Definition/General
Introduction:
Flat epithelial atypia (FEA) is a proliferative breast lesion characterized by the replacement of the native ductal epithelium by a single or 3-5 layers of cuboidal to columnar cells with low-grade cytological atypia
It is considered a low-risk lesion, but it is often associated with other atypical lesions and DCIS.
Origin:
FEA arises from the terminal duct-lobular unit (TDLU)
It is thought to be a non-obligate precursor to low-grade DCIS and invasive carcinoma.
Classification:
FEA is classified as a benign proliferative breast lesion with atypia
It is also known as columnar cell change with atypia or columnar cell hyperplasia with atypia.
Epidemiology:
FEA is a common incidental finding on breast biopsies, especially those performed for microcalcifications
It is most common in perimenopausal and postmenopausal women.
Clinical Features
Presentation:
FEA is asymptomatic and is not associated with a palpable mass
It is typically detected due to its association with mammographic calcifications.
Symptoms:
Asymptomatic.
Risk Factors:
The risk factors are similar to those for breast cancer in general.
Screening:
FEA is often associated with amorphous or punctate microcalcifications on mammography.
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Gross Description
Appearance:
There are no specific gross findings for FEA.
Characteristics:
Gross findings are not specific for this microscopic diagnosis.
Size Location:
Gross findings are not specific for this microscopic diagnosis.
Multifocality:
FEA can be multifocal.
Microscopic Description
Histological Features:
The terminal duct-lobular units are lined by one to several layers of cuboidal or columnar cells with monomorphic, round to oval nuclei
The cells have lost the normal polarity and hobnail appearance of apocrine cells
The lumens often contain calcifications.
Cellular Characteristics:
The cells show low-grade atypia, with mild nuclear enlargement, hyperchromasia, and inconspicuous nucleoli
Mitotic activity is low.
Architectural Patterns:
The key feature is the "flat" nature of the proliferation, without the formation of complex architectural patterns like cribriform structures or micropapillae.
Grading Criteria:
FEA is by definition a low-grade lesion.
Immunohistochemistry
Positive Markers:
The cells are strongly and diffusely positive for ER
They are positive for low molecular weight cytokeratins (e.g., CK7, CK8/18).
Negative Markers:
They are negative for high molecular weight cytokeratins (e.g., CK5/6).
Diagnostic Utility:
IHC is not usually necessary for the diagnosis of FEA but can be used to differentiate it from UDH.
Molecular Subtypes:
Molecular subtyping is not relevant for this pre-invasive lesion.
Molecular/Genetic
Genetic Mutations:
FEA shows some of the same genetic alterations as low-grade DCIS and tubular carcinoma, such as loss of heterozygosity at 16q.
Molecular Markers:
No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
FEA is associated with a small increased risk (about 1.5-2 fold) of developing invasive breast cancer
The main clinical significance is its frequent association with ADH, DCIS, and invasive carcinoma.
Therapeutic Targets:
If FEA is the only finding on a core needle biopsy, management is controversial
Some recommend excision to rule out a more significant lesion, while others recommend follow-up.
Differential Diagnosis
Similar Entities:
Columnar cell change/hyperplasia without atypia
Atypical ductal hyperplasia (ADH)
Low-grade DCIS.
Distinguishing Features:
Columnar cell change/hyperplasia lacks the cytological atypia of FEA
ADH and low-grade DCIS show more complex architectural patterns (e.g., cribriform, micropapillary).
Diagnostic Challenges:
The main challenge is distinguishing FEA from columnar cell change without atypia and from low-grade DCIS that has a flat pattern.
Rare Variants:
There are no specific rare variants.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
[diagnosis name]
Classification
Classification: [classification system] [grade/type]
Histological Features
Shows [architectural pattern] with [nuclear features] and [mitotic activity]
Size and Extent
Size: [X] cm, extent: [local/regional/metastatic]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [marker]: [result]
Molecular: [test]: [result]
[other study]: [result]
Final Diagnosis
Final diagnosis: [complete diagnosis]