Current Understanding and Management of Plasma Cell Mastitis: Can We Benefit from What We Know?

Abstract

Background: Plasma cell mastitis (PCM), also known as mammary duct ectasia, is a chronic nonbacterial breast inflammation characterized by duct expansion and plasma cell infiltration. The severe and intense clinical manifestations profoundly affect the quality of life of female patients. Although the pathological process of PCM is known to include four stages (duct dilatation, inflammation, abscess and fistula), there is still lack of imaging techniques and serum markers with high specificity in clinical practice. Due to recurrent acute attacks and the prolonged healing process of the disease, most patients choose to accept mastectomy.

Summary: We searched for studies, reports and reviews referring to PCM in the past 20 years; more than half of the results were related to animal studies, and little attention has been paid to human beings, which may explain the frequent misdiagnosis of PCM as breast cancer and the limited treatment options. This review focuses on the current diagnostic methods and markers for PCM and hierarchically discusses the typical clinical features, etiological causes and relevant molecular mechanisms of PCM.

Key messages: We herein highlight the urgent need to develop more specific and sensitive biomarkers in the clinical laboratory. It will help to establish a standardized flowchart for the diagnosis and treatment of PCM in order to improve recovery for female patients.

Keywords: Clinical manifestation; Differential diagnosis; Pathogenic mechanism; Plasma cell mastitis.

Fig. 1

Molybdenum target X-ray scanning of a typical PCM patient. The examination shows bilateral nipple retraction, hyperplasia and multiple calcifications and reveals a slightly high-density shadow (3.5 cm in diameter) in the right breast, Breast Imaging Reporting and Data System category 2.

Fig. 2

Molecular mechanisms of mammary ductal epithelium interaction with the breast microenvironment. PRL promotes proinflammatory activity by activating the NF-κB pathway in mammary epithelial cells to trigger the secretion of cytokines, such as IL-1β, IL-6, IL-8, GM-CSF, and TNF-α, among which IL-6 binds to gp130 in plasma cells to activate the JAK/STAT signaling pathway followed by the upregulation of Bcl-2 (prolonged survival) and ICAM-1 (enhanced penetration and aggregation). Moreover, PRL promotes the secretion of TNF-α and IL-12 via NF-κB and IRF-1 in WBCs. In the presence of IL-6, B cells differentiate into plasma cells, which effectively forms a positive feedback loop of IL-6/JAK/STAT signaling, followed by local accumulation in the breast, while IL-6 from plasma cells promotes B-cell differentiation, and vice versa. In mammary ductal epithelium, SOCS2 binds to the growth hormone receptor phosphopeptide to cause its interaction with the JAK/STAT signaling pathway, which is inhibited by SOCS2 p.R96C point mutations that induce an uncontrolled inflammatory response. The PI₃K-Akt-mTOR signaling pathway is prominently upregulated in human PCM tissue with an unknown activator. Bacterial MDP specifically binds to NOD2 on mammary ductal epithelium and activates the NF-κB signaling pathway to produce chemokines and proinflammatory factors. PCM, plasma cell mastitis; PRL, serum prolactin; NF, nuclear factor; IL, interleukin; GM-CSF, colony-stimulating factor 2; TNF, tumor necrosis factor; JAK, Janus kinase; STAT, signal transducers and activators of transcription; IRF-1, interferon regulatory factor 1; WBCs, white blood cells; SOCS2, suppressor of cytokine signaling 2; ICAM, intercellular adhesion molecule; NOD2, nucleotide-binding oligomerization domain containing 2; MDP, muramyl dipeptide; gp130, glycoprotein 130.