Definition/General

Introduction:
-Breast adenoid cystic carcinoma (ACC) is a rare malignant epithelial tumor accounting for less than 0.1% of all breast carcinomas
-It is characterized by a distinctive cribriform pattern with dual cell population of ductal and myoepithelial cells, similar to its salivary gland counterpart.
Origin:
-Adenoid cystic carcinoma arises from terminal duct lobular units of the breast
-It shows biphasic differentiation with both ductal epithelial cells and myoepithelial cells, maintaining basement membrane production capabilities.
Classification:
-WHO Classification of Breast Tumors (2019) categorizes ACC as a special type of invasive breast carcinoma
-Three histological patterns are recognized: cribriform (most common), tubular, and solid patterns.
Epidemiology:
-Peak incidence occurs in women aged 50-70 years
-More common in African American women
-Associated with BRCA1 mutations in some cases
-Generally has better prognosis compared to invasive ductal carcinoma NOS.

Clinical Features

Presentation:
-Patients typically present with a painless, well-circumscribed breast mass
-Median size at presentation is 2-3 cm
-May be detected on routine mammographic screening.
Symptoms:
-Palpable breast lump (most common)
-Usually painless
-No nipple discharge
-No skin changes or nipple retraction
-Axillary lymphadenopathy is rare.
Risk Factors:
-Advanced age (>50 years)
-BRCA1 mutation carriers
-African American ethnicity
-Previous radiation exposure
-Family history of breast cancer.
Screening:
-Routine mammographic screening per guidelines
-Clinical breast examination
-MRI screening in high-risk patients
-Genetic counseling for BRCA1 carriers.

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Gross Description

Appearance:
-Well-circumscribed to partially circumscribed mass
-Firm to hard consistency
-Cut surface shows gray-white to tan color
-May have small cystic spaces.
Characteristics:
-Size ranges from 0.5-5 cm (median 2.5 cm)
-Spherical to oval shape
-Smooth or slightly irregular borders
-No obvious necrosis or hemorrhage.
Size Location:
-Most commonly located in upper outer quadrant
-Can occur in any breast quadrant
-Usually unilateral
-Bilateral occurrence is extremely rare.
Multifocality:
-Typically unifocal
-Multifocal disease is uncommon
-Multicentric involvement is rare
-Contralateral involvement requires genetic evaluation.

Microscopic Description

Histological Features:
-Cribriform pattern with round to oval spaces (pseudocysts)
-Biphasic cell population with ductal and myoepithelial cells
-Basement membrane material in pseudocysts.
Cellular Characteristics:
-Small, uniform cells with round to oval nuclei
-Minimal nuclear pleomorphism
-Low mitotic activity (<5 per 10 HPF)
-Dual cell population pattern.
Architectural Patterns:
-Cribriform pattern (most common - 70%)
-Tubular pattern (20%)
-Solid pattern (10% - associated with worse prognosis)
-Mixed patterns possible.
Grading Criteria:
-Generally considered low-grade malignancy
-Solid pattern indicates higher grade
-Nuclear grade is typically low (Grade 1)
-Mitotic count is low.

Immunohistochemistry

Positive Markers:
-Ductal cells: CK7+, CK8/18+, EMA+, E-cadherin+
-Myoepithelial cells: p63+, SMA+, calponin+, CK14+, S-100+.
Negative Markers:
-ER negative (>95%)
-PR negative (>95%)
-HER2 negative
-Ki-67 low (<10%)
-CK20 negative.
Diagnostic Utility:
-Dual cell population pattern confirms diagnosis
-Helps differentiate from invasive ductal carcinoma
-Rules out salivary gland primary.
Molecular Subtypes:
-Triple-negative breast cancer (TNBC) subtype
-Basal-like immunophenotype
-Low proliferation index
-Special type carcinoma classification.

Molecular/Genetic

Genetic Mutations:
-MYB-NFIB fusion (50-60% of cases)
-MYBL1 rearrangements (20-30%)
-BRCA1 mutations (10-15%)
-TP53 mutations (rare).
Molecular Markers:
-MYB protein overexpression
-NFIB protein expression
-Low Ki-67 labeling index
-Absence of PIK3CA mutations.
Prognostic Significance:
-MYB-NFIB fusion associated with better prognosis
-Solid pattern indicates worse outcome
-BRCA1 mutations may affect treatment response.
Therapeutic Targets:
-Limited targeted therapy options
-MYB pathway potential target
-PARP inhibitors for BRCA1-associated cases
-CDK4/6 inhibitors under investigation.

Differential Diagnosis

Similar Entities:
-Invasive ductal carcinoma with cribriform pattern
-Metastatic adenoid cystic carcinoma from salivary gland
-Invasive cribriform carcinoma
-Microglandular adenosis.
Distinguishing Features:
-ACC: Dual cell population, basement membrane material, triple-negative
-IDC cribriform: Single cell type, ER/PR positive
-Metastatic ACC: Clinical history, imaging findings.
Diagnostic Challenges:
-Distinction from primary salivary gland tumor
-Separation from invasive cribriform carcinoma
-Recognition of solid pattern variant
-Assessment of margins.
Rare Variants:
-Solid variant (worse prognosis)
-Basaloid variant
-High-grade transformation (rare)
-Combined with other histologic types.

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: [Lumpectomy/Mastectomy]\nSpecimen Size: [X x Y x Z cm]\nTumor Location: [Quadrant/Clock position]

Diagnosis

Invasive adenoid cystic carcinoma, breast\nHistologic Pattern: [Cribriform/Tubular/Solid/Mixed]

Tumor Size

Invasive Carcinoma Size: [X.X cm]\nIn Situ Component: [Present/Absent]

Histologic Grade

Nottingham Grade: [1/2/3] (Tubule formation: [1-3], Nuclear grade: [1-3], Mitotic rate: [1-3])

Margins

Superior: [Negative/Positive] - closest distance [X mm]\nInferior: [Negative/Positive] - closest distance [X mm]\nAnterior: [Negative/Positive] - closest distance [X mm]\nPosterior: [Negative/Positive] - closest distance [X mm]\nMedial: [Negative/Positive] - closest distance [X mm]\nLateral: [Negative/Positive] - closest distance [X mm]

Lymphovascular Invasion

Lymphovascular invasion: [Not identified/Present]\n[If present: Extensive/Focal]

Hormone Receptors

Estrogen Receptor: Negative (0%)\nProgesterone Receptor: Negative (0%)\nHER2: [Score 0/1+/2+/3+]\n[If 2+: HER2 ISH result]

Special Studies

Immunohistochemistry: p63: Positive (myoepithelial cells)\nSMA: Positive (myoepithelial cells)\nCK7: Positive (ductal cells)\nKi-67: [X]% (low proliferation)

Molecular Studies: [If performed]\nMYB-NFIB fusion: [Positive/Negative/Not performed]

Lymph Nodes

Lymph Nodes: [Number examined]\nPositive Nodes: [Number positive]\nExtranodal Extension: [Present/Absent/Not applicable]

Pathologic Stage (AJCC 8th Edition)

pT: [T1a/T1b/T1c/T2/T3/T4]\npN: [N0/N1/N2/N3]\nOverall Stage: [I/II/III]

Additional Findings

Background Breast Tissue: [Normal/Benign changes]\nCalcifications: [Present/Absent]\nOther: [Specify any additional findings]

Comments

Adenoid cystic carcinoma is a rare special type breast carcinoma with generally favorable prognosis. Triple-negative immunophenotype is characteristic. Consider genetic counseling for BRCA1 testing.