Paget's disease of the breast (also known as mammary Paget's disease) is a rare skin change at the nipple nearly always associated with underlying

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

. Paget's disease of the breast was first described by Sir James Paget in 1874. The condition is an uncommon disease accounting for 1 to 4% of all breast cancers cases. 92% to 100% of patients with Paget's disease of the breast have an underlying breast cancer. The condition in itself often appears innocuous, limited to a surface appearance and it is sometimes dismissed, although it is actually indicative of underlying breast cancer.

Signs and symptoms

Paget's disease of the breast can affect the

nipple The nipple is a raised region of tissue on the surface of the breast from which, in lactating females, breast milk, milk from the mammary gland leaves the body through the lactiferous ducts to Breastfeeding, nurse an infant. The milk can flow th ...

and

areola The human areola (''areola mammae'', or ) is the pigmented area on the breast around the nipple. More generally, an areola is a small circular area on the Human body, body with a different histology from the surrounding Tissue (biology), tissue ...

: the nipple is typically affected first and then the skin changes spread to the areola. It is common for symptoms to wax and wane. Symptoms typically only affect one breast and may include: * ''Skin:'' The first symptom is usually an

eczema Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

-like rash. The skin of the nipple and areola may be red, itchy, or tingly. After a period of time, the skin may become flaky, scaly, or thickened. Many patients do not visit the doctor because they assume Paget's disease of the breast to be minor contact dermatitis or eczema. * ''Nipple discharge:'' A discharge, which may be yellow or bloody, may ooze from the area. * ''Nipple changes:'' The nipple may become inverted. * ''Breast changes:'' Palpable lumps or masses may be present. There may be redness, oozing and crusting, and a sore that does not heal. A person with Paget's disease of the breast may experience

signs and symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

for several months before a diagnosis is made.

Pathophysiology

Paget's disease of the breast is characterized by Paget cells: large cells with clear

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

(clear halo) and eccentric (not centered), hyperchromic (darkly colored) nuclei found throughout the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

. There is some controversy as to whether these cancer cells travel through the ductal system of the breast to the nipple, or whether these cells result from

in situ is a Latin phrase meaning 'in place' or 'on site', derived from ' ('in') and ' ( ablative of ''situs'', ). The term typically refers to the examination or occurrence of a process within its original context, without relocation. The term is use ...

malignant transformation. The most widely accepted theory of how Paget's disease of the breast arises is the migratory theory: ductal carcinoma in situ cancerous cells migrate into the lactiferous sinuses and out of the nipple onto the skin. Cancer cells disrupt the normal epithelial barrier and fluid accumulates on the surface of the skin, resulting in the crusting of the skin of the nipple and/ or areola.

Diagnosis

During a physical examination, the provider will likely conduct a breast examination: evaluating the appearance of the skin on and around the nipples, and feeling for any lumps or areas of thickening in the breast and armpit. Paget's disease of the breast is difficult to diagnose by physical exam alone due to its resemblance to dermatitis and eczema. One helpful differentiator is that eczema tends to affect the areola first, and then the nipple, whereas Paget's disease of the breast typically begins at the nipple and spreads outwards. In addition, nipple eczema is typically responsive to topical steroid application, while Paget's disease of the breast will not improve with topical steroid use. Mammogram and

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

with cytopathology are common confirmatory tests. In biopsy, a tissue sample removed from the affected area is then examined under the microscope by a pathologist, who distinguishes Paget cells from other cell types by staining tissues to identify specific cells (

immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

). Less commonly, samples of nipple discharge may also be examined under the microscope to determine whether Paget cells are present. In addition, ultrasound of the breast may be performed in the absence of positive findings on mammography.

Treatment

Paget's disease of the breast is a symptom of underlying breast cancer. Treatment is variable and is determined by the type of breast cancer in addition to its staging and prognostic considerations. Management often involves a lumpectomy or mastectomy to surgically remove the tumour.

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and/or

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

may also be necessary. Patients with Paget's disease of the breast that has not spread beyond the nipple are often treated with breast-conserving surgery: removal of the cancerous area of the nipple and areola, but conservation of the rest of the breast. Patients then usually undergo

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

after surgery as an adjuvant treatment to prevent recurrence. In most cases, adjuvant treatment is part of the treatment schema. Adjuvant therapy is given to patients with cancer as a secondary form of treatment to minimize the risk of recurrence by targeting undetectable metastases. Whether adjuvant therapy is needed depends upon the type of cancer and its staging. In Paget's disease of the breast, the most common type of adjuvant therapy is radiation following breast-conservative surgery as discussed above. Paget's disease of the breast with underlying breast cancer is primarily treated with mastectomy. In cases of invasive cancer, radical mastectomy is performed: removal of the breast, the lining over the chest muscles, and affected

lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...

from under the arm. In cases of noninvasive cancers, simple mastectomy are performed in which only the breast with the lining over the chest muscles is removed.

Prognosis

Three factors are evaluated when determining prognosis for breast cancer: whether there is a palpable mass, whether lymph nodes have cancer cells in them, and whether there is an underlying metastatic cancer. Prognosis of Paget's disease of the breast with underlying breast cancer depends on these three factors of the underlying cancer. Whether or not a patient has Paget's disease of the breast does not affect their prognosis in the presence of underlying breast cancer. Patients with Paget's disease of the breast and no underlying breast cancer have a 5-year relative survival rate of 82.6%.

Epidemiology

Most patients diagnosed with Paget's disease of the breast are over age 50, but rare cases have been diagnosed in patients in their 20s. The average age at diagnosis is 57. The disease is rare among both women and men, but more common in women.

References

External links

National Cancer Institute fact sheet
{{Breast neoplasia Breast cancer Epidermal nevi, neoplasms, and cysts Diseases named after discoverers