Columnar Cell Change, Flat Epithelial Atypia, and Atypical Ductal Epithelial Hyperplasia

Clinical Presentation and Imaging

Most patients with columnar cell change (CCC) and FEA are found to have calcifications on mammographic screening. The observed mammographic calcifications are almost always seen to be intimately involved with CCC and FEA on microscopic sections of breast core biopsies (determinate calcifications). The calcifications are often irregular, within the lumen, and sometimes associated with flocculent intraluminal secretion material. On rare occasions, there may be marked dilatation of ducts with eosinophilic material simulating thyroid follicles. The epithelium should be scrutinized in these areas because this type of luminal content is rarely seen with fibrocystic change. Less commonly, CCLs may be seen in a breast biopsy in which the calcifications are seen in other areas of the breast tissue (nondeterminate calcifications).

CCL ranks fifth among the common findings associated with mammographic calcifications, behind fibrocystic change, fibroadenoma, ductal carcinoma in situ (DCIS), and sclerosing adenosis. Mammographic calcifications ( Fig. 19.1 ) may appear rounded, branching, amorphous, indistinct, or pleomorphic and are usually interpreted as suspicious; in the United States, they are most often assigned Breast Imaging Reporting and Data System (BI-RADS) category 4, which is indication for biopsy. Images with suspicious calcium are typically followed up with biopsies with vacuum assistance to maximize tissue volume, or execute complete removal of calcium.

Gross Pathology

There are no specific gross tissue findings of CCC or FEA.

Microscopic Pathology

The current World Health Organization (WHO) classification (5th Edition) provides three diagnostic categories: CCC, columnar cell hyperplasia (CCH), and FEA. The 5th Edition of the WHO classification also includes CCC with atypia and CCH with atypia as acceptable terms. Use of the terms clinging carcinoma (monomorphic type), atypical cystic lobules , and atypical lobules type A is not recommended. The frequent association of FEA with ADH, low-grade DCIS, tubular carcinomas, and lobular neoplasia lends support to the concept of a low-grade breast neoplasia pathway. Management recommendations vary, but many patients with FEA diagnosed on CNB are offered surgical excision to exclude coexisting carcinoma (see “Clinical Relevance, Management, and Risk/Prognosis”).

CCC involves dilated acinar spaces of the TDLU that may have irregular contours and are lined by columnar epithelial cells with ovoid nuclei oriented perpendicularly to the basement membrane. The nuclei are bland, have a fine chromatin, and have no visible nucleoli. The columnar cells have scant apical cytoplasm and apical cytoplasmic blebs or snouts that are extruded into the lumen ( Fig. 19.2 ). The flocculent secretions subsequently formed are invariably calcified to some degree.

CCH has the same overall appearance at low magnification, with irregularly dilated TDLUs. The cells lining these acini have identical morphological features, although there is cellular stratification of more than two cell layers ( Fig. 19.3 ). There may be cellular crowding or overlapping and, rarely, small tufts or mounds of cells, but no blunt micropapillary projections. Flocculent secretions and calcifications are universal.

In FEA, the dilated acini of the TDLU are single layered, or lined by three to five flat layers of epithelial cells with low-grade monomorphic cytology, increased nuclear/cytoplasmic ratios, and loss of polarity. The cell population is mostly low cuboidal and sometimes columnar, and the enlarged acini have more regular, round contours. The cytomorphology of these cells is clearly abnormal, manifested as a low-grade monomorphic atypia, in which the nuclei are generally larger, more than twice the size of the nuclei seen in CCC/CCH, rounded, and clearly abnormal in shape, with abnormally shaped nuclear membranes, mild hyperchromasia, occasional small nucleoli, and increased nucleus-to-cytoplasm (N/C) ratios ( Figs. 19.4 to 19.15 ). The cytomorphological features of these cells are virtually identical to those of ADH and low-grade DCIS when present on the same slide. Architecturally, FEA may manifest cellular stratification, but there are no blunt, club-shaped micropapillary projections or Roman bridges ( Fig. 19.16 ). In addition, FEA, including the stratified type, may demonstrate cytoplasmic apocrine features. Recognize that the term flat does not exclude cellular stratification, but it does exclude the architectural manifestations of ADH, namely, rigid bars, arches, and blunt micropapillae. Cytoplasmic blebs/snouts are present but, in general, are reduced. Mitotic figures are very uncommon but may be observed. The diagnosis of FEA must not rest on the presence of mitotic figures. The terminology applied to FEA throughout the years is supplied in Table 19.1 . An algorithmic approach to aid in the differential diagnosis and morphological assessment of columnar cell alterations is illustrated in Fig. 19.17 . Several studies have documented the reproducibility of the diagnosis of FEA and distinction from CCL, with pathologist agreement of 92% and kappa value of 0.83.