Definition/General
Introduction:
Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer where malignant epithelial cells are confined to the breast ducts, without invasion of the basement membrane
It is considered a precursor lesion to invasive ductal carcinoma.
Origin:
DCIS arises from the terminal duct-lobular unit (TDLU)
It is a clonal proliferation of malignant cells that fill and distend the ducts.
Classification:
DCIS is classified based on architectural patterns (e.g., comedo, cribriform, solid, papillary, micropapillary) and nuclear grade (low, intermediate, high)
The presence of necrosis is also an important feature.
Epidemiology:
The incidence of DCIS has increased dramatically with the widespread use of screening mammography
It now accounts for about 20% of all breast cancer diagnoses
It is most common in postmenopausal women.
Clinical Features
Presentation:
Most cases of DCIS are asymptomatic and are detected by mammography as calcifications
Less commonly, it can present as a palpable mass or nipple discharge.
Symptoms:
Usually asymptomatic
When symptoms occur, they can include a breast lump, nipple discharge (often bloody), or Paget disease of the nipple.
Risk Factors:
The risk factors are similar to those for invasive breast cancer, including age, family history, and hormonal factors.
Screening:
Mammography is the primary method of detection
The characteristic finding is pleomorphic microcalcifications in a linear or branching distribution.
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Gross Description
Appearance:
DCIS is often not grossly visible
When it is, it may appear as a poorly defined, firm, white area
In comedo-type DCIS, the cut surface may show ducts filled with cheesy, necrotic material.
Characteristics:
The involved area may feel slightly firmer than the surrounding tissue.
Size Location:
The extent of DCIS can be variable, from a small focus to widespread involvement of a breast quadrant.
Multifocality:
DCIS can be multifocal and multicentric.
Microscopic Description
Histological Features:
The ducts are filled with a malignant epithelial proliferation
The cells are confined by the basement membrane, and a myoepithelial cell layer is preserved
The key features are the architectural pattern and nuclear grade.
Cellular Characteristics:
The tumor cells show varying degrees of atypia, from bland, monotonous cells in low-grade DCIS to highly pleomorphic cells with prominent nucleoli in high-grade DCIS
Mitotic activity is variable.
Architectural Patterns:
Comedo: solid sheets of high-grade cells with central necrosis
Cribriform: sieve-like spaces
Solid: ducts completely filled with tumor cells
Papillary: fibrovascular cores
Micropapillary: tufts of cells without fibrovascular cores.
Grading Criteria:
Grading is based on nuclear pleomorphism and the presence of necrosis
Low grade: monotonous nuclei, rare mitoses, no necrosis
High grade: pleomorphic nuclei, frequent mitoses, comedonecrosis
Intermediate grade: features in between.
Immunohistochemistry
Positive Markers:
The tumor cells are positive for cytokeratins (e.g., CK7)
Most DCIS is ER-positive
HER2 is overexpressed in a subset of cases, particularly high-grade DCIS.
Negative Markers:
The myoepithelial cell layer, which is preserved, is positive for myoepithelial markers like p63 and calponin
This is a key feature to distinguish DCIS from invasive carcinoma.
Diagnostic Utility:
IHC for myoepithelial markers is crucial to differentiate DCIS from invasive carcinoma
ER, PR, and HER2 status are important for predicting the risk of recurrence and for guiding therapy.
Molecular Subtypes:
DCIS can be classified into molecular subtypes similar to invasive cancer, with the luminal type being the most common.
Molecular/Genetic
Genetic Mutations:
The genetic alterations in DCIS are similar to those in invasive ductal carcinoma, including loss of heterozygosity at several loci and mutations in genes like PIK3CA and TP53.
Molecular Markers:
The molecular profile of DCIS is often similar to that of the invasive carcinoma that it may progress to.
Prognostic Significance:
The main risk associated with DCIS is the potential for progression to invasive carcinoma
The risk of recurrence after treatment depends on the grade, size, and margin status.
Therapeutic Targets:
Treatment is aimed at preventing progression to invasive cancer and includes surgery (lumpectomy or mastectomy) and often radiation
Endocrine therapy (e.g., tamoxifen) is used for ER-positive DCIS.
Differential Diagnosis
Similar Entities:
Atypical ductal hyperplasia (ADH)
Usual ductal hyperplasia (UDH)
Invasive ductal carcinoma.
Distinguishing Features:
ADH is distinguished from low-grade DCIS by its size (<2 mm) and extent (involving <2 ducts)
UDH has a mixed cell population and irregular slit-like spaces
Invasive carcinoma lacks a myoepithelial layer around the tumor nests.
Diagnostic Challenges:
The distinction between ADH and low-grade DCIS can be subjective and is a common reason for consultation in breast pathology.
Rare Variants:
DCIS can show various special features, such as apocrine, clear cell, or signet ring cell morphology.
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]