Definition/General
Introduction:
Vulvar villoglandular carcinoma is an extremely rare variant of adenocarcinoma characterized by papillary architecture with surface villous projections
It comprises less than 0.5% of all vulvar malignancies
Shows well-differentiated glandular features
Often associated with HPV infection (types 16, 18)
Demonstrates better prognosis than conventional squamous carcinoma.
Origin:
Arises from glandular epithelium of vulvar region
May originate from Bartholin glands or minor vestibular glands
Shows papillary growth pattern similar to cervical counterpart
Associated with HPV-induced glandular dysplasia
Demonstrates müllerian-type differentiation.
Classification:
Classified as adenocarcinoma, villoglandular type
WHO classification includes under glandular tumors
Shows similar morphology to cervical villoglandular carcinoma
Well-differentiated malignancy
Grade I adenocarcinoma by definition.
Epidemiology:
Peak incidence in 3rd-4th decades
Younger than conventional vulvar cancers
Strong association with HPV infection (>90% cases)
Higher incidence in sexually active women
No racial predilection
Better prognosis than conventional types.
Clinical Features
Presentation:
Exophytic papillary mass
May present as warty growth
Bleeding (contact or postcoital)
Vulvar itching and discomfort
Slow growth pattern
May be mistaken for condyloma.
Symptoms:
Vulvar itching (70-80%)
Bleeding episodes (60-70%)
Painless growth initially
Vulvar discomfort (40-50%)
Warty appearance may cause concern
Usually asymptomatic initially.
Risk Factors:
High-risk HPV infection (types 16, 18)
Multiple sexual partners
Early sexual activity
Immunosuppression (HIV, transplant)
Smoking
Previous cervical dysplasia
Young age (relative to other vulvar cancers).
Screening:
Regular gynecological examination
HPV testing in high-risk patients
Colposcopy for suspicious lesions
Biopsy of any persistent warty lesion
Annual follow-up in high-risk patients.
Master Villoglandular Carcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Exophytic papillary mass with villous surface
Tan to pink coloration
Soft, friable consistency
May resemble condyloma acuminatum
Well-demarcated from surrounding tissue.
Characteristics:
Size typically 1-5 cm in diameter
Papillary surface with finger-like projections
Cut surface shows glandular architecture
May have areas of superficial ulceration
Relatively well-circumscribed.
Size Location:
Variable size (usually 2-4 cm)
Can arise from any vulvar site
Vestibule common location
May involve labia minora
Bartholin gland area possible
Usually unifocal.
Multifocality:
Usually unifocal at presentation
May be associated with multicentric HPV disease
Local extension uncommon
Lymph node involvement rare
Distant metastases very rare.
Microscopic Description
Histological Features:
Characterized by papillary architecture with complex branching
Columnar epithelium lining papillae
Minimal cytological atypia
Low mitotic activity
Fibrovascular cores in papillae
Surface villous pattern.
Cellular Characteristics:
Columnar to cuboidal cells
Minimal nuclear pleomorphism
Basally located nuclei
Mucin-containing cytoplasm
Occasional mitotic figures
Well-differentiated appearance.
Architectural Patterns:
Complex papillary pattern
Glandular architecture
Villous surface projections
Branching papillae
Minimal stromal invasion
Orderly maturation pattern.
Grading Criteria:
Considered Grade I (well-differentiated)
Minimal nuclear atypia
Low mitotic index (<5/10 HPF)
Orderly architecture
Minimal stromal invasion
Better differentiation than conventional types.
Immunohistochemistry
Positive Markers:
p16 (block-type staining)
CK7 (positive)
CEA (positive)
PAX8 (variable)
ER (variable)
PR (variable)
EMA (positive).
Negative Markers:
CK20 (negative)
p63 (negative)
CK5/6 (negative)
TTF-1 (negative)
CDX2 (negative)
Vimentin (negative).
Diagnostic Utility:
p16 confirms HPV-related etiology
CK7 positivity supports glandular differentiation
p63 negativity excludes squamous differentiation
CEA helpful for glandular phenotype
Pattern consistent with müllerian differentiation.
Molecular Subtypes:
HPV-related type (p16 positive, >90% cases)
Well-differentiated adenocarcinoma
Better prognosis than conventional types
Hormonal receptor variability.
Molecular/Genetic
Genetic Mutations:
HPV integration (types 16, 18 predominantly)
PIK3CA mutations (20-30%)
PTEN alterations (10-15%)
Fewer TP53 mutations compared to conventional types
KRAS mutations (rare).
Molecular Markers:
p16 overexpression (HPV-related)
HPV DNA detection (PCR/ISH)
Low Ki-67 proliferation index (<20%)
Wild-type p53 pattern common
ER/PR expression variable.
Prognostic Significance:
Better prognosis than conventional vulvar cancers
HPV-positive status favorable
Low metastatic potential
Stage at presentation most important
Excellent prognosis when detected early.
Therapeutic Targets:
HPV-targeted therapy
Surgical excision primary treatment
Conservative management possible
Hormonal therapy (ER-positive cases)
Immunomodulatory therapy.
Differential Diagnosis
Similar Entities:
Condyloma acuminatum
Villoglandular papilloma
Conventional adenocarcinoma
Cervical extension
Metastatic adenocarcinoma.
Distinguishing Features:
Villoglandular carcinoma: True invasion
Villoglandular carcinoma: Cytological atypia
Condyloma: No invasion
Condyloma: Koilocytosis
Papilloma: Benign cytology
Conventional adenocarcinoma: Higher grade
Conventional adenocarcinoma: More atypia.
Diagnostic Challenges:
Differentiation from condyloma acuminatum
Distinction from benign papilloma
Assessment of invasion depth
Recognition of glandular differentiation
HPV typing helpful.
Rare Variants:
Mixed patterns with squamous carcinoma
Predominantly surface growth
Deep invasion variant (rare)
Mixed with conventional adenocarcinoma.
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 Villoglandular Carcinoma
Classification
Classification: Adenocarcinoma, villoglandular type, Grade I
Histological Features
Shows papillary architecture with [glandular differentiation] and [minimal atypia]
Size and Extent
Size: [X] cm, invasion depth: [X] mm
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
HPV Status
p16 immunostaining: [positive/negative] (block-type pattern)
Immunohistochemistry
CK7: [positive/negative], CEA: [positive/negative]
p16: [positive/negative]
p63: [negative], CK5/6: [negative]
Prognostic Factors
Tumor size, invasion depth, HPV status, margin status
Final Diagnosis
Vulvar Villoglandular Carcinoma (Adenocarcinoma, villoglandular type, Grade I)