Flat Epithelial Atypica: FEA

"Columnar Cell hyperplasia"

Flat epithelial atypica is a proliferation of epithelial cells in the terminal duct-lobular units (TDLU) of the breast. Sometimes this neoplasm is called 'columnar cell hyperplasia' due to the architecture of the growth pattern. It tends to grow in a 'flat' pattern, without any strange build-ups or uneveness, and tends to grow into 'columns'; growing taller without growing wider. Flat epithelial atypica can grow to a thicknes of 5 or 6 epithelial cells, as opposed to the normal thickness of the breast duct lining of about 2 cells. It is generally considered to be a benign neoplasm, although there is still some debate as to whether or not flat epithelial atypica is associated with a very low grade ductal carcinoma in situ. There can also be functional breast complications with flat epithelial atypia as it does tend to cause the terminal duct lobular units to become distended, and to partially or fully block breast ducts.

 

flat epithelial breast atypia

 

'Atypical' features of flat epithelial hyperplasia

When a neoplasm (an unexpected growth of new cells) is described as 'atypical', that tends to be a bit more worrisome in terms of whether or not the hyperplasia is associated with breast cancer. Usually, the kinds of atypical developments that cause concern are unsual cell shapes, unusual variations in the nuclei, and pleomorphic formations (many different shapes). Flat epithelial hyperplasia is a somewhat atypical cell formation, but since it is so consisent it would probably not qualify as a 'low grade' atypia.(Atypical, cancer-related formations tend to be random and bizarre). But flat epithelia hyperplasia tends to have other, mildy atypical features. At the nuclear level, it is possible that some new cells will have nuclei 2 to 3 times the size of a red blood cell (RBC). Sometimes 'apical snouts' appear in the luminal cells, but most often without any exagerated or prominent features. In short, the atypical features of these developments tend not to meet the informal criteria for 'atypical ductal hyperplasia'.

Breast epithelial hyperplasia may show 'atypical' architectural structures

However, sometimes flat epithelial hyperplasia does show odd and complex architectural patterns such as well-developed micropapillations, bars and arcades, rigid cellular bridges,punched-out fenestrations, possibly some evidence of 'cellular polarization' within these structures. In these situations the lesion crosses into that 'grey area' and would likely be described as 'atypical ductal hyperplasia'.

Why is flat epithelial atypia sometimes associated with DCIS?

The hub of the current debate on these neoplasms is whether or not it is a completley benign finding, or is somehow related to DCIS. A few researchers think that flat epithelial atypia is very, very early presentation of DCIS, like a 'pre-pre-cancerous' finding. But the majority of evidence shows no proven relationship between the two. The problem is that flat epithelial atypia is sometimes found 'along with' ductal carcinoma in situ. That is not to say that the one caused the other, or that FEA somehow 'evolves' into DCIS; these are unfounded conclusions.

 

breast flat epithelial atypia

 

Risk of progression to breast cancer is very low.

Flat epithelial atypia sometimes makes an appearance around lesions which have been removed or otherwise treated, raising concerns that it might suggest an imminent 'return' of breast carcinoma. However, data at the present time suggests that the risk of either progression or 'local recurrence' of breast carcinoma with these neoplasms is extremely low.

Is flat epithelial atypia 'on the rise'?

Increased numbers of women screening for breast cancer, and also improved screening methods ( and more frequent biopsies) have led to this condition being 'discovered' more often. When the flat epithelial hyperplasia takes on a distinctive 'columnar' shape, it bears a resemblence to the 'tubules' of tubular breast carcinoma, so it is an important differential diagnosis. Flat epithelial atypia can also resemble other benign breast conditions such as apocrine metaplasia and blunt duct adenosis and since it has a slighlty higher risk connotation it is important to differentiate between them. But there is, at the same time, a considerable tendency to 'overstage' and 'overtreat' a finding of flat epithelial hyperplasia-atypia. Even among cancer researchers who feel FEA to be a very early indication of a more serious DCIS, there is no indication that this progression would be 'obligatory', and there is no apparant time-course for this progression. Prudent medical advice would be careful follow up observation.

References

  1. Lerwill MF. Flat epithelial atypia of the breast. Arch Pathol Lab Med. 2008 Apr;132(4):615-21.
  2. Schnitt, SJ. Flat epithelial atypia — classification, pathologic features and clinical significance. Breast Cancer Res 2003, 5:263-268
  3. Rosen PP: Columnar cell hyperplasia is associated with lobular carcinoma in situ and tubular carcinoma [letter]. Am J Surg Pathol 1999, 23:1561.
  4. Otterbach F, Bankfalvi A, Bergner S, Decker T, Krech R, Boecker W: Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 2000, 37:232-240.
  5. Schnitt SJ, Vincent-Salomon A: Columnar cell lesions of thebreast. Adv Anat Pathol 2003, 10:113-124.
  6. Nasser S. Flat epithelial atypia of the breast. J Med Liban 2009 ; 57 (2) : 105-109.
  7. Simpson PT, Gale T, Reis-Filho JS et al. Columnar cell lesions of the breast : the missing link in breast cancer progression ? A morphological and molecular analysis. Am J Surg Pathol 2005 ; 29 : 734-46.

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Copyright Steven B. Halls, MD Last edited 11-August-2011

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