Infiltration of epithelium by pale cells and stromal inflammation in Paget disease involving the areola
Pigmented Paget disease and pigmented epidermotropic metastatic breast cancer have been reported. In contrast with melanoma, pigmented Paget disease usually is negative for S100, Melan A, and HMB-45.
In contrast with SCC in situ, Paget disease cells typically express low–molecular-weight keratins 7 and CAM 5.2 but not keratin 20 or high–molecular-weight keratins.
Paget disease tends to be estrogen- and progesterone-receptor negative and androgen-receptor positive, especially in patients with high-grade underlying ductal carcinoma.
HER2 overexpression often is a feature of cases associated with underlying ductal carcinoma.
Immunohistochemical stain for keratin 7 highlights epithelial infiltration with Paget disease cells
Immunohistochemical stain for Cam 5.2 highlights epithelial infiltration with Paget disease cells.
HER2 expression in Paget disease.
The histopathologic differential diagnosis also should include benign conditions characterized by pale-clear intraepidermal cells; these include pagetoid dyskeratosis, thought to be due to chronic irritation of the nipples, and clear-cell papulosis, a rare eruption affecting children that manifests as hypopigmented macules, mainly along milk lines.
These 2 disorders of large pale cells usually are distinguishable from Paget disease morphologically. Both are characterized by pale cells with limited (if any) pleomorphism; these cells tend to be larger than surrounding keratinocytes and are distributed singly or in small clusters set neatly in an otherwise normal-appearing epidermis, without discohesion. The clear cells of pagetoid dyskeratosis are positive for high–molecular-weight keratins, rather than low–molecular-weight keratins. Clear-cell papulosis typically has a profile similar to that of Paget disease, including expression of keratin 7, CAM5.2, and lack of staining for estrogen receptor, but appears to be negative for HER2.
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