Definition/General
Introduction:
Fallopian tube small cell carcinoma is an extremely rare and aggressive malignant tumor composed of small undifferentiated cells
It represents less than 1% of all fallopian tube malignancies
It resembles pulmonary small cell carcinoma morphologically
It has an extremely poor prognosis with rapid metastatic spread.
Origin:
Arises from totipotent stem cells within the tubal epithelium
May develop from neuroendocrine cells or reserve cells
Dedifferentiation from other carcinoma types possible
Association with HPV infection reported in some cases
Genetic predisposition in rare familial cases.
Classification:
Classified as poorly differentiated neuroendocrine carcinoma (Grade 3)
Part of high-grade neuroendocrine carcinoma spectrum
May be pure or combined with other histological types
Pulmonary-type vs hypercalcemic-type variants
SCLC vs large cell neuroendocrine carcinoma.
Epidemiology:
Extremely rare with fewer than 30 reported cases worldwide
Peak incidence in 5th-6th decades
Mean age around 50-60 years
No specific racial predilection
Often associated with paraneoplastic syndromes
Smoking history not consistently associated.
Clinical Features
Presentation:
Rapidly enlarging pelvic mass
Severe abdominal pain
Abnormal vaginal bleeding
Abdominal distension
Paraneoplastic syndromes (hypercalcemia, SIADH)
Constitutional symptoms (weight loss, fatigue)
Bowel obstruction.
Symptoms:
Severe pelvic pain (80% cases)
Postmenopausal bleeding
Rapid abdominal enlargement
Hypercalcemia symptoms (confusion, nausea)
SIADH symptoms (hyponatremia)
Neurological symptoms (paraneoplastic)
Dyspnea (pulmonary metastases).
Risk Factors:
Advanced age (>45 years)
Family history of neuroendocrine tumors
Genetic syndromes (rare)
Previous malignancy
Chronic inflammatory conditions
Nulliparity
HPV infection (controversial).
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Gross Description
Appearance:
Tumor appears as a soft, friable mass with gray-pink color
Hemorrhage and necrosis are prominent
Infiltrative growth through tubal wall
Cut surface shows fleshy, homogeneous appearance
Cystic degeneration may be present.
Characteristics:
Unilateral involvement in most cases
Size ranges from 3-12 cm
Soft consistency with areas of necrosis
Gray-white to hemorrhagic cut surface
Rapid growth pattern
Extension beyond tube common
Vascular invasion prominent.
Size Location:
Commonly involves ampullary portion
Average size 6-10 cm at presentation
May involve entire fallopian tube
Bilateral involvement rare (15%)
Extension to ovary and peritoneum frequent
Distant metastases at presentation (50%).
Microscopic Description
Histological Features:
Small, undifferentiated cells with high nuclear-cytoplasmic ratio
Hyperchromatic nuclei with fine chromatin
Inconspicuous nucleoli
Scant cytoplasm
Nuclear molding and crushing artifact
Extensive necrosis and high mitotic rate.
Cellular Characteristics:
Cells are 2-3 times the size of lymphocytes
Round to oval nuclei with stippled chromatin
Nuclear molding prominent
Fragile cytoplasm with frequent crushing
Mitotic figures abundant (>20/10 HPF)
Individual cell necrosis common.
Architectural Patterns:
Solid sheets and nests of cells
Diffuse growth pattern predominant
Rosette formation rare
Vascular invasion prominent
Perineural invasion may be present
Geographic necrosis
Crush artifact in small biopsies.
Immunohistochemistry
Positive Markers:
Synaptophysin positive (85-90%)
Chromogranin A positive (70-80%)
CD56 (NCAM) positive (95%)
INSM1 positive (highly sensitive)
TTF-1 negative (distinguishes from lung)
Cytokeratin (CAM 5.2) dot-like positivity.
Negative Markers:
TTF-1 negative (key difference from lung SCLC)
Napsin A negative
CDX2 negative
CK20 negative
Thyroglobulin negative
Calcitonin negative
PSA negative.
Diagnostic Utility:
Neuroendocrine markers confirm diagnosis
TTF-1 negativity excludes pulmonary origin
INSM1 highly sensitive for neuroendocrine differentiation
Ki-67 shows high proliferation (>50%)
p53 often overexpressed
Rb loss in majority.
Molecular/Genetic
Genetic Mutations:
RB1 mutations (70-80% cases)
TP53 mutations (80-90%)
CREBBP mutations
EP300 mutations
NOTCH family mutations
PIK3CA mutations (20%)
MYC amplification.
Therapeutic Targets:
Platinum-based chemotherapy (first-line)
Topoisomerase inhibitors (etoposide, irinotecan)
Immune checkpoint inhibitors (pembrolizumab, nivolumab)
PARP inhibitors for DNA repair defects
CDK4/6 inhibitors
Aurora kinase inhibitors.
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]
Clinical Presentation
Presented with [pelvic mass/pain/bleeding] and [paraneoplastic syndrome if present]
Macroscopic Features
Soft, friable tumor measuring [size] with extensive [hemorrhage/necrosis]
Microscopic Features
Shows small cell carcinoma with [nuclear molding], [high N:C ratio], and [extensive necrosis]
Neuroendocrine Markers
Synaptophysin: [positive], CD56: [positive], INSM1: [positive], TTF-1: [negative]
Proliferation Index
Ki-67 proliferation index: [percentage]% (high-grade)
Extent of Disease
Shows [local/regional/distant] extension with [lymphovascular invasion present/absent]
Staging
Stage: [stage] based on extent of disease
Final Diagnosis
Small cell carcinoma of fallopian tube with [extent of disease]