Definition/General
Introduction:
Apocrine carcinoma of the breast is a rare subtype of invasive ductal carcinoma characterized by cells with apocrine features, such as abundant eosinophilic granular cytoplasm and prominent nucleoli
It accounts for about 1-4% of all breast cancers.
Origin:
It is thought to arise from the terminal duct-lobular unit (TDLU) and shows differentiation towards apocrine-type cells, similar to those found in apocrine sweat glands.
Classification:
It is classified as a special subtype of invasive ductal carcinoma
The diagnosis requires that at least 90% of the tumor cells show apocrine morphology
It can be in situ (apocrine DCIS) or invasive.
Epidemiology:
It tends to occur in older women, with a peak incidence in the 6th and 7th decades
The clinical presentation and risk factors are generally similar to those of invasive ductal carcinoma of no special type.
Clinical Features
Presentation:
Usually presents as a palpable breast mass
Nipple discharge is uncommon
It can be detected by mammography, often as an irregular mass with or without calcifications.
Symptoms:
A firm, often painless breast lump is the most common symptom
Skin changes or nipple retraction are less frequent unless the tumor is large or centrally located.
Risk Factors:
General risk factors for breast cancer apply, such as age, family history, and hormonal factors
There are no specific risk factors uniquely associated with apocrine carcinoma.
Screening:
Mammography and ultrasound are the primary imaging modalities
The imaging features are often indistinguishable from common types of invasive ductal carcinoma.
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Gross Description
Appearance:
The gross appearance is not specific and resembles that of invasive ductal carcinoma, no special type
It is typically a firm, gray-white mass with irregular or spiculated margins.
Characteristics:
The tumor can range in size
Necrosis may be present in larger tumors
The consistency is usually firm to hard.
Size Location:
Can occur anywhere in the breast, with no specific predilection for any quadrant
Size is variable at diagnosis.
Multifocality:
Multifocality and multicentricity can occur, similar to other types of invasive ductal carcinoma.
Microscopic Description
Histological Features:
The tumor is composed of sheets, nests, or glands of large polygonal cells with abundant, granular, eosinophilic cytoplasm
The cell borders are distinct
Apical snouts or decapitation secretions are characteristic features.
Cellular Characteristics:
The nuclei are typically large, round to oval, and often have prominent, centrally located eosinophilic nucleoli
Nuclear pleomorphism can be variable
Mitotic figures are usually present.
Architectural Patterns:
The growth pattern can be solid, glandular, or papillary
A desmoplastic stromal response is common.
Grading Criteria:
Grading is done using the Nottingham grading system, similar to other invasive breast carcinomas
Most apocrine carcinomas are high-grade (Grade 2 or 3).
Immunohistochemistry
Positive Markers:
Characteristically positive for Androgen Receptor (AR)
Also positive for GCDFP-15 (Gross Cystic Disease Fluid Protein-15)
Most are negative for Estrogen Receptor (ER) and Progesterone Receptor (PR)
HER2 overexpression is common (about 30-50% of cases).
Negative Markers:
Usually negative for ER and PR
A significant portion are HER2 negative as well, making them triple-negative (but AR positive).
Diagnostic Utility:
IHC is crucial for diagnosis
AR and GCDFP-15 positivity confirms apocrine differentiation
ER, PR, and HER2 status are vital for determining treatment options.
Molecular Subtypes:
Most apocrine carcinomas fall into the molecular apocrine or luminal B (HER2-positive) subtypes
A subset are triple-negative but AR positive.
Molecular/Genetic
Genetic Mutations:
PIK3CA and TP53 mutations are common
There is a characteristic pattern of chromosomal gains and losses, including gains of 1q and losses of 1p, 16q, and 22q.
Molecular Markers:
High expression of androgen-regulated genes
The molecular profile is distinct from other breast cancer subtypes.
Prognostic Significance:
The prognosis is generally similar to or slightly better than that of grade-matched invasive ductal carcinoma, no special type
Prognosis is largely dependent on tumor size, grade, lymph node status, and HER2 status.
Therapeutic Targets:
HER2-positive cases are treated with HER2-targeted therapies (e.g., trastuzumab)
For AR-positive, ER/PR-negative tumors, anti-androgen therapy is a potential treatment strategy under investigation.
Differential Diagnosis
Similar Entities:
Invasive ductal carcinoma with apocrine metaplasia
Oncocytic carcinoma
Granular cell tumor
Lipid-rich carcinoma.
Distinguishing Features:
Apocrine metaplasia is benign and lacks the malignant nuclear features
Oncocytic carcinomas have similar eosinophilic cytoplasm but are typically AR negative
Granular cell tumors are S100 positive
Lipid-rich carcinomas have clear, vacuolated cytoplasm.
Diagnostic Challenges:
The main challenge is distinguishing pure apocrine carcinoma from invasive ductal carcinoma with focal apocrine features
The 90% cutoff for apocrine morphology is used for diagnosis of pure apocrine carcinoma.
Rare Variants:
Apocrine DCIS is the in-situ counterpart
Invasive apocrine carcinoma can have various patterns, including papillary and 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]