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]