Definition/General
Introduction:
Vulvar signet ring cell carcinoma is an extremely rare variant of adenocarcinoma characterized by signet ring cells with intracytoplasmic mucin
Comprises less than 0.1% of all vulvar malignancies
Shows aggressive clinical behavior
Most cases are primary vulvar tumors
Requires differentiation from metastatic signet ring carcinoma.
Origin:
Can arise from Bartholin glands or other vulvar glands
May originate from surface epithelium with glandular differentiation
Can arise from endometriotic foci
Shows mucin-producing phenotype
Primary vulvar origin must be established.
Classification:
Classified as adenocarcinoma, signet ring cell type
WHO classification includes under glandular tumors
High-grade malignancy by definition
Morphologically similar to gastric signet ring carcinoma
Requires extensive workup to exclude metastases.
Epidemiology:
Peak incidence in 5th-6th decades
Extremely rare with few reported cases
More common as metastatic disease to vulva
Primary vulvar cases exceptional
Poor prognosis in most cases.
Clinical Features
Presentation:
Vulvar mass or induration
May present as diffuse thickening
Ulceration with indurated edges
Rapid progression
Early lymph node involvement
May mimic inflammatory conditions.
Symptoms:
Vulvar pain (70-80%)
Rapid symptom progression
Bleeding episodes (50-60%)
Vulvar swelling and induration
Constitutional symptoms (advanced cases)
May cause dysuria.
Risk Factors:
History of gastrointestinal malignancy
Previous gynecologic cancers
Family history of hereditary cancer syndromes
Advanced age
No established HPV association.
Screening:
Extensive metastatic workup required
Upper and lower GI endoscopy
CT chest/abdomen/pelvis
Tumor marker assessment
Multidisciplinary evaluation.
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Gross Description
Appearance:
Ill-defined indurated mass
Firm to hard consistency
Gray-white cut surface
May show diffuse infiltration
Areas of ulceration possible.
Characteristics:
Size variable (typically 2-8 cm)
Poorly circumscribed borders
Cut surface shows solid firm tissue
May have gelatinous areas
Often involves deep structures.
Size Location:
Variable size and location
Can involve any vulvar site
May show multifocal involvement
Deep extension common
Often involves subcutaneous tissue.
Multifocality:
May show multifocal disease
Lymphatic involvement common
May present as diffuse infiltration
Nodal metastases frequent
Systemic disease workup essential.
Microscopic Description
Histological Features:
Characterized by signet ring cells with eccentric nuclei
Intracytoplasmic mucin vacuoles
Cells arranged in single file pattern
Desmoplastic stroma
May show glandular differentiation.
Cellular Characteristics:
Signet ring morphology (nucleus pushed to periphery)
Large mucin vacuoles
Moderate to marked nuclear pleomorphism
High nuclear-cytoplasmic ratio
Variable mitotic activity.
Architectural Patterns:
Diffuse infiltrative pattern
Single cell infiltration
May form small glands
Lymphatic involvement common
Perineural invasion possible
Desmoplastic stromal response.
Grading Criteria:
Considered high-grade by definition
High nuclear grade
Infiltrative growth pattern
High metastatic potential
Aggressive behavior typical.
Immunohistochemistry
Positive Markers:
CK7 (variable)
CK20 (variable)
CEA (positive)
MUC1 (positive)
MUC2 (variable)
CDX2 (gastric-type)
PAX8 (if gynecologic origin).
Negative Markers:
p63 (negative)
CK5/6 (negative)
ER/PR (negative)
TTF-1 (negative)
p16 (negative)
Vimentin (negative).
Diagnostic Utility:
Mucin stains (Alcian blue, PAS) highlight intracytoplasmic mucin
CK7/CK20 pattern helps determine origin
CDX2 suggests gastrointestinal origin
PAX8 supports gynecologic origin
Extensive panel needed for primary site.
Molecular Subtypes:
Primary vulvar vs metastatic types
Gastric-type (CDX2+, CK20+)
Gynecologic-type (PAX8+, CK7+)
Different therapeutic implications.
Molecular/Genetic
Genetic Mutations:
Variable mutation profile depending on primary site
TP53 mutations common
KRAS mutations (gastric-type)
PIK3CA mutations
CDH1 mutations (hereditary gastric cancer)
Limited data for primary vulvar cases.
Molecular Markers:
Loss of E-cadherin (CDH1)
β-catenin expression patterns
MLH1/MSH2 (microsatellite instability)
p53 overexpression common
Variable HER2 expression.
Prognostic Significance:
Generally poor prognosis
Stage at presentation crucial
Primary vs metastatic distinction important
Early systemic spread common
Requires aggressive treatment approach.
Therapeutic Targets:
Platinum-based chemotherapy
Targeted therapy based on primary site
HER2-targeted therapy (if positive)
Immunotherapy (MSI-high cases)
Palliative care often required.
Differential Diagnosis
Similar Entities:
Metastatic signet ring carcinoma (gastric, colorectal)
Lobular breast carcinoma
Primary vulvar adenocarcinoma
Lymphoma with signet ring features
Melanoma (signet ring variant).
Distinguishing Features:
Primary vulvar: PAX8 positive (some cases)
Primary vulvar: No other primary site
Gastric metastasis: CDX2 positive
Gastric metastasis: CK20 positive
Breast metastasis: ER/PR positive
Breast metastasis: GCDFP-15 positive
Lymphoma: CD45 positive.
Diagnostic Challenges:
Excluding metastatic disease
Determining primary site
Extensive immunohistochemical panel required
Clinical correlation essential
May require molecular studies.
Rare Variants:
Mixed patterns with conventional adenocarcinoma
Focal signet ring features
Mucinous component
Association with other rare vulvar tumors.
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
Signet Ring Cell Carcinoma
Classification
Classification: Adenocarcinoma, signet ring cell type, high-grade
Histological Features
Shows signet ring cells with [intracytoplasmic mucin] and [infiltrative pattern]
Size and Extent
Size: [X] cm, extent: [infiltrative pattern]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
CK7: [positive/negative], CK20: [positive/negative]
CDX2: [positive/negative], PAX8: [positive/negative]
CEA: [positive/negative], MUC1: [positive/negative]
Primary Site Assessment
Immunoprofile [consistent with/suggests] [primary vulvar/metastatic] origin
Recommendations
Recommend [extensive metastatic workup] and [multidisciplinary evaluation]
Final Diagnosis
Vulvar Signet Ring Cell Carcinoma (primary vs metastatic - see recommendations)