Definition/General
Introduction:
Vulvar metaplastic carcinoma is a rare aggressive variant characterized by mixture of epithelial and mesenchymal elements
Comprises less than 1% of all vulvar malignancies
Shows spindle cell and squamous components
Similar to breast metaplastic carcinoma
Demonstrates poor prognosis.
Origin:
Arises from surface squamous epithelium with metaplastic transformation
Can originate from glandular epithelium
Shows epithelial-mesenchymal transition
Associated with HPV infection in some cases
Demonstrates stem cell-like properties.
Classification:
Classified as carcinoma with mesenchymal differentiation
WHO classification includes under rare vulvar tumors
Subtypes include spindle cell, squamous cell carcinoma with spindle cell features, and carcinosarcoma
High-grade malignancy by definition.
Epidemiology:
Peak incidence in 6th-7th decades
Variable HPV association
More aggressive than conventional squamous carcinoma
Higher incidence in elderly patients
Poor overall survival in most series.
Clinical Features
Presentation:
Rapidly growing vulvar mass
May present as polypoid lesion
Ulceration common
Bleeding (spontaneous or contact)
Early metastases
May cause pain and discomfort.
Symptoms:
Vulvar pain (80-90%)
Bleeding episodes (70-80%)
Rapid symptom progression
Vulvar mass effect
Constitutional symptoms (advanced cases)
Ulceration and infection.
Risk Factors:
Advanced age (>60 years)
HPV infection (variable association)
Previous vulvar intraepithelial neoplasia
Immunosuppression
Chronic vulvar inflammation
Radiation exposure.
Screening:
Regular gynecological examination
Prompt biopsy of suspicious lesions
HPV testing as indicated
Imaging for staging
Multidisciplinary evaluation.
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Gross Description
Appearance:
Polypoid or fungating mass
Tan to gray-white cut surface
Firm to hard consistency
Areas of necrosis and hemorrhage
May show heterogeneous appearance.
Characteristics:
Size typically 3-10 cm in diameter
Irregular, infiltrative margins
Cut surface shows solid and necrotic areas
May have cystic degeneration
Often involves deep structures.
Size Location:
Variable size (usually 4-8 cm)
Can arise from any vulvar site
Labia majora common location
May involve clitoral area
Often shows extensive involvement.
Multifocality:
May show multifocal disease
Aggressive local growth
Early nodal involvement
Distant metastases possible
Requires comprehensive staging.
Microscopic Description
Histological Features:
Characterized by biphasic pattern with epithelial and mesenchymal components
Spindle cell areas
Squamous differentiation
High-grade nuclear features
Sarcomatoid transformation.
Cellular Characteristics:
Pleomorphic spindle cells
Epithelioid cells
High nuclear grade
Frequent mitotic figures
Atypical mitoses
Giant cells may be present.
Architectural Patterns:
Spindle cell fascicles
Storiform pattern
Areas of squamous differentiation
Sarcomatoid areas
Heterologous elements (cartilage, bone) possible
Infiltrative growth.
Grading Criteria:
Considered high-grade by definition
High nuclear grade
High mitotic index (>10/10 HPF)
Pleomorphic morphology
Infiltrative pattern
Aggressive behavior typical.
Immunohistochemistry
Positive Markers:
Pan-cytokeratin (epithelial areas)
p63 (squamous areas)
CK5/6 (squamous areas)
Vimentin (spindle areas)
p40 (squamous areas)
Variable mesenchymal markers.
Negative Markers:
CK7 (usually negative)
CK20 (negative)
TTF-1 (negative)
CDX2 (negative)
S-100 (negative in most)
Desmin (variable).
Diagnostic Utility:
Biphasic staining pattern diagnostic
Cytokeratin confirms epithelial component
p63 supports squamous differentiation
Vimentin highlights mesenchymal areas
Specific sarcoma markers exclude pure sarcoma.
Molecular Subtypes:
Spindle cell squamous carcinoma
Carcinosarcoma (with heterologous elements)
Pleomorphic carcinoma
Different therapeutic implications.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (70-90%)
PIK3CA mutations (30-40%)
PTEN loss (20-30%)
RB1 alterations
CDKN2A deletions
EMT pathway activation.
Molecular Markers:
p53 overexpression (mutant pattern)
High Ki-67 proliferation index (>50%)
Loss of E-cadherin
Vimentin overexpression
EMT markers upregulated.
Prognostic Significance:
Poor prognosis overall
Early metastatic spread
Resistance to therapy
Tumor size correlates with outcome
Nodal involvement common.
Therapeutic Targets:
Aggressive surgical approach
Combination chemotherapy
Radiation therapy
Targeted therapy (PI3K/AKT pathway)
Immunotherapy trials.
Differential Diagnosis
Similar Entities:
Spindle cell sarcoma
Poorly differentiated squamous carcinoma
Malignant melanoma
Atypical fibroxanthoma
Undifferentiated pleomorphic sarcoma.
Distinguishing Features:
Metaplastic carcinoma: Biphasic pattern
Metaplastic carcinoma: Cytokeratin positive
Sarcoma: Pure mesenchymal
Sarcoma: Cytokeratin negative
Melanoma: S-100 positive
Melanoma: Melanoma markers
Squamous carcinoma: Pure epithelial.
Diagnostic Challenges:
Recognition of biphasic pattern
Differentiation from pure sarcoma
Assessment of epithelial component
Extensive sampling may be required
Immunohistochemistry essential.
Rare Variants:
Matrix-producing variant (cartilage, bone)
Predominantly spindle cell
Giant cell variant
Mixed with conventional carcinoma.
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 Metaplastic Carcinoma
Classification
Classification: Metaplastic carcinoma, [spindle cell/carcinosarcoma] type, high-grade
Histological Features
Shows biphasic pattern with [epithelial component X%] and [mesenchymal component X%]
Size and Extent
Size: [X] cm, extent: [infiltrative with aggressive features]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Component Assessment
Epithelial component: [X]% (squamous differentiation), Mesenchymal component: [X]% (spindle cell)
Immunohistochemistry
Pan-cytokeratin: [positive in epithelial areas], p63: [positive in squamous areas]
Vimentin: [positive in spindle areas]
S-100: [negative], Desmin: [negative/positive]
Heterologous Elements
Heterologous elements: [present/absent] - [specify type if present]
Prognostic Factors
High-grade morphology, biphasic pattern, tumor size, margin status
Final Diagnosis
Vulvar Metaplastic Carcinoma - AGGRESSIVE TUMOR WITH POOR PROGNOSIS