Definition/General
Introduction:
Papillary lesions of the breast encompass a spectrum ranging from benign intraductal papilloma to malignant papillary carcinoma
On FNAC, they present characteristic papillary fragments with fibrovascular cores lined by epithelial cells
The challenge lies in distinguishing benign from malignant papillary lesions based on cytological features alone.
Origin:
Arise from ductal epithelium within major lactiferous ducts (central papillomas) or peripheral ducts (peripheral papillomas)
Benign papillomas may undergo malignant transformation to papillary DCIS or invasive papillary carcinoma.
Classification:
Benign papillary lesions include intraductal papilloma and papillomatosis
Malignant lesions include papillary DCIS, invasive papillary carcinoma, and solid papillary carcinoma
Atypical papillary lesion represents intermediate category.
Epidemiology:
Intraductal papillomas account for 2-3% of breast lesions
Peak incidence in 4th-5th decade
Central papillomas more common in perimenopausal women
Peripheral papillomas associated with higher malignancy risk (15-20%).
Clinical Features
Presentation:
Central papillomas present with nipple discharge (bloody or serous) in 80% cases
Peripheral papillomas may present as palpable masses
Subareolar location typical for central type.
Symptoms:
Spontaneous nipple discharge, often unilateral and single duct
Discharge may be bloody, serous, or serosanguineous
Palpable subareolar mass in large papillomas
Breast pain uncommon.
Risk Factors:
Reproductive hormones exposure
Multiple papillomas (papillomatosis) carry higher malignancy risk
Atypical ductal hyperplasia in adjacent tissue
Family history of breast cancer.
Screening:
Clinical breast examination for nipple discharge evaluation
Ductography shows intraductal filling defects
Mammography may show dilated ducts or mass
Ultrasound demonstrates intraductal mass with vascularity.
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Gross Description
Appearance:
Soft, friable, pink to tan papillary growth within dilated duct
Size ranges from few millimeters to several centimeters
May be pedunculated or sessile
Blood clots may be associated.
Characteristics:
Delicate branching architecture
Fragile nature leads to easy fragmentation during handling
Central fibrovascular core with epithelial lining
May show areas of infarction or hemorrhage.
Size Location:
Central papillomas: subareolar location, usually <1 cm
Peripheral papillomas: any location, may be larger (1-3 cm)
Multiple papillomas may involve extensive ductal system.
Multifocality:
Solitary papillomas more common
Multiple papillomas (papillomatosis) associated with higher malignancy risk
Bilateral occurrence possible
Associated atypical ductal hyperplasia in 20% cases.
Microscopic Description
Histological Features:
Papillary architecture with fibrovascular cores lined by epithelial and myoepithelial cells
Benign papillomas show intact myoepithelial layer
Malignant lesions lack myoepithelial cells and show nuclear atypia.
Cellular Characteristics:
Benign: bland epithelial cells with uniform nuclei and intact myoepithelial layer
Malignant: nuclear pleomorphism, increased mitotic activity, loss of myoepithelial cells, cellular crowding.
Architectural Patterns:
True papillary pattern with fibrovascular cores essential
Benign lesions maintain orderly cell arrangement
Malignant lesions show architectural disarray, solid growth areas, necrosis.
Grading Criteria:
Nuclear grade assessment important for malignant lesions
Low-grade: uniform nuclei, minimal pleomorphism
High-grade: marked nuclear pleomorphism, prominent nucleoli, frequent mitoses.
Immunohistochemistry
Positive Markers:
CK7 positive in epithelial cells
CK8/18 positive
Myoepithelial markers (p63, CK5/6, smooth muscle actin) positive in benign lesions
ER/PR often positive in malignant lesions.
Negative Markers:
Myoepithelial markers negative in malignant papillary carcinoma
CK20 typically negative
TTF-1 negative
Calretinin negative (helps exclude mesothelial origin).
Diagnostic Utility:
p63 and smooth muscle actin crucial for myoepithelial layer assessment
Loss indicates malignancy
CK5/6 helps identify myoepithelial cells
ER/PR status important for treatment planning.
Molecular Subtypes:
Papillary carcinomas usually hormone receptor positive (ER+/PR+)
HER2 status variable
Low-grade lesions typically luminal subtype
High-grade may show triple-negative phenotype.
Molecular/Genetic
Genetic Mutations:
PIK3CA mutations common in papillary carcinomas (40-50%)
TP53 mutations in high-grade lesions
AKT1 mutations described
PTEN loss in subset of cases.
Molecular Markers:
p53 expression correlates with grade
Ki-67 proliferation index higher in malignant lesions
Cyclin D1 may be overexpressed
β-catenin alterations rare.
Prognostic Significance:
Benign papillomas excellent prognosis with complete excision
Papillary carcinomas generally favorable prognosis
Node involvement rare in pure papillary carcinoma.
Therapeutic Targets:
Hormone receptor positive lesions respond to endocrine therapy
mTOR pathway targeting for PIK3CA mutated cases
HER2-targeted therapy when overexpressed.
Differential Diagnosis
Similar Entities:
Benign vs malignant papillary lesions
Ductal carcinoma in situ with cribriform pattern
Invasive ductal carcinoma with papillary features
Papillary thyroid carcinoma metastasis
Mesothelial proliferation.
Distinguishing Features:
Benign papilloma: intact myoepithelial layer, bland nuclei, no necrosis
Papillary carcinoma: loss of myoepithelial cells, nuclear atypia, architectural disarray
Thyroid metastasis: TTF-1 positive, thyroglobulin positive.
Diagnostic Challenges:
Cytological distinction between benign and malignant papillary lesions difficult
Myoepithelial cells may be sparse in FNAC samples
Fragmented papillary cores may mimic other lesions.
Rare Variants:
Solid papillary carcinoma with neuroendocrine features
Invasive papillary carcinoma with micropapillary pattern
Papillary lesions with squamous metaplasia
Secretory carcinoma with papillary pattern.
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.
Site and Procedure
Site: [breast location], Procedure: Fine needle aspiration cytology
Adequacy
Adequate for evaluation
Cellularity
Moderate cellularity
Architectural Pattern
Papillary tissue fragments with fibrovascular cores
Epithelial Cells
Cohesive clusters with [bland/atypical] nuclear morphology
Myoepithelial Cells
[Present/Absent/Cannot assess] - biphasic pattern
Nuclear Features
[Grade] nuclear features with [minimal/moderate/marked] pleomorphism
Background
Blood, proteinaceous material, occasional foam cells
Cytological Diagnosis
Papillary lesion - [Category III/IV] - definitive classification requires histological examination
Recommendation
Core biopsy/surgical excision recommended for definitive diagnosis and myoepithelial assessment