Mammary Pagets Disease: Symptoms, Types, Causes and Treatment

Mammary Paget’s disease (MPD) is a rare and often misunderstood condition that primarily affects the skin of the nipple and areola, sometimes signaling a deeper, underlying breast malignancy. With symptoms that mimic benign skin disorders and a complex pathology, MPD poses diagnostic and therapeutic challenges for both patients and clinicians. This comprehensive article explores the key symptoms, the various types, underlying causes, and evolving treatment strategies for mammary Paget’s disease, synthesizing the latest research and real-world data.

Symptoms of Mammary Paget’s Disease

Recognizing the symptoms of mammary Paget’s disease is the first step toward timely diagnosis and treatment. MPD often masquerades as common dermatological conditions, which can delay proper management. Understanding its clinical presentation is crucial for early detection, especially since it can be the first visible sign of an underlying breast carcinoma.

Typical Clinical Presentation

MPD commonly presents as a unilateral, ulcerated or eczematous lesion on the nipple-areola complex. Patients often notice persistent redness, scaling, or crusting that does not improve with standard topical treatments. Itching and pain are frequent complaints, and many experience a burning sensation. In some cases, there may be a watery or bloody discharge from the nipple. These symptoms are often mistaken for eczema or dermatitis, leading to delays in diagnosis 1 2 10.

Diagnostic Challenges

One of the hallmarks of MPD is its ability to mimic benign dermatological conditions such as eczema, psoriasis, or simple dermatitis. This “masking” effect means many patients are initially misdiagnosed and treated with ineffective topical therapies 2 10. A high index of suspicion is warranted, especially when symptoms persist or recur despite standard interventions.

Association with Underlying Mass

While the superficial skin changes are the most noticeable, about 14–44% of patients will also have a palpable breast mass at diagnosis. The presence of a mass is a significant red flag, as it often correlates with invasive carcinoma and a poorer prognosis 2 9 12. However, MPD can exist without any lump, underscoring the importance of thoroughly investigating persistent nipple-areola abnormalities.

Unilateral Nature

MPD almost exclusively affects one breast and tends to be localized to the nipple and surrounding areola, rarely crossing to the opposite side 1.

Types of Mammary Paget’s Disease

MPD is not a uniform disease. Understanding its types and related subtypes helps inform prognosis and guide treatment decisions. The disease can be classified based on clinical features, association with underlying carcinoma, and molecular characteristics.

Classic (Primary) vs. Secondary Paget’s Disease

• Classic/Primary MPD: Characterized by malignant glandular cells confined to the epidermis of the nipple and areola. These cases may arise de novo or, more commonly, as a manifestation of underlying breast carcinoma 3 4 8.
• Secondary MPD: Resulting from the intraepidermal spread of ductal carcinoma in situ (DCIS) or invasive ductal carcinoma through the lactiferous ducts to the nipple skin 4 8. Most cases of MPD are associated with underlying carcinoma—studies report rates up to 92% 12.

Molecular Subtypes

Recent immunohistochemical analyses have shown that MPD, like breast cancers, can be further classified into molecular subtypes:

• HER2-enriched: The most frequent molecular subtype in MPD, found in about half of all cases 6. This subtype is characterized by overexpression of the HER2 protein, which is less common in overall breast carcinoma.
• Luminal A/B: These subtypes are hormone-receptor positive and generally associated with a better prognosis. They are less common in MPD compared to breast carcinoma overall 6.
• Basal-like: Triple-negative for estrogen, progesterone, and HER2 receptors, this subtype is present in about 20% of MPD cases 6.

Male Mammary Paget’s Disease

Although rare, MPD can also occur in men, comprising a slightly higher proportion of male breast cancers than in females. Clinical presentation is similar, with ulceration, itching, and nipple changes, but delays in diagnosis are common due to misattribution to benign skin conditions 2.

Causes of Mammary Paget’s Disease

The precise cause of MPD remains a topic of scientific debate, but two main theories have emerged to explain its origin. Understanding these mechanisms is vital, as it shapes both diagnostic and therapeutic strategies.

The Epidermotropic Theory

The most widely accepted explanation for MPD is the epidermotropic spread of malignant cells. According to this theory, cancer cells originate from an underlying ductal carcinoma (often DCIS or invasive ductal carcinoma) and migrate along the milk ducts to infiltrate the epidermis of the nipple and areola 8 10 12. Immunohistochemical studies show that Paget’s cells and the associated carcinoma usually share the same antigenic profile, supporting a common origin 8.

In Situ Transformation

A minority of cases may arise from in situ malignant transformation of the epidermal cells of the nipple, independent of any underlying carcinoma. This “de novo” mechanism is less common but is important to recognize, as management may differ 8 10.

Association with Underlying Carcinoma

The vast majority of MPD cases (82–92%) are linked to underlying ductal carcinoma, either in situ or invasive 4 8 9 12. In some patients, the carcinoma may be multifocal and not palpable or visible on imaging, making diagnosis challenging 12.

Molecular and Immune Factors

HER2 overexpression is notably frequent in MPD, distinguishing it from other breast carcinomas where luminal (hormone receptor-positive) subtypes predominate 6. Immune profiling shows an intense lymphocytic response in MPD, though PD-L1 mediated immunosuppression is typically absent, with occasional CTLA-4 expression 5. These findings may have future implications for targeted therapies.

Treatment of Mammary Paget’s Disease

The management of MPD has evolved, with options ranging from surgery to radiotherapy and newer, minimally invasive techniques. Treatment is tailored to individual patient factors, the presence or absence of underlying carcinoma, and disease extent.

Surgical Management

• Mastectomy: Removal of the entire breast and nipple-areola complex has long been the standard, especially when an invasive or multifocal carcinoma is present. It offers the lowest recurrence rates but may be more extensive than necessary for confined disease 12 13.
• Breast-Conserving Surgery (BCS): In selected patients with localized, non-invasive MPD and no palpable mass, conserving surgery with removal of the nipple-areola complex may be considered. Adding radiotherapy significantly reduces recurrence compared to BCS alone 13.
• BCS Alone: Not recommended when there is underlying ductal carcinoma (in situ or invasive) due to higher recurrence rates 13.

Sentinel Lymph Node Biopsy

SLNB should be considered, especially when a palpable mass or invasive disease is present, as lymph node involvement is associated with poorer prognosis. About 17% of patients have positive sentinel nodes 13.

Radiotherapy

Adjunctive radiotherapy is often used after BCS to reduce the risk of local recurrence, particularly when complete excision may be challenging or when there's associated carcinoma 13.

Photodynamic Therapy (PDT)

PDT is a minimally invasive approach, particularly explored in cases where surgery may be too morbid or for patients unable to undergo extensive procedures. Early results are promising, but data is limited due to the rarity of MPD 11.

Other Approaches and Considerations

• Topical treatments (e.g., corticosteroids, antifungal creams) are not effective for MPD and may delay accurate diagnosis 2 10.
• Male MPD is managed similarly to female cases, but with even greater emphasis on early biopsy due to frequent diagnostic delays 2.

Conclusion

Mammary Paget’s disease is a rare but significant breast disorder often signaling an underlying carcinoma. Its varied presentation and mimicry of benign conditions mean it can be easily overlooked. Advancements in molecular characterization and minimally invasive therapies continue to shape management, but surgical excision remains the cornerstone of treatment.

Key Takeaways:

• MPD commonly presents with persistent nipple/areola changes such as ulceration, erythema, itching, and pain, often unresponsive to topical therapy.
• Most cases are linked to underlying ductal carcinoma, emphasizing the need for thorough evaluation even in the absence of a palpable mass.
• MPD can be classified into classic/primary and secondary types, with further stratification based on molecular subtypes (HER2-enriched, luminal, basal-like).
• The leading cause is the epidermotropic spread of malignant ductal cells, though some arise de novo from the nipple epidermis.
• Treatment is individualized, with mastectomy or breast-conserving surgery plus radiotherapy being most effective; sentinel lymph node biopsy is warranted in invasive or mass-associated cases.
• New therapies, such as photodynamic therapy, are emerging but require further study.

Early recognition and multidisciplinary management are essential for optimal patient outcomes in mammary Paget’s disease.