Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS.