Definition/General
Introduction:
Secretory carcinoma of the breast, also known as juvenile secretory carcinoma, is a very rare subtype of breast cancer
It is characterized by the presence of intracellular and extracellular secretions
It typically has an indolent clinical course and an excellent prognosis.
Origin:
It is believed to arise from the terminal duct-lobular unit (TDLU)
The tumor cells are characterized by their ability to produce and secrete a milk-like substance.
Classification:
It is classified as a special subtype of invasive ductal carcinoma
The diagnosis is based on its characteristic histology, which includes solid, microcystic, and glandular patterns with abundant secretions.
Epidemiology:
It is most common in children and adolescents, hence the name "juvenile" secretory carcinoma, but it can occur at any age
It is extremely rare, accounting for less than 0.15% of all breast cancers.
Clinical Features
Presentation:
Typically presents as a well-circumscribed, mobile, painless mass
It can occur in both females and males
Nipple discharge may be present.
Symptoms:
A slow-growing, non-tender breast lump is the most common symptom
The mass is usually small at diagnosis.
Risk Factors:
There are no well-defined risk factors
Unlike other breast cancers, it is not strongly associated with hormonal factors or family history.
Screening:
Due to its rarity and occurrence in young patients, it is usually not detected by routine screening
Diagnosis is typically made after a palpable mass is investigated.
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Gross Description
Appearance:
The tumor is typically well-circumscribed, firm, and lobulated
The cut surface is gray-white and may have a mucoid or gelatinous appearance due to the secretions.
Characteristics:
The size is usually small, often less than 3 cm
The consistency is firm but can be soft if there is a large cystic component.
Size Location:
Can occur anywhere in the breast, with no specific quadrant predilection.
Multifocality:
Multifocality is rare.
Microscopic Description
Histological Features:
The tumor is composed of glands and microcysts containing abundant eosinophilic, PAS-positive secretions
The cells are arranged in solid, glandular, and papillary patterns
The stroma is typically fibrous.
Cellular Characteristics:
The tumor cells are bland, with uniform, round to oval nuclei, and pale to eosinophilic cytoplasm
The cytoplasm often contains secretory vacuoles
Mitotic activity is low.
Architectural Patterns:
Three main patterns are described: solid, microcystic, and ductal
A mixture of these patterns is common
The secretions are a key diagnostic feature.
Grading Criteria:
These tumors are almost always low-grade (Grade 1) due to their bland cytology and low mitotic rate.
Immunohistochemistry
Positive Markers:
Positive for S100 protein and mammaglobin
Often positive for ER and PR, but this can be variable
E-cadherin is positive
GCDFP-15 can be positive.
Negative Markers:
Usually negative for HER2
Myoepithelial markers are absent around the invasive components.
Diagnostic Utility:
S100 positivity is a key feature
The presence of the characteristic ETV6-NTRK3 gene fusion is diagnostic.
Molecular Subtypes:
Most are considered a distinct molecular entity defined by the ETV6-NTRK3 fusion, not fitting neatly into the standard luminal/HER2/triple-negative classification.
Molecular/Genetic
Genetic Mutations:
The pathognomonic genetic alteration is the t(12;15)(p13;q25) translocation, which results in the ETV6-NTRK3 gene fusion
This fusion is the driving mutation.
Molecular Markers:
Detection of the ETV6-NTRK3 fusion by FISH or RT-PCR is the gold standard for diagnosis.
Prognostic Significance:
Excellent prognosis, especially in children
The risk of lymph node metastasis is low, and distant metastasis is very rare
Recurrence can occur after a long interval, so long-term follow-up is recommended.
Therapeutic Targets:
The NTRK fusion is a therapeutic target
Larotrectinib and entrectinib, which are TRK inhibitors, have shown efficacy in tumors with NTRK fusions, including secretory carcinoma.
Differential Diagnosis
Similar Entities:
Mucinous carcinoma
Lipid-rich carcinoma
Acinic cell carcinoma
Benign secretory changes in pregnancy/lactation.
Distinguishing Features:
Mucinous carcinoma has extracellular mucin, not the eosinophilic secretions of secretory carcinoma
Lipid-rich carcinoma has clear, vacuolated cells but lacks the ETV6-NTRK3 fusion
Acinic cell carcinoma has granular cytoplasm but is typically S100 negative.
Diagnostic Challenges:
The main challenge is its rarity
Distinguishing it from other breast lesions with secretory features requires a high index of suspicion and molecular testing for the ETV6-NTRK3 fusion.
Rare Variants:
The entity itself is a rare variant of breast cancer.
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]