Bilateral plasma cell mastitis simulating breast cancer: a case report and literature review

Abstract

Plasma cell mastitis (PCM) is a chronic inflammatory disease of the breast. It is a benign entity mainly found in nonpregnant and nonlactating women. PCM presents with symptoms of inflammation, breast erythema, masses, and indurations. We herein describe a 26-year-old woman with a 2-year history of right breast swelling and a 1-year history of left breast swelling during pregnancy and lactation. She was clinically diagnosed with bilateral breast cancer, but a biopsy specimen revealed PCM. During pregnancy and lactation, PCM can present as bilateral lesions. Early presentation and diagnosis are crucial because PCM, a benign disease, can lead to remarkable morbidity if allowed to progress to an advanced stage.

Introduction

Plasma cell mastitis (PCM), also known as mammary duct ectasia or granulomatous lobular mastitis, is a chronic inflammatory disease of the breast.^1,2 It is a benign entity that has no risk of malignant transformation. ³ PCM was first described by Cheatle and Cutler ⁴ in 1931.^5,6 It is rare in clinical practice, and its etiology is unknown. Two theories of autoimmune/hypersensitivity processes and an infectious pathogenesis have been proposed.^1,5 PCM is mainly found in nonpregnant and nonlactating women and presents with symptoms of inflammation, breast erythema, masses, and indurations. ³ The skin may demonstrate a peau d’orange (orange peel) appearance, ulceration, and fistulas, as may be seen in breast carcinoma. ¹ Histology is the definitive method of diagnosis and reveals infiltration of plasma cells and lymphocytes.^1,3 There is no consensus on the most appropriate treatment for PCM. Surgical excision and corticosteroids have shown good responses in some cases. ¹ The present case report describes a 26-year-old woman with bilateral breast disease and discusses some clinical features associated with the different stages of the disease process. PCM is rare during pregnancy and lactation. The related challenges of management in this case are highlighted.

Case report

A 26-year-old woman (para 2) presented to our facility with a 2-year history of right breast swelling and a 1-year history of left breast swelling. A right breast lump was noticed 11 months after childbirth. The patient breastfed using the contralateral (left) breast, after which the swelling in the right breast appeared to subside. During evaluation of the right breast lesion, however, she stopped attending appointments because of another pregnancy. During this time, she sought treatment elsewhere but without improvement in her condition. She returned to our facility 1 year later with a similar complaint now involving her previously unaffected left breast. The patient reported breast pain and discomfort and the presence of a breast mass. She had no history of bloody nipple discharge, but she had noticed right nipple retraction during the disease course followed by a decrease in the size of the right breast. The patient had no appetite loss, weight loss, or rise in body temperature. She had no known diabetes or asthma, and she had no history of allergies.

On examination, the patient was in satisfactory general condition. She exhibited asymmetry of the breasts, with the right being smaller than the left. The right breast appeared shriveled with a completely inverted nipple–areolar complex. A mass was present, involving the entire breast; the mass was hard, fixed to both the overlying skin and underlying muscle, and associated with a solitary enlarged axillary lymph node. The left breast showed a retracted nipple and a peau d’orange appearance. A mass was present in the upper outer quadrant; it was spherical and measured approximately 12 cm in the widest diameter, was hard and immobile, and was associated with a solitary mobile enlarged axillary lymph node (Figure 1).

Figure 1.

Clinical photograph of bilateral plasma cell mastitis.

Blood tests included a full blood cell count, urea and electrolytes, and liver function tests, all of which were unremarkable. Urinalysis results were also normal. Further workup included breast ultrasound, which showed bilateral suspicious breast masses (Breast Imaging-Reporting and Data System (BI-RADS) category 5). Chest X-rays and abdominopelvic ultrasound revealed no abnormalities. Histologic examination of bilateral Tru-cut biopsy specimens showed a granulomatous reaction mostly involving aggregates of plasma cells, histiocytes, lymphocytes, and a few neutrophils. No proliferation was noted (Figure 2(a) and (b)). The patient was definitively diagnosed with bilateral PCM. She was informed and counseled on the result of the histologic examination, including possible options for treatment, to which she consented. The patient was lost to follow-up after the last visit.

Figure 2.

Histologic images of plasma cell mastitis. (a) Right breast and (b) Left breast. Hematoxylin and eosin, ×40 and ×100.

During treatment in the surgical outpatient department, the patient provided verbal informed consent for the reporting of this case and accompanying images. She was thereafter lost to follow-up, preventing us from obtaining written consent. The requirement for ethics approval was waived because this study was a report of a case managed by a clinical team at the University of Calabar Teaching Hospital and not an interventional study (i.e., no intervention or experimentation was conducted for the purpose of the study). The reporting of this study conforms to the CARE guidelines. ⁷

Discussion

PCM is an uncommon chronic inflammatory disease of the breast. ³ It is a non-bacterial inflammatory benign disease also known as idiopathic granulomatous mastitis, and it is mostly found in nonpregnant and nonlactating women.^1,5,8 PCM most often occurs several years (average, 4 years) after cessation of lactation in middle-aged women.^3,5 By contrast, our patient presented with bilateral disease during pregnancy and lactation. PCM is typically found in women in the second to fourth decades of life. Consistent with this, our patient presented in her third decade of life. PCM is rarely found in men.^2,5

Nipple retraction (nipple inversion) is the primary cause of PCM,^8,9 as demonstrated in the chronic stage (Figure 3(a) (right breast)) and acute stage (Figure 3(b) (left breast)) of this disease in our patient. Following the process of inversion, the lactiferous ducts become stenosed and eventually obstructed. Extravasation of milk results in an autoimmune response in the periductal tissue and subsequent pathological changes. ⁵ The pathogenesis of PCM is not completely clear and is an area of ongoing research. Rodman and Ingleby ¹⁰ suggested that PCM may be due to the enzymes that split milk-like substances in non-lactating women.^2,5 Extravasation of intraductal secretions into the periductal connective tissue result in aseptic inflammation.^3,5 In most cases, PCM appears to be aseptic; however, cases of coinfection with Corynebacterium species have been reported in some European countries. ⁹ Infiltration of the breast tissue by many plasma cells and T lymphocytes is a major feature of PCM. It is hypothesized that secreted chemokines and some signaling pathways, such as those involving interleukin 6 and signal transducer and activator of transcription 3 (STAT3), can promote plasma cell differentiation and maintain their survival in this disease. ³ Proinflammatory cytokines (interferon-gamma and interleukin 12A) are associated with PCM, and the T-helper 1 immune response may be related to PCM. ⁹ Furthermore, immunolocalized intercellular adhesion molecules 1 and 2 and E-selectin may affect the inflammatory process in PCM through margination, extravasation, and attachment of plasma cells and lymphocytes. ¹¹ Smoking and long-term use of contraceptives have been described as risk factors for PCM.^2,8

Figure 3.

Clinical photographs. (a) Right breast and (b) Left breast.

The four stages of the developmental process of PCM are duct dilatation, inflammation, abscess formation, and fistula/fibrosis formation. These stages in turn determine the clinical features. The clinical presentation of PCM includes erythema, breast lumps, breast induration, and a peau d’orange appearance (Figure 1). Other symptoms include ulceration and even fistulas with discharge of pus. ¹ The skin is thick, adherent to the breast, and associated with nipple retraction (Figure 3(a)), and bloody nipple discharge may be mistaken for a sign of breast cancer. ⁵ The peau d’orange appearance (Figure 3(b)) may also be mistaken for breast cancer. ² The acute (Figure 3(b)) and chronic (Figure 3(a)) stages of PCM may be mistaken for different diseases: idiopathic granulomatous mastitis, sclerosing lymphocytic mastitis, lactational breast abscess, tuberculosis, periductal mastitis, inflammatory cancer of the breast, or diffuse ductal cancer of the breast.^3,12,13

No serum markers for PCM have been established. IgM, IgA, C₃, and C₄ in patients with nonlactating mastitis were found to be increased in several independent clinical studies. ² The lack of specificity on imaging (ultrasound, computed tomography, and magnetic resonance imaging) sometimes results in PCM being mistaken for breast cancer,^2,8 as in our patient (BI-RADS category 5). Some of the magnetic resonance imaging features differ between PCM and invasive ductal cancer. An integrated analysis of multiparametric magnetic resonance imaging features can assist in the differential diagnosis of PCM and invasive ductal cancer. ⁸ The histologic appearance of PCM can be characterized by infiltrates of neutrophils, lymphocytes, and histiocytes with a predominance of plasma cells^2,9 (Figure 2). Although these findings may mimic tuberculosis, no caseation is present. ⁹ In some cases of PCM, it is difficult to differentiate lesions clinically and radiologically from cancer; this is consistent with our experience. Histology is the definitive method of diagnosis ⁹ (Figure 2).

Our patient was lost to follow-up twice, with the most recent loss occurring after biopsy. The first loss to follow-up occurred because of pregnancy, and the later loss was associated with a fear of malignancy. During the intervening period, the patient sought care in other medical facilities, including alternative medical care. This pattern is common and concerning in our setting, often stemming from poverty and cultural beliefs that favor alternative medical practices. There is high patronage of alternative medical care as a result. Advocating for health education tailored to local experiences is therefore essential.

Treatment of PCM is based on the stage of the disease. ¹ The treatment options include observation, antibiotics, steroids, drainage, excision, and mastectomy. The optimal therapy is still difficult to determine for many clinicians, and it is always individualized. Drainage is controversial because the incision wound may not heal easily, resulting in a fistula. ¹ Total mastectomy is recommended for extensive lesions (Figure 3(a)), including large lumps (Figure 3(b)), to avoid local recurrence. ⁵ Patients may benefit from bilateral mastectomy and breast reconstruction.

In conclusion, histologic examination is the definitive method of diagnosing PCM considering its clinical similarities with breast cancer. PCM can uncommonly present during pregnancy and lactation. Early presentation and diagnosis are crucial because PCM, despite being a benign disease, can pose significant challenges and lead to substantial morbidity when diagnosed at an advanced stage.