Definition/General
Introduction:
Atypical lobular hyperplasia (ALH) is a proliferative breast lesion characterized by the proliferation of small, discohesive cells within the breast lobules, but not meeting the criteria for lobular carcinoma in situ (LCIS)
It is a risk factor for developing invasive breast cancer.
Origin:
ALH arises from the terminal duct-lobular unit (TDLU)
It is part of the spectrum of lobular neoplasia and is characterized by the loss of E-cadherin.
Classification:
ALH is a benign proliferative breast lesion with atypia
The distinction from LCIS is quantitative: ALH is diagnosed when the characteristic cells fill less than 50% of the acini within a lobule.
Epidemiology:
ALH is often an incidental finding on breast biopsies
It is most common in premenopausal women.
Clinical Features
Presentation:
ALH is typically asymptomatic and is usually found incidentally on a biopsy performed for other reasons.
Symptoms:
Asymptomatic.
Risk Factors:
The risk factors are similar to those for breast cancer in general.
Screening:
ALH does not typically produce mammographic findings
It is an incidental microscopic finding.
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Gross Description
Appearance:
There are no specific gross findings for ALH.
Characteristics:
Gross findings are not specific for this microscopic diagnosis.
Size Location:
Gross findings are not specific for this microscopic diagnosis.
Multifocality:
ALH can be multifocal and bilateral.
Microscopic Description
Histological Features:
ALH is characterized by a proliferation of small, uniform, discohesive cells within the acini of a lobule
The cells are identical to those of LCIS, but the proliferation involves less than 50% of the acini.
Cellular Characteristics:
The cells are small and monotonous with scant cytoplasm and round, uniform nuclei
Intracytoplasmic mucin vacuoles can be seen.
Architectural Patterns:
The acini are partially filled with the discohesive cells
The underlying lobular architecture is preserved.
Grading Criteria:
ALH is a low-grade lesion.
Immunohistochemistry
Positive Markers:
The cells are positive for ER and PR
They are positive for cytokeratins.
Negative Markers:
The hallmark is the loss of E-cadherin expression
HER2 is negative.
Diagnostic Utility:
IHC for E-cadherin is essential for diagnosis and to differentiate ALH from atypical ductal hyperplasia (ADH).
Molecular Subtypes:
Molecular subtyping is not relevant for this pre-invasive lesion.
Molecular/Genetic
Genetic Mutations:
Loss of the CDH1 gene is the key genetic event.
Molecular Markers:
Loss of E-cadherin is the key molecular marker.
Prognostic Significance:
ALH 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 clinical follow-up
Risk-reducing medication (e.g., tamoxifen) may be considered.
Differential Diagnosis
Similar Entities:
Lobular carcinoma in situ (LCIS)
Atypical ductal hyperplasia (ADH).
Distinguishing Features:
The distinction between ALH and LCIS is quantitative, based on the extent of acinar involvement
ADH is E-cadherin positive and has different cytological and architectural features.
Diagnostic Challenges:
The main challenge is the quantitative distinction from LCIS, which can be subjective.
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]