Definition/General
Introduction:
Endometrial cribriform carcinoma is a rare morphologic variant of endometrial adenocarcinoma
It is characterized by cribriform architecture resembling breast invasive cribriform carcinoma
It represents less than 1% of all endometrial carcinomas
It typically has an intermediate prognosis.
Origin:
Arises from endometrial glandular epithelium
May develop from atypical hyperplasia
Can occur as pure cribriform pattern
May be mixed with conventional adenocarcinoma
Architectural pattern defining feature.
Classification:
Classified as architectural variant of endometrial adenocarcinoma by WHO
Type I endometrial carcinoma typically
Grade 2 morphology usually
May show squamous differentiation
Intermediate-grade malignancy.
Epidemiology:
Rare variant of endometrial carcinoma
Peak incidence in 5th-6th decades
Postmenopausal women predominantly affected
Associated with estrogen exposure
Better prognosis than solid high-grade carcinomas.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Postmenopausal bleeding
Enlarged uterus
Pelvic pressure symptoms
Early detection possible.
Symptoms:
Heavy menstrual bleeding
Intermenstrual bleeding
Pelvic pain
Dysmenorrhea
Constitutional symptoms uncommon
Early stage presentation typical.
Risk Factors:
Unopposed estrogen exposure
Obesity
Nulliparity
Late menopause
Diabetes mellitus
Tamoxifen therapy
Lynch syndrome (rare association).
Screening:
Standard endometrial cancer screening
Endometrial sampling for abnormal bleeding
Transvaginal ultrasound
Hysteroscopy for direct visualization
No specific screening for this variant.
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Gross Description
Appearance:
Polypoid or sessile mass in endometrial cavity
Gray-white cut surface
Soft to firm consistency
Lobulated external surface
Minimal necrosis typically.
Characteristics:
Size ranges from 2-8 cm
Well-demarcated margins
Cut surface shows uniform appearance
Solid consistency
Hemorrhagic areas may be present.
Size Location:
Variable size at presentation
Involves endometrial cavity
Superficial myometrial invasion common
Deep invasion less frequent
Polypoid growth typical.
Multifocality:
Usually unifocal presentation
Limited local invasion
Lymphovascular invasion uncommon
Lymph node metastases rare
Early stage disease common.
Microscopic Description
Histological Features:
Cribriform architecture with sieve-like spaces
Back-to-back glands with intervening stroma
Round to oval luminal spaces
Uniform nuclear features
Moderate mitotic activity
Minimal nuclear pleomorphism.
Cellular Characteristics:
Columnar epithelial cells
Uniform nuclear features
Moderate nuclear atypia
Vesicular chromatin
Small nucleoli
Eosinophilic cytoplasm.
Architectural Patterns:
Cribriform pattern predominant (>50%)
Sieve-like spaces
Roman bridge formation
Back-to-back glands
May show conventional glandular areas
Squamous differentiation possible.
Grading Criteria:
Usually FIGO Grade 2
Architectural grading based on solid areas (<5-50%)
Nuclear grade typically intermediate
Mitotic count moderate
Better differentiated than solid carcinomas.
Immunohistochemistry
Positive Markers:
Cytokeratins (CK7 positive)
EMA
ER (usually positive)
PR (usually positive)
PAX8
Vimentin (may be positive)
p16 (patchy staining).
Negative Markers:
CK20 (negative)
TTF-1 (negative)
CDX2 (negative)
WT1 (negative)
p53 (wild-type pattern)
Napsin A (negative).
Diagnostic Utility:
ER/PR positivity supports endometrial origin
PAX8 positivity confirms mullerian origin
p53 wild-type pattern typical
CK7+/CK20- profile
Mismatch repair proteins usually retained.
Molecular Subtypes:
PTEN mutations common
PIK3CA mutations
ARID1A mutations
CTNNB1 mutations
Microsatellite stable usually
POLE mutations rare.
Molecular/Genetic
Genetic Mutations:
PTEN mutations (50-60% cases)
PIK3CA mutations (30-40%)
ARID1A mutations (25-35%)
CTNNB1 mutations (15-25%)
KRAS mutations (10-20%)
TP53 mutations uncommon.
Molecular Markers:
PTEN loss by immunohistochemistry
β-catenin nuclear expression (CTNNB1 mutants)
Wild-type p53 pattern
Microsatellite stability
Low copy number alterations.
Prognostic Significance:
Intermediate prognosis between grade 1 and 3 carcinomas
Early stage at presentation favorable
CTNNB1 mutations may indicate better prognosis
Architectural pattern influences behavior
Lymphovascular invasion important prognostic factor.
Therapeutic Targets:
Hormone therapy (ER/PR positive cases)
PI3K/mTOR inhibitors (PTEN-deficient tumors)
Immunotherapy (mismatch repair deficient cases)
Standard chemotherapy regimens
Targeted therapy based on molecular profile.
Differential Diagnosis
Similar Entities:
Conventional endometrial adenocarcinoma
Villoglandular adenocarcinoma
Microglandular hyperplasia
Atypical hyperplasia
Metastatic cribriform carcinoma (breast).
Distinguishing Features:
Conventional: Lacks cribriform pattern
Villoglandular: Papillary architecture
Hyperplasia: Benign cytology
Cribriform: Sieve-like spaces
Metastatic breast: ER+, GATA3+
Endometrial: PAX8+.
Diagnostic Challenges:
Distinguishing from atypical hyperplasia with cribriform features
Recognizing cribriform architecture
Excluding metastatic breast carcinoma
Assessing percentage of cribriform pattern
Immunohistochemistry helpful.
Rare Variants:
Pure cribriform carcinoma
Mixed with conventional adenocarcinoma
Cribriform with squamous differentiation
Micropapillary-cribriform pattern.
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
Endometrial adenocarcinoma, cribriform variant
WHO Classification
Endometrial adenocarcinoma, architectural variant (cribriform type)
Histological Features
Cribriform architecture in [percentage]% of tumor with sieve-like spaces
Grade
FIGO Grade: [1/2/3], predominantly Grade 2 morphology
Myometrial Invasion
Myometrial invasion: [depth] mm, [percentage]% of wall thickness
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
Hormone receptors: ER [+/-], PR [+/-]
Epithelial markers: CK7 [+/-], EMA [+/-], PAX8 [+/-]
p53: [wild-type/overexpressed], Ki-67: [percentage]%
Final Diagnosis
Endometrial adenocarcinoma, cribriform variant, FIGO Grade [grade]