Definition/General
Introduction:
Fallopian tube endometrioid carcinoma is a rare primary malignancy accounting for 15-20% of all fallopian tube carcinomas
It resembles endometrial endometrioid carcinoma morphologically and has a better prognosis compared to high-grade serous carcinoma
The tumor may be associated with Lynch syndrome and shows microsatellite instability (MSI) in a subset of cases
Hormone receptor positivity is characteristic and may guide therapy.
Origin:
Originates from the epithelial lining of the fallopian tube with endometrioid differentiation
May arise from tubal endometriosis or metaplastic epithelium
The tumor shows glandular architecture resembling endometrial tissue
Lynch syndrome predisposes to development through mismatch repair deficiency
Estrogen stimulation may play a role in tumor development
Most commonly affects the ampullary portion of the fallopian tube.
Classification:
WHO classification recognizes endometrioid adenocarcinoma as a distinct subtype
Grading system follows the same criteria as endometrial endometrioid carcinoma
Grade 1 (<5% solid growth), Grade 2 (6-50% solid growth), Grade 3 (>50% solid growth)
FIGO staging follows ovarian carcinoma staging system
Molecular classification includes MSI-high and microsatellite stable subtypes
Squamous differentiation may be present (adenosquamous carcinoma).
Epidemiology:
Peak incidence in 5th-6th decades (median age 55-60 years)
Lynch syndrome associated in 10-15% of cases
Better prognosis compared to serous carcinoma
Association with endometriosis in some cases
Hormone receptor positivity in majority (80-90%)
Earlier stage at presentation compared to serous carcinoma
Lower propensity for peritoneal spread compared to high-grade serous carcinoma.
Clinical Features
Presentation:
Pelvic pain (50-60% of cases) due to tubal distension
Abnormal vaginal bleeding (irregular or postmenopausal)
Vaginal discharge (watery or bloody)
Palpable adnexal mass (40-50% of cases)
Abdominal pain and discomfort
Ascites less common than in serous carcinoma
Earlier stage at diagnosis compared to high-grade serous carcinoma.
Symptoms:
Postmenopausal bleeding or irregular cycles in premenopausal women
Pelvic pressure and cramping
Watery vaginal discharge (less common than in serous)
Abdominal bloating and fullness
Urinary symptoms (frequency, urgency) due to mass effect
Constitutional symptoms (fatigue, weight loss) in advanced cases
Family history of Lynch syndrome-associated cancers may be present.
Risk Factors:
Lynch syndrome (MLH1, MSH2, MSH6, PMS2 mutations)
Family history of colorectal, endometrial, or ovarian cancer
Personal history of colorectal or endometrial cancer
Nulliparity and infertility
Late menopause and early menarche
Hormone replacement therapy (unopposed estrogen)
Obesity and metabolic syndrome
PTEN mutations (Cowden syndrome).
Screening:
Lynch syndrome screening for patients with family history
Tumor testing for mismatch repair proteins and MSI
Genetic counseling for patients meeting Amsterdam or Bethesda criteria
Annual gynecological examination for high-risk women
Endometrial biopsy for abnormal bleeding in Lynch syndrome patients
Prophylactic hysterectomy and salpingo-oophorectomy for Lynch syndrome carriers.
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Gross Description
Appearance:
Polypoid or nodular growth within tubal lumen
Gray-white to tan cut surface with soft consistency
Glandular architecture may be visible grossly
Less friable compared to serous carcinoma
Cystic areas may be present
Hemorrhage and necrosis in larger tumors
Well-circumscribed borders compared to infiltrative serous carcinoma.
Characteristics:
Soft, fleshy consistency with glandular cut surface
Tan to yellow coloration depending on secretions
Smooth surface with less ulceration than serous carcinoma
Cystic degeneration may occur in larger tumors
Minimal calcification (unlike serous with psammoma bodies)
Squamous areas may appear more keratinized in adenosquamous variant.
Size Location:
Size ranges from small nodules to large masses (up to 15 cm)
Ampullary portion most commonly affected (60-70%)
Fimbrial involvement less common than serous carcinoma
Unilateral involvement in majority of cases
Bilateral disease in 15-20% of cases
Extension to ovary may occur but less common than serous.
Multifocality:
Multifocal disease less common than serous carcinoma (10-15%)
Synchronous endometrial carcinoma in 15-20% of cases
Concurrent ovarian endometrioid carcinoma may occur
Lynch syndrome patients may have multiple primary tumors
Adenomatous hyperplasia may be present in adjacent tubal epithelium.
Microscopic Description
Histological Features:
Glandular architecture resembling endometrial adenocarcinoma
Tubular and cribriform patterns with round to oval glands
Columnar epithelial cells with eosinophilic cytoplasm
Nuclear stratification and atypia varying with grade
Squamous differentiation in 20-30% of cases
Ciliated cells may be present
Stromal invasion with desmoplastic response.
Cellular Characteristics:
Columnar cells with oval to elongated nuclei
Eosinophilic cytoplasm with distinct cell borders
Nuclear atypia proportional to grade (mild to severe)
Prominent nucleoli in high-grade tumors
Mitotic activity varies with grade
Squamous morules in adenosquamous variant
Ciliated cells suggest tubal origin.
Architectural Patterns:
Back-to-back glands without intervening stroma
Cribriform pattern with bridging epithelium
Papillary areas may be present (papillary variant)
Solid growth in poorly differentiated areas
Villoglandular pattern (rare variant)
Secretory pattern with subnuclear vacuoles
Squamous differentiation (morules or mature squamous epithelium).
Grading Criteria:
Grade 1: <5% solid growth, mild nuclear atypia, low mitotic rate
Grade 2: 6-50% solid growth, moderate nuclear atypia
Grade 3: >50% solid growth, severe nuclear atypia, high mitotic rate
Nuclear grade assessment independent of architecture
Notable nuclear atypia upgrades by one grade
Squamous differentiation does not affect grading.
Immunohistochemistry
Positive Markers:
PAX8 (nuclear, positive in >90% of cases)
ER (nuclear, positive in 80-90% of cases)
PR (nuclear, positive in 70-80% of cases)
CK7 (cytoplasmic, diffusely positive)
EMA (cytoplasmic/luminal, positive)
Vimentin (cytoplasmic, positive)
CDX2 (nuclear, positive in intestinal-type areas)
β-catenin (membranous pattern, nuclear in CTNNB1-mutated cases).
Negative Markers:
WT1 (negative, helps distinguish from serous carcinoma)
p53 (wild-type pattern, not overexpressed)
CK20 (negative except in intestinal differentiation)
TTF-1 (negative, excludes lung metastasis)
Napsin A (negative, excludes clear cell carcinoma)
p40/p63 (negative except in squamous areas)
Inhibin (negative, excludes sex cord-stromal tumors).
Diagnostic Utility:
ER/PR positivity supports endometrioid differentiation and guides hormonal therapy
PAX8 positivity confirms müllerian origin
WT1 negativity helps distinguish from serous carcinoma
p53 wild-type pattern excludes high-grade serous carcinoma
Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) to assess for Lynch syndrome
β-catenin nuclear staining indicates CTNNB1 mutations.
Molecular Subtypes:
Microsatellite instable (MSI-high) (10-15% of cases, Lynch syndrome-associated)
Microsatellite stable (MSS) (majority of cases)
CTNNB1-mutated subtype (β-catenin nuclear accumulation)
PTEN-deficient subtype (loss of PTEN expression)
Hormone receptor positive subtype (majority of cases)
PIK3CA-mutated subtype (subset of cases).
Molecular/Genetic
Genetic Mutations:
PTEN mutations (40-60% of cases, tumor suppressor loss)
PIK3CA mutations (30-40% of cases, PI3K pathway activation)
CTNNB1 mutations (20-30% of cases, Wnt pathway activation)
ARID1A mutations (20-30% of cases, chromatin remodeling)
KRAS mutations (15-25% of cases)
Mismatch repair genes (MLH1, MSH2, MSH6, PMS2 in Lynch syndrome)
TP53 mutations (rare, <10% of cases).
Molecular Markers:
PTEN loss by immunohistochemistry (correlates with mutations)
β-catenin nuclear accumulation (CTNNB1 mutations)
PI3K pathway activation (pAKT, pmTOR expression)
Mismatch repair protein loss (MLH1, MSH2, MSH6, PMS2)
MLH1 promoter hypermethylation (sporadic MSI cases)
High microsatellite instability (MSI-H by PCR)
p53 wild-type pattern (unlike serous carcinoma).
Prognostic Significance:
Grade is most important prognostic factor (Grade 1 best, Grade 3 worst)
Stage at diagnosis correlates with survival
MSI status may predict immunotherapy response
CTNNB1 mutations associated with better prognosis
Age at diagnosis influences outcome
Hormone receptor status predicts hormonal therapy response
Lynch syndrome patients may have better overall survival.
Therapeutic Targets:
Estrogen/progesterone receptors (hormonal therapy with tamoxifen, aromatase inhibitors, progestins)
PI3K/AKT/mTOR pathway (mTOR inhibitors, PI3K inhibitors)
PD-1/PD-L1 (pembrolizumab for MSI-high tumors)
PARP inhibitors (for homologous recombination deficient tumors)
CDK4/6 inhibitors (palbociclib for ER-positive tumors)
Wnt pathway inhibitors (for CTNNB1-mutated tumors, investigational).
Differential Diagnosis
Similar Entities:
Primary endometrial endometrioid carcinoma with tubal involvement
Metastatic endometrial carcinoma to fallopian tube
Primary ovarian endometrioid carcinoma
Tubal adenomatoid tumor (benign mesothelial tumor)
Tubal hyperplasia and metaplasia
Arias-Stella reaction in pregnancy
Clear cell carcinoma with endometrioid features.
Distinguishing Features:
Primary tubal vs endometrial: Normal endometrium, tubal mucosal origin, absence of endometrial involvement
Endometrioid vs serous: ER/PR positive vs negative, WT1 negative vs positive, p53 wild-type vs aberrant
Endometrioid vs clear cell: ER positive vs negative, Napsin A negative vs positive
Malignant vs hyperplasia: Stromal invasion, severe nuclear atypia, high mitotic rate.
Diagnostic Challenges:
Determining primary site when endometrium also involved
Distinguishing from metastatic endometrial carcinoma requires clinical correlation
Grading may be difficult in small specimens
Squamous differentiation should not be mistaken for squamous cell carcinoma
Lynch syndrome screening requires systematic approach
Frozen section interpretation may be challenging.
Rare Variants:
Adenosquamous carcinoma (benign-appearing squamous differentiation)
Secretory variant (subnuclear vacuoles, resembles secretory endometrium)
Ciliated variant (abundant ciliated cells)
Papillary variant (papillary architecture with fibrovascular cores)
Microglandular variant (small glands resembling microglandular hyperplasia)
Oxyphilic variant (abundant eosinophilic cytoplasm)
Undifferentiated carcinoma (loss of glandular 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
[Unilateral/Bilateral] salpingo-oophorectomy, fallopian tube measuring [size] cm
Diagnosis
Endometrioid adenocarcinoma of fallopian tube
Classification and Grade
Endometrioid adenocarcinoma, Grade [1/2/3] ([well/moderately/poorly] differentiated)
Histological Features
Shows glandular architecture with [percentage]% solid growth, [mild/moderate/severe] nuclear atypia
Squamous Differentiation
Squamous differentiation: [present/absent], Type: [morules/mature squamous epithelium]
Invasion and Extent
Invasion: [through tubal wall], Size: [X] cm, Serosal involvement: [present/absent]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Special Studies
ER: [positive/negative], PR: [positive/negative]
PAX8: positive, WT1: negative
MMR proteins: MLH1: [intact/lost], MSH2: [intact/lost], MSH6: [intact/lost], PMS2: [intact/lost]
Lynch Syndrome Screening
MMR status: [intact/deficient], Lynch syndrome testing: [recommended/not indicated]
FIGO Staging
FIGO Stage: [IA/IB/IC/II/III/IV] - [staging description]
Prognostic Factors
Grade: [1/2/3], Stage: [I/II/III/IV], ER/PR: [positive/negative], MMR: [intact/deficient]
Final Diagnosis
Primary fallopian tube endometrioid adenocarcinoma, Grade [1/2/3], FIGO Stage [IA/IB/IC/II/III/IV]