Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review-Based Management Using Excision or Imaging Surveillance

Abstract

Objective: To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade.

Methods: This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade.

Results: Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer.

Conclusion: Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.

Keywords: benign with upgrade potential; flat epithelial atypia; multidisciplinary review.

Graphical Abstract

Figure 1.

Isolated flat epithelial atypia (FEA) in a 46-year-old woman after stereotactic biopsy of calcifications. Surgical excision was recommended, but the patient elected to undergo surveillance. The patient presented with a palpable abnormality 2 years later in the same breast but at a different location, which was shown to be microinvasive, high-grade ductal carcinoma in situ (DCIS). A: Initial magnification mediolateral (ML) view demonstrates amorphous calcifications in the left breast at the 9 o’clock position (circled). Stereotactic guided biopsy revealed isolated FEA. B: Two years later, magnification ML view demonstrates an increased number of calcifications in the left breast at the 3-o’clock position (circled). C: Two years later (obtained at the same time as the mammogram in B), longitudinal grayscale US demonstrates a lhypoechoic mass containing microcalcifications (arrows) in the left breast at the 3 o’clock position. Core needle biopsy and surgical excision revealed microinvasive high-grade DCIS.

Figure 2.

Flowchart of FEA cases. Abbreviations: BWUP, benign with upgrade potential; DCIS, ductal carcinoma in situ; FEA, flat epithelial atypia; IDC, invasive ductal carcinoma.

Figure 3.

Isolated flat epithelial atypia with usual pathologic atypia in a 42-year-old woman. Six cores were obtained with <50% of calcifications sampled. Because of insufficient sampling, surgical excision was recommended, which showed no evidence of cancer. A: Magnification lateromedial view shows loosely grouped amorphous calcifications in the left superior breast (circle). B: Hematoxylin and eosin stained high-power magnification (×10) photomicrograph shows coarse calcium oxalate microcalcifications (arrow) associated with atypia.

Figure 4.

Isolated flat epithelial atypia with significant pathologic atypia in a 66-year-old woman for which immediate surgical excision was recommended. Subsequent segmental mastectomy showed intermediate grade ductal carcinoma in situ. A: Magnification lateromedial view demonstrates a 2.8-cm area of amorphous calcifications in the right superior breast (oval). B: Hematoxylin and eosin stained low-power magnification (×4) photomicrograph shows dilated ducts lined by hyperchromatic enlarged cells with apical snouts (arrow). C: Hematoxylin and eosin–stained high-power magnification (×40) photomicrograph shows multiple cell layers with significant cytologic atypia, increased nuclear to cytoplasmic ratio, hyperchromasia, and irregular nuclear contours (arrow), consistent with significant pathologic atypia.