Mucin immunohistochemistry in the diagnosis and mapping of extramammary Paget's disease

Abstract

Extramammary Paget's disease (EMPD) is a rare skin cancer of the genital region in which cancer cells with enlarged nuclei and pale cytoplasm are scattered singly in the affected epidermis. These cancer cells, called Paget cells, contain mucin, which is never found in normal epidermis. The oligosaccharide side chains of Paget cell mucin end with sialic acid. Sialic acid is easily detected by zirconyl haematoxylin or alcian blue. The other sugars in the oligosaccharide chains can be detected by the periodic acid-Shiff reaction. Rarely, the diagnosis of EMPD is complicated by the absence of mucin from the Paget cells. We have examined such an atypical case. The oligosaccharide side chains, including the sialic acids, are absent. In both this case and a typical case, the Paget cells contain epithelial membrane antigen mucin (MUC1) core protein and usually contain gastric surface-type mucin (MUC5AC) core protein, which can be stained by antibodies. Since neither core protein is found in normal epidermis, epithelial membrane antigen core protein may be the most reliable diagnostic marker for extramammary Paget's disease. In both the atypical case and the typical case of Paget's disease, some cells that look like keratinocytes contain mucin core proteins. These may be incipient Paget cells. We suggest that using th epithelial membrane antigen core protein as a marker for the true extent of extramammary Paget's disease could facilitate complete excision and reduce the rate of recurrence.

1

Sialomucin in typical Paget cells stains purple with zirconyl haematoxylin. The nuclei stain with methylene green.

2

Paget cells in mucin-negative extramammary Paget's disease fail to stain with zirconyl haematoxylin. The nuclei and rough ER stain with methylene green.

3

Paget cells in mucin-positive extramammary Paget's disease contain MUC5AC core protein (red–brown reaction product).

4

Many Paget cells in mucin-negative extramammary Paget's disease contain MUC5AC core protein (red–brown reaction product). A morphologically normal cell (arrow) also contains MUC5AC core protein (red–brown reaction product).

5

No cells in a control labium minus stain for MUC5AC core protein. Melanin in the stratum basale is grey–brown unlike the red–brown of Nova Red. The sebaceous gland (arrow) is unstained.

6

Mucin-negative extramammary Paget's disease. The Paget cells and two morphologically normal cells (arrows) contain epithelial membrane antigen (red–brown reaction product).

7

Mucin-positive extramammary Paget's disease. The Paget cells and two morphologically normal cells (arrows) contain epithelial membrane antigen (red–brown reaction product).

8

Normal labium minus incubated with antibody to epithelial membrane antigen. Note the difference between the red–brown stain in the sebaceous gland and the grey–brown melanin in the stratum basale.