FNAC and Biopsy Reports for Gallbladder Cancer
For gallbladder cancer, preoperative biopsy or FNAC is generally NOT recommended when the tumor appears resectable on imaging, due to the significant risk of tumor seeding along the needle tract, but tissue diagnosis is mandatory before initiating any non-surgical oncological therapy such as chemotherapy or radiotherapy. 1
When Tissue Diagnosis is Required
Pathological confirmation must be obtained before starting chemotherapy, radiotherapy, or other non-surgical oncological treatments. 1 However, tissue diagnosis is not critical for planning surgery in patients with characteristic imaging findings of resectable gallbladder cancer. 1
Acceptable Methods for Tissue Acquisition:
- EUS-guided fine needle aspiration (EUS-FNA) for regional lymph nodes or the primary tumor, depending on location 1
- Open or laparoscopic biopsy during surgical exploration 2
- Ultrasound-guided FNAC only in cases where the tumor is clearly unresectable or metastatic 2, 3
FNAC Performance Characteristics
When ultrasound-guided FNAC is performed for gallbladder masses, the diagnostic accuracy shows:
The main limitation is the false-negative rate of approximately 27%, meaning repeat biopsy or surgical confirmation is recommended when clinical suspicion remains high despite negative initial FNAC. 3
What FNAC/Biopsy Reports Show
Cytological Findings:
The most common findings on FNAC smears include: 2
- Adenocarcinoma (most common histological type, approximately 90% of cases) 1, 3
- Undifferentiated carcinoma
- Dysplasia or suspicious for malignancy (requires repeat sampling or surgical biopsy)
- Hemorrhagic background without malignant cells (non-diagnostic, requires repeat)
- Inflammatory cells only (may represent benign disease but requires clinical correlation)
Histological Assessment:
When tissue biopsy is obtained (via surgery or core needle), the pathology report will provide: 1
- Histological type according to WHO classification (adenocarcinoma most common)
- Grade of differentiation (well, moderate, or poorly differentiated)
- Depth of invasion (critical for TNM staging)
- Presence of lymphovascular invasion
- Margin status (if surgical specimen)
Critical Pitfalls and Caveats
Risk of Tumor Seeding:
The most important caveat is that percutaneous biopsy or FNAC carries a risk of tumor seeding along the needle tract, which can convert a potentially curable tumor into an incurable one. 1 Therefore:
- Surgical assessment of resectability should be established BEFORE performing any biopsy 1
- Avoid transperitoneal approaches (including EUS-FNA) in potentially resectable tumors unless decided in multidisciplinary team meeting 1
False-Negative Results:
Negative cytology does NOT exclude malignancy. 1 When suspicion remains high based on imaging (wall thickening >4mm with gallstones, mass lesion, or scleroatrophic gallbladder), proceed with: 4
- Repeat FNAB if tumor is unresectable 3
- Surgical exploration with intraoperative biopsy if tumor appears resectable 1
Emerging Diagnostic Techniques:
Liquid biopsy of bile using next-generation sequencing (NGS) shows promise with 58.3% sensitivity compared to 45.8% for cytology, and 87.5% concordance with tissue DNA. 5 This may complement traditional cytology in the future, particularly when obtained during ERCP for biliary drainage.
Clinical Algorithm for Tissue Diagnosis
For resectable gallbladder cancer on imaging:
- Proceed directly to surgery without preoperative biopsy 1, 6
- Obtain tissue diagnosis intraoperatively 1
For unresectable or metastatic disease:
- Obtain tissue diagnosis via ultrasound-guided FNAC or EUS-FNA before starting systemic therapy 1, 2
- If first FNAC is negative but suspicion remains high, perform repeat FNAC or surgical biopsy 3
For incidentally discovered gallbladder cancer: