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Paget’s Disease
Key Points
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Mammary Paget's disease (MPD) is almost always associated with underlying breast carcinoma. If an underlying mass is palpated, the patient should be referred for a fine needle biopsy of the mass or an excisional biopsy.
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The immunostaining pattern of MPD and extramammary Paget's disease (EMPD) show substantial overlap, but EMPD is more likely to stain positively for gross cystic disease fluid protein 15 and less likely to stain for the human milk-fat-globule membrane protein MFGM-gp 155.
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Expression of histo-blood group A type 1/2, and type 3 antigens by tumor cells of EMPD may correlate with a greater risk of invasive carcinoma.
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CK20 staining in EMPD suggests underlying carcinoma of the colon.
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Recent evidence suggests that EMPD tumor cells grow in a contiguous fashion, and that long finger-like projections may account for the high incidence of local recurrence.
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Mohs micrographic surgery (MMS) is a valuable technique for the removal of tumors with irregular growth patterns, and has proved useful as a tissue-sparing form of surgical therapy for EMPD. Immunostains can improve the sensitivity of margin control with MMS.
Introduction
The term Paget's disease incorporates two unrelated groups of disorders. The first is Paget's disease of the bone, also known as osteitis deformans. The second comprise malignant neoplasms affecting the skin. When occurring on the breast or nipple, the condition is referred to as mammary Paget's disease (MPD). It is called extramammary Paget's disease (EMPD) if it occurs anywhere else. Both may be associated with underlying malignancies. An underlying malignancy is almost always present in MPD ( Table 14.1 ).
Table 14.1
Mammary vs Extramammary Paget's Disease
| Mammary Paget's Disease | Extramammary Paget's Disease | |
|---|---|---|
| Epidemiology | 0.6–3.2% of all breast carcinomas Median age of onset 54–57 years Male to female ratio 1:50–200 |
14% of all Paget's disease Median age of onset 72–75 years Male to female ratio 1:1.2 |
| Anatomic locations | Breast | Vulva, perineal region, scrotum, axillae |
| Pathology | Large cells with pale cytoplasm within the epidermis, usually appear to ‘crush’ the basal epidermal layer Common markers: EMA, CEA, CK7 Specific markers * : Her2/Neu, ER |
Large cells with pale cytoplasm within the epidermis, usually appear to ‘crush’ the basal epidermal layer Common markers: EMA, CEA, CK7 * Specific markers * : GCDFP-15, CK20 † Histo-blood group A type 1, 2, 3 antigens ‡ |
| Prognosis | 5-year survival rate of 88–93% for invasive and 98–100% for non-invasive disease | 5-year-survival rate of 85% for minimally invasive and as low as 25% for deeply invasive disease |
| Therapy | Treatment based on the standards for the underlying breast malignancy, usually breast-conserving surgery + XRT+ SNLB | Local excision preferably by Mohs surgery for isolated lesions Otherwise, treatment based on the standards for the underlying malignancy and the depth of invasion |
* Positive only in certain percentage of cases.
† Usually positive when EMPD is associated with underlying colorectal carcinoma or transitional cell carcinoma of the bladder.
‡ May correlate with greater risk of invasive disease in EMPD.
Mammary Paget's disease
History
The initial clinical description of the disease was provided by a French physician, Alfred Velpeau, in his book entitled A Treatise on the Diseases of the Breast and Mammary Region , published in 1856. He described the condition as an unusual irritation of the nipple resembling eczema or psoriasis, where ‘the nipple looked like a raspberry or strawberry’. However, Velpeau classified this condition as a benign eczematous process and provided no clear etiology for the disease. It was the British physician Sir James Paget who described the association of the condition with an underlying malignancy, and his name is now associated with the disease. In his report, which was published in 1874 in St. Bartholomew's Hospital Reports in London, Paget gave a similar clinical description to that of Velpeau, but he noted that in every case there was an underlying carcinoma identified within 2 years. In all the patients described by Paget, the skin eruption preceded the malignancy, and Paget concluded that the malignancy was likely a secondary event due to chronic irritation of the underlying structures. It was not until 1881 that George Thin described the pathology of the lesions and was first to state that the observed skin condition was a neoplastic process secondary to an underlying ductal carcinoma.
Epidemiology
Paget's disease of the breast is a relatively rare condition, and it accounts for roughly 0.6–3.2% of all the breast carcinomas. The median age of onset is 54–57 years, with a male to female ratio of 1:50–200. In 82–100% of patients, MPD is associated with an underlying breast malignancy. Of these malignancies, 74–90% are either invasive or in-situ ductal adenocarcinomas, 18% are unspecified adenocarcinomas, and 1% are lobular carcinomas. Survival rates vary, but with recent advances in diagnostic and surgical techniques, the 5-year survival rate is estimated to be 88–93% for invasive disease and 98–100% for non-invasive disease. The 5-year disease-free survival rate is approximately 75% in both groups.
Pathogenesis and etiology
While the majority of cases of MPD represent extensions of underlying breast adenocarcinoma, rarely, cases can be limited to the epidermis and are referred to as primary MPD. Some cases of primary MPD may arise from Toker cells, while other apparent cases of primary MPD may simply represent tissue sampling error. Toker cells, first described by Cyril Toker, are large intraepidermal cells with ample pale cytoplasm. They are usually found in the basal layer of normal nipple epidermis at the openings of the lactiferous ducts, and appear to give rise to clear cell papulosis as well as EMPD. Some regard clear cell papulosis as the benign counterpart of EMPD and primary MPD.
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