Definition/General
Introduction:
Vulvar cribriform carcinoma is a rare variant of adenocarcinoma characterized by cribriform (sieve-like) architecture
Comprises less than 1% of all vulvar malignancies
Shows glandular differentiation with distinctive perforated pattern
May arise from Bartholin glands or surface epithelium
Demonstrates intermediate prognosis.
Origin:
Most commonly arises from Bartholin glands
Can originate from minor vestibular glands
May arise from surface epithelium with glandular metaplasia
Shows ductal differentiation
Associated with background adenosis in some cases.
Classification:
Classified as adenocarcinoma, cribriform type
WHO classification includes under glandular tumors
Similar morphology to breast cribriform carcinoma
Intermediate-grade malignancy
May show mixed patterns with other adenocarcinoma types.
Epidemiology:
Peak incidence in 5th-6th decades
Slightly younger than conventional vulvar cancers
No clear HPV association
Higher incidence in multiparous women
Better prognosis than high-grade adenocarcinomas.
Clinical Features
Presentation:
Vulvar mass or nodule
May present as Bartholin gland enlargement
Bleeding (contact or spontaneous)
Vulvar pain and discomfort
Slow to moderate growth
May be asymptomatic initially.
Symptoms:
Vulvar pain (60-70%)
Bleeding episodes (50-60%)
Vulvar swelling (50%)
Mass effect symptoms
Dysuria (30-40%)
Initially asymptomatic (20-30%).
Risk Factors:
Advanced age (>50 years)
History of vulvar inflammatory conditions
Previous Bartholin gland infections
Nulliparity (some studies)
No established HPV association.
Screening:
Regular gynecological examination
Clinical examination of vulva
Imaging for Bartholin masses
Biopsy of persistent lesions
Multidisciplinary approach for management.
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Gross Description
Appearance:
Well-circumscribed nodular mass
Tan to gray-white cut surface
Firm consistency
May show cystic areas
Solid and cystic components.
Characteristics:
Size typically 2-6 cm in diameter
Relatively well-demarcated borders
Cut surface shows solid areas with small cysts
May have hemorrhagic areas
Usually well-circumscribed.
Size Location:
Variable size (usually 3-5 cm)
Most commonly Bartholin gland region
May involve vestibular area
Posterior vulva common site
Usually unilateral.
Multifocality:
Usually unifocal
May be associated with adjacent glandular lesions
Local extension possible
Lymph node involvement uncommon
Metastases rare with adequate treatment.
Microscopic Description
Histological Features:
Characterized by cribriform (sieve-like) pattern
Back-to-back glands with luminal spaces
Moderate cytological atypia
Uniform cell population
Basement membrane may be focally disrupted.
Cellular Characteristics:
Cuboidal to low columnar cells
Moderate nuclear pleomorphism
Prominent nucleoli
Eosinophilic cytoplasm
Moderate mitotic activity
Uniform cell size.
Architectural Patterns:
Cribriform architecture predominates
Rounded glandular spaces
Back-to-back arrangement
Sieve-like pattern
May have solid areas
Stromal invasion present.
Grading Criteria:
Considered intermediate-grade (Grade II)
Moderate nuclear atypia
Moderate mitotic activity (5-15/10 HPF)
Architectural complexity
Stromal invasion assessment important.
Immunohistochemistry
Positive Markers:
CK7 (positive)
CK19 (positive)
EMA (positive)
CEA (positive)
PAX8 (variable)
ER (variable)
PR (variable).
Negative Markers:
CK20 (negative)
p63 (negative)
CK5/6 (negative)
TTF-1 (negative)
CDX2 (negative)
S-100 (negative).
Diagnostic Utility:
CK7 positivity supports glandular differentiation
p63 negativity excludes squamous differentiation
CEA helpful for adenocarcinoma diagnosis
Hormone receptor status variable
Helps distinguish from other tumors.
Molecular Subtypes:
Bartholin gland-type
Hormone receptor variable subtypes
Well-differentiated adenocarcinoma
Better prognosis than high-grade types.
Molecular/Genetic
Genetic Mutations:
PIK3CA mutations (30-40%)
TP53 mutations (20-30%)
PTEN alterations (15-20%)
KRAS mutations (10-15%)
Different profile from squamous carcinomas.
Molecular Markers:
Low Ki-67 proliferation index (<30%)
Wild-type p53 pattern common
Variable ER/PR expression
Intact mismatch repair proteins
Low mutational burden.
Prognostic Significance:
Intermediate prognosis
Better than high-grade adenocarcinomas
Stage at presentation most important
Size correlates with outcome
Lymph node status crucial.
Therapeutic Targets:
Surgical excision primary treatment
Hormonal therapy (ER-positive cases)
Chemotherapy (advanced cases)
Targeted therapy under investigation.
Differential Diagnosis
Similar Entities:
Adenoid cystic carcinoma
Conventional adenocarcinoma
Bartholin gland adenocarcinoma
Metastatic breast carcinoma
Clear cell carcinoma.
Distinguishing Features:
Cribriform carcinoma: True glandular spaces
Cribriform carcinoma: Moderate atypia
Adenoid cystic: Basaloid cells
Adenoid cystic: MYB rearrangement
Breast metastasis: ER/PR positive
Breast metastasis: GCDFP-15 positive
Clear cell: Clear cytoplasm.
Diagnostic Challenges:
Differentiation from adenoid cystic carcinoma
Distinction from metastatic breast carcinoma
Assessment of invasion vs in situ
Grading assessment
Immunohistochemistry helpful.
Rare Variants:
Mixed patterns with solid areas
Micropapillary component
Mucinous differentiation
Neuroendocrine features (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 Cribriform Carcinoma
Classification
Classification: Adenocarcinoma, cribriform type, Grade II
Histological Features
Shows cribriform pattern with [back-to-back glands] and [moderate atypia]
Size and Extent
Size: [X] cm, extent: [local invasion present]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Grade Assessment
Grade: [II] (intermediate-grade) based on [nuclear atypia] and [architectural pattern]
Immunohistochemistry
CK7: [positive], CEA: [positive]
p63: [negative], CK5/6: [negative]
ER: [positive/negative], PR: [positive/negative]
Prognostic Factors
Tumor size, grade, lymphovascular invasion, margin status
Final Diagnosis
Vulvar Cribriform Carcinoma (Adenocarcinoma, cribriform type, Grade II)