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| Year:
2026 |
Month:
October
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Volume:
15 |
Issue:
4 |
Page:
PO18 - PO23 |
Role of CD56 and Galectin-3 in the Diagnosis of Solitary Thyroid Nodules on Fine Needle Aspiration Cytology: A Prospective Diagnostic Test Evaluation Study
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Correspondence
Punjdath Baby Sreya, C Ramaswamy Jyothi, M Feroze,
Dr. Punjdath Baby Sreya,
Assistant Professor, Department of Pathology, Amala Institute of Medical
Sciences, Amalanagar, Thrissur-680555, Kerala, India.
E-mail: drsreya@gmail.com :
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Introduction: Fine Needle Aspiration Cytology (FNAC) is the primary diagnostic test for thyroid nodules, but cytomorphological overlap limits definitive classification of some follicular-patterned and indeterminate lesions.
Aim: To evaluate the diagnostic performance of CD56 and Galectin-3 (Gal-3) Immunocytochemistry (ICC) on FNAC smears for differentiating benign from malignant solitary thyroid nodules, using histopathology as the reference standard.
Materials and Methods: This prospective diagnostic test evaluation study was conducted at the Department of Pathology, Government Medical College, Thrissur, Kerala, India. It included 42 consecutive patients with clinically palpable solitary thyroid nodules who underwent FNAC followed by surgical excision during an 18-month study period (1 January 2016 to 30 June 2017). All eligible patients during the time-bound study were consecutively included to reduce selection bias. ICC for CD56 and Gal-3 was performed on destained Papanicolaou-stained FNAC smears. Loss of CD56 expression and Gal-3 positivity were evaluated as index-test findings. Histopathology served as the reference standard. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), diagnostic accuracy, and exact 95% Confidence Intervals (CIs) were calculated. Comparison of diagnostic accuracy between FNAC alone and the combined FNAC + ICC panel was performed using McNemar’s test for paired binary outcomes.
Results: Histopathology confirmed 18/42 (42.9%) benign and 24/42 (57.1%) malignant nodules. Loss of CD56 expression yielded a sensitivity of 91.7% (95% CI: 73.0%-99.0%), specificity of 100% (81.5%-100%), PPV of 100% (84.6%-100%), NPV of 90.0% (68.3%-98.8%), and diagnostic accuracy of 95.2% (83.8%-99.4%; p<0.001). Gal-3 positivity yielded a sensitivity of 100% (85.8%-100%), specificity of 88.9% (65.3%-98.6%), PPV of 92.3% (74.9%-99.1%), NPV of 100% (79.4%-100%), and accuracy of 95.2% (83.8%-99.4%; p<0.001). The combined CD56/Gal-3 panel achieved a sensitivity of 100% (85.8%-100%), specificity of 88.9% (65.3%-98.6%), PPV of 92.3% (74.9%-99.1%), NPV of 100% (79.4%-100%), and accuracy of 95.2% (83.8%-99.4%). The combined panel correctly classified 22/23 (95.7%) cytologically indeterminate cases (Bethesda III and IV) when compared to FNAC alone (accuracy 85.7% (71.5%-94.6%)); the adjunct application of the dual-marker ICC panel increased overall diagnostic accuracy from 85.7% to 95.2%. Statistical significance of this paired comparison should be reported based on the reconstructed patient-level 2×2 table and McNemar’s test.
Conclusion: Loss of CD56 expression and Gal-3 positivity demonstrate complementary diagnostic performance when applied directly to Papanicolaou-stained FNAC smears. In this cohort, CD56 loss provided high diagnostic specificity, whereas Gal-3 offered maximum sensitivity. The combined Immunocytochemical (ICC) panel significantly improved diagnostic accuracy over conventional FNAC alone and successfully resolved the vast majority of cytologically indeterminate (Bethesda III and IV) lesions. These findings support the routine integration of a dual-marker CD56/Gal-3 panel as a cost-effective triage tool in thyroid cytopathology, though larger multicentre studies in unselected populations are warranted to confirm its impact on reducing unnecessary surgeries.
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