The incidence of carcinomas having apocrine cytomorphology in at least 90% of the tumor is unknown. Carcinomas with apocrine features represent 1% (1) to 3% (2) of all breast carcinomas.

Apocrine carcinomas can occur at any age, but most arise in postmenopausal women (1,2,3,4,5,6). The mean age of patients with invasive apocrine carcinoma in one series (2) was 58.5 years, significantly higher than the mean age of 54.4 years for women with invasive nonapocrine ductal carcinoma. Apocrine carcinomas are rare in men.

Breast lesions in patients with Cowden syndrome (germline PTEN mutation) often have apocrine morphology (7,8,9) but not exclusively. Apocrine carcinoma is not specifically linked to Cowden syndrome.

The findings are similar to those in patients with nonapocrine carcinomas. Bilateral apocrine carcinomas are uncommon (10). Apocrine ductal carcinoma in situ (DCIS) can be mass-forming. Apocrine DCIS often involves sclerosing lesions such as radial sclerosing lesion (RSL) and sclerosing adenosis (SA) (11), and can mimic invasive carcinoma clinically, radiologically, and microscopically. Calcifications are common in invasive apocrine carcinomas, in apocrine DCIS, and in atypical apocrine adenosis.

Apocrine metaplasia is a benign epithelial alteration that is part of fibrocystic changes (FCCs). It often involves benign cysts and has a papillary or micropapillary configuration (Fig. 15.1). In the absence of a true papilloma/papillary lesion, the qualification of “papillary” should not be used for apocrine metaplasia in the report of a needle core biopsy (NCB) specimen, as it might trigger an unnecessary excision. Calcium oxalate crystals with characteristic “broken glass” appearance are common in apocrine cysts (Fig. 15.1). Mammographically, they are detected as “milk of calcium,” and might be the target of NCB. Calcium oxalate crystals are almost invariably associated with benign apocrine metaplasia. Rarely, psammomatous calcifications can also occur in apocrine cysts (Fig. 15.1).

Apocrine DCIS has the same architectural patterns as non-apocrine DCIS (Figs. 15.4, 15.5, 15.6, 15.7). Involvement of lobules is common. Intermediate- to high-grade neoplastic apocrine cells have enlarged, hyperchromatic, and often pleomorphic nuclei, with prominent, and sometimes multiple and irregular, nucleoli. Binucleation and intranuclear inclusions are common. The nuclear chromatin is coarse and clumped, or deeply basophilic and smudged. Three-fold or greater variation of the nuclear diameter in adjacent neoplastic cells is common. High-grade apocrine DCIS often shows necrosis. It can have densely eosinophilic cytoplasm and resemble squamous DCIS, but it lacks keratin formation. Apocrine DCIS with intermediate nuclear grade usually shows obvious apocrine cytology. Low-grade apocrine DCIS is less frequent and more difficult to recognize. The nuclei are slightly larger than those of benign apocrine metaplastic cells, and the chromatin is denser; nucleoli are visible, but they are not conspicuous (Fig. 15.7). The cytoplasm of neoplastic apocrine cells is usually abundant and shows dense eosinophilia; it can also be granular. Focal cytoplasmic vacuolization or clearing may be present in atypical apocrine lesions,



but it is prominent in high-grade apocrine carcinomas. Foam cells are sometimes admixed with apocrine DCIS (Fig. 15.8).

The diagnosis of low-grade apocrine DCIS rests on the identification of expansive growth and/or complex and rigid architectural patterns characteristic of DCIS. The definitive diagnosis of low-grade apocrine DCIS can be very challenging, especially based on review of NCB material. The differential diagnosis includes apocrine atypia and apocrine metaplasia.

Apocrine DCIS often harbors calcifications, which are coarse, heterogenous, and associated with necrosis in high-grade DCIS, and punctate and small in low-grade DCIS. Periductal fibrosis and inflammation are common near ducts and lobules involved by apocrine DCIS or atypical apocrine epithelium. Foamy histiocytes in the stroma adjacent to apocrine DCIS may mimic invasive carcinoma with histiocytoid cells. Foam cells can be present in ducts involved by apocrine DCIS (Fig. 15.8).

Apocrine DCIS and AAA often arise within or near sclerosing lesions, such as RSL and SA (11). Papillary lesions often harbor apocrine metaplasia, and apocrine DCIS can be papillary and/or arise in a papillary lesion. When evaluating a papillary apocrine lesion, it is critical to determine whether the apocrine epithelial proliferation has cytologic and architectural atypia, and these parameters need to guide the diagnostic interpretation. The finding of very scant to absent myoepithelium around cytologically benign cystic and papillary apocrine lesions has been described (16,17,18). In the absence of cytologic and architectural atypia, the absence of myoepithelium does not justify a diagnosis of carcinoma, particularly of invasive carcinoma (Fig. 15.9). On the contrary, immunohistochemical stains for cytokeratin and myoepithelial markers are usually very useful for detecting minute invasive foci near apocrine DCIS and for ruling out invasion in cases of apocrine DCIS involving a sclerosing lesion.