Definition/General
Introduction:
Atypical ductal hyperplasia (ADH) is a proliferative breast lesion with some, but not all, of the features of low-grade ductal carcinoma in situ (DCIS)
It is considered a risk factor for developing invasive breast cancer.
Origin:
ADH arises from the terminal duct-lobular unit (TDLU)
It is a clonal proliferation of epithelial cells that is limited in extent.
Classification:
ADH is a benign proliferative breast lesion with atypia
The key distinction from low-grade DCIS is quantitative: ADH is diagnosed when the lesion measures less than 2 mm or involves fewer than two ducts.
Epidemiology:
ADH is often an incidental finding on breast biopsies
It is most common in perimenopausal and postmenopausal women.
Clinical Features
Presentation:
ADH is typically asymptomatic and is usually found incidentally on a biopsy performed for mammographic calcifications or another lesion.
Symptoms:
Asymptomatic.
Risk Factors:
The risk factors are similar to those for breast cancer in general.
Screening:
ADH is often associated with microcalcifications on mammography.
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Gross Description
Appearance:
There are no specific gross findings for ADH.
Characteristics:
Gross findings are not specific for this microscopic diagnosis.
Size Location:
Gross findings are not specific for this microscopic diagnosis.
Multifocality:
Can be multifocal.
Microscopic Description
Histological Features:
ADH is characterized by a proliferation of monotonous, evenly spaced cells forming cribriform structures, arches, or micropapillae, similar to low-grade DCIS
The key is the limited extent of the lesion.
Cellular Characteristics:
The cells are small and uniform with round nuclei and inconspicuous nucleoli
Mitotic activity is low.
Architectural Patterns:
The architectural patterns are the same as in low-grade DCIS (cribriform, micropapillary, solid), but the lesion is quantitatively limited.
Grading Criteria:
ADH is by definition a low-grade lesion.
Immunohistochemistry
Positive Markers:
The cells are positive for ER in most cases
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), which helps distinguish ADH from usual ductal hyperplasia (UDH).
Diagnostic Utility:
IHC for CK5/6 is very useful to differentiate ADH (negative) from UDH (mosaic pattern of positivity).
Molecular Subtypes:
Molecular subtyping is not relevant for this pre-invasive lesion.
Molecular/Genetic
Genetic Mutations:
ADH shows some of the same genetic alterations as low-grade DCIS and invasive carcinoma, such as loss of heterozygosity at 16q.
Molecular Markers:
No specific molecular markers are routinely used for diagnosis.
Prognostic Significance:
ADH is a risk factor for developing invasive breast cancer, with a 4-5 fold increased risk
The risk applies to both breasts.
Therapeutic Targets:
Management typically involves surgical excision of the area to rule out an associated DCIS or invasive carcinoma
Risk-reducing medication (e.g., tamoxifen) may be considered.
Differential Diagnosis
Similar Entities:
Low-grade DCIS
Usual ductal hyperplasia (UDH).
Distinguishing Features:
The distinction between ADH and low-grade DCIS is based on size (<2 mm for ADH)
UDH has a heterogeneous cell population, irregular slit-like spaces, and a mosaic pattern of CK5/6 staining.
Diagnostic Challenges:
The main challenge is the quantitative distinction from low-grade DCIS, which can be difficult on core needle biopsies due to sampling
This is why excision is often recommended.
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]