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]