'Flat epithelial atypia' is better considered a descriptive term that encompasses several different lesions, rather than a specific pathologic diagnosis per se
. Despite the diversity of published descriptions and the wide assortment of names applied to breast lesions that would currently be included in the category of flat epithelial atypia [2
] (Table ), for practical purposes these lesions can be grouped into one of two diagnostic categories: columnar cell change with atypia or columnar cell hyperplasia with atypia [12
]. Although 'flat epithelial atypia' will be used for purposes of discussion in the present review, we use the more specific diagnostic terms 'columnar cell change with atypia' and 'columnar cell hyperplasia with atypia' in clinical practice and in surgical pathology reporting.
Other names used to describe lesions within the category of flat epithelial atypia
Columnar cell change with atypia
Columnar cell change with atypia is characterized by terminal duct lobular units that display variably dilated acini lined by one or two layers of epithelial cells that are columnar in shape, although the height of these columnar cells varies. Apical cytoplasmic blebs or snouts are often present at the luminal surface of the epithelial cells and, in some cases, may be prominent or exaggerated, which may impart an irregular contour to the luminal aspect of the acini.
Flocculent secretions are often present in the acinar lumina. In addition, the acini often contain luminal calcifications that may be irregular or may have the appearance of psammoma bodies (Fig. ). The cells lining the involved acini show cytologic atypia, which is usually of low grade. This atypia is characterized by the presence of columnar epithelial cells with round to ovoid nuclei that are not regularly oriented perpendicular to the basement membrane, with a slight increase in the nuclear/cytoplasmic ratio. The nuclear chromatin may be evenly dispersed or slightly marginated, and the nucleoli are variably prominent. Mitotic figures may be seen but are uncommon (Fig. ). In other cases, the columnar cells may resemble the cells comprising the tubules of tubular carcinoma. The cytologic atypia in these cases may be quite subtle.
Figure 1 Flat epithelial atypia: columnar cell change with atypia. (a) This terminal duct lobular unit shows variably dilated acini, many of which contain intraluminal secretions and calcifications. Most acini are lined by only one or two layers of columnar epithelial (more ...)
In some cases of columnar cell change with atypia, the lesion may be overlooked entirely on low-power microscopic examination due to the lack of significant cellular proliferation and the subtle nature of the cytologic atypia [8
]. In fact, terminal duct lobular units exhibiting this alteration are often misinterpreted on low-power microscopic examination as either normal or as showing only microcysts. It is only after examination of such foci under high magnification that the subtle cytologic atypia becomes evident.
Columnar cell hyperplasia with atypia
The term columnar cell hyperplasia with atypia is used to describe lesions composed of terminal duct lobular units with variably dilated acini lined by columnar cells that have cytologic features similar to those seen in columnar cell change with atypia but that also show cellular stratification of more than two cell layers. The proliferating epithelial cells may form small mounds, tufts or short micropapillations. However, complex architectural patterns, such as well-developed micropapillations, rigid cellular bridges, bars and arcades, or sieve-like fenestrations, with evidence of cellular polarization within the micropapillations and bars or around the fenestrations, are absent (Fig. ). Thus, while these lesions are included under the heading 'flat epithelial atypia', it should be apparent that 'flat' is a relative term, simply denoting the absence of complex architectural patterns as described earlier. Exaggerated apical cytoplasmic snouts and abundant flocculent intraluminal secretions are often present, and some of the cells comprising such lesions may have a hobnail appearance. These lesions frequently show intraluminal calcifications, which in some instances may have the configuration of psammoma bodies.
Figure 2 Flat epithelial atypia: columnar cell hyperplasia with atypia. The acini in this terminal duct lobular unit are lined by a few layers of columnar epithelial cells that show low-grade cytologic atypia, characterized by relatively round, monotonous nuclei (more ...)
High-grade cytologic atypia with nuclear pleomorphism of the type seen in high-grade DCIS is not a feature of lesions we include in the categories of columnar cell change with atypia or of columnar cell hyperplasia with atypia [12
]. The presence of such high-grade nuclear features merits the designation of high-grade DCIS, even if the cells comprise only a single cell layer [6
]. However, such lesions are rarely seen in the absence of high-grade DCIS exhibiting other architectural patterns.
It is important to note that while the flat lesions we have designated columnar cell change with atypia and columnar hyperplasia with atypia may be observed in isolation, they often coexist with more complex proliferative lesions that are composed of cytologically similar cells and that fulfill the diagnostic criteria for ADH or DCIS. In fact, their presence should prompt a diligent search for such areas.