Definition/General
Introduction:
Ovarian Brenner tumor is a rare ovarian neoplasm with transitional cell differentiation
It accounts for 1-2% of all ovarian tumors
It demonstrates transitional epithelium resembling urothelium
Most cases are benign with excellent prognosis.
Origin:
Originates from ovarian surface epithelium or celomic mesothelium
Shows transitional cell differentiation (Walthard cell rests theory)
The neoplastic transformation involves unknown molecular pathways
Metaplastic theory most accepted origin
Association with mucinous tumors in 30% cases.
Classification:
Classified as benign (90%), borderline (5%), or malignant (5%)
Benign: no cellular atypia or invasion
Borderline: cellular atypia without invasion
Malignant: stromal invasion present
WHO classification system used.
Epidemiology:
Peak incidence in 5th-6th decades
Postmenopausal women primarily affected
Association with mucinous tumors in 30%
Unilateral in 95% of cases
Excellent prognosis for benign and borderline forms.
Clinical Features
Presentation:
Asymptomatic pelvic mass (most common)
Incidental finding on imaging
Abdominal discomfort or fullness
CA-125 usually normal
No specific symptoms in benign cases.
Symptoms:
Pelvic pressure or fullness (40% cases)
Abdominal distension (large tumors)
Urinary symptoms (mass effect)
Pain uncommon in benign forms
Postmenopausal bleeding (if hormone-producing).
Risk Factors:
Postmenopausal status
Age >50 years
No clear risk factors identified
No hereditary predisposition
No association with endometriosis or BRCA mutations.
Screening:
No specific screening available
CA-125 usually normal
Imaging shows solid or mixed mass
Frozen section helpful for intraoperative diagnosis
Hormone levels usually normal.
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Gross Description
Appearance:
Solid, firm, white-gray mass with smooth surface
Fibrous consistency
Cystic areas may be present
Calcifications common
Well-circumscribed borders.
Characteristics:
White to gray-white cut surface
Firm, fibrous consistency
Whorled appearance
Cystic degeneration in large tumors
Calcifications visible as gritty areas.
Size Location:
Variable size (2-20 cm, average 5-8 cm)
Unilateral in 95% cases
Any ovary can be affected
Usually single mass
Associated mucinous tumor in 30%.
Multifocality:
Usually solitary
Bilateral involvement rare (<5%)
Coexistent mucinous tumor common
No metastases in benign forms
Peritoneal involvement rare.
Microscopic Description
Histological Features:
Transitional epithelium in solid nests
Coffee-bean nuclei characteristic
Dense fibrous stroma
Basement membrane intact (benign)
Epithelial-stromal interface smooth.
Cellular Characteristics:
Oval to elongated nuclei with grooves (coffee-bean appearance)
Pale, eosinophilic cytoplasm
No mitotic activity (benign)
Bland chromatin
Inconspicuous nucleoli.
Architectural Patterns:
Solid nests and trabeculae
Occasionally cystic with transitional lining
Squamous metaplasia may be present
Mucinous differentiation in associated areas
Walthard-like nests.
Grading Criteria:
Benign: bland cytology, no invasion
Borderline: moderate atypia, complex architecture, no invasion
Malignant: marked atypia, mitotic activity, stromal invasion
Nuclear grade important in borderline cases.
Immunohistochemistry
Positive Markers:
CK7 (positive)
CK20 (positive)
Uroplakin III (positive, specific)
Thrombomodulin (positive)
p63 (positive)
CK5/6 (positive).
Negative Markers:
PAX8 (negative or weak)
WT1 (negative)
ER/PR (negative)
Inhibin (negative)
Calretinin (negative)
TTF1 (negative).
Diagnostic Utility:
Uroplakin III positivity confirms transitional differentiation
p63 positivity supports urothelial phenotype
CK7/CK20 co-expression characteristic
PAX8 negativity distinguishes from Müllerian tumors
Profile distinguishes from TCC metastases.
Molecular Subtypes:
Classical Brenner (uroplakin III+, p63+)
Malignant Brenner (similar profile with invasion)
Associated mucinous component (different profile).
Molecular/Genetic
Genetic Mutations:
Limited molecular data available
KRAS mutations rare
TP53 mutations in malignant forms
PIK3CA mutations occasionally
No specific driver mutations identified.
Molecular Markers:
p53 wild-type pattern in benign forms
p53 overexpression in malignant cases
Low Ki-67 in benign forms
Microsatellite stable
Chromosomally stable.
Prognostic Significance:
Histological type most important factor
Benign forms excellent prognosis
Borderline forms very good prognosis
Malignant forms variable prognosis
Stage important in malignant cases.
Therapeutic Targets:
Surgery curative for benign forms
Limited targeted options for malignant forms
Conventional chemotherapy for advanced malignant cases
Hormone therapy not effective.
Differential Diagnosis
Similar Entities:
Metastatic transitional cell carcinoma (bladder)
Transitional cell carcinoma of ovary
Fibroma
Thecoma
Metastatic urothelial carcinoma.
Distinguishing Features:
Brenner: uroplakin III+, benign morphology
Metastatic TCC: clinical history, bilateral, higher grade
Primary TCC: no transitional nests, malignant
Fibroma: spindle cells, no epithelium
Thecoma: lipid-rich cells, hormonal.
Diagnostic Challenges:
Distinguishing primary from metastatic TCC
Identifying malignant transformation
Associated mucinous component recognition
Frozen section interpretation
Small biopsy samples.
Rare Variants:
Brenner tumor with mucinous differentiation
Malignant Brenner with sarcomatous elements
Brenner tumor with clear cell features.
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
[laterality] salpingo-oophorectomy, measuring [size] cm
Diagnosis
[Benign/Borderline/Malignant] Brenner tumor
Classification
Brenner tumor, [benign/borderline/malignant] type
Histological Features
Shows transitional epithelium in solid nests with coffee-bean nuclei and fibrous stroma
Size and Extent
Tumor size: [X] cm, [unilateral/bilateral], [confined to ovary/extraovarian extension]
Lymphovascular Invasion
Lymphovascular invasion: [absent/present]
Lymph Node Status
Lymph nodes: [not submitted/negative]
Special Studies
IHC: Uroplakin III (+), p63 (+), CK7 (+), CK20 (+), PAX8 (-)
Not performed
Associated tumors: [mucinous component present/absent]
Prognostic Factors
Type: [benign/borderline/malignant]; Size: [X] cm; Stage: [if applicable]
Final Diagnosis
[Benign/Borderline/Malignant] Brenner tumor of [left/right] ovary