Flat Epithelial Atypia

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1 Flat Epithelial Atypia Richard Owings, M.D. University of Arkansas for Medical Sciences Department of Pathology

2 Flat epithelial atypia can be a difficult lesion May be a subtle diagnosis Lots of changes in the breast Numerous previous names and different descriptions Patient management is ambiguous.

3 Why so difficult Often occurs around definitively neoplastic lesions. Often occurs in the setting other columnar cell and proliferative lesions. Relative interpretation of atypia and flat

4 World Health Organization Flat epithelial atypia A presumably neoplastic intraductal alteration characterized by replacement of the native epithelial cells by a single or 3-5 layers of mildly atypical cells.

5 Histologic criteria Enlarged ductules or lobules Normal epithelial cells replaced by 1-4 cell layers of cytological atypical cells which are usually monomorphic The glands typically have rounded contours No complex architecture (Flat) Attenuated myoepithelial cells Atypia is small, round, and monomorphic

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13 Clinical significance Low grade non-obligate pre-neoplastic lesion Association with other lesions Atypical ductal hyperplasia Lobular neoplasia Low grade ductal carcinoma in situ (cribiform and micropapillary types) Low grade invasive carcinoma (Tubular carcinoma) FEA lesions are typically excised following diagnosis by biopsy. Excision may demonstrate a worse lesion.

14 At least some columnar cell lesions, particularly FEA, are neoplastic proliferations that may well represent either a precursor to, or at least the earliest morphologic manifestation of, a low grade DCIS as well as a precursor to invasive carcinoma. Stuart Schnitt and Laura Collins (2008). Biopsy interpretation of the breast.

15 Excisions following FEA on CNB ADH was found in 17.3% (37/214 cases) of pure FEA cases on the first set of biopsy levels by cutting 3 additional levels. A worse lesion (ADH, DCIS, LN) was found in 23 of 35 (67%) follow up excisions after complete submission. 14% of patients with FEA only on CNB may have DCIS or invasive carcinoma (5/35) on excision. Similar to ADH on CNB. Chivuklua, M., Bhargova, R, Tseng, G, Dabbs, D. Clinicopathologic implications of FEA in CNB specimens of the breast. Anatomic pathology. 2009:131:

16 Excisions following FEA on CNB 3/15 (20%) patients with FEA only by CNB were found to have worse lesions. 1 was DCIS and 2 were IDC Not correlated to residual microcalcifications 6/46 (16%) patients with ADH only by CNB were found to have DCIS. Anna Ingegnoli, et al. FEA and ADH: Carcinoma Underestimation rate. The Breast Journal, Volume 16 Number 1,

17 FEA-Molecular Clonally and molecularly related to ADH, lobular neoplasia, and low grade tubular carcinoma Similar chromosomal aberrations most commonly involving chromosomes 11q and 16q FEA colliding or merging into a low grade DCIS has similar chromosomal aberrations

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26 Differential Diagnosis From a trainee perspective, FEA, columnar cell lesions, and ADH are probably the most difficult to understand This is likely due recognizing atypia Separating benign from atypial is difficult Lots of things are atypical (both benign and malignant Instead we have to recognize these lesions as neoplastic

27 Atypical looking breast lesions/differential diagnosis Myoepthelial hyperplasia Fibrocystic change (low power cysts) Usual ductal hyperplasia Columnar cell lesions without atypia Apocrine metaplasia Lactation changes Blunt duct adenosis Flat ductal carcinoma in situ

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40 Interobserver variability Most studies have shown good reproducibility Typically compared after brief tutorial with digitized images. Little variability in separating ADH, DCIS, and normal breast Most variable lesions were those classified as columnar cell lesion with and without atypia. 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: Tan PH, Ho BC, Selvarajan S, Yap WM, Hanby A. Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility? J Clin Pathol 2005;58: O Malley FP, Mohsin SK, Badve S, et al. Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast. Mod Pathol 2006;19:172-9.

41 Management FEA on CNB is usually followed by excision. Size of the core biopsy Upgrade rate in cases of ADH is inversely proportional to core size (14 g to 11 g). Complete removal of microcalcifications Adjacent foci of DCIS or invasive carcinoma without calcifications has been documented Follow up MRI Clinical features such as age, size of lesion, patient desires

42 Closing remarks FEA can be a tricky lesion due in a large part to its history, evolving terminology, and place in the classification system. The low grade end of any classification system can be difficult Separating FEA from other proliferative lesion Over calling benign lesions Separating more malignant lesions from FEA. Under calling malignant lesions

43 Closing remarks

44 Flat Epithelial Atypia Richard Owings, M.D. University of Arkansas for Medical Science Little Rock, Ar

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