Paget’s Disease of the Breast - Symptoms, Diagnosis, and Treatment

Introduction:

Every year, October is celebrated as breast cancer awareness month. This is done to educate women on the subject and to see a healthier society growing. Sir James Paget first described this disease in 1874. Paget’s disease is a rare form of cancer. It is usually seen as an invasive form of ductal carcinoma. This means it spreads to the surrounding areas and develops from the ducts which produce milk. Paget’s disease is manifested as rashes of the breasts.

What Is Paget’s Disease of the Breast?

The tumor cells are seen within the duct and spread through the ducts by entering into the epithelial cells. These cells enter the epidermis or outer skin by escaping through the ducts without disturbing the basement membrane. In the epidermis, these tumor cells squeeze between the squamous cells, breaking the contact between the two adjacent cells. As a result, the extracellular fluid in the background starts leaking and comes outside, creating a scaly outer crust on the skin surface of the nipple.

How Is Paget’s Disease of Breast Developed?

Paget’s disease is caused by Toker cells. These cells are present in normal nipples constituting about ten percent. Toker cells are considered to be the benign counterparts of the Paget cells. Paget’s disease is also caused due to underlying carcinoma of the breast or invasion of cancer cells (DCIS). Women without palpable mass show only ductal carcinoma in situ (DCIS). The overall prognosis of Paget’s disease of the breast is poor.

During the microscopic evaluation of the sample, it shows normal cells turning into giant cells with a prominent nucleus and an abundant pale cytoplasm present in it. The nucleus has a prominent nucleolus, and the cells are poorly differentiated. The cells beneath the surface show chronic inflammation, and the outer layer shows hyperpigmentation and ulcerations.

What Are the Signs and Symptoms Associated With Paget’s Disease?

The patients show clinical signs such as:

• Pruritis or itch formation in the nipple area with a reddened surface and scaly outer skin crust. These symptoms of the skin mimic eczema and are also known as an eczematous lesion of the skin. The difference between Paget's disease and eczema is that it is unilateral in appearance, whereas eczema is bilateral.

• Erythematous or reddish lesions on the nipple.

• Discharge from nipples is seen rarely.

• In fifty percent of cases, a palpable mass is noted, indicative of invasive carcinoma.

• Scaly outer skin.

• Fever.

• Increase in the size of one breast or unilateral breast.

• Varicose veins are noted.

• Nipples deviate to one side laterally.

• Bleeding from nipples.

• Itchy skin.

• The nipple also may have ulceration which is a secondary feature. The normal squamous cells are replaced by Paget’s cells.

• Unilateral or one-sided rashes are observed.

• Pain and burning sensation in the nipple area.

• Thickening and swelling of the nipples and areola region are seen.

How Can We Test for Paget’s Breast Cancer?

Various tests, from local examination to cellular study, are conducted to evaluate the disease.

• Immunohistochemistry (IHC): During this study, the estrogen receptor will be negative (ER-), the progesterone receptor will be positive (PR+), and the HER-2 protein will be positive. This is useful in diagnosing difficult cases. The cells of Paget’s disease show positive for HER2 protein and negative for Toker cells. It also shows mucicarmine and PAS positive in about fifty to sixty percent of cases. In about ninety percent of cases, HER-2-neu and p53 genes show positivity. The S-100 protein shows a negative result.

• Mammogram: In the mammogram report, the cells show epithelial proliferation with or without lump formation. Most breast cancers arise from the tip of the nipple, with multifocal areas seen.

• Blood Tests: Several pagetoid cells are present in the blood. Various oncogenes like CA125 and HER2 can be checked using blood tests. The immunomarkers like cytokeratin seven and CAM5, 2 are positive for both Paget and Toker cells. The hemoglobin shows fewer values and is seen as normocytic normochromic anemia with thrombocytopenia in some cases.

• Ultrasonography (USG): This test analyzes normal internal structures from pathological structures.

• Fine Needle Aspiration Cytology (FNAC): The tissue is collected from the lump or scarred area. This is done using a punch biopsy or by aspirating the tissue using a fine needle. The collected tissue sample is then evaluated under the microscope. The presence of oncogenes and the structure of the cell are studied.

• Computed Tomography (CT): CT scan is done to visualize the internal structure using radiation beams.

• Magnetic Resonance Imaging (MRI): This test uses high-voltage magnetic radiation to study soft tissue distortion.

What Are the Treatments Taken to Cure Paget’s Disease of the Breast?

The first phase of treatment includes steroid therapy to relieve symptoms. Other treatments include the following procedures.

• Surgery: The lump is removed surgically, or a mastectomy is done. Though mastectomy does not cure the condition completely, the chances of recurrence are high. Hence, mastectomy is not highly advisable.

• Chemotherapy: The doctor may prescribe drugs like CHOP for six cycles Cyclophosphamide 750 mg/m2 intravenously on the first day, Doxorubicin 50 mg/m2 intravenously on the first day, Vincristine 1.4 mg/m2 intravenously on the first day and Prednisone drug 100 mg orally daily for one to the fifth day. Drug Rituximab is effective against CD20+ B cell lymphomas.

• Radiotherapy: If the lump persists, radiation therapy is done after the chemotherapy session.

Paget’s disease is also observed during pregnancy and postpartum under the influence of various hormones. About eighty percent of Paget’s breast lymphoma are B-cell lymphomas with CD20 positive.

Conclusion:

Paget’s disease of the breast is the rarest form of malignancy. Scarring of the nipple tissue can be misdiagnosed as eczema. Eczema is seen bilaterally and in younger patients. At the same time, Paget’s disease is seen unilaterally and in older women who have exceeded the menopause age. The edges are distinct in Paget’s disease and are not distinct in eczema. Most of the time, Paget’s disease does not respond to treatment, but eczema does. An early screening of the disease can bring a better outcome. This condition can develop in men also but very rarely.