Plasma cell mastitis: a comprehensive review of etiological advances and future directions

Plasma cell mastitis (PCM), a complex and refractory chronic inflammatory-like breast disease, remains a critical global female healthcare challenge. Over the past decade, although considerable effects have been gained on understanding of the clinical and pathological features of PCM, the exact cause of PCM remains clinically challenging, as the pathogenesis of this disease involves multiple factors. This narrative review systematically synthesizes current evidence on PCM, mainly focusing on its etiology, clinical manifestations, diagnosis, and treatment strategies, which aims to unravel the etiological landscape of PCM from ductal microecology to systemic autoimmunity. We comprehensively demonstrated the etiology of PCM including the anatomical factors, immunological factors, microbial infections, and other factors. Anatomically, inverted nipples and duct structural abnormalities lead to a pathological chain of ductal obstruction - dilation - rupture - stromal inflammation; Immunologically, pro-inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-17 (IL-17) are significantly elevated, and helper T cell 1 (Th1)/Th17 cells are overly activated, supporting the possibility that PCM may be an immune-mediated disease; The role of microbial factors is controversial, with most cultures being sterile and a few associated with anaerobic bacteria or mycobacteria; Smoking and obesity are involved in the pathogenesis through hormonal disorders and chronic inflammation. This review also provides diagnostic criteria and key points for differential diagnosis of PCM, and summarizes the current treatment strategies mainly based on glucocorticoids and surgery. Future research needs to establish reliable animal models and conduct multi-omics studies to reveal the complete causal chain.