Definition/General
Introduction:
Fallopian tube adenocarcinoma is a rare primary malignancy accounting for 0.3-1.1% of all gynecological cancers
It includes various histological subtypes with high-grade serous carcinoma being the most common
Recent evidence suggests that many ovarian high-grade serous carcinomas actually originate from the fallopian tube
Primary fallopian tube carcinoma has a strong association with BRCA1/2 mutations and hereditary breast-ovarian cancer syndrome.
Origin:
Originates from the epithelial lining of the fallopian tube, particularly from the fimbriated end
Serous tubal intraepithelial carcinoma (STIC) is recognized as the precursor lesion for high-grade serous carcinoma
The tumor arises from secretory cells within the tubal epithelium
BRCA1/2 mutations predispose to malignant transformation
The fimbrial end is most susceptible due to its proximity to the ovary and exposure to ovarian hormones.
Classification:
WHO classification includes several subtypes: High-grade serous adenocarcinoma (most common, 60-70%)
Endometrioid adenocarcinoma (15-20%)
Clear cell adenocarcinoma (5-10%)
Mucinous adenocarcinoma (rare, <5%)
Mixed carcinomas with multiple histological patterns
FIGO staging follows the same system as ovarian carcinoma
Molecular classification based on genetic alterations is increasingly important.
Epidemiology:
Peak incidence in 6th-7th decades (median age 60-65 years)
Strong association with BRCA1/2 mutations (40-60% of cases)
Hereditary breast-ovarian cancer syndrome accounts for significant proportion
Nulliparity and infertility are risk factors
Previous breast cancer increases risk
Family history of ovarian/breast cancer is common
Jewish ancestry (Ashkenazi) has higher prevalence of BRCA mutations.
Clinical Features
Presentation:
Pelvic pain (50-60% of cases) due to tubal distension
Abnormal vaginal bleeding (postmenopausal or irregular)
Vaginal discharge (watery, serosanguineous)
Palpable adnexal mass (30-40% of cases)
Abdominal distension and bloating
Ascites in advanced cases
Hydrops tubae profluens (intermittent discharge of clear fluid)
Constitutional symptoms (weight loss, fatigue) in advanced disease.
Symptoms:
Postmenopausal bleeding or irregular menstrual cycles
Pelvic pressure and discomfort
Intermittent watery discharge (pathognomonic when present)
Abdominal pain and cramping
Early satiety and bloating
Urinary frequency due to mass effect
Bowel symptoms (constipation, changes in bowel habits)
Fatigue and malaise in advanced cases.
Risk Factors:
BRCA1/2 germline mutations (strongest risk factor)
Family history of breast/ovarian cancer
Personal history of breast cancer
Hereditary breast-ovarian cancer syndrome
Nulliparity and infertility
Late menopause (>55 years)
Hormone replacement therapy (controversial)
Jewish ancestry (Ashkenazi population)
Lynch syndrome (increased risk for endometrioid type).
Screening:
No routine screening for general population due to rarity
BRCA carriers benefit from risk-reducing salpingo-oophorectomy (RRSO)
Transvaginal ultrasound and CA-125 for high-risk women
MRI may be used in BRCA carriers
Annual pelvic examination for high-risk individuals
Genetic counseling for women with strong family history
Prophylactic surgery recommended for BRCA carriers after completion of childbearing.
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Gross Description
Appearance:
Enlarged, distended fallopian tube with solid and cystic areas
Papillary growths projecting into tubal lumen
Gray-white to tan cut surface with areas of necrosis and hemorrhage
Firm consistency in solid areas
Friable, easily bleeding surface
Involvement of fimbrial end is common
Extension to ovary may be present.
Characteristics:
Tubal distension with loss of normal architecture
Papillary and solid growth patterns on cut surface
Necrotic areas with yellow-tan discoloration
Hemorrhage within tumor and tubal lumen
Calcifications may be present (psammoma bodies)
Mucoid secretions in some cases
Extension through tubal wall in advanced cases.
Size Location:
Size varies from microscopic foci to large masses (up to 15-20 cm)
Fimbrial end most commonly involved (80-90% of high-grade serous)
Unilateral involvement in most cases initially
Bilateral involvement may occur with advanced disease
Ampullary portion commonly affected
Isthmic involvement less common
Entire tube may be involved in extensive cases.
Multifocality:
Multifocal STIC lesions often present in high-grade serous carcinoma
Bilateral tubal involvement in 10-20% of cases
Concurrent ovarian involvement common (may represent metastasis or synchronous primary)
Peritoneal implants may be present at diagnosis
Skip lesions along the fallopian tube
Field effect in BRCA carriers affecting both tubes.
Microscopic Description
Histological Features:
Invasive adenocarcinoma arising from tubal epithelium with various architectural patterns
High-grade serous: complex papillary architecture with high-grade nuclear atypia
Endometrioid: glandular pattern resembling endometrial adenocarcinoma
Clear cell: clear cells with hobnail morphology
Mucinous: mucin-containing cells with glandular architecture
Stromal invasion through tubal wall.
Cellular Characteristics:
High-grade nuclear atypia with enlarged, pleomorphic nuclei
Prominent nucleoli and irregular nuclear membranes
High mitotic activity (>12 mitoses per 10 HPF in high-grade)
Serous type: eosinophilic cells with moderate cytoplasm
Endometrioid type: columnar cells with eosinophilic cytoplasm
Clear cell type: cells with clear, glycogen-rich cytoplasm
Bizarre multinucleated cells may be present.
Architectural Patterns:
Complex papillary architecture in serous carcinoma with hierarchical branching
Solid sheets and nests in poorly differentiated areas
Glandular pattern in endometrioid type
Tubulocystic pattern in clear cell type
Slit-like spaces and pseudoendometrioid glands
Psammoma bodies (calcified concentric laminations) in serous type
Necrosis commonly present in high-grade tumors.
Grading Criteria:
High-grade serous is by definition high-grade (Grade 3)
Endometrioid grading: Grade 1 (<5% solid), Grade 2 (6-50% solid), Grade 3 (>50% solid)
Clear cell adenocarcinoma is typically considered high-grade
Nuclear grade assessment: size, pleomorphism, nucleoli
Mitotic count and architectural complexity contribute to grading
Necrosis indicates aggressive behavior.
Immunohistochemistry
Positive Markers:
PAX8 (nuclear, positive in >90% of müllerian carcinomas)
WT1 (nuclear, positive in serous carcinoma, 80-90%)
p53 (nuclear, aberrant pattern in high-grade serous, 95%)
CK7 (cytoplasmic, positive in most adenocarcinomas)
CA125 (cytoplasmic/luminal, positive in serous)
p16 (nuclear/cytoplasmic, positive in high-grade serous)
ER/PR (nuclear, variable in different subtypes).
Negative Markers:
CK20 (negative, helps exclude gastrointestinal origin)
CDX2 (negative except in rare mucinous intestinal type)
TTF-1 (negative, helps exclude lung metastasis)
Napsin A (negative in serous, positive in clear cell)
Hepatocyte antigen (negative, excludes hepatoid carcinoma)
p40/p63 (negative, excludes squamous differentiation)
Inhibin (negative, excludes sex cord-stromal tumors).
Diagnostic Utility:
PAX8 positivity supports müllerian origin and helps distinguish from other primaries
WT1 positivity favors serous over endometrioid histology
p53 aberrant pattern (overexpression or null) characteristic of high-grade serous
p16 block positivity supports high-grade serous diagnosis
ER/PR status guides hormonal therapy decisions
HER2 testing may be performed for targeted therapy.
Molecular Subtypes:
High-grade serous (p53 aberrant, WT1+, p16+, BRCA pathway altered)
Endometrioid (ER/PR+, β-catenin variable, MMR proteins intact/lost)
Clear cell (Napsin A+, ER-, HNF1β+, ARID1A loss)
Mucinous (CK20 variable, CDX2 may be positive)
BRCA-deficient subtype (homologous recombination deficiency signature)
Microsatellite instable subtype (MLH1/MSH2/MSH6/PMS2 loss).
Molecular/Genetic
Genetic Mutations:
TP53 mutations (95% of high-grade serous carcinomas)
BRCA1/2 germline mutations (40-60% of cases)
BRCA1/2 somatic mutations (additional 10-15%)
Homologous recombination pathway genes (PALB2, RAD51C, RAD51D)
PIK3CA mutations (endometrioid and clear cell types)
ARID1A mutations (clear cell and endometrioid types)
KRAS mutations (mucinous type)
Microsatellite instability (subset of endometrioid cases).
Molecular Markers:
p53 protein expression (aberrant pattern correlates with TP53 mutations)
PARP1 expression (potential therapeutic target)
Homologous recombination deficiency score (HRD testing)
Microsatellite instability markers (MSI-H in subset)
PD-L1 expression (variable, immunotherapy biomarker)
HER2 amplification (subset of serous carcinomas)
Ki-67 proliferation index (typically high in aggressive tumors).
Prognostic Significance:
BRCA mutation status (BRCA-associated tumors have better prognosis and PARP inhibitor sensitivity)
Homologous recombination deficiency predicts platinum sensitivity and PARP inhibitor response
Stage at diagnosis is most important prognostic factor
Histological subtype influences prognosis (serous worse than endometrioid)
Grade correlates with survival
Age at diagnosis affects outcome
Residual disease after surgery is crucial prognostic factor.
Therapeutic Targets:
PARP inhibitors (olaparib, niraparib, rucaparib for BRCA-mutated and HRD tumors)
Anti-angiogenic agents (bevacizumab for advanced disease)
PD-1/PD-L1 inhibitors (pembrolizumab for MSI-H or TMB-high tumors)
HER2-targeted therapy (trastuzumab for HER2-amplified cases)
Hormonal therapy (ER/PR positive tumors)
CDK4/6 inhibitors (investigational in ER+ cases)
WEE1 inhibitors (synthetic lethality in p53-mutated tumors).
Differential Diagnosis
Similar Entities:
Primary ovarian carcinoma (especially high-grade serous)
Metastatic carcinoma to fallopian tube (breast, gastrointestinal, lung)
Primary peritoneal carcinoma (serous type)
Endometrial carcinoma with tubal involvement
Serous tubal intraepithelial carcinoma (STIC) without invasion
Tubal hyperplasia and metaplasia
Chronic salpingitis with reactive changes.
Distinguishing Features:
Primary tubal vs ovarian: Tubal origin, normal ovaries, tubal epithelium transition
Primary vs metastatic: Clinical history, pattern of spread, immunohistochemistry panel
High-grade serous vs endometrioid: WT1 positive vs negative, p53 aberrant vs wild-type
Invasive vs STIC: Stromal invasion vs confined to epithelium
Malignant vs reactive: Nuclear atypia, mitotic activity, architectural complexity.
Diagnostic Challenges:
Determining primary site when both tube and ovary involved
Distinguishing from ovarian carcinoma requires careful gross examination
Small tumor burden may be missed without thorough sampling
STIC vs invasive carcinoma requires assessment of basement membrane integrity
Frozen section interpretation can be challenging
Bilateral involvement may suggest metastatic disease.
Rare Variants:
Transitional cell carcinoma (urothelial-like morphology)
Mixed müllerian tumor (carcinosarcoma) (epithelial and mesenchymal components)
Small cell carcinoma (neuroendocrine differentiation)
Squamous cell carcinoma (extremely rare primary)
Adenosquamous carcinoma (mixed glandular and squamous)
Undifferentiated carcinoma (lack of specific differentiation)
Serous borderline tumor (low malignant potential).
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
Primary fallopian tube adenocarcinoma, [histological subtype]
Classification and Grade
[High-grade serous/Endometrioid/Clear cell/Mucinous] adenocarcinoma, Grade [1/2/3/high-grade]
Histological Features
Shows [architectural pattern] with [nuclear features] arising from tubal epithelium
Site and Extent
Primary site: [fimbrial/ampullary/isthmic], Size: [X] cm, Extent: [confined to tube/extension beyond]
Invasion
Depth of invasion: [through tubal wall/confined to mucosa], Serosal involvement: [present/absent]
STIC (Serous Tubal Intraepithelial Carcinoma)
STIC: [present/absent], Location: [specify if present]
Ovarian Involvement
Ovarian involvement: [present/absent], Pattern: [surface implants/parenchymal involvement]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Special Studies
PAX8: [positive/negative], WT1: [positive/negative], CK7: [positive/negative]
p53: [aberrant overexpression/null pattern/wild-type]
ER: [positive/negative], PR: [positive/negative]
Molecular Testing Recommendation
BRCA1/2 germline testing: [recommended due to family history/young age/tumor characteristics]
FIGO Staging
FIGO Stage: [IA/IB/IC/II/III/IV] - [staging description]
Prognostic Factors
Subtype: [specify], Grade: [1/2/3], Stage: [I/II/III/IV], LVI: [present/absent]
Final Diagnosis
Primary fallopian tube [subtype] adenocarcinoma, Grade [1/2/3], FIGO Stage [IA/IB/IC/II/III/IV]