Definition/General
Introduction:
Phyllodes tumor with secretory carcinoma is an exceptionally rare malignant phyllodes tumor where the stromal component contains secretory carcinoma characterized by microcystic and tubular architecture with abundant eosinophilic secretions.
Origin:
Develops from intralobular breast stroma with differentiation toward secretory carcinoma
May arise through specific genetic alterations leading to secretory phenotype similar to mammary analog secretory carcinoma.
Classification:
WHO Classification categorizes this as malignant phyllodes tumor with heterologous elements
Secretory carcinoma component shows characteristic ETV6-NTRK3 gene fusion.
Epidemiology:
Exceptionally rare with fewer than 5 cases reported worldwide
Can occur at any age but peak in young adults
Female predominance
Generally associated with favorable prognosis.
Clinical Features
Presentation:
Well-circumscribed breast mass
Usually presents as slow-growing, non-tender mass
May occur in young women and adolescents
Often clinically benign appearance.
Symptoms:
Painless breast mass
Usually completely asymptomatic
May be discovered on routine examination
Breast asymmetry in younger patients
No constitutional symptoms.
Risk Factors:
Previous phyllodes tumor history
Young age (adolescent/young adult)
No established environmental risk factors
Genetic predisposition unknown.
Screening:
No specific screening indicated
Clinical examination important in young women
Imaging with ultrasound preferred in young patients
MRI may be helpful.
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Gross Description
Appearance:
Well-circumscribed, soft to firm mass
Cut surface shows gray-white to tan areas with possible cystic spaces
Gelatinous areas may be present.
Characteristics:
Size variable (1-8 cm)
Soft to firm consistency
Well-circumscribed borders
May have microcystic areas
Gelatinous or mucoid appearance possible.
Size Location:
Can occur in any breast region
Usually well-demarcated from surrounding tissue
Unilateral presentation
Circumscribed borders typical.
Multifocality:
Typically unifocal mass
Secretory areas may be multifocal within tumor
Expansile growth pattern
No infiltrative borders.
Microscopic Description
Histological Features:
Biphasic tumor with epithelial and mesenchymal components
Secretory carcinoma areas show microcystic, tubular, and solid patterns with abundant intracellular and extracellular eosinophilic secretions.
Cellular Characteristics:
Small to medium-sized cells with granular eosinophilic cytoplasm
Low nuclear grade
Minimal pleomorphism
Abundant secretory material
Low mitotic activity.
Architectural Patterns:
Microcystic pattern with small rounded spaces
Tubular structures
Solid areas with secretory cells
Abundant pink secretory material
Well-demarcated borders.
Grading Criteria:
Low nuclear grade (Grade 1)
Low mitotic rate (<5 per 10 HPF)
Secretory differentiation
Well-differentiated architecture
Minimal pleomorphism.
Immunohistochemistry
Positive Markers:
S-100 positive
Mammaglobin positive
GCDFP-15 may be positive
Cytokeratins positive
α-lactalbumin positive
Lysozyme positive.
Negative Markers:
Estrogen receptor usually negative
Progesterone receptor usually negative
HER2 negative
TTF-1 negative
CDX2 negative.
Diagnostic Utility:
S-100 and mammaglobin support secretory differentiation
NTRK immunostain may be positive
Hormone receptors typically negative.
Molecular Subtypes:
Secretory carcinoma subtype
Triple-negative but with favorable prognosis
NTRK-rearranged tumor.
Molecular/Genetic
Genetic Mutations:
ETV6-NTRK3 gene fusion (characteristic)
Rare cases with other NTRK fusions
Low tumor mutational burden
Favorable genetic profile.
Molecular Markers:
NTRK3 overexpression
ETV6-NTRK3 fusion transcript
Secretory gene expression profile
Low Ki-67 index.
Prognostic Significance:
ETV6-NTRK3 fusion associated with favorable prognosis
Low grade and secretory features predict excellent outcome
NTRK fusion status important for targeted therapy.
Therapeutic Targets:
NTRK inhibitors (larotrectinib, entrectinib)
Targeted therapy for NTRK-rearranged tumors
Generally excellent prognosis with surgery alone.
Differential Diagnosis
Similar Entities:
Mammary analog secretory carcinoma
Secretory carcinoma of salivary gland type
Acinic cell carcinoma
Apocrine carcinoma
Lactating adenoma.
Distinguishing Features:
Phyllodes with secretory: Leaf-like areas, ETV6-NTRK3+
MASC: No phyllodes component
Acinic cell: Different architecture, no ETV6-NTRK3.
Diagnostic Challenges:
Recognition of secretory features
Distinction from other secretory tumors
Assessment of phyllodes components
Molecular testing interpretation.
Rare Variants:
Secretory carcinoma with papillary features
Mixed secretory and ductal carcinoma
Secretory carcinoma with apocrine differentiation.
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]
Prognostic Factors
Prognostic factors: [list factors]
Final Diagnosis
Final diagnosis: [complete diagnosis]