Definition/General
Introduction:
Endometrial mesonephric carcinoma is an extremely rare malignant tumor that morphologically resembles mesonephric carcinoma of the cervix
It represents less than 1% of all endometrial carcinomas
It is also termed mesonephric-like adenocarcinoma
It has distinct morphological and molecular features.
Origin:
The exact origin is controversial
May arise from mesonephric remnants in the endometrium
More likely represents müllerian epithelium with mesonephric-like differentiation
Shows morphological mimicry of true mesonephric carcinoma
Molecular studies suggest müllerian origin.
Classification:
WHO classification includes under other epithelial tumors
Also termed mesonephric-like adenocarcinoma
Distinguished from true cervical mesonephric carcinoma
Characterized by specific molecular alterations
All cases considered high-grade tumors.
Epidemiology:
Extremely rare with fewer than 100 cases reported in literature
Peak incidence in 5th-6th decades
Mean age 55-65 years
Younger than typical endometrial carcinoma
No specific risk factors identified
Aggressive behavior with poor prognosis.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Postmenopausal bleeding
Pelvic mass or enlarged uterus
Advanced stage at presentation common
Pelvic pain
Rapid symptom progression
Constitutional symptoms (weight loss, fatigue).
Symptoms:
Abnormal uterine bleeding (80-90%)
Pelvic pressure and pain
Bulky uterine mass
Vaginal discharge
Abdominal distension
Urinary symptoms (advanced cases)
Bowel symptoms (rare)
Metastatic symptoms at presentation possible.
Risk Factors:
No specific risk factors identified
Age (perimenopausal/postmenopausal)
No association with typical endometrial carcinoma risk factors
No hormonal associations
May have genetic predisposition
Rare tumor with unknown etiology.
Screening:
No specific screening guidelines
Endometrial sampling for abnormal bleeding
Imaging studies (ultrasound, MRI)
Advanced imaging for staging
Tumor markers not specific
Molecular testing important for diagnosis.
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Gross Description
Appearance:
Solid, firm, gray-white mass with well-defined margins
Cut surface shows homogeneous appearance
May have cystic areas
Size variable but often large at presentation
Hemorrhage and necrosis less common than other high-grade tumors.
Characteristics:
Firm consistency with gray-white coloration
Well-circumscribed appearance
May show microcystic areas
Solid growth pattern predominates
Areas of calcification possible
Less necrotic than typical high-grade carcinomas.
Size Location:
Usually involves entire endometrial cavity
Size ranges from 4-12 cm
Deep myometrial invasion common
May extend to cervix
Extrauterine extension frequent at presentation
Lymphovascular invasion often present.
Multifocality:
Usually unifocal
Multicentric growth possible
Lymph node metastases common
Peritoneal implants may be present
Distant metastases at presentation possible
Aggressive spread pattern.
Microscopic Description
Histological Features:
Small, closely packed tubules and glands with minimal intervening stroma
Round to oval glands with eosinophilic secretions
Cuboidal to low columnar epithelial cells
Uniform nuclear features
Mitotic activity variable but present
Desmoplastic stroma uncommon.
Cellular Characteristics:
Cuboidal to low columnar cells
Uniform, round nuclei with fine chromatin
Eosinophilic cytoplasm
Inconspicuous nucleoli
Minimal nuclear pleomorphism
Mitotic figures present but variable
Apoptotic bodies may be seen.
Architectural Patterns:
Tubular pattern predominates
Closely packed small glands
Solid areas may be present
Papillary areas uncommon
Retiform pattern possible
Cribriform areas rare
Minimal stromal component.
Grading Criteria:
All mesonephric carcinomas considered high-grade by definition
Architectural complexity varies
Nuclear grade typically low to intermediate
Mitotic activity variable
Biological behavior aggressive despite morphology.
Immunohistochemistry
Positive Markers:
GATA3 (diffusely positive, highly specific)
TTF-1 (positive in most cases)
CD10 (may be positive)
Calretinin (variable)
Inhibin (variable)
PAX8 (usually negative, helps distinguish from müllerian tumors)
Cytokeratins (CK7, CAM5.2).
Negative Markers:
Hormone receptors (ER, PR) - typically negative
PAX8 - usually negative (key distinguishing feature)
WT1 - negative
Napsin A - negative
HNF-1β - negative
p16 - usually negative or patchy.
Diagnostic Utility:
GATA3 positivity is highly characteristic and diagnostic
PAX8 negativity distinguishes from müllerian tumors
TTF-1 positivity supports diagnosis
Hormone receptor negativity typical
Combination panel essential for accurate diagnosis.
Molecular Subtypes:
Specific molecular signature
KRAS mutations common
PIK3CA mutations frequent
ARID1A mutations
p53 wild-type pattern usually
Microsatellite stable
Distinct molecular profile from typical endometrial carcinomas.
Molecular/Genetic
Genetic Mutations:
KRAS mutations (70-80%)
PIK3CA mutations (40-50%)
ARID1A mutations (30-40%)
SMARCA4 mutations
PTEN mutations (less common)
p53 mutations rare
Mismatch repair genes usually intact.
Molecular Markers:
KRAS overexpression
PI3K/AKT pathway activation
ARID1A loss
Microsatellite stability
p53 wild-type expression
Low Ki-67 despite aggressive behavior
Chromosomal stability pattern.
Prognostic Significance:
Aggressive behavior despite molecular features
KRAS mutations may predict resistance to certain therapies
PIK3CA mutations may indicate sensitivity to PI3K inhibitors
Stage most important prognostic factor
Early stage has better prognosis.
Therapeutic Targets:
PI3K/AKT inhibitors for PIK3CA mutations
KRAS pathway inhibitors under investigation
MEK inhibitors for KRAS-mutant tumors
Standard chemotherapy for advanced disease
Targeted therapy combinations promising.
Differential Diagnosis
Similar Entities:
Cervical mesonephric carcinoma
Endometrioid carcinoma (tubular variant)
Clear cell carcinoma
Serous carcinoma
Metastatic adenocarcinoma (renal, lung)
Sex cord-stromal tumor.
Distinguishing Features:
Endometrial mesonephric: GATA3 positive
Endometrial mesonephric: PAX8 negative
Endometrial mesonephric: Location in endometrium
Cervical mesonephric: Cervical location
Cervical mesonephric: Associated mesonephric remnants
Endometrioid: PAX8 positive
Endometrioid: ER/PR positive
Clear cell: HNF-1β positive
Clear cell: Clear cytoplasm.
Diagnostic Challenges:
Distinguishing from cervical mesonephric carcinoma
Separating from endometrioid carcinoma variants
Excluding metastatic adenocarcinoma
Recognizing rare morphological patterns
Immunohistochemical confirmation essential
Molecular testing may be needed.
Rare Variants:
Solid variant
Papillary variant
Retiform variant
Mixed patterns
Spindle cell areas
Sex cord-like differentiation.
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
Hysterectomy specimen measuring [X x Y x Z] cm, weighing [X] grams
Diagnosis
Endometrial mesonephric carcinoma (mesonephric-like adenocarcinoma)
Classification
WHO Classification: Mesonephric-like adenocarcinoma, FIGO Grade: High-grade
Histological Features
Small tubular glands with cuboidal epithelium and eosinophilic secretions
Morphological Pattern
[Tubular/solid/mixed] pattern with mesonephric-like features
Size and Extent
Tumor size: [X] cm, myometrial invasion: [depth/total thickness], [percent]%
Margins
Margins: [involved/uninvolved], closest margin: [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Cervical Involvement
Cervical involvement: [present/absent]
Special Studies
IHC: GATA3: [positive], PAX8: [negative], TTF-1: [result], ER/PR: [negative]
Molecular studies: KRAS: [result], PIK3CA: [result] (if performed)
Molecular Features
Molecular alterations: [list if performed], consistent with mesonephric-like carcinoma
FIGO Staging
FIGO Stage: [stage] ([staging criteria])
Prognostic Factors
High-grade tumor with aggressive behavior, Stage: [X]
Final Diagnosis
Endometrial mesonephric carcinoma (mesonephric-like adenocarcinoma), FIGO Stage [X]