Friday, December 19, 2025

Paget's Disease of Breast: Epidemiology, Etiology, Pathogenesis, Pathology, Symptoms, Diagnosis, Treatment, Therapy and Prevention

Paget’s Disease of the Breast

~Introduction


Paget’s disease of the breast is a rare type of breast cancer that primarily affects the nipple–areola complex. It was first described in 1874 by Sir James Paget, a British surgeon, who noticed a relationship between eczematous changes of the nipple and underlying breast malignancy. Although it appears initially as a skin condition, Paget’s disease is almost always associated with an underlying carcinoma of the breast, either ductal carcinoma in situ (DCIS) or invasive ductal carcinoma.

Paget’s disease of the breast accounts for 1–4% of all breast cancers. It commonly affects women over the age of 50, but it can also occur in men, though very rarely. Early diagnosis is often delayed because the disease mimics benign skin conditions such as eczema or dermatitis. Understanding its pathology, clinical features, diagnosis, and management is essential for improving patient outcomes.

~Definition

Paget’s disease of the breast is defined as a malignant condition characterized by the presence of Paget cells in the epidermis of the nipple, usually associated with an underlying breast carcinoma.

~Epidemiology

  • Accounts for 1–4% of all breast cancers

  • More common in women, but can occur in men

  • Usually affects individuals aged 50–70 years

  • Rare in younger patients

  • Most cases are associated with ductal carcinoma

~Etiology and Pathogenesis

The exact cause of Paget’s disease of the breast is not fully understood. However, two main theories explain its development:

1. Epidermotropic Theory (Most Accepted)

  • Malignant cells originate from an underlying ductal carcinoma

  • These cancer cells migrate through the lactiferous ducts

  • They spread into the epidermis of the nipple

  • These malignant cells are called Paget cells

This theory explains why most patients have an underlying breast tumor.

2. In Situ Transformation Theory

  • Cells in the epidermis of the nipple undergo malignant transformation

  • Occurs independently of an underlying carcinoma

  • This theory explains rare cases without detectable breast tumors

~Pathology

Gross Pathology

  • Red, scaly, crusted, or ulcerated nipple

  • Thickened or flattened nipple

  • Possible serous or bloody discharge

  • Underlying breast mass may or may not be palpable

Microscopic Pathology

  • Presence of Paget cells in the epidermis

  • Paget cells are:

    • Large

    • Round or oval

    • Pale cytoplasm

    • Large nuclei with prominent nucleoli

  • Cells are usually found singly or in small clusters

  • Associated with DCIS or invasive ductal carcinoma

Immunohistochemistry

Paget cells are typically:

  • HER2/neu positive

  • CK7 positive

  • EMA positive

  • Negative for melanocytic markers (helps differentiate from melanoma)

~Clinical Features

Paget’s disease often presents with nipple changes, which may be mistaken for benign skin disorders.

Early Symptoms

  • Itching or tingling of the nipple

  • Redness and scaling

  • Mild irritation

  • Burning sensation

Progressive Symptoms

  • Persistent eczema-like lesion

  • Crusting or ulceration of the nipple

  • Bloody or serous nipple discharge

  • Flattening or retraction of the nipple

  • Pain or tenderness

Associated Findings

  • Palpable breast mass (in ~50% of cases)

  • Axillary lymph node enlargement (if invasive cancer present)

~Differential Diagnosis

Paget’s disease must be differentiated from other nipple conditions, including:

  • Eczema

  • Contact dermatitis

  • Psoriasis

  • Nipple adenoma

  • Melanoma

  • Bowen’s disease

Failure of symptoms to respond to topical treatment should raise suspicion of Paget’s disease.

~Diagnosis

Clinical Examination

  • Careful inspection of nipple–areola complex

  • Palpation of both breasts and axillary lymph nodes

Imaging Studies

1. Mammography

  • May show underlying mass

  • May reveal microcalcifications (DCIS)

  • Normal mammogram does not exclude disease

2. Ultrasound

  • Useful in detecting underlying lesions

  • Helps guide biopsy

3. MRI

  • Highly sensitive

  • Useful when mammography is normal

  • Helps assess disease extent

Biopsy

Definitive diagnosis requires biopsy

Types:

  • Punch biopsy of nipple skin

  • Wedge biopsy

  • Excisional biopsy

Histological confirmation of Paget cells is diagnostic.

~Staging

Paget’s disease itself is not staged separately. Staging depends on the associated breast carcinoma, using the TNM staging system.

~Treatment

Treatment depends on:

  • Presence or absence of underlying carcinoma

  • Tumor size

  • Lymph node involvement

  • Patient preference

Surgical Management

1. Mastectomy (Traditional Treatment)

  • Simple or modified radical mastectomy

  • Includes removal of nipple–areola complex

  • Sentinel lymph node biopsy is performed

2. Breast-Conserving Surgery

  • Wide local excision of nipple–areola complex

  • Removal of underlying tumor

  • Followed by radiotherapy

  • Suitable for selected patients

Axillary Management

  • Sentinel lymph node biopsy

  • Axillary lymph node dissection if nodes are positive

~Adjuvant Therapy

Radiotherapy

  • Given after breast-conserving surgery

  • Reduces local recurrence

Chemotherapy

  • Used if invasive carcinoma is present

  • Depends on tumor grade and stage

Hormonal Therapy

  • Given if estrogen or progesterone receptor positive

  • Examples: Tamoxifen, Aromatase inhibitors

Targeted Therapy

  • HER2-positive tumors treated with Trastuzumab

~Prognosis

Prognosis depends mainly on the underlying breast cancer.

Good Prognostic Factors

  • No palpable mass

  • DCIS only

  • Negative lymph nodes

Poor Prognostic Factors

  • Invasive carcinoma

  • Lymph node involvement

  • Large tumor size

Overall survival rates are similar to those of other breast cancers when matched by stage.

~Complications

  • Local recurrence

  • Surgical complications

  • Lymphedema

  • Psychological impact

  • Treatment-related side effects

~Paget’s Disease in Men

  • Extremely rare

  • Often diagnosed late

  • Worse prognosis compared to women

  • Managed similarly to female patients

~Prevention and Early Detection

  • Awareness of persistent nipple changes

  • Early medical consultation

  • Regular breast screening

  • Biopsy of non-healing nipple lesions

~Conclusion

Paget’s disease of the breast is a rare but important manifestation of breast cancer. Although it presents as a skin lesion of the nipple, it is usually associated with an underlying carcinoma. Early diagnosis is challenging due to its resemblance to benign skin conditions, leading to delayed treatment in many cases. A high index of suspicion, timely biopsy, and appropriate imaging are essential for diagnosis.

Advances in breast-conserving surgery, imaging, and targeted therapies have significantly improved outcomes. Prognosis depends largely on the presence and extent of underlying malignancy. Awareness among clinicians and patients plays a crucial role in early detection and better survival.

No comments:

Post a Comment

Mantle Cell Lymphoma: Causes, Symptoms, Diagnosis, Treatment, and Outlook

Mantle Cell Lymphoma: Causes, Symptoms, Diagnosis, Treatment, and Outlook Mantle Cell Lymphoma (MCL) is a rare and aggressive subtype of no...