Information on the following diseases can be found in the Related Disorders section of this report:

• Extramammary Paget's Disease
• Eczema
• Bowen's Disease
• Malignant Melanoma
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Paget's disease of the breast is a malignant (cancerous) condition that initially appears as chronic, inflammatory, "eczema-like" changes of the nipple and adjacent areas. The term "cancer" refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may potentially spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means.

In individuals with Paget's disease of the breast, initial, characteristic skin changes may include the appearance of reddish (erythematous), scaling, crusting, and/or abnormally thickened skin patches (plaques) or lesions on the nipple that may extend to adjacent areas of the areola. Some affected individuals may also have abnormal discharge from the nipple. Additional symptoms and findings may include itching (pruritic) or burning sensations and/or oozing or bleeding of the affected area. According to reports in the medical literature, the condition usually affects one breast (unilateral). However, there have also been some cases in which both breasts were involved (bilateral).

Because initial skin changes may appear relatively "benign looking," many individuals with Paget's disease of the breast may initially tend to overlook such symptoms, attributing them to inflammatory skin conditions or infection. As a result, diagnosis may be delayed in such cases, often up to six months or more. Most with the condition eventually seek medical attention due to associated itching or burning sensations, soreness, or pain of the affected area.

Some individuals with Paget's disease of the breast may have additional symptoms or findings. For example, in some instances, the nipple may turn inward (retracted nipple). In addition, up to 45 percent or more of affected individuals may have a lump or mass that may be felt (palpated) below the nipple, whereas, in many others, non-invasive or invasive malignant cells are detected upon microscopic diagnostic evaluation. (For further information, please see the "Standard Therapies: Diagnosis" section below.) In individuals with Paget's disease of the breast, the underlying malignancy may be completely contained within the milk ducts (ductal carcinoma in situ) or may have invaded surrounding tissue, potentially spreading to lymph nodes under the arms (axillary lymph nodes) and other regions of the body (metastatic disease). The overall disease course may vary greatly from case to case, depending upon the nature and size of an underlying malignancy, whether a palpable breast tumor is present upon diagnosis, whether metastatic disease is present, specific treatment measures followed, and other possible factors.
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As mentioned above, Paget's disease of the breast is characterized by the presence of distinctive tumor cells, known as Paget cells, within the outermost layer of skin (epidermis) of the nipple that may extend to involve adjacent regions of the areola. Paget cells are relatively large, undifferentiated (anaplastic) tumor cells with a distinctive appearance as detected upon microscopic evaluation.

The specific relationship between Paget cells within the nipple and underlying breast cancer has been unclear. Some investigators have suggested that the presence of Paget cells represents a distinct disease process originating in the outer skin layer of the nipple. However, the most widely accepted theory indicates that nipple involvement occurs secondary to the extension or infiltration of cancerous (malignant) cells from an underlying breast tumor (neoplasm). Supportive evidence includes laboratory studies demonstrating that Paget cells and the underlying breast cancer share certain characteristics, thus appearing to originate from the same cell population. In addition, malignant cells have been shown to extend along breast ductal tissue from the underlying breast tumor to the nipple. Accordingly, many researchers have concluded that Paget cells appear to be derived from the lining (epithelium) of milk (lactiferous) ducts, invading and multiplying (proliferating) within the surface tissue (epidermis) of the nipple and adjacent areas of the areola.

As with other cancers, the exact underlying cause or causes of breast malignancy associated with Paget's disease remain unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators at the National Cancer Institute and elsewhere are conducting ongoing basic research to learn more about the many factors that may result in cancer.

In individuals with cancer, including breast malignancies, tumor development results from abnormal changes in the structure of certain cells. The specific cause of such changes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. In many cases, these abnormal changes may appear to occur spontaneously for unknown reasons (sporadically).

Cells that undergo malignant transformation typically revert to a less specialized, more primitive form (anaplasia or loss of "differentiation"), meaning that they are no longer capable of performing their "intended," specialized functions within the tissue in question. Malignant cells pass their abnormal changes on to their "daughter" cells and typically grow and divide at an unusually rapid, uncontrolled rate. This uncontrolled cellular growth may eventually result in invasion of surrounding tissues, infiltration of regional lymph nodes, and spread of the malignancy (metastasis) via the bloodstream, the lymphatic circulation, or other means.
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Paget's disease of the breast is a rare form of breast cancer that almost exclusively affects women. However, there have been rare cases in which the disorder has occurred in men. Paget's disease of the breast most commonly affects middle-aged individuals, primarily occurring between 50 to 60 years of age. It is thought to represent approximately two to four percent of breast cancers.
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Symptoms of the following disorders may be similar to those of Paget's disease of the breast. Comparisons may be useful for a differential diagnosis:

Extramammary Paget's disease (EMPD) is characterized by the development of a reddish, scaling lesion that resembles that seen in Paget's disease of the breast but does not occur on the breasts. (The term "extramammary" refers to regions other than or outside of the breasts.) In those with EMPD, additional symptoms and findings may include itching, burning, pain, and/or bleeding of the affected area. EMPD often involves the female or male external genitals (e.g., vulva, glans penis) and/or the region around the anus (perianal region). EMPD of the vulva is associated with an underlying cancer (carcinoma) in about 30 percent of cases; involvement of the perianal area is associated with a distant or underlying carcinoma in up to approximately 73 percent of cases.

Eczema is a common inflammatory condition characterized by itching (pruritus) and redness (erythema) of upper skin layers (i.e., superficial dermatitis). The condition is also often associated with blistering or scabbing, scaling, oozing, crusting, and thickening of affected skin areas. There are multiple types of eczema that may result from various internal (endogenous) and/or external (exogenous) factors, including an excessive immune response to certain, usually environmental agents.

Bowen's disease is a localized skin malignancy (i.e., squamous cell carcinoma in situ) consisting of solitary or multiple, sharply defined, reddish brown skin patches that may be scaly and slightly thickened. It frequently resembles dermatitis or other inflammatory skin conditions and most often occurs on sun-exposed areas of the skin. (For more information on this disorder, choose "Bowen" as your search term in the Rare Disease Database.)

Malignant melanoma is a common form of skin cancer that originates in pigment-producing cells (melanocytes). Most malignant melanomas develop from existing moles, although they may sometimes originate as new, pigmented growths, particularly in sun-exposed areas of the skin. Malignant melanomas are considered highly invasive, often spreading (metastasizing) through the blood and lymph circulation to distant areas of the body. (For more information on this disorder, choose "malignant melanoma" as your search term in the Rare Disease Database.)
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Diagnosis
Paget's disease of the breast is diagnosed based upon thorough clinical examination, identification of characteristic physical findings, a complete patient history, and a variety of specialized tests. These may include blood tests; mammography or specialized x-ray imaging of the breasts; microscopic evaluation of any nipple discharge for cancerous cells (cytologic smear); and/or surgical removal (biopsy) and microscopic examination of affected breast tissue.

Treatment
The treatment of Paget's disease of the breast may vary, depending upon the nature, size, and invasiveness of an underlying breast malignancy and the presence or absence of metastatic disease. Treatment has traditionally included surgical removal of breast tissue, adjacent lymph nodes, and, in some cases, underlying muscles of the upper chest wall and other tissues (modified radical or radical mastectomy). However, evidence suggests that, in selected individuals without a palpable breast mass and negative mammograms--or in those with disease confined to the nipple and areola--surgical removal of the nipple and areola, possibly in combination with radiation therapy, may be an appropriate alternative to mastectomy; in other selected cases, recommended treatment may consist of radiation therapy alone. For such individuals, mastectomy may be reserved in case of local recurrences. Experts indicate that further research is necessary to determine the long-term effectiveness of such breast-conserving measures in selected individuals with Paget's disease of the breast.

In other cases, such as for those with larger or more invasive malignancies, recommended treatment may include mastectomy, possibly in combination with radiation or therapy with certain anticancer drugs (chemotherapy). Decisions concerning the most appropriate treatment measures must be based upon the specifics of each individual's case.
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Research on breast cancer is ongoing at the National Cancer Institute and elsewhere. For information concerning investigational therapies and clinical trials, please consider contacting the organizations listed in the "Resources" section of this report below.

NORD does not promote, endorse, or encourage participation in any specific medical research study. This information is presented to further scientific understanding that could lead to the prevention, treatment, and/or cure of rare disorders. NORD recommends that anyone interested in participating in a clinical research program seek the advice or counsel of his or her own personal physician(s).
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TEXTBOOKS
Beers MH, et al., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1974, 1982-1983.

Raghaven D, et al., eds. Textbook of Uncommon Cancer. 2nd ed. West Sussex, England: John Wiley & Sons Ltd.; 1999:1585-1586, 2409.

DeVita VT, Jr., et al., eds. Cancer: Principles and Practice of Oncology. Philadelphia, PA: Lippincott-Raven Publishers; 1997:202-203.

JOURNAL ARTICLES
Bodnar M, et al. Paget's disease of the male breast associated with intraductal carcinoma. J Am Acad Dermatol. 1999;40:829-831.

Kollmorgen DR, et al. Paget's disease of the breast: a 33-year experience. J Am Coll Surg. 1998;187:171-177.

Burke ET, et al. Paget disease of the breast: a pictorial essay. Radiographics. 1998;18:1459-1464.

Pierce LJ, et al. The conservative management of Paget's disease of the breast with radiotherapy. Cancer. 1997;80:1065-1072.

Edeiken S. Mammography in the symptomatic woman. Cancer. 1989;1:1412-1414.

Stockdale AD, et al. Radiotherapy for Paget's disease of the nipple: a conservative alternative. 1989;16:664-666.

Fourquet A, et al. Paget's disease of the nipple without detectable breast tumor: conservative management with radiation therapy. Int J Radiol Oncol Biol Phys. 1987;13:1463-1465.

Sanchez JA, et al. Paget's disease of the breast. Am Fam Physician. 1987;36:145-147.