Definition/General

Introduction:
-Vulvar adenocarcinoma is a rare malignant tumor with glandular differentiation arising from the vulva
-Represents 5-10% of all vulvar malignancies
-Can be primary (arising from vulvar structures) or secondary (metastatic from distant sites)
-Primary adenocarcinoma may arise from Bartholin glands, Skene glands, or ectopic breast tissue
-Has variable prognosis depending on origin and stage.
Origin:
-Primary vulvar adenocarcinoma arises from various glandular structures: Bartholin glands (most common)
-Skene glands (paraurethral)
-Ectopic mammary tissue (milk line remnants)
-Sweat glands (apocrine/eccrine)
-Minor vestibular glands
-Cloacogenic remnants
-Müllerian remnants
-Can also be metastatic from cervix, endometrium, breast, GI tract.
Classification:
-Classified by site of origin: Bartholin gland adenocarcinoma
-Skene gland adenocarcinoma
-Mammary-type adenocarcinoma
-Apocrine adenocarcinoma
-Clear cell adenocarcinoma
-Mucinous adenocarcinoma
-Papillary adenocarcinoma
-Adenocarcinoma NOS
-Metastatic adenocarcinoma.
Epidemiology:
-Peak incidence in 5th-7th decades
-Rare tumor with variable presentation
-Primary adenocarcinoma more common than metastatic in vulva
-Bartholin gland origin most frequent primary type
-Worse prognosis than squamous cell carcinoma
-Deep location leads to delayed diagnosis
-Indian population data limited due to rarity.

Clinical Features

Presentation:
-Vulvar mass or nodule (most common)
-Ulceration with irregular borders
-Bleeding (spontaneous or contact)
-Pain or discomfort
-Discharge (mucoid or bloody)
-Pruritus
-Firm, fixed lesion
-Inguinal lymphadenopathy.
Symptoms:
-Vulvar mass (80-90% cases)
-Bleeding (60-70%)
-Pain (50-60%)
-Discharge (40-50%)
-Pruritus (30-40%)
-Dyspareunia
-Urinary symptoms (if large)
-Difficulty with hygiene
-Secondary infection common.
Risk Factors:
-Advanced age (>50 years)
-Chronic vulvar inflammation
-Lichen sclerosus (for some types)
-HPV infection (controversial)
-Immunosuppression
-Previous malignancy (for metastatic disease)
-Radiation exposure
-Genetic predisposition (rare).
Screening:
-No specific screening guidelines
-Careful vulvar examination in routine gynecologic visits
-Biopsy of suspicious lesions
-Imaging (MRI/CT) for extent assessment
-Investigation for primary site if metastatic suspected
-Multidisciplinary approach for diagnosis and staging.

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Gross Description

Appearance:
-Irregular, nodular mass with firm consistency
-Gray-white to tan coloration
-Ulcerated surface common
-Areas of necrosis and hemorrhage
-Infiltrative margins
-Size varies from 1-15 cm
-May show mucin production (mucinous types).
Characteristics:
-Solid, firm consistency
-Irregular borders with infiltrative growth
-Cut surface: gray-white, fleshy
-Areas of necrosis and cystic change
-Calcifications may be present
-Mucoid areas (mucinous types)
-Gritty texture (if calcified).
Size Location:
-Size ranges from 1-20 cm (mean 4-6 cm)
-Location varies by site of origin: Bartholin gland area (posterolateral)
-Paraurethral area (Skene glands)
-Labia majora (mammary-type)
-Clitoral area
-Vestibule
-May be multifocal.
Multifocality:
-Usually unifocal (primary types)
-Multifocal disease suggests metastatic origin
-Local invasion into surrounding tissues
-Lymphatic spread to regional nodes
-Hematogenous metastasis to distant organs
-Skip metastases possible.

Microscopic Description

Histological Features:
-Glandular architecture with tubules, acini, or papillary structures
-Mucin production variable
-Infiltrative growth pattern
-Desmoplastic stromal reaction
-Nuclear pleomorphism and enlarged nucleoli
-Mitotic activity variable
-Necrosis common in high-grade tumors.
Cellular Characteristics:
-Columnar or cuboidal epithelial cells
-Enlarged, pleomorphic nuclei
-Prominent nucleoli
-Eosinophilic or clear cytoplasm
-Mucin vacuoles (mucinous types)
-Mitotic figures variable
-Apoptotic cells
-Intracytoplasmic lumina may be present.
Architectural Patterns:
-Tubular pattern: well-formed glands
-Papillary pattern: papillary projections
-Solid pattern: sheets without glandular formation
-Cribriform pattern: sieve-like appearance
-Mucinous pattern: abundant extracellular mucin
-Clear cell pattern: glycogen-rich cells.
Grading Criteria:
-Well-differentiated (Grade 1): >75% glandular architecture
-Moderately differentiated (Grade 2): 50-75% glandular
-Poorly differentiated (Grade 3): <50% glandular
-Assessment based on architectural pattern
-Nuclear atypia
-Mitotic rate
-Necrosis.

Immunohistochemistry

Positive Markers:
-CK7 (85-95% positive)
-CEA (70-80%)
-EMA (90-95%)
-CK19 (glandular epithelium)
-Mucin stains (PAS, mucicarmine)
-ER/PR (variable, depends on type)
-GCDFP-15 (apocrine types)
-Mammaglobin (mammary-type).
Negative Markers:
-CK5/6 (negative, excludes squamous)
-p63 (negative)
-TTF-1 (negative, excludes lung)
-CDX2 (negative, excludes GI)
-PAX8 (usually negative)
-WT1 (negative)
-Melanoma markers (negative)
-Neuroendocrine markers (usually negative).
Diagnostic Utility:
-Essential for subtype classification
-CK7/CK20 profile helps determine origin
-Site-specific markers (mammaglobin, GCDFP-15) identify subtype
-ER/PR status guides therapy
-Exclude metastatic disease with organ-specific markers
-Mucin stains confirm glandular differentiation.
Molecular Subtypes:
-Mammary-type: ER+, PR+, mammaglobin+, GCDFP-15+
-Apocrine type: AR+, GCDFP-15+
-Mucinous type: mucin+, variable hormones
-Clear cell type: specific pattern
-Bartholin type: variable markers
-Metastatic: organ-specific markers.

Molecular/Genetic

Genetic Mutations:
-TP53 mutations (40-60%)
-PIK3CA mutations (20-30%)
-KRAS mutations (mucinous types)
-PTEN loss (15-25%)
-Her2/neu amplification (mammary-type)
-ARID1A mutations
-CTNNB1 mutations (rare)
-BRCA1/2 mutations (rare).
Molecular Markers:
-p53 overexpression common
-Ki-67 proliferation index variable
-Her2/neu expression (mammary-type)
-Microsatellite stability (most cases)
-Chromosomal instability
-DNA methylation patterns
-Hormone receptor expression.
Prognostic Significance:
-Stage at presentation most important factor
-Histological grade correlates with outcome
-Tumor size affects prognosis
-Lymph node involvement critical
-Her2/neu status (mammary-type)
-Hormone receptor status
-Primary vs metastatic affects treatment.
Therapeutic Targets:
-Surgical excision: wide local excision
-Lymph node assessment
-Adjuvant radiation
-Chemotherapy: platinum-based
-Hormone therapy (ER/PR positive)
-Her2/neu targeting (amplified cases)
-Immunotherapy under investigation.

Differential Diagnosis

Similar Entities:
-Metastatic adenocarcinoma
-Bartholin gland carcinoma
-Skene gland carcinoma
-Adenosquamous carcinoma
-Clear cell carcinoma
-Mammary-type carcinoma
-Sweat gland carcinoma
-Adenoid cystic carcinoma.
Distinguishing Features:
-Primary: appropriate immunoprofile, anatomic location
-Metastatic: organ-specific markers, clinical history
-Bartholin: specific location, mixed patterns
-Skene: paraurethral location
-Mammary-type: mammaglobin+, GCDFP-15+
-Clinical correlation essential.
Diagnostic Challenges:
-Distinguishing primary from metastatic
-Subtype classification affects treatment
-Small biopsy may be inadequate
-Mixed patterns complicate diagnosis
-Poorly differentiated tumors difficult to classify
-Extensive immunohistochemistry often needed.
Rare Variants:
-Clear cell adenocarcinoma
-Signet ring cell adenocarcinoma
-Mucinous adenocarcinoma
-Papillary adenocarcinoma
-Adenocarcinoma with neuroendocrine features
-Minimal deviation adenocarcinoma
-Adenocarcinoma arising in endometriosis.

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 from [site], measuring [size] cm

Diagnosis

Vulvar adenocarcinoma, [subtype if determined]

Classification and Grade

Primary/Secondary: [assessment], Grade: [1/2/3], Type: [subtype]

Histological Features

Shows [glandular pattern] with [differentiation] and [stromal reaction]

Glandular Architecture

Architecture: [tubular/papillary/solid], mucin production: [present/absent]

Tumor Size

Tumor size: [X] cm in greatest dimension

Margins

Margins: [clear/involved], closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Special Studies

IHC: CK7: [result], CEA: [result], [organ-specific markers]: [results]

Hormone receptors: ER: [result], PR: [result]

[other study]: [result]

Primary vs Metastatic Assessment

Assessment: [primary vulvar/metastatic from [site]/indeterminate]

Prognostic Factors

Prognostic factors: grade, size, stage, hormone receptor status

Final Diagnosis

Vulvar adenocarcinoma, [subtype], [grade], [primary/metastatic]