Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application

Abstract

The distinction of benign from malignant follicular thyroid neoplasms remains a difficult task in diagnostic fine-needle aspiration cytology, and some discrepant results have been reported for the individual immunocytochemical markers of malignancy proposed so far. The aim of this study was to test if the combined use of a panel of markers could improve the diagnostic accuracy in the preoperative cytological evaluation of 'follicular neoplasms' in an attempt to reduce the number of thyroidectomies performed for benign lesions. The immunocytochemical expression of galectin-3, HBME-1, thyroperoxidase, cytokeratin-19 and keratan-sulfate was retrospectively analyzed in 125 consecutive fine-needle aspiration samples (cell blocks) of indeterminate diagnoses of 'follicular thyroid neoplasm', and compared with their corresponding surgical specimens, including 33 follicular carcinomas, 42 papillary carcinomas and 50 follicular adenomas. Statistical analysis on each marker confirmed that galectin-3 and HBME-1 were the most sensitive (92% and 80% respectively) and specific (94% and 96% respectively) molecules. The use of these two markers sequentially in non-oncocytic lesions (testing HBME-1 as a second marker whenever galectin-3 proved negative) increased the sensitivity and specificity up to 97% and 95% respectively. In oncocytic lesions, HBME-1 proved to be less sensitive, and the sequential combination of galectin-3 and cytokeratin-19 reached 100% of both specificity and sensitivity. Our data showed that, as compared with the use of single markers, the sequential combination of two markers represents the most accurate immunohistochemical panel in managing patients with a fine-needle aspiration biopsy diagnosis of 'follicular neoplasms', especially in otherwise controversial categories such as oncocytic tumours. The combination of three or more markers did not substantially improve the diagnostic accuracy of the test.

Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV

“…To our knowledge, all but two previous studies of HBME on thyroid FNA (Sack et al, 1997;Rossi et al, 2005) were carried out on cell blocks (van Hoeven et al, 1998;Saggiorato et al, 2005). However, overall results obtained on fresh tissue, including our study, and cell blocks are rather concordant.…”

“…It should be noted that a previous study comparing the diagnostic value of HBME1 and TPO on cell blocks yielded different results, that is, lower Se (80%) and higher Sp (96 and 86%, respectively) for both markers (Saggiorato et al, 2005). Several possible explanations can be proposed for this difference.…”

“…A number of other molecules have been described later on as malignancy markers for thyroid carcinoma. Three of them, that is, HBME-1, galectine-3 (GAL3), and cytokeratine-19 (CK19), have been tried on cytological material and are considered useful (van Hoeven et al, 1998;Saggiorato et al, 2005;Rossi et al, 2006). However, almost all these studies were performed on cell blocks or thin-prep samples because of poor results on conventional smears.…”

“…However, overall results obtained on fresh tissue, including our study, and cell blocks are rather concordant. The sensitivity of HBME-1 staining was excellent (490%) for classical PC (van Hoeven et al, 1998;Ito et al, 2005;Rossi et al, 2005), disappointing for PCFV, and poor (o65%) for follicular and undifferentiated cancers (Cheung et al, 2001;Mai et al, 2002;Ito et al, 2005;Prasad et al, 2005;Saggiorato et al, 2005). The reported specificity of HBME-1 staining ranged from 70% to more than 90% (Cheung et al, 2001;Prasad et al, 2005;Saggiorato et al, 2005).…”

“…Most studies using HBME-1 for diagnosis of thyroid tumours have been performed on tissue samples (Mai et al, 2002;Ito et al, 2005;Papotti et al, 2005;Prasad et al, 2005). A few studies using FNA products have been carried out on cell blocks or thin layers (Sack et al, 1997;van Hoeven et al, 1998;Rossi et al, 2005;Saggiorato et al, 2005). We have developed an HBME-1 staining technique for air-dried thyroid FNA smears.…”