Definition/General
Introduction:
Fallopian tube cribriform carcinoma is a rare variant of tubal adenocarcinoma characterized by cribriform (sieve-like) architecture with punched-out spaces
It represents approximately 3-5% of all fallopian tube carcinomas
The tumor demonstrates back-to-back glands with characteristic cribriform spaces
It typically shows intermediate-grade features between well and poorly differentiated carcinomas
The cribriform pattern must predominate (>50%) for diagnosis.
Origin:
Originates from the epithelial cells of the fallopian tube with retained glandular organization but altered architecture
The cribriform spaces result from central necrosis or secretory activity
May develop from hyperplastic or dysplastic tubal epithelium
The architectural pattern reflects intermediate differentiation
Luminal secretions may contribute to space formation.
Classification:
WHO classification recognizes it as a morphological variant of tubal adenocarcinoma
Cribriform pattern must be predominant (>50% of tumor)
Intermediate-grade carcinoma (Grade 2) in most cases
May show mixed patterns with conventional adenocarcinoma
Distinguished from micropapillary by presence of true luminal spaces
FIGO staging follows standard criteria.
Epidemiology:
Rare entity with limited published series (fewer than 100 cases)
Peak incidence in 5th-6th decades (similar to other tubal carcinomas)
No specific racial predilection
Intermediate prognosis between low and high-grade variants
No established BRCA association
May be underrecognized due to morphological overlap
Better than high-grade serous but worse than Grade 1 tumors.
Clinical Features
Presentation:
Pelvic mass with moderate growth rate
Pelvic pain and pressure symptoms
Abnormal vaginal bleeding (irregular or postmenopausal)
Watery vaginal discharge (less common)
Abdominal distension in larger tumors
Intermediate clinical aggressiveness
Stage II-III at presentation commonly.
Symptoms:
Pelvic pain and cramping (moderate severity)
Irregular menstrual bleeding or postmenopausal bleeding
Abdominal fullness and bloating
Urinary frequency due to mass effect
Bowel symptoms (mild bloating)
Constitutional symptoms (fatigue, mild weight loss)
Gradual onset over months.
Risk Factors:
Advanced age (>50 years)
Nulliparity and infertility
Family history of gynecological cancers
Personal history of breast cancer
No clear BRCA association for this variant
Hormone replacement therapy (possible association)
Late menopause (>55 years).
Screening:
No specific screening protocols due to rarity
Standard gynecological examination and imaging
Transvaginal ultrasound for pelvic mass evaluation
CA-125 levels may be moderately elevated
MRI may show characteristic cribriform features
Genetic counseling based on family history.
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Gross Description
Appearance:
Solid tumor with lobulated surface
Tan to gray-pink cut surface
Firm consistency with focal soft areas
Cystic spaces may be visible grossly
Minimal necrosis compared to high-grade tumors
Well-circumscribed to focally infiltrative
Calcifications may be present.
Characteristics:
Heterogeneous appearance with solid and cystic components
Pink-tan coloration
Firm to moderately soft consistency
Smooth to slightly irregular surface
Focal hemorrhage may be present
Cystic degeneration in some areas
Well-demarcated margins.
Size Location:
Size ranges from 3-10 cm (variable)
May involve entire tube or be focal
Ampullary and fimbrial involvement common
Unilateral in majority of cases
Limited extension beyond tube initially
Ovarian surface involvement may occur
Peritoneal implants in advanced cases.
Multifocality:
Usually unifocal within the fallopian tube
May show satellite nodules
Bilateral involvement uncommon (<20%)
Peritoneal seeding in intermediate to advanced stages
Lymphatic spread to regional nodes
Hematogenous metastases less common than high-grade tumors.
Microscopic Description
Histological Features:
Cribriform architecture with sieve-like spaces predominating
Back-to-back glands with punched-out lumina
Cuboidal to columnar epithelium lining spaces
Moderate nuclear atypia
Moderate mitotic activity (10-20 per 10 HPF)
Minimal to focal necrosis
Desmoplastic stromal response.
Cellular Characteristics:
Cuboidal to low columnar cells with moderate cytoplasm
Eosinophilic cytoplasm (predominantly)
Enlarged nuclei with moderate pleomorphism
Prominent nucleoli
Maintained cellular polarity around luminal spaces
Mitotic figures present but not abundant
Apoptotic bodies may be seen.
Architectural Patterns:
Cribriform pattern predominates (>50% of tumor)
Sieve-like spaces of varying sizes
Back-to-back glandular arrangement
Solid areas may be focal
Papillary areas may be present
Micropapillary pattern (focal, <20%)
Single cell infiltration uncommon.
Grading Criteria:
Intermediate-grade carcinoma (Grade 2) typically
Architectural grade 2 (cribriform predominant)
Nuclear grade 2 (moderate atypia)
Mitotic activity moderate (10-20 per 10 HPF)
Focal necrosis may be present
Overall assessment usually Grade 2.
Immunohistochemistry
Positive Markers:
CK7 (diffusely positive in epithelial cells)
PAX8 (nuclear, positive in 95% confirming müllerian origin)
CA125 (positive in luminal surface and cytoplasm)
WT1 (may be positive, nuclear staining)
ER (positive in 50-70% of cases)
PR (positive in 40-60%)
EMA (epithelial membrane antigen).
Negative Markers:
CK20 (negative, excludes gastrointestinal origin)
CDX2 (negative, excludes intestinal differentiation)
TTF-1 (negative, excludes lung origin)
p63 (negative in tumor cells, positive in basal cells if present)
Calretinin (negative, excludes mesothelioma)
Inhibin (negative, excludes sex cord-stromal tumors).
Diagnostic Utility:
PAX8 positivity confirms müllerian/gynecological origin
CK7+/CK20- pattern supports gynecological primary
WT1 positivity may suggest serous-like differentiation
ER/PR status important for treatment planning
p63 negativity excludes squamous differentiation
Negative TTF-1 excludes pulmonary metastasis.
Molecular Subtypes:
Hormone receptor positive subtype (ER+, PR+)
Intermediate proliferation subtype (moderate Ki-67)
p53 wild-type to intermediate subtype
Serous-like subtype (WT1 positive)
Endometrioid-like subtype (strong ER/PR)
Mixed differentiation subtype.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (present in 40-60% of cases, intermediate frequency)
PIK3CA mutations (20-30% of cases)
CTNNB1 mutations (Wnt pathway, 10-15%)
KRAS mutations (uncommon, <10%)
PTEN alterations (may be present)
BRCA1/2 mutations (no established association)
ARID1A mutations (chromatin remodeling).
Molecular Markers:
p53 expression (wild-type to intermediate pattern)
β-catenin (may show nuclear accumulation)
Ki-67 proliferation index (intermediate, 30-50%)
Cyclin D1 (may be overexpressed)
PTEN protein (may show loss)
MSI markers (usually stable)
PD-L1 expression (variable).
Prognostic Significance:
Intermediate prognosis between Grade 1 and Grade 3 carcinomas
Stage II-III at diagnosis commonly
Moderate metastatic potential
Better response to treatment than high-grade tumors
5-year survival 60-70%
Recurrence rate moderate
ER/PR status influences hormone therapy response.
Therapeutic Targets:
Hormone therapy (for ER/PR positive cases)
Platinum-based chemotherapy (standard for advanced cases)
PI3K/mTOR inhibitors (for PIK3CA-mutated cases)
Wnt pathway inhibitors (for CTNNB1-mutated cases)
Anti-angiogenic agents (bevacizumab)
CDK4/6 inhibitors (hormone receptor positive)
Immunotherapy (limited role).
Differential Diagnosis
Similar Entities:
Serous carcinoma with cribriform features
Endometrioid carcinoma with cribriform pattern
Micropapillary carcinoma (lacks true luminal spaces)
Adenoid cystic carcinoma (different morphology and markers)
Metastatic cribriform carcinoma from breast or prostate
Serous borderline tumor with cribriform features
Transitional cell carcinoma.
Distinguishing Features:
Cribriform vs micropapillary: True luminal spaces vs tufting without spaces
Primary tubal vs metastatic: PAX8 positivity, clinical history, imaging
Carcinoma vs borderline: Stromal invasion, nuclear atypia, mitotic activity
Adenocarcinoma vs adenoid cystic: Different immunoprofile and morphology.
Diagnostic Challenges:
Distinguishing from micropapillary carcinoma
Determining grade (intermediate features)
Recognizing cribriform pattern in limited tissue
Differentiating from metastatic disease
Mixed histological patterns
Sampling issues in small biopsies.
Rare Variants:
Mixed cribriform and serous pattern
Cribriform with micropapillary areas
Solid cribriform variant
Cribriform with endometrioid features
Cystic cribriform pattern
Cribriform with clear cell areas
Pleomorphic cribriform variant.
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
[Unilateral/Bilateral] salpingo-oophorectomy, fallopian tube measuring [size] cm with solid tumor
Diagnosis
Cribriform carcinoma of fallopian tube
Classification
Intermediate-grade adenocarcinoma with cribriform pattern (Grade 2)
Histological Features
Shows cribriform (sieve-like) architecture with back-to-back glands and punched-out spaces
Cribriform Pattern
Cribriform architecture present in >50% of tumor, sieve-like spaces of varying sizes, moderate nuclear atypia
Histological Grading
Grade 2: Cribriform architecture, moderate nuclear atypia, mitotic count [10-20/10 HPF]
Extent of Disease
Size: [X] cm, Growth pattern: [cribriform/infiltrative], Necrosis: [minimal/focal]
Special Studies
CK7: positive, PAX8: positive (confirming müllerian origin)
ER: [positive/negative], PR: [positive/negative]
WT1: [positive/negative], CK20: negative
Molecular Features
p53: [wild-type to intermediate pattern], Ki-67: [intermediate proliferation, 30-50%]
FIGO Staging
FIGO Stage: [IB/IC/II/III] - [staging details]
Prognostic Factors
Cribriform carcinoma (intermediate prognosis), Grade 2, Hormone receptor status: [ER/PR status]
Final Diagnosis
Primary fallopian tube cribriform carcinoma, FIGO Stage [IB/IC/II/III]