Original article / research
Year : 2026 Month : October Volume : 15 Issue : 4 Page : PO18 - PO23 Full Version

Role of CD56 and Galectin-3 in the Diagnosis of Solitary Thyroid Nodules on Fine Needle Aspiration Cytology: A Prospective Diagnostic Test Evaluation Study
Punjdath Baby Sreya, C Ramaswamy Jyothi, M Feroze
1. Assistant Professor, Department of Pathology, Amala Institute of Medical Sciences, Thrissur, Kerala, India. 2. Professor, Department of Pathology, PK Das Institute of Medical Sciences, Palakkad, Kerala, India. 3. Professor, Department of Pathology, MES Medical College, Malappuram, Kerala, India.
 
Correspondence Address :
Dr. Punjdath Baby Sreya,
Assistant Professor, Department of Pathology, Amala Institute of Medical
Sciences, Amalanagar, Thrissur-680555, Kerala, India.
E-mail: drsreya@gmail.com
 
ABSTRACT
: 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.
Keywords : Diagnostic accuracy, Immunocytochemistry, Papillary thyroid carcinoma, The Bethesda system for reporting thyroid cytopathology, Thyroid neoplasm
DOI and Others : DOI: 10.7860/NJLM/2026/91006.3007 Date of Submission: Jun 09, 2026 Date of Peer Review: Jun 30, 2026 Date of Acceptance: Aug 06, 2026 Date of Publishing: Oct 01, 2026 AUTHOR DECLARATION: • Financial or Other Competing Interests: None • Was Ethics Committee Approval obtained for this study? Yes • Was informed consent obtained from the subjects involved in the study? Yes • For any images presented appropriate consent has been obtained from the subjects. Yes PLAGIARISM CHECKING METHODS: • Plagiarism X-checker: Jun 17, 2026 • Manual Googling: Aug 01, 2026 • iThenticate Software: Aug 05, 2026 (6%) ETYMOLOGY: Author Origin EMENDATIONS: 8
 
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