Definition/General
Introduction:
Fallopian tube neuroendocrine carcinoma is an extremely rare malignant tumor arising from the neuroendocrine cells of the fallopian tube
It represents less than 1% of all fallopian tube malignancies
It shows neuroendocrine differentiation with characteristic morphology and markers
It generally has an aggressive clinical course.
Origin:
Arises from dispersed neuroendocrine cells within the tubal epithelium
May develop from pre-existing adenocarcinoma with neuroendocrine differentiation
Stem cell origin with multipotent differentiation
Possible association with chronic inflammation
Hormonal influences may play a role.
Classification:
Classified according to WHO 2020 classification
Well-differentiated NET (Grade 1)
Moderately differentiated NET (Grade 2)
Poorly differentiated NEC (Grade 3)
Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN)
Based on mitotic rate and Ki-67 index.
Epidemiology:
Extremely rare with fewer than 50 reported cases worldwide
Peak incidence in 6th-7th decades
Mean age around 60-65 years
No specific racial predilection
Associated with other primary tumors in some cases
Hereditary syndromes rarely associated.
Clinical Features
Presentation:
Abdominal or pelvic mass (most common)
Abnormal vaginal bleeding
Pelvic pain
Abdominal distension
Carcinoid syndrome (rare, if functional)
Bowel obstruction in advanced cases
Constitutional symptoms.
Symptoms:
Postmenopausal bleeding (60% cases)
Lower abdominal pain and discomfort
Pelvic pressure
Urinary symptoms
Carcinoid syndrome (flushing, diarrhea, rarely)
Weight loss
Fatigue
Early satiety.
Risk Factors:
Advanced age (>55 years)
Family history of neuroendocrine tumors
Multiple endocrine neoplasia (MEN) syndromes
Genetic predisposition
Chronic inflammatory conditions
Previous malignancy
Nulliparity.
Screening:
No specific screening protocols available
Pelvic examination
Transvaginal ultrasonography
Chromogranin A and synaptophysin levels
5-HIAA (24-hour urine) if carcinoid syndrome suspected
CT/MRI for staging
Octreotide scan for functional tumors.
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Gross Description
Appearance:
Tumor appears as a firm, gray-white mass within the fallopian tube
Well-circumscribed or infiltrative margins
Cut surface shows homogeneous, fleshy appearance
Hemorrhage and necrosis may be present
Cystic changes less common.
Characteristics:
Unilateral involvement in majority
Size ranges from 1-10 cm
Solid consistency with uniform cut surface
Yellow-tan color
Vascular pattern may be prominent
Extension through tubal wall common
Lymph node involvement frequent.
Size Location:
Usually involves ampullary portion
Average size 3-6 cm
May involve entire tube length
Bilateral involvement rare (10-15%)
Extension to ovary and peritoneum
Metastases to liver and lung common.
Microscopic Description
Histological Features:
Uniform small to medium-sized cells with round to oval nuclei
Salt-and-pepper chromatin pattern
Inconspicuous nucleoli
Moderate eosinophilic cytoplasm
Organoid, trabecular or sheet-like growth patterns
Rosette formation may be present.
Cellular Characteristics:
Cells show monotonous appearance
High nuclear-cytoplasmic ratio
Stippled chromatin (salt-and-pepper)
Mitotic activity varies with grade
Necrosis in high-grade tumors
Apoptotic bodies
Nuclear molding may be seen.
Architectural Patterns:
Nested (Zellballen) pattern
Trabecular arrangement
Rosette-like structures
Solid sheets in poorly differentiated tumors
Ribbon-like patterns
Perivascular arrangement
Invasion of lymphatics and vessels.
Grading Criteria:
Grade 1 (G1): <2 mitoses/10 HPF, Ki-67 <3%
Grade 2 (G2): 2-20 mitoses/10 HPF, Ki-67 3-20%
Grade 3 (G3): >20 mitoses/10 HPF, Ki-67 >20%
Necrosis assessment
Nuclear pleomorphism degree.
Immunohistochemistry
Positive Markers:
Chromogranin A positive (90-95%)
Synaptophysin positive (85-90%)
CD56 (NCAM) positive (80-85%)
Neuron-specific enolase (NSE) positive
INSM1 positive (highly specific)
PAX8 may be positive (müllerian origin).
Negative Markers:
Cytokeratin 20 usually negative
CDX2 negative (excludes GI origin)
TTF-1 negative (excludes lung origin)
Thyroglobulin negative (excludes thyroid)
Calcitonin negative (excludes medullary thyroid carcinoma).
Diagnostic Utility:
Chromogranin A and synaptophysin confirm neuroendocrine differentiation
INSM1 highly sensitive and specific marker
Ki-67 essential for grading
PAX8 supports müllerian origin
Site-specific markers exclude metastases.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60-70% in high-grade)
RB1 mutations (small cell type)
MEN1 mutations (sporadic and familial)
ATRX/DAXX mutations (well-differentiated NETs)
PIK3CA mutations (20%)
KRAS mutations (15%).
Therapeutic Targets:
Somatostatin analogs (octreotide, lanreotide)
mTOR inhibitors (everolimus)
Tyrosine kinase inhibitors (sunitinib)
PARP inhibitors for DNA repair defects
Immunotherapy for high-grade tumors
Peptide receptor radionuclide therapy (PRRT).
Differential Diagnosis
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
Fallopian tube specimen with tumor, measuring [dimensions]
Tumor Location
Tumor located in [ampullary/isthmic] portion of [right/left] fallopian tube
Macroscopic Features
Firm, gray-white tumor measuring [size] with [circumscribed/infiltrative] margins
Microscopic Features
Shows neuroendocrine carcinoma with [organoid/trabecular] pattern and [salt-and-pepper chromatin]
Grading
Grade [1/2/3] based on mitotic count: [number]/10 HPF and Ki-67: [percentage]%
Neuroendocrine Markers
Chromogranin A: [positive/negative], Synaptophysin: [positive/negative], INSM1: [positive/negative]
Invasion Assessment
Shows [depth] invasion with lymphovascular invasion [present/absent]
Staging
Stage: [stage] based on [extent of disease]
Final Diagnosis
Neuroendocrine carcinoma of fallopian tube, Grade [grade]