Definition/General
Introduction:
Lobular carcinoma in situ (LCIS) is a non-invasive breast lesion characterized by the proliferation of abnormal cells within the breast lobules
It is considered a risk factor for developing invasive breast cancer in both breasts, rather than a direct precursor lesion.
Origin:
LCIS arises from the terminal duct-lobular unit (TDLU)
It is characterized by the loss of the cell adhesion molecule E-cadherin, which leads to the discohesive growth pattern.
Classification:
LCIS is part of the spectrum of lobular neoplasia, which also includes atypical lobular hyperplasia (ALH)
Variants of LCIS include the classic, pleomorphic, and florid types.
Epidemiology:
LCIS is most often an incidental finding in breast biopsies performed for other reasons
It is most common in premenopausal women.
Clinical Features
Presentation:
LCIS is typically asymptomatic and does not form a palpable mass or produce mammographic calcifications
It is usually an incidental finding.
Symptoms:
Asymptomatic.
Risk Factors:
The risk factors are similar to those for invasive breast cancer.
Screening:
LCIS is not typically detected by mammography
It is found incidentally on biopsy.
Master LCIS Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
There are no specific gross findings for LCIS.
Characteristics:
Gross findings are not specific for this microscopic diagnosis.
Size Location:
Gross findings are not specific for this microscopic diagnosis.
Multifocality:
LCIS is often multifocal and bilateral.
Microscopic Description
Histological Features:
The lobules are expanded and filled with a monotonous population of small, discohesive cells
The cells have scant cytoplasm and round, uniform nuclei
The underlying lobular architecture is preserved.
Cellular Characteristics:
The cells are small and uniform with round nuclei and inconspicuous nucleoli
Intracytoplasmic mucin vacuoles (signet ring cells) can be seen
Mitotic activity is low.
Architectural Patterns:
The key feature is the filling and distension of the acini of the TDLU by a discohesive population of cells
Pagetoid spread into ducts can occur.
Grading Criteria:
Classic LCIS is considered a low-grade lesion
Pleomorphic LCIS has larger cells with more nuclear atypia and is considered a more significant lesion.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for ER and PR in almost all cases
They are positive for cytokeratins.
Negative Markers:
The hallmark of LCIS is the complete loss of E-cadherin expression
HER2 is negative.
Diagnostic Utility:
IHC for E-cadherin is essential for diagnosis and to differentiate LCIS from low-grade DCIS
A negative E-cadherin stain confirms a lobular lesion.
Molecular Subtypes:
Not applicable in the same way as for invasive cancer.
Molecular/Genetic
Genetic Mutations:
The key genetic event is the loss of the CDH1 gene (which codes for E-cadherin), often due to a mutation or promoter methylation.
Molecular Markers:
Loss of E-cadherin is the key molecular marker.
Prognostic Significance:
LCIS is a risk factor for subsequent invasive carcinoma, which can be ductal or lobular, in either breast
The risk is about 1% per year
Pleomorphic LCIS may have a higher risk of progression.
Therapeutic Targets:
Management is controversial and ranges from observation to risk-reducing medication (e.g., tamoxifen) to bilateral mastectomy in high-risk patients.
Differential Diagnosis
Similar Entities:
Atypical lobular hyperplasia (ALH)
Low-grade DCIS
Invasive lobular carcinoma.
Distinguishing Features:
ALH is distinguished from LCIS by the degree of acinar involvement
in ALH, the acini are not completely filled and distended
Low-grade DCIS is E-cadherin positive
Invasive lobular carcinoma shows infiltration of the stroma.
Diagnostic Challenges:
The distinction between ALH and LCIS can be subjective
Differentiating LCIS with pagetoid spread into ducts from DCIS can be challenging without E-cadherin IHC.
Rare Variants:
Pleomorphic LCIS and florid LCIS are important variants to recognize due to their potential for being associated with invasive carcinoma.
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]