Definition/General
Introduction:
Vulvar Bartholin gland carcinoma is a rare malignant tumor arising from the Bartholin glands or their ductal system
Represents 2-7% of all vulvar malignancies
Can present as adenocarcinoma (most common), squamous cell carcinoma, or adenosquamous carcinoma
Often misdiagnosed initially as benign Bartholin gland cyst or abscess
Has poor prognosis due to late diagnosis and deep location.
Origin:
Arises from Bartholin gland epithelium (major vestibular glands)
Can originate from acinar epithelium (adenocarcinoma) or ductal epithelium (various types)
Malignant transformation of pre-existing benign lesions possible
Chronic inflammation and obstruction may predispose
Deep location in posterolateral vulva
Bilateral glands rarely involved simultaneously.
Classification:
Histological subtypes: Adenocarcinoma (40-50%, most common)
Squamous cell carcinoma (30-40%)
Adenosquamous carcinoma (10-15%)
Adenoid cystic carcinoma (5-10%)
Transitional cell carcinoma (rare)
Undifferentiated carcinoma (rare)
Mixed histology possible.
Epidemiology:
Peak incidence in 5th-6th decades (mean age 50-60 years)
Rare tumor with poor prognosis
Delayed diagnosis common (often mistaken for cyst)
Deep lymphatic drainage leads to early metastasis
5-year survival 50-85% depending on stage
Indian population data limited due to rarity.
Clinical Features
Presentation:
Unilateral vulvar mass in posterolateral location
Initially painless but may become painful
Rapid growth (distinguishing from cyst)
Firm, fixed mass
Ulceration of overlying skin
Inguinal lymphadenopathy
May present as recurrent "cyst".
Symptoms:
Vulvar mass or swelling (90-95% cases)
Pain or discomfort (60-70%)
Dyspareunia
Bleeding (if ulcerated)
Discharge
Difficulty sitting
Urinary symptoms (if large)
Recurrent "infections" (misdiagnosed cases).
Risk Factors:
Age >40 years
Chronic Bartholin gland inflammation
Recurrent Bartholin cysts
Previous radiation therapy
Immunosuppression
HPV infection (for squamous type)
Genetic predisposition (rare)
Environmental carcinogens.
Screening:
No specific screening guidelines
High index of suspicion for solid masses in women >40 years
Biopsy of all solid Bartholin masses
MRI for extent assessment
Careful examination for lymphadenopathy
Avoid repeated drainage without tissue diagnosis.
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Gross Description
Appearance:
Firm, solid mass in posterolateral vulva
Gray-white cut surface with areas of necrosis
Irregular borders with infiltrative growth
Size ranges from 2-15 cm
May show cystic degeneration
Hemorrhage and necrosis common in large tumors.
Characteristics:
Solid, firm consistency (unlike soft cysts)
Infiltrative margins
Gray-white to tan coloration
Areas of necrosis and hemorrhage
Gritty texture (if calcifications)
May have residual cystic areas
Extension into surrounding tissues.
Size Location:
Size varies from 2-20 cm (mean 5-8 cm)
Location: posterolateral vulva (4 and 8 o'clock positions)
Deep location beneath labia majora
May extend to vaginal wall
Perirectal extension possible
Unilateral involvement typical.
Multifocality:
Usually unifocal
Local invasion into surrounding tissues
Lymphatic spread to inguinal and pelvic nodes
Hematogenous metastasis to lungs, liver, bones
Bilateral involvement extremely rare
Skip metastases possible.
Microscopic Description
Histological Features:
Adenocarcinoma: glandular architecture with mucin production
Squamous cell carcinoma: keratinizing or non-keratinizing patterns
Adenosquamous: mixed glandular and squamous elements
Infiltrative growth pattern
Desmoplastic stromal reaction
Lymphovascular invasion common.
Cellular Characteristics:
Pleomorphic cells with enlarged nuclei
Prominent nucleoli
Increased nuclear-cytoplasmic ratio
Mitotic activity (variable)
Mucin production (adenocarcinoma)
Keratinization (squamous type)
Necrosis and apoptosis frequent.
Architectural Patterns:
Glandular pattern: tubules, acini, papillary structures
Squamous pattern: sheets, nests, keratinization
Solid pattern: sheets of cells without specific differentiation
Cribriform pattern (adenoid cystic type)
Infiltrative growth
Perineural invasion common.
Grading Criteria:
Well-differentiated (Grade 1): preserved glandular architecture
Moderately differentiated (Grade 2): partial loss of architecture
Poorly differentiated (Grade 3): solid growth, minimal differentiation
Assessment based on architectural pattern
Nuclear pleomorphism
Mitotic rate.
Immunohistochemistry
Positive Markers:
CK7 (adenocarcinoma, 80-90%)
CK20 (variable, 30-50%)
CEA (glandular differentiation)
EMA (epithelial nature)
CK5/6 (squamous areas)
p63 (squamous differentiation)
ER/PR (variable)
GCDFP-15 (apocrine differentiation).
Negative Markers:
TTF-1 (negative, excludes lung primary)
CDX2 (negative, excludes GI primary)
PAX8 (usually negative)
WT1 (negative)
Melanoma markers (S-100, HMB-45 negative)
Neuroendocrine markers (usually negative)
Vimentin (negative).
Diagnostic Utility:
Essential for subtype classification
CK7/CK20 profile helps determine origin
p63 and CK5/6 identify squamous differentiation
Site-specific markers exclude metastases
ER/PR status may guide therapy
Her2/neu testing in selected cases.
Molecular Subtypes:
Adenocarcinoma type: CK7+, CK20 variable, CEA+
Squamous type: CK5/6+, p63+, CK7 variable
Adenosquamous type: mixed pattern
Apocrine type: GCDFP-15+, AR+
Primary vs metastatic: site-specific markers help.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (50-70%)
KRAS mutations (adenocarcinoma subtype)
PIK3CA mutations (20-30%)
PTEN loss (15-25%)
EGFR amplification (variable)
HPV integration (squamous type)
BRCA1/2 mutations (rare).
Molecular Markers:
p53 overexpression common
Ki-67 proliferation index high
EGFR expression variable
Her2/neu amplification (10-20%)
Microsatellite stability (most cases)
Chromosomal instability
DNA methylation changes.
Prognostic Significance:
Tumor size most important prognostic factor
Lymph node status critical
Histological grade correlates with outcome
Lymphovascular invasion indicates poor prognosis
p53 mutations associated with aggressive behavior
Stage at diagnosis crucial.
Therapeutic Targets:
Surgical excision: wide local excision or radical vulvectomy
Lymph node dissection
Radiation therapy (adjuvant)
Chemotherapy: platinum-based regimens
Her2/neu targeting (amplified cases)
EGFR targeting under investigation.
Differential Diagnosis
Similar Entities:
Bartholin gland cyst
Bartholin gland abscess
Metastatic adenocarcinoma
Primary vulvar adenocarcinoma
Skene gland carcinoma
Hidradenoma
Leiomyosarcoma
Melanoma.
Distinguishing Features:
Carcinoma: solid, infiltrative growth, cytological atypia
Cyst: benign lining, no atypia
Abscess: inflammatory infiltrate, no malignant cells
Metastatic: site-specific markers, clinical history
Primary vulvar: different anatomic location
Immunohistochemistry essential.
Diagnostic Challenges:
Distinguishing primary from metastatic adenocarcinoma
Early diagnosis challenging due to deep location
Sampling adequacy important
Subtype classification affects treatment
Residual benign gland vs invasive carcinoma
Clinical correlation essential.
Rare Variants:
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Neuroendocrine carcinoma
Clear cell carcinoma
Papillary adenocarcinoma
Sebaceous carcinoma
Undifferentiated 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
Vulvar excision with Bartholin gland area, measuring [size] cm
Diagnosis
Bartholin gland carcinoma, [histological subtype]
Classification and Grade
Histological type: [adenocarcinoma/squamous/adenosquamous], Grade: [1/2/3]
Histological Features
Shows [growth pattern] with [differentiation] and [stromal reaction]
Tumor Size and Extent
Tumor size: [X] cm, extent: [local/regional infiltration]
Margins
Margins: [clear/involved], closest margin [X] mm from tumor
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: CK7: [result], CK20: [result], p63: [result], CEA: [result]
Molecular: [test if performed]: [result]
[other study]: [result]
Staging
TNM stage: T[X]N[X]M[X], Overall stage: [I/II/III/IV]
Prognostic Factors
Prognostic factors: tumor size, grade, lymph node status, stage
Final Diagnosis
Bartholin gland carcinoma, [subtype], [grade], Stage [stage]