Definition/General
Introduction:
Adenoid cystic carcinoma (ACC) of the breast is a rare type of invasive breast cancer, accounting for less than 0.1% of all cases
It is histologically identical to ACC found in the salivary glands and is characterized by a dual population of epithelial and myoepithelial cells.
Origin:
The cell of origin is thought to be from the terminal duct-lobular unit (TDLU), with differentiation towards both luminal and myoepithelial cells.
Classification:
It is a special subtype of invasive breast carcinoma
It is characterized by three main architectural patterns: cribriform, tubular, and solid
The presence of a solid component is associated with a worse prognosis.
Epidemiology:
It typically occurs in postmenopausal women, with a wide age range
It presents as a palpable mass and is generally slow-growing.
Clinical Features
Presentation:
Presents as a well-circumscribed, often tender or painful mass
Pain is a more common feature than in other breast cancers
Nipple discharge is rare.
Symptoms:
A palpable, firm, and sometimes painful breast lump
The tumor is usually slow-growing.
Risk Factors:
There are no well-established risk factors specific to ACC of the breast
General breast cancer risk factors may apply.
Screening:
Mammographically, it can appear as a well-defined or irregular mass, sometimes with calcifications
Ultrasound may show a complex cystic and solid mass.
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Gross Description
Appearance:
The tumor is typically a well-circumscribed, firm, gray-white mass
It can have a cystic or solid appearance on cut section.
Characteristics:
The size is variable, but they are often small at diagnosis
The consistency is firm.
Size Location:
No specific predilection for any breast quadrant.
Multifocality:
Multifocality is uncommon.
Microscopic Description
Histological Features:
The tumor is composed of nests of basaloid cells arranged in cribriform, tubular, or solid patterns
The cribriform spaces often contain eosinophilic, PAS-positive basement membrane-like material
A dual population of luminal (epithelial) and basal (myoepithelial) cells is characteristic.
Cellular Characteristics:
The cells are small and basaloid with scant cytoplasm and hyperchromatic nuclei
Mitotic activity is usually low.
Architectural Patterns:
Cribriform pattern is the most common, with back-to-back glands forming punched-out spaces
Tubular and solid patterns can also be seen
The presence of a solid pattern (>30%) is associated with a worse prognosis.
Grading Criteria:
These tumors are typically considered low to intermediate grade.
Immunohistochemistry
Positive Markers:
The luminal cells are positive for CK7 and EMA
The basal/myoepithelial cells are positive for p63, CK5/6, and SMMHC
CD117 (c-kit) is often positive.
Negative Markers:
Usually negative for ER, PR, and HER2, making it a type of triple-negative breast cancer.
Diagnostic Utility:
IHC is essential to demonstrate the dual cell population, which is key to the diagnosis
p63 and CK5/6 are useful for highlighting the myoepithelial component.
Molecular Subtypes:
Most ACCs are classified as triple-negative/basal-like, but they have a much better prognosis than typical triple-negative breast cancers.
Molecular/Genetic
Genetic Mutations:
The characteristic genetic alteration is a t(6;9) translocation resulting in a MYB-NFIB gene fusion
This is found in a high percentage of cases and is a key diagnostic marker.
Molecular Markers:
Detection of the MYB rearrangement by FISH or RT-PCR can confirm the diagnosis in difficult cases.
Prognostic Significance:
Excellent prognosis with a high long-term survival rate
Lymph node metastasis is rare, but distant metastasis (typically to the lungs) can occur, sometimes many years after initial diagnosis
The presence of a solid growth pattern is the most important adverse prognostic factor.
Therapeutic Targets:
Due to its triple-negative status, it does not respond to hormonal or HER2-targeted therapies
Treatment is primarily surgical
The role of adjuvant chemotherapy is not well-established due to the rarity of the tumor.
Differential Diagnosis
Similar Entities:
Collagenous spherulosis (benign)
Cribriform DCIS
Invasive cribriform carcinoma
Solid papillary carcinoma.
Distinguishing Features:
Collagenous spherulosis has a myoepithelial layer and lacks the MYB rearrangement
Cribriform DCIS and invasive cribriform carcinoma are composed of a single (luminal) cell type and are ER-positive and p63-negative
Solid papillary carcinoma is also composed of a single cell type and is ER-positive.
Diagnostic Challenges:
Distinguishing ACC from other cribriform lesions of the breast is the main challenge
IHC for myoepithelial markers and molecular testing for MYB rearrangement are key.
Rare Variants:
The main variants are based on the architectural pattern (cribriform, tubular, solid).
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]