Differentiation of benign from malignant follicular-cell-derived thyroid lesions: an immunohistochemical study

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Histopathological criteria in some cases do not allow the differentiation between benign and malignant follicular-cell-derived thyroid tumors/lesions, making the distinction between these two groups quite subtle and challenging. Consequently, immunohistochemistry may provide additional support in the evaluation and diagnosis of these thyroid tumors/lesions.


The aim of this study was to determine the diagnostic value of insulin-like growth factor mRNA binding protein-3 (IMP-3), galectin-3, cytokeratin-19 (CK-19), and fragile histidine triad (FHIT), used alone and in different combinations, in differentiating benign from malignant follicular-cell-derived thyroid lesions.

Materials and methods

The study was carried out on 60 selected archival cases (20 benign and 40 malignant thyroid lesions). Paraffin sections of 4–5 μm thickness were stained with H&E to confirm their histological diagnosis and with IMP-3, galectin-3, CK-19, and FHIT for immunohistochemical evaluation. Sensitivity, specificity, and positive likelihood ratio were calculated for each of the markers and for different combinations of these markers in the benign versus malignant.


Comparison between immunohistochemical expressions of IMP-3, galectin-3, CK-19, and FHIT in different thyroid lesions revealed a significant difference between benign thyroid lesions and malignant lesions with the exception of FHIT, which did not reach statistical significance for distinction between different thyroid lesions. Therefore, this marker was excluded from the combination of immunohistochemical markers. Immunohistochemical expression of combined markers (galectin-3 and CK-19; galectin-3 and IMP-3; and CK-19 and IMP-3) showed highest statistical difference between malignant and benign thyroid lesions, but did not markedly increase the sensitivity or specificity over using a single marker (galectin-3 for differentiating benign from malignant lesions).


Combined use of markers such as galectin-3 and CK-19 and IMP-3 did not markedly increase the sensitivity or specificity over using a single marker. Each studied marker has sensitivity and specificity for certain thyroid lesion. Immunohistochemical stains of galectin-3, CK-19, and IMP-3, especially when used in combination, can be a useful adjunct in the histopathological diagnoses of thyroid lesions.

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