Definition/General

Introduction:
-Mucinous carcinoma of the breast, also known as colloid carcinoma, is a rare special type of invasive ductal carcinoma characterized by abundant extracellular mucin production
-On FNAC, it shows distinctive cytological features with clusters of epithelial cells floating in abundant mucoid background
-This accounts for 1-7% of all breast carcinomas and has a relatively favorable prognosis compared to invasive ductal carcinoma NOS.
Origin:
-Pure mucinous carcinoma arises from ductal epithelium and shows >90% mucin component
-Mixed mucinous carcinoma contains 30-90% mucinous component with conventional ductal carcinoma
-Type A (hypercellular) has increased cellularity and Grade 1 nuclei, while Type B (hypocellular) has lower cellularity and more abundant mucin.
Classification:
-WHO classification recognizes pure mucinous carcinoma (>90% mucin) and mixed mucinous carcinoma (30-90% mucin)
-Histological subtypes include Type A (hypercellular pattern) and Type B (hypocellular pattern)
-Cytological grading follows nuclear morphology assessment.
Epidemiology:
-Predominantly affects elderly women with median age 65-71 years
-More common in postmenopausal women (85% cases)
-Indian studies show slightly younger age distribution (50-60 years)
-Associated with favorable hormone receptor status and excellent prognosis when pure type.

Clinical Features

Presentation:
-Well-circumscribed, mobile breast mass typically measuring 2-5 cm
-Slow-growing tumor with indolent course
-Often mimics fibroadenoma on clinical examination
-Skin changes and nipple discharge are uncommon.
Symptoms:
-Painless breast lump in elderly women
-Mass may feel soft and fluctuant due to high mucin content
-No associated skin dimpling or nipple retraction
-Bilateral occurrence reported in 5-10% cases.
Risk Factors:
-Advanced age >65 years
-Postmenopausal status
-No strong association with BRCA1/2 mutations
-Favorable hormone receptor profile (ER+/PR+)
-Previous history of breast cancer.
Screening:
-Regular mammographic screening in women >50 years
-Mammography shows circumscribed mass with mixed density
-Ultrasound demonstrates hypoechoic lesion with posterior enhancement
-MRI shows high T2 signal intensity.

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Gross Description

Appearance:
-Well-circumscribed, gelatinous tumor with smooth borders
-Cut surface shows glistening, mucoid appearance
-Color ranges from gray-white to translucent
-Consistency is soft and slimy due to abundant mucin.
Characteristics:
-Tumor size typically 2-5 cm diameter
-Encapsulated or pseudo-encapsulated appearance
-No necrosis or hemorrhage
-Mucoid material may leak from cut surface
-Associated DCIS component may be present.
Size Location:
-Usually located in upper outer quadrant
-Size ranges from 1-10 cm with average 3 cm
-Pure type tends to be larger than mixed type
-Multifocal occurrence in 15-20% cases.
Multifocality:
-Bilateral synchronous occurrence in 5-10% cases
-Multifocal disease within same breast in 15-20%
-Associated DCIS may extend beyond invasive component
-Lymph node metastasis rare in pure type.

Microscopic Description

Histological Features:
-Abundant extracellular mucin pools containing clusters and single epithelial cells
-Mucin occupies >90% of tumor volume in pure type
-Epithelial cells show low-grade nuclear features
-Minimal stromal component between mucin lakes.
Cellular Characteristics:
-Type A shows increased cellularity with small clusters and micropapillary groups
-Type B demonstrates sparse cellularity with single cells and small clusters
-Nuclear features are uniformly bland with Grade 1 morphology
-Mitotic activity is low.
Architectural Patterns:
-Floating clusters of epithelial cells in mucin lakes
-Micropapillary architecture in some areas
-Cribriform patterns may be present
-Absence of significant stromal desmoplasia
-Well-defined tumor borders.
Grading Criteria:
-Nuclear grade predominantly Grade 1 (low grade)
-Architectural score typically 1-2
-Mitotic count usually <10 per 10 HPF
-Overall histological grade I-II
-Nottingham grading system applicable.

Immunohistochemistry

Positive Markers:
-ER positive (85-95% cases)
-PR positive (70-80% cases)
-CK7 positive
-CK8/18 positive
-E-cadherin positive
-EMA positive
-Mammaglobin positive (70% cases).
Negative Markers:
-HER2/neu negative (90-95% cases)
-CK5/6 negative
-p63 negative
-CK14 negative
-GCDFP-15 variable (30-50%)
-TTF-1 negative.
Diagnostic Utility:
-Hormone receptor positivity confirms epithelial origin
-CK7+/CK20- pattern supports breast primary
-Mammaglobin helpful for breast origin confirmation
-HER2 negativity associated with favorable prognosis.
Molecular Subtypes:
-Predominantly Luminal A subtype (ER+/PR+/HER2-/Ki67 low)
-Excellent prognosis associated with this profile
-Low proliferation index
-Triple-negative cases extremely rare.

Molecular/Genetic

Genetic Mutations:
-PIK3CA mutations in 30-40% cases
-Low frequency of TP53 mutations (<5%)
-BRCA1/2 mutations rare
-Lower overall mutation burden compared to ductal carcinoma NOS.
Molecular Markers:
-High expression of MUC2 and MUC5AC
-Low Ki-67 proliferation index (<10%)
-p53 expression typically wild-type pattern
-Cyclins E and D1 may be expressed.
Prognostic Significance:
-Excellent prognosis with 10-year survival >90% for pure type
-Mixed type has intermediate prognosis
-Node-negative disease in majority of cases
-Low recurrence risk.
Therapeutic Targets:
-Hormone receptor positivity indicates endocrine therapy responsiveness
-Anti-HER2 therapy not indicated due to negativity
-CDK4/6 inhibitors may be considered in advanced cases.

Differential Diagnosis

Similar Entities:
-Fibroadenoma with myxoid change
-Mucinous cystadenocarcinoma
-Invasive lobular carcinoma with mucin
-Primary mucinous tumors from other sites
-Mucocele-like lesions.
Distinguishing Features:
-Fibroadenoma: benign epithelial cells, no nuclear atypia, biphasic pattern
-Invasive lobular: single file pattern, E-cadherin negative
-Metastatic mucinous carcinoma: CK7-/CK20+ pattern, site-specific markers positive.
Diagnostic Challenges:
-Distinction from mucinous cystadenocarcinoma requires architectural assessment
-Low cellularity may mimic benign lesions
-Mixed type may be confused with ductal carcinoma
-Metastatic disease exclusion important.
Rare Variants:
-Signet ring cell variant with intracytoplasmic mucin
-Neuroendocrine differentiation rare
-Micropapillary variant with complex architecture
-Solid variant with minimal mucin production.

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

Background

Abundant mucoid/colloid material

Cellularity

Low to moderate cellularity relative to abundant mucin

Cellular Features

Cohesive clusters of epithelial cells with bland nuclear morphology floating in mucin

Nuclear Features

Grade 1 nuclei with minimal pleomorphism and rare mitosis

Special Features

Absence of myoepithelial cells, minimal inflammatory cells

Cytological Diagnosis

Suspicious for mucinous carcinoma of breast (Category V)

Recommendation

Histopathological confirmation recommended with cell block/core biopsy