Definition/General
Introduction:
Vulvar medullary carcinoma is a rare variant of carcinoma characterized by solid growth pattern with prominent lymphocytic infiltrate
Comprises less than 0.5% of all vulvar malignancies
Shows pushing borders and syncytial growth
Similar to breast medullary carcinoma
Demonstrates better prognosis than conventional squamous carcinoma.
Origin:
May arise from surface epithelium with dedifferentiation
Can originate from glandular epithelium
Shows loss of differentiation
Associated with immune response
May be related to viral infections (EBV, HPV).
Classification:
Classified as carcinoma, medullary type
WHO classification includes under rare vulvar tumors
Shows features of both squamous and glandular differentiation loss
High-grade morphology but better prognosis
Requires specific histological criteria.
Epidemiology:
Peak incidence in 5th-6th decades
Extremely rare with few reported cases
May be associated with immunosuppression
Better prognosis than conventional high-grade carcinomas
Immune-mediated component important.
Clinical Features
Presentation:
Well-circumscribed vulvar mass
May present as firm nodule
Usually non-ulcerated initially
Rapid growth possible
Mobile mass
May be associated with enlarged lymph nodes.
Symptoms:
Vulvar mass (90-100%)
Usually painless initially
Bleeding (if ulcerated)
Vulvar discomfort (moderate)
No pruritus typically
Constitutional symptoms rare.
Risk Factors:
Immunosuppression (HIV, transplant)
Viral infections (EBV, HPV)
Previous autoimmune conditions
Advanced age
Family history of medullary carcinomas.
Screening:
Regular examination in immunocompromised patients
Viral screening (EBV, HPV)
Clinical examination for lymphadenopathy
Imaging for extent assessment.
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Gross Description
Appearance:
Well-circumscribed soft mass
Gray-white to tan cut surface
Soft, fleshy consistency
Pushing borders
Areas of necrosis uncommon.
Characteristics:
Size typically 2-8 cm in diameter
Well-demarcated from surrounding tissue
Cut surface shows homogeneous appearance
Soft consistency
May have focal hemorrhage.
Size Location:
Variable size (usually 3-6 cm)
Can arise from any vulvar site
Labia majora common location
May involve vestibular area
Usually unifocal.
Multifocality:
Usually unifocal
Well-circumscribed growth pattern
Pushing borders characteristic
Lymph node involvement variable
Metastases uncommon when typical.
Microscopic Description
Histological Features:
Characterized by solid sheets of large cells
Syncytial growth pattern
Dense lymphocytic infiltrate
Pushing borders
Minimal glandular or squamous differentiation.
Cellular Characteristics:
Large polygonal cells
Vesicular nuclei with prominent nucleoli
Abundant eosinophilic cytoplasm
High nuclear-cytoplasmic ratio
Frequent mitotic figures.
Architectural Patterns:
Solid growth pattern
Syncytial arrangement
Pushing invasion borders
Dense lymphocytic infiltrate at periphery
Lack of desmoplastic stroma
Minimal differentiation.
Grading Criteria:
Requires specific diagnostic criteria
>75% solid growth pattern
Pushing borders
Dense lymphocytic infiltrate
High nuclear grade
Syncytial architecture.
Immunohistochemistry
Positive Markers:
Pan-cytokeratin (positive)
p53 (usually wild-type)
Ki-67 (high proliferation index)
EMA (positive)
CK8/18 (positive)
Variable squamous markers.
Negative Markers:
Specific lineage markers often negative
ER/PR (negative)
TTF-1 (negative)
CDX2 (negative)
S-100 (negative)
Melanoma markers (negative).
Diagnostic Utility:
Pan-cytokeratin confirms epithelial origin
p53 pattern helps distinguish from other tumors
High Ki-67 supports high-grade morphology
Lineage markers help exclude metastases
Lymphoid markers highlight infiltrate.
Molecular Subtypes:
Undifferentiated carcinoma subtype
Immune-reactive phenotype
Different from conventional carcinomas
Better prognostic group.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (variable pattern)
Mismatch repair deficiency possible
BRCA pathway alterations
Viral integration (EBV, HPV)
Different profile from conventional carcinomas.
Molecular Markers:
High tumor mutational burden possible
Microsatellite instability (some cases)
PD-L1 expression common
Immune infiltration markers positive
Viral antigens detectable.
Prognostic Significance:
Better prognosis than conventional high-grade carcinomas
Immune response correlates with outcome
Stage at presentation important
Pushing borders favorable feature.
Therapeutic Targets:
Immunotherapy (PD-1/PD-L1 inhibitors)
Conventional chemotherapy
Surgical excision
Radiation therapy
Antiviral therapy (if indicated).
Differential Diagnosis
Similar Entities:
Poorly differentiated squamous carcinoma
Undifferentiated carcinoma
Large cell lymphoma
Melanoma (amelanotic)
Metastatic carcinoma.
Distinguishing Features:
Medullary: Pushing borders
Medullary: Dense lymphocytic infiltrate
Squamous carcinoma: Infiltrative borders
Squamous carcinoma: Desmoplastic stroma
Lymphoma: CD45 positive
Melanoma: S-100 positive.
Diagnostic Challenges:
Recognition of specific criteria
Differentiation from undifferentiated carcinoma
Assessment of pushing vs infiltrative borders
Lymphocytic infiltrate evaluation
May require expert consultation.
Rare Variants:
Mixed patterns with conventional carcinoma
Focal glandular differentiation
Squamous features (focal)
Neuroendocrine differentiation (rare).
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 Medullary Carcinoma
Classification
Classification: Carcinoma, medullary type, high-grade
Histological Features
Shows solid growth pattern with [pushing borders] and [dense lymphocytic infiltrate]
Size and Extent
Size: [X] cm, extent: [well-circumscribed with pushing borders]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Growth Pattern
Shows [>75% solid growth] with [syncytial pattern] and [pushing borders]
Lymphocytic Infiltrate
Dense lymphocytic infiltrate present at [tumor periphery/throughout]
Immunohistochemistry
Pan-cytokeratin: [positive], EMA: [positive]
Ki-67: [high proliferation index]
CD45: [negative], S-100: [negative]
Diagnostic Criteria Met
[Solid growth >75%], [pushing borders], [dense lymphocytic infiltrate], [syncytial pattern]
Prognostic Factors
Medullary phenotype (favorable), tumor size, stage, immune response
Final Diagnosis
Vulvar Medullary Carcinoma - BETTER PROGNOSIS THAN CONVENTIONAL HIGH-GRADE CARCINOMA