Definition/General
Introduction:
Endometrial micropapillary carcinoma is a rare aggressive variant of endometrial adenocarcinoma
It is characterized by micropapillary architecture similar to breast and lung micropapillary carcinomas
It represents less than 1% of all endometrial carcinomas
It has a poor prognosis.
Origin:
Arises from endometrial glandular epithelium
May develop from conventional adenocarcinoma
Can occur as pure micropapillary pattern
May be mixed with other histotypes
Morphologic pattern defining feature.
Classification:
Classified as architectural variant of endometrial adenocarcinoma by WHO
Type II endometrial carcinoma behavior
High-grade morphology
Aggressive clinical behavior
Poor prognostic variant.
Epidemiology:
Rare variant of endometrial carcinoma
Peak incidence in 6th-7th decades
Postmenopausal women predominantly affected
Not associated with estrogen exposure
Advanced stage at presentation common
Worse prognosis than conventional carcinomas.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Postmenopausal bleeding
Rapidly enlarging uterus
Pelvic pain
Advanced disease at presentation
Ascites may be present.
Symptoms:
Heavy uterine bleeding
Pelvic pain and pressure
Abdominal distension
Weight loss
Constitutional symptoms
Bowel/bladder symptoms (advanced disease).
Risk Factors:
Age >60 years
No association with typical endometrial cancer risk factors
Not related to estrogen exposure
Lynch syndrome association unclear
TP53 mutations common.
Screening:
No specific screening recommendations
Endometrial sampling for abnormal bleeding
Advanced imaging for staging
CA-125 may be elevated
Peritoneal cytology important.
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Gross Description
Appearance:
Polypoid or ulcerative mass in endometrial cavity
Gray-white cut surface
Soft, friable consistency
Areas of necrosis and hemorrhage
Myometrial invasion common.
Characteristics:
Size ranges from 3-10 cm
Infiltrative margins
Cut surface shows heterogeneous appearance
Necrotic areas common
Hemorrhagic foci present.
Size Location:
Usually large at presentation
Involves endometrial cavity
Deep myometrial invasion common
Cervical extension frequent
Extrauterine spread at diagnosis.
Multifocality:
Usually unifocal but aggressive
Extensive local invasion
Lymphovascular invasion common
Peritoneal seeding frequent
Lymph node metastases common.
Microscopic Description
Histological Features:
Small micropapillary clusters lacking fibrovascular cores
Morular-like structures
Tight cell clusters in lacunar spaces
High nuclear grade
High mitotic activity
Extensive lymphovascular invasion.
Cellular Characteristics:
Small clusters of malignant cells
High nuclear-to-cytoplasmic ratio
Pleomorphic nuclei
Prominent nucleoli
Eosinophilic cytoplasm
Mitotic figures abundant.
Architectural Patterns:
Micropapillary pattern without fibrovascular cores
Morular clusters in clear spaces
Inverted polarity
Reverse polarity with apical surfaces facing stroma
May show conventional glandular areas.
Grading Criteria:
Considered high-grade by definition
FIGO Grade 3 equivalent
High mitotic rate (>20/10 HPF)
Marked nuclear atypia
Extensive necrosis
Aggressive behavior.
Immunohistochemistry
Positive Markers:
Cytokeratins (CK7 positive)
EMA (reverse polarity pattern)
E-cadherin
MUC1 (reverse polarity)
p53 (often overexpressed)
PAX8
ER (variable).
Negative Markers:
CK20 (negative)
TTF-1 (negative)
CDX2 (negative)
WT1 (negative)
Vimentin (negative)
PR (usually negative).
Diagnostic Utility:
MUC1 reverse polarity characteristic feature
PAX8 positivity confirms mullerian origin
p53 overexpression common
CK7+/CK20- profile
EMA apical pattern reversed.
Molecular Subtypes:
TP53 mutations common
PIK3CA mutations
PTEN loss
FBXW7 mutations
Copy number high subtype
Chromosomal instability.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (70-80% cases)
PIK3CA mutations (30-40%)
PTEN loss (25-35%)
FBXW7 mutations (20-30%)
PPP2R1A mutations (15-20%)
ARID1A mutations.
Molecular Markers:
p53 overexpression or complete loss
High Ki-67 index (>50%)
Chromosomal instability
Copy number alterations
Aneuploidy.
Prognostic Significance:
TP53 mutations indicate poor prognosis
Micropapillary pattern correlates with aggressive behavior
Advanced stage common at presentation
Chemoresistance frequent
Overall survival poor.
Therapeutic Targets:
Platinum-based chemotherapy
Immunotherapy (pembrolizumab)
PARP inhibitors (if HRD positive)
PI3K/mTOR inhibitors
Anti-angiogenic agents
Combination therapy approaches.
Differential Diagnosis
Similar Entities:
Conventional endometrial adenocarcinoma
Papillary serous carcinoma
Villoglandular adenocarcinoma
Metastatic micropapillary carcinoma (breast, lung)
Clear cell carcinoma.
Distinguishing Features:
Conventional: Lacks micropapillary pattern
Serous: True papillae with cores
Villoglandular: Long papillae
Micropapillary: No fibrovascular cores
Micropapillary: Reverse polarity
Clear cell: Clear cytoplasm.
Diagnostic Challenges:
Distinguishing from other papillary patterns
Recognizing reverse polarity
Identifying lack of fibrovascular cores
Excluding metastatic disease
MUC1 staining pattern helpful.
Rare Variants:
Pure micropapillary carcinoma
Mixed with conventional adenocarcinoma
Micropapillary component in carcinosarcoma
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, micropapillary variant
WHO Classification
Endometrial adenocarcinoma, architectural variant (micropapillary type)
Histological Features
Micropapillary architecture in [percentage]% of tumor, reverse polarity present
Grade
FIGO Grade: 3 (high-grade by definition)
Polarity Pattern
Reverse polarity: [present/absent], MUC1 pattern: [reverse/normal]
Myometrial Invasion
Myometrial invasion: [depth] mm, [percentage]% of wall thickness
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
Polarity markers: MUC1 [reverse/normal], EMA [reverse/normal]
Epithelial markers: CK7 [+/-], PAX8 [+/-]
p53: [overexpressed/wild-type/null], Ki-67: [percentage]%
Final Diagnosis
Endometrial adenocarcinoma, micropapillary variant, FIGO Grade 3