Definition/General
Introduction:
Vulvar micropapillary carcinoma is a rare aggressive variant of adenocarcinoma characterized by small papillary clusters without fibrovascular cores
Comprises less than 0.5% of all vulvar malignancies
Shows high propensity for lymphatic invasion
Morphologically similar to breast micropapillary carcinoma
Demonstrates poor prognosis.
Origin:
Can arise from Bartholin glands or surface epithelium
May originate from minor vestibular glands
Shows adenocarcinoma differentiation
Associated with lymphatic tropism
May arise from preexisting glandular lesions.
Classification:
Classified as adenocarcinoma, micropapillary variant
WHO classification includes under glandular tumors
High-grade malignancy by definition
Similar morphology to breast and lung counterparts
Requires >50% micropapillary pattern for diagnosis.
Epidemiology:
Peak incidence in 6th-7th decades
Extremely rare with few reported cases
More aggressive than conventional adenocarcinomas
High metastatic potential
Poor overall survival in most series.
Clinical Features
Presentation:
Vulvar mass or nodule
May present with early lymphadenopathy
Bleeding (contact or spontaneous)
Vulvar pain and discomfort
Rapid progression
May ulcerate early.
Symptoms:
Vulvar pain (70-80%)
Bleeding episodes (60-70%)
Early nodal symptoms
Vulvar swelling and mass effect
Constitutional symptoms (advanced cases)
Rapid symptom progression.
Risk Factors:
Advanced age (>60 years)
History of vulvar glandular lesions
Previous gynecologic malignancies
Immunosuppression
No clear HPV association.
Screening:
Regular gynecological examination
Early lymph node assessment
Imaging for extent (CT/MRI)
Multidisciplinary evaluation
Aggressive staging workup.
Master Micropapillary Carcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Ill-defined infiltrative mass
Tan to gray-white cut surface
Firm to hard consistency
May show areas of necrosis
Often poorly circumscribed.
Characteristics:
Size typically 2-8 cm in diameter
Infiltrative margins
Cut surface shows solid areas
May have cystic degeneration
Often involves deep structures.
Size Location:
Variable size (usually 3-6 cm)
Can arise from any vulvar site
Bartholin gland area common
May involve deep vulvar structures
Often shows extensive involvement.
Multifocality:
May show multifocal disease
Early lymphatic spread common
Nodal involvement frequent
Distant metastases possible
Requires comprehensive staging.
Microscopic Description
Histological Features:
Characterized by small papillary clusters without fibrovascular cores
Morular pattern in lacunar-like spaces
High-grade cytology
Marked nuclear pleomorphism
Extensive lymphatic invasion.
Cellular Characteristics:
Cuboidal to columnar cells
High nuclear grade
Prominent nucleoli
High nuclear-cytoplasmic ratio
Frequent mitotic figures
Pleomorphic nuclei.
Architectural Patterns:
Micropapillary clusters floating in clear spaces
Morular or ball-like arrangements
Inside-out pattern (EMA staining)
Extensive lymphatic invasion
May have conventional adenocarcinoma areas.
Grading Criteria:
Considered high-grade by definition
High nuclear grade
High mitotic index (>20/10 HPF)
Micropapillary pattern >50% required
Aggressive behavior typical.
Immunohistochemistry
Positive Markers:
EMA (inside-out pattern)
CK7 (positive)
CEA (positive)
MUC1 (apical and cytoplasmic)
CK19 (positive)
E-cadherin (positive).
Negative Markers:
CK20 (negative)
p63 (negative)
CK5/6 (negative)
TTF-1 (negative)
ER/PR (usually negative)
Vimentin (negative).
Diagnostic Utility:
EMA inside-out pattern pathognomonic
CK7 positivity supports adenocarcinoma
MUC1 shows characteristic pattern
p63 negativity excludes squamous differentiation
Pattern recognition most important.
Molecular Subtypes:
High-grade adenocarcinoma subtype
Lymphatic-tropic phenotype
Different from conventional adenocarcinomas
Aggressive behavior pattern.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60-80%)
PIK3CA mutations (30-40%)
PTEN alterations (20-30%)
KRAS mutations (15-25%)
Similar profile to high-grade adenocarcinomas.
Molecular Markers:
p53 overexpression (mutant pattern)
High Ki-67 proliferation index (>50%)
MUC1 overexpression
Loss of E-cadherin function
Angiogenic factors upregulated.
Prognostic Significance:
Poor prognosis by definition
Early metastatic spread
High propensity for lymphatic invasion
Nodal involvement common at presentation
Reduced overall survival.
Therapeutic Targets:
Aggressive surgical approach
Adjuvant chemotherapy usually required
Radiation therapy for local control
Targeted therapy under investigation
Immunotherapy trials.
Differential Diagnosis
Similar Entities:
Conventional adenocarcinoma
Papillary adenocarcinoma
Metastatic micropapillary carcinoma
Lymphangioendothelioma
Lymphoma with micropapillary pattern.
Distinguishing Features:
Micropapillary: EMA inside-out pattern
Micropapillary: No fibrovascular cores
Conventional adenocarcinoma: Glandular architecture
Papillary: Fibrovascular cores
Metastatic: Primary site elsewhere
Lymphoma: CD45 positive.
Diagnostic Challenges:
Recognition of micropapillary pattern
Differentiation from lymphatic invasion
Distinction from metastatic disease
EMA staining pattern crucial
May require expert consultation.
Rare Variants:
Mixed patterns with conventional adenocarcinoma
Pure micropapillary pattern
Focal micropapillary areas
Association with other rare patterns.
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
Vulvar Micropapillary Carcinoma
Classification
Classification: Adenocarcinoma, micropapillary variant, high-grade
Histological Features
Shows micropapillary pattern ([X]% of tumor) with [extensive lymphatic invasion]
Size and Extent
Size: [X] cm, extent: [infiltrative with lymphatic invasion]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present - extensive/focal]
Micropapillary Pattern
Micropapillary pattern comprises [X]% of tumor (minimum 50% required for diagnosis)
Immunohistochemistry
EMA: [inside-out pattern positive]
CK7: [positive], CEA: [positive]
p63: [negative], CK5/6: [negative]
Prognostic Factors
High-grade morphology, extensive lymphovascular invasion, micropapillary pattern
Final Diagnosis
Vulvar Micropapillary Carcinoma (Adenocarcinoma, micropapillary variant) - AGGRESSIVE TUMOR