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]