Demographic characteristics and clinical analysis of patients with plasma cell mastitis: a single-center, retrospective, cross-sectional study

Introduction

Background

Breast diseases are common health concerns in women, among which nonlactational mastitis (NLM) has attracted clinical attention due to its complex etiology and consequent diagnostic challenges. Plasma cell mastitis (PCM), a chronic nonbacterial inflammation characterized pathologically by ductal ectasia and plasma cell infiltration, is a significant subtype of mastitis (1). Its clinical manifestations vary and can include breast masses, nipple inversion, nipple discharge, or abscesses. Due to the imaging characteristics and palpable texture closely resembling those breast cancer, PCM is prone to being misdiagnosed in clinical practice, potentially resulting in inappropriate treatment strategies and unnecessary physical and psychological burdens for patients (2,3).

Rationale and knowledge gap

In recent years, a series of investigation into the etiology, diagnosis, and therapeutic management of PCM have been conducted, and it has been speculated that PCM may be related to multiple factors such as autoimmune reaction (4), ductal obstruction (5), and previous history of lactation (6); however, the pathogenic process of this disease has not yet been fully elucidated (7). The related studies have been largely based on small sample studies (usually less than 200 cases) (8-10), while large-scale case series remain scarce.

Objective

In this study, we retrospectively analyzed the clinical data from a large cohort of patients with PCM to systematically characterize the demographic distribution, clinical characteristics, and examination features and thus generate real-world evidence for clinical practice. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-439/rc).

Methods

Research design

The single-center study included a retrospective, cross-sectional design.

Data source

Patient data were extracted from a specialized NLM database, which includes detailed records of patients with pathologically confirmed PCM or granulomatous lobular mastitis treated at the Breast Department of Chongqing Hospital of Traditional Chinese Medicine. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Database establishment received approval from the Ethics Committee of Chongqing Hospital of Traditional Chinese Medicine (No. 2020-ky-38). All patients provided written informed consent for data collection. We identified all patients diagnosed pathologically with PCM from October 2020 through October 2024 in the NLM database. Electronic medical records were screened according to predetermined inclusion and exclusion criteria (Figure 1).

Figure 1 Flowchart of patient inclusion. NLM, nonlactational mastitis; PCM, plasma cell mastitis.

Diagnostic criteria

Histopathological examination was the main diagnostic criterion. Microscopically, PCM is characterized by the mammary ducts being markedly dilated, filled with eosinophilic granular material, and surrounded by foam cells, plasma cells, and neutrophilic infiltration (11).

Inclusion and exclusion criteria

Patients fulfilling the PCM diagnostic criteria and with complete clinical data were included. Meanwhile, males, patients with other breast diseases, pregnant or lactating women, and those with incomplete records were excluded.

Data extraction

Extracted variables included demographic characteristics [sex, age, marital status, and body mass index (BMI)], reproductive history (parity, age at first birth, breastfeeding duration, and abortion history), lifestyle factors (smoking, alcohol use, and dietary habits), disease duration, age at onset, inducement factors, family and medical history (including breast disease), medication history, clinical signs, complications, and laboratory results.

Variable definition

Identifiable inducement factors were considered to be events or conditions occurring within 3 months prior to symptom onset as self-reported by patients and derived from “present illness” or “personal history” sections of medical records. The examined factors were defined as follows: Psychological factors comprised significant negative psychological states or life events shortly preceding disease onset, self-attributed and reported during consultation (e.g., high stress, anxiety, insomnia, and excessive fatigue). Endocrine factors included clearly recorded events such as recent miscarriage, oral contraceptive use, and menstrual disorders. Breast trauma was defined as a history of mechanical injury (e.g., being kicked by a child and crushing injury). Dietary factors included increased consumption of particular foods before disease onset as reported by patients or physicians as potentially related, such as beef, mutton, and seafood.

Clinical signs (e.g., palpable mass, breast pain, erythematous skin, nipple retraction, axillary lymphadenopathy, nipple discharge, skin ulceration, mammary duct fistula, and abscess formation) were considered to be positive physical examination findings. Cases labeled as “nipple inversion” did not include congenital cases documented in patient history.

Figure 2 presents a simple and practical three-zone classification for accurate localization of breast lesions, in addition to the traditional quadrant method.

Figure 2 Schematic diagram of the three-zone classification method. Zone A (nipple-areolar complex): nipple and areola. Zone B (central parenchyma): region from the areolar edge to the midpoint between the areolar edge and the lateral chest wall. Zone C (peripheral parenchyma): region from the midpoint to the lateral chest wall.

Statistical analysis

The data were analyzed via SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables are expressed as medians with ranges, while categorical variables are expressed as counts and percentages.

Results

Demographic characteristics

A total of 1,260 patients with PCM were included (Table 1). The median age was 31 years old (range, 10–57 years), with a peak incidence in the 30 to 39 years age group (718/1,260, 57.0%). Overweight or obese status (BMI ≥24 kg/m²) was present in 32.2% (406/1,260) of the patients. The majority of patients had a history of childbirth (92.8%) and breastfeeding (67.6%). The median age at first birth was 28 years (range, 17–41 years). PCM onset occurred within 3 years after delivery in 44.9% of patients. The median breastfeeding duration was 9.1 months (range, 0.5–49 months). A history of abortion was reported by 54.7% (689/1,260) of patients, and only 2.8% (35/1,260) had a significant smoking history. A history of prior breast disease, notably lactation mastitis (182/1,260, 14.4%), was common. Oral contraceptive use was reported by 22.06% (278/1,260) of the participants. The duration of symptoms ranged from 0.07 to 52 months (median 2.7 months).

Inducement factors

Identifiable inducement factors prior to disease onset were reported by 656 (52.1%) of patients. These factors mainly included psychological factors (258/1,260, 20.5%), endocrine factors (149/1,260, 11.8%), breast trauma (117/1,260, 9.3%), and dietary factors (104/1,260, 8.3%).

Comorbidities

Comorbidities at consultation were documented in 93 (7.4%) patients and included psychiatric disorders (n=29), thyroid diseases (n=26), hyperprolactinemia (n=19), prolactinomas (n=5), polycystic ovary syndrome (n=5), autoimmune diseases (n=4; Hashimoto thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome), and diabetes mellitus (n=4).

Clinical signs

The predominant clinical manifestations were palpable mass (92.5%), breast pain (64.4%), erythematous skin changes (61.5%), and nipple retraction (37.4%). The median mass size was 6.8 cm (range, 1.5–12 cm). Disease was unilateral in 97.3% (1,226/1,260) of patients and bilateral in 2.7% (34/1,260). Lesions were predominantly located in the central area including the areola (78.9%) and upper outer quadrant (55.4%) (Table 2). Local breast manifestations are illustrated in Figure 3. Systemic symptoms included fever (16.3%), arthralgia (6.0%), cough (5.0%), headache (4.6%), and erythema nodosum (4.0%).

Figure 3 Local breast manifestations of patients with plasma cell mastitis.

Laboratory examination data

Of the 1163 patients with complete blood count results at initial visit, abnormalities included elevated white blood cell count (WBC; >9.5×10⁹/L; 336/1,163, 28.9%), elevated neutrophil ratio (NEUT; >64.0%; 425/1,136, 36.5%), elevated erythrocyte count (>5.1×10¹²/L; 71/1,163, 6.1%), and elevated platelet count (>350×10⁹/L; 114/1,163, 9.8%). Additional laboratory abnormalities included elevated C-reactive protein (CRP; >8 mg/L; 490/1,131, 43.3%), increased erythrocyte sedimentation rate (ESR; >20 mm/h; 311/870, 35.7%), and elevated prolactin (>23.3 ng/mL; 249/1,152, 21.6%).

Pathogenic microorganism examination

Pus cultures were performed in 462 patients, yielding positive results in 17.2% (133/772). Bacilli were the predominant isolates (7.0%, 54/772), followed by staphylococci (6.6%, 51/772), including Staphylococcus epidermidis and Staphylococcus aureus. Gram-positive bacilli were isolated in 22 patients, and other bacteria in 6 patients.

Discussion

This study comprehensively delineated the spectrum of PCM’s clinical phenotypes through an analysis of a large, single-center, pathologically confirmed cohort (N=1,260). Our findings confirm that PCM predominantly affects young women of childbearing age within 3 years postpartum, with large, sterile inflammatory masses in the areolar region being the typical presentation. Patient-reported psychological stress was the most common inciting factor. These data provide important real-world evidence to support a reappraisal of this disorder.

Analysis of demographic and reproductive characteristics

This study found that the peak incidence of PCM was concentrated in the age group of 30–39 years old (57.0%). The median age of onset was 31 years old, 92.8% of patients had a history of childbirth, 67.6% had a history breastfeeding ≥6 months, and 44.9% developed the disease within 3 years after delivery, which is consistent with other studies that have reported PCM to mainly affect women of childbearing age (12). Women in this age group have active ovarian function, and the levels of hormones (estrogen, progesterone, and prolactin) fluctuate, especially in the postpartum period, when the drastic changes in the hormone environment may affect the physiological state of the mammary ducts. Another potential issue is stasis and poor ductal emptying during lactation, and these factors may collectively constitute the physiological basis for disease development (13,14). In our study, 14.4% of patients had a history of breastfeeding mammary gland inflammation, a figure within the previously reported range of 2.5–20% (15). It further suggests that there is a pathophysiological continuity between breastfeeding mammary inflammation and chronic PCM and that the microenvironmental changes triggered by milk stasis may have a long-term impact on ductal function, eventually contributing to subsequent inflammatory responses.

Clinical features and differential diagnosis value

This study clarified the hallmark clinical features of PCM. The most common symptom was a palpable breast mass (92.5%), and the median size was 6.8 cm. The majority of lesions (78.9%) were in the central area surrounding the areola and were accompanied by breast pain (64.4%), erythematous skin (61.5%), and nipple inversion (37.4%). This lesion distribution corresponds to the mammary duct anatomy: PCM’s core pathology involves ductal dilation and plasma cell infiltration (1), with inflammatory reactions concentrated in the dominant ducts located in the areolar region. Notably, the prevalence of nipple inversion (37.4%) was markedly higher than the 3–4% prevalence of congenital nipple inversion in women (16,17). This suggests that nipple inversion in patients with PCM is typically a secondary manifestation related to ductal inflammation and fibrosis-induced tissue contraction. This feature can facilitate a differential diagnosis against breast cancer, where masses predominantly occur in the upper quadrants; meanwhile, nipple inversion is usually congenital or occurs in late-stage tumor invasion, with distinct accompanying symptoms.

Using the three-zone classification method, we found that 5.4% of lesions extended to the upper outer quadrant beyond the central area. This pattern indicates PCM lesions may involve periductal acinar tissues, a fact which may help refine guidance for physical examination and imaging assessment. Moreover, PCM was unilateral in 97.3% of cases, and systemic symptoms such as fever and arthralgia were uncommon (≤16.3%). This discovery may inform the differentiation of PCM from systemic diseases involving the breast.

Laboratory examination and treatment implications

Laboratory assessments revealed that several inflammatory markers were elevated in patients with PCM, notably CRP (43.3%) and ESR (35.7%). Conversely, abnormalities in routine blood parameters such as WBC (28.9%) and NEUT (36.5%) were less frequent. The low bacterial culture positivity rate (17.2%), predominantly for bacilli (7.0%) and staphylococci (6.6%), supports the concept of PCM as a “sterile inflammation” (1) and suggests infection is more likely to be secondary than causative. This has important clinical treatment implications. Specifically, management should prioritize anti-inflammatory and immunomodulatory therapies over empirical antibiotic use. Meanwhile, overreliance on antibiotics risks microbial dysbiosis and antimicrobial resistance, aligning with recommendations to avoid antibiotic overuse in PCM treatment (18).

Additionally, elevated prolactin levels were found in 21.6% of patients. A portion of patients also exhibited endocrine-related comorbidities—including thyroid disease, hyperprolactinemia, and polycystic ovary syndrome—which collectively affected 7.4% of the cohort. This suggests that hormonal dysregulation may contribute to PCM pathogenesis, and this indicates a potential role for endocrine-targeted interventions, although the exact targets and treatment protocols remain to be further investigated.

Related factors and patient management

Among the included patients, 52.1% reported clear inciting events prior to disease onset, with psychological factors being the most prevalent (20.5%), followed by endocrine disturbances (11.8%), breast trauma (9.3%), and dietary factors (8.3%), including consumption of beef, mutton, and seafood. These findings highlight the importance of screening for psychosocial stressors and endocrine history during clinical evaluations. Integrating psychosomatic interventions within patient management frameworks may be crucial for relapse prevention.

Psychological stress is frequently subjectively attributed by patients as a trigger for PCM onset, reflecting patient awareness of potential psychosomatic interactions and underscoring the importance of incorporating psychosocial histories into physician–patient communication. However, these data could not quantify the true risk magnitude of psychosocial stress in PCM etiology. Future prospective studies should employ standardized instruments such as the Life Events Scale and validated anxiety and depression scales to objectively assess psychosocial factors preceding or concurrent with disease onset.

Certain limitations to this study should be noted. First, the cohort examined was from a single center, which might have introduced regional biases and limit the external validity. Second, the use of a retrospective, cross-sectional design precluded the establishment of causal relationships, and the identified associations can only generate hypotheses. Third, as we relied on patient self-reporting for variables such as psychological status and dietary preferences, objective quantification was lacking, and information bias could have been introduced. Finally, although exclusion due to incomplete data was minimal, potential selection bias cannot be ruled out, which may limit the generalizability of the findings to patients who completed comprehensive specialist outpatient assessments.

Conclusions

Despite the above limitations, this study provides a solid descriptive foundation for the clinical understanding of PCM. The findings observed in this study (such as the concentration of postpartum onset and the high frequency of psychological factors) can be used as a basis for generating hypotheses in subsequent etiological research. However, further verification through analyses that can establish causal relationships, such as cohort studies and case–control studies, are still needed. Future research should focus on prospective data collection and standardized follow-up, more intensively clarify the pathogenesis of PCM, and provide stronger evidence to support the optimization of disease management models.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-439/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-439/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-439/prf

Funding: This study was supported by the Chongqing Municipal Research Institution Performance Incentive Guidance Project (No. jxyn-2021-1-19), and Chongqing College of Traditional Chinese Medicine’s “Challenge and Appointment” Project (No. JBGS2024-003).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-439/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Database establishment received approval from the Ethics Committee of Chongqing Hospital of Traditional Chinese Medicine (No. 2020-ky-38). All patients provided written informed consent for data collection.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)