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Invasive breast carcinoma - IARC

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A<br />

B<br />

Fig. 1.158 Paget disease of the nipple. A Atypical cells with clear cytoplasm admixed with those with dense cytoplasm. B, C Immunostaining for cytokeratin 7 (B)<br />

and ERBB2 (C) decorate the neoplastic cells predominantly located in the lower portion of the epidermis.<br />

C<br />

ters which are often closely packed in<br />

the centre of the lesion and lower portion<br />

of the epidermis but tend to be dispersed<br />

in single cells at the periphery<br />

and upper portion of the epidermis. The<br />

underlying lactiferous ducts contain a<br />

usually high grade DCIS that merges<br />

with the PD. Rare l y, lobular intraepithelial<br />

neoplasia is encountered. Even<br />

when the in situ <strong>carcinoma</strong> is in the<br />

deep <strong>breast</strong> tissue, an involved lactiferous<br />

duct with or without skip areas can<br />

almost always be identified by serial<br />

s e c t i o n i n g .<br />

An associated infiltrating carc i n o m a<br />

occurs in one-third of patients who present<br />

without a palpable mass and in more<br />

than 90% of those with a palpable mass.<br />

Special stains reveal the presence of<br />

mucin in the Paget cells in a large number<br />

of cases. Paget cells occasionally<br />

contain melanin pigment granules as a<br />

result of phagocytosis.<br />

Immunoprofile<br />

I m m u n o h i s t o c h e m i c a l l y, Paget cells<br />

demonstrate similar pro p e rties to the<br />

underlying intraductal <strong>carcinoma</strong> cells<br />

with positive immunoreactivity for carc i-<br />

n o e m b ryonic antigen, low molecular<br />

weight cytokeratin and ERBB2. On<br />

occasion, one of these antisera may be<br />

negative. Squamous <strong>carcinoma</strong> is commonly<br />

non-reactive for these antisera,<br />

but rarely may be immunoreactive for<br />

cytokeratin 7 {3128}. Contrary to malignant<br />

melanoma, PD is usually S-100<br />

p rotein and HMB45 negative. In PD,<br />

TP53 and estrogen receptor may be<br />

negative or positive, depending on the<br />

i m m u n o p rofile of the corre s p o n d i n g<br />

underlying <strong>carcinoma</strong>.<br />

Differential diagnosis<br />

PD occasionally poses diff e rential diagnostic<br />

problems with malignant<br />

melanoma due to the pagetoid pattern<br />

of spread and the presence of pigment<br />

granules and also with squamous cell<br />

c a rcinoma in situ, due to the pro l i f e r a-<br />

tion of atypical dark cells. The application<br />

of histochemical techniques and<br />

the use of immunostains will solve the<br />

question in most cases.<br />

Prognosis and predictive factors<br />

The prognosis is dependent on the<br />

p resence or absence of underlying<br />

intraductal <strong>carcinoma</strong> and associated<br />

invasive <strong>carcinoma</strong> in the deep bre a s t<br />

t i s s u e .<br />

106 Tumours of the <strong>breast</strong>

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