Flat epithelial atypia (FEA) probably represents one of the earliest morphologically detectible findings towards the development of low-grade in situ and invasive carcinomas and lobular neoplasia. Molecular studies have shown recurrent loss of 16q, which is characteristic of low grade lesions, and gene expression profiles similar to low-grade in situ and invasive carcinomas. In the past there have been many other terms used to characterize a heterogeneous spectrum of lesions that fall under the umbrella of FEA: “small ecstatic ducts lined by atypical ductal cells with apocrine snouts,” “clinging in situ duct carcinoma flat type,” atypical cystic duct,” “DIN 1-flat type,” and “columnar alteration with prominent apical snouts and secretions with atypia.” The important take home point is that there must be low-grade atypia present to fall within this category. No atypia, then it will be described in another way (e.g. columnar cell change). If the atypic is “high-grade,” then the diagnosis of DCIS (clinging carcinoma) is warranted.
Histology
FEA is characterized first and foremost by the presence of low-grade nuclear atypia without evidence of papillary changes or the formation of architectural structures (e.g. characteristic of ADH or DCIS).
Key Features
- Dilated and enlarged terminal duct-lobar unit
- Low grade cytologic atypia (monomorphic, hyperchromatic, and mildly enlarged without grooves or notches)
- Epithelial thickness is uniform around the entire dilated gland structure
- Flat layer of cells (cuboidal but usually columnar and simple to stratified to pseudostratified) lining the distended glands
- Attenuated myopithelial cell layer (glands are distended which makes the myoepithelial layer less conspicuous
Clinical Significance
While most experts will agree that FEA is a precursor lesion to low-grade breast neoplasms, the finding of FEA in isolation in a biopsy or excision specimen is more difficult. The data is limited, but it appears that about 1/3 of subsequent excisions after finding just FEA demonstrates a more advanced lesion (e.g. DCIS, ADH).
Important Thoughts/Recommendations for Management
- Isolated finding on biopsy or excision should prompt further close search for a more advanced lesion (including deeper levels or the submission of more blocks)
- Isolated finding on biopsy – excision is routinely performed to exclude a more advanced lesion (not dissimilar to ADH)
- When found as an isolated finding in an excision specimen, no further work-up is probably indicated other than close examination of the specimen (see above).
- FEA is not used in calculating size of DCIS when associated with such lesions, or in consideration of margin status in DCIS excisions.
References
Lerwill MF. Flat epithelial atypia of the breast. Arch Pathol Lab Med. 2008;132: 615–621.
Calhoun BC, Sobel A, White RL, Gromet M, Flippo T, Sarantou T, et al. Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies. Mod Pathol. 2015;28: 670–676. doi:10.1038/modpathol.2014.159
Schnitt SJ. The diagnosis and management of pre-invasive breast disease: flat epithelial atypia–classification, pathologic features and clinical significance. Breast Cancer Res. 2003;5: 263–268. doi:10.1186/bcr625