findings include a hypoechoic fluid collection with increased peripheral vascularity. Edema and hypervascularity of the tissue are also often noted throughout the adjacent breast parenchyma. Ultrasound-guided aspiration and drainage with antibiotic therapy has been found effective in the treatment of both puerperal and nonpuerperal abscesses.6 When outside the peripartum period or when the clinical course is prolonged, underlying inflammatory breast cancer should be considered.5

Postsurgical Fat Necrosis

Another common finding in patients presenting with a tender palpable lump is fat necrosis. Histologically, fat necrosis appears as foamy histiocytes and giant cells that surround lipid vacuoles and adipocytes.7 This can vary based on the time of patient presentation since fat necrosis tends to result from trauma. It occurs after vascular damage causes inflammation in the fatty tissue. There are resultant edematous changes that ensue as the interstitium becomes engorged with fluid. With time, fibrosis can occur, leading to formation of granulation tissue and fibrous scarring. When fat is encapsulated in calcified granulation tissue, an oil cyst results, mammographically presenting as a rim calcification. Prior to calcified oil cysts, fat necrosis may appear as a focal asymmetry, asymmetry, or mass. Sonographically, fat necrosis follows the histologic timeline, initially seen as edema throughout the tissues. This is accompanied by increased echogenicity of the fat or even discrete cyst formation with hyperechoic masses throughout the parenchyma. Later, findings of a cyst with peripheral calcification (oil cyst) or architectural distortion from fibrosis can follow. MRI T2-weighted images may demonstrate hyperintense signal from edema and, later, T1-weighted images without fat saturation often demonstrate central hyperintense signal.8

Diabetic Mastopathy

Diabetic mastopathy is an uncommon benign inflammatory condition predominantly seen in premenopausal women with long-standing insulin-dependent diabetes. The typical presentation is single or multiple palpable breast masses that are firm but mobile. Patients typically have other diabetic complications such as retinopathy or neuropathy. Although the pathophysiology is not clear, the proposed mechanism is a localized autoimmune reaction. An inflammatory response leads to lymphocyte infiltration of the periductal, perilobular, and perivascular spaces resulting in dense keloid-like fibrosis that is seen on histopathology.9,10 Because of the typical clinical presentation, diabetic mastopathy is usually evaluated with mammogram and ultrasound. Mammography may demonstrate various types of asymmetries or, less likely, a high-density mass. Ultrasound will show a nonvascular, irregular, hypoechoic mass with margins that are not circumscribed. Prominent posterior acoustic shadowing is characteristic. MRI findings are not well established and typically noncontributory in diagnosis. Both the clinical and imaging features of diabetic mastopathy mimic those of breast cancer and core-needle biopsy is necessary for diagnosis.10,11

Lupus Mastitis

Certain autoimmune processes may also present with breast symptoms. A rare breast phenomenon manifesting in patients with systemic lupus erythematosus (SLE) is lupus mastitis, which can present as a painful palpable lump or unilateral swelling. Lupus mastitis should remain in the differential diagnoses of patients with SLE; however, it needs to be a diagnosis of exclusion, and tissue sampling should exclude other more common etiologies. Patients presenting with lupus mastitis may note one or many discrete palpable lumps that wax and wane, occasionally even ulcerating through skin. Other clinical presentations include an overall asymmetric, enlarged, and painful affected breast. Histologically, lupus mastitis involves hyaline fat necrosis with intervening lymphoid cells. Fibrotic changes eventually ensue. Immunofluorescence may show IgG and C3 along the basement membranes of vessels and along the junction of the dermis and epidermis.12 Mammographic findings range from discrete masses to global asymmetries. Sonographically, irregular masses are indistinguishable from malignancy. In many cases fluid collections occur, sometimes mimicking abscesses. MRI is nonspecific with fluid collections and nonmass enhancement being most common.13

Sarcoid

A rare differential diagnosis for a tender breast lump includes breast involvement in sarcoidosis. Sarcoidosis is a systemic inflammatory disease of unknown etiology that generates non-necrotizing granulomas in affected organs.14 It generally manifests in the third and fourth decades of life. Breast involvement with sarcoidosis is rare and primary breast sarcoid is even more infrequent. On histopathologic examination, parenchymal granulomas can be seen among breast lobules and ducts. A similar pathologic process may affect lymph nodes, causing nodal enlargement.15 Imaging findings of breast sarcoidosis are often concerning for malignancy. Mammography commonly shows irregular, spiculated masses. Ultrasound correlates are often irregular hypoechoic masses. Small, circumscribed, round masses have also been described. Calcifications within the breast parenchyma are typically absent.15 Diagnosis requires exclusion of other causes, including biopsy with negative stains and cultures for bacteria, mycobacteria, and fungus. The clinical evidence of sarcoidosis elsewhere in the body is most helpful in reaching this diagnosis.14

Mondor’s Disease

Mondor’s disease is an acute thrombophlebitis of one or more superficial breast veins and is most common in middle-aged women. The typical presentation is a palpable cord or mass with associated focal breast pain and redness. Although many cases are idiopathic, the disease is frequently associated with prior trauma, such as surgery.16 Ultrasound is almost always diagnostic, but because of the typical presenting symptoms, both mammogram and ultrasound are usually performed. On mammography, the thrombosed vein can be seen as a tubular-shaped focal asymmetry in the superficial breast. Ultrasound will show a dilated superficial vessel with a lack of compressibility and no intraluminal flow on Doppler imaging.10

Diagnosis

Idiopathic granulomatous mastitis

Summary

Granulomatous lobular mastitis is a benign, rare, chronic inflammatory condition of the breast with a nonspecific clinical presentation. There is significant overlap between the imaging features of IGM, other benign inflammatory entities, and malignancy. This overlap can lead to misdiagnosis; however, additional imaging and tissue sampling help ensure exclusion of the main differential entities. Ultimately, the goal is to reach the correct diagnosis and prevent treatment delay. Correlation with clinical presentation and risk factors may be helpful. The final diagnosis relies on exclusion of other causes and the appropriate pathologic findings on biopsy.

References

  1. Kessler E, Wolloch Y. Granulomatous mastitis: a lesion clinically simulating carcinoma. Am J Clin Pathol 1972;58(6):642-646.
  2. Pluguez-Turull CW, Nanyes JE, Quintero CJ, et al. Idiopathic granulomatous mastitis: manifestations at multimodality imaging and pitfalls. RadioGraphics 2018;38(2):330-356.
  3. Yilmaz E, Lebe B, Usal C, Balci P. Mammographic and sonographic findings in the diagnosis of idiopathic granulomatous mastitis. Euro Radiol 2001;11(11):2236-2240.
  4. Chu AN, Seiler SJ, Hayes JC, Wooldridge R, Porembka JH. Magnetic resonance imaging characteristics of granulomatous mastitis. Clin Imaging 2017;43:199-201.
  5. Trop I, Dugas A, David J, et al. Breast abscesses: evidence-based algorithms for diagnosis, management, and follow-up. RadioGraphics 2011;31(6): 1683-1699.
  6. Kasales CJ, Han B, Smith JS Jr, et al. Nonpuerperal mastitis and subareolar abscess of the breast. Am J Roentgenol. 2014;202(2):W133-139. doi: 10.2214/AJR.13.10551.
  7. Cibas ES, Ducatman BS. Cytology E-Book: Diagnostic Principles and Clinical Correlates. 4th Ed. Elsevier Health Sciences; 2013.
  8. Atasoy MM, Oren NC, Ilica AT, et al. Sonography of fat necrosis of the breast: correlation with mammography and MR imaging. J Clin Ultrasound 2013;41(7):415-423.
  9. Tomaszewski JE, Brooks JS, Hicks D, Livolsi VA. Diabetic mastopathy: a distinctive clinicopathologic entity. Hum Pathol 1992;23(7):780-786.
  10. Cao MM, Hoyt AC, Bassett LW. Mammographic signs of systemic disease. RadioGraphics 2011;31(4):85-100.
  11. Dilaveri CA, MacBride MB, Sandhu, et al. Breast manifestations of systemic diseases. Int J Womens Health 2012;4:35-43.
  12. Goulabchand R, Hafidi A, Van de Perre P, et al. Mastitis in autoimmune diseases: review of the literature, diagnostic pathway, and pathophysiological key players. J Clin Med 2020;9(4):958.
  13. Lee SJ, Saidian L, Wahab RA, Khan S, Mahoney MC. The evolving imaging features of lupus mastitis. Breast J 2019;25(4):753-754.
  14. Illman JE, Terra SB, Clapp AJ, et al. Granulomatous diseases of the breast and axilla: radiological findings with pathological correlation. Insights Imaging 2018;9(1):59-71.
  15. Sabate JM, Clotet M, Gomez A, et al. Radiologic evaluation of uncommon inflammatory and reactive breast disorders. RadioGraphics 2005;25(2):411-424.
  16. Bejanga BI. Mondor’s disease: analysis of 30 cases. J R Coll Surg Edinb 1992;37(5):322-324.
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Guddanti B, Guerrero-Calderon J, Allen E, Woodard SA.  Benign Inflammatory Conditions of the Breast.  J Am Osteopath Coll Radiol.  2021;10(1):33-36.

About the Author

Bhargavi Guddanti, M.D., Juan Guerrero-Calderon, M.D., Elizabeth Allen, M.D., Stefanie A. Woodard, D.O.

Bhargavi Guddanti, M.D., Juan Guerrero-Calderon, M.D., Elizabeth Allen, M.D., Stefanie A. Woodard, D.O.

Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL


 

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