[Diagnostic values of cyclin D1 immunocytochemistry and molecular testing in preoperative fine needle aspiration of...

Objective: To assess the value of cyclin D1 immunocytochemistry combined with a small panel molecular analysis in indeterminate cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 96 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and December 2021 in Department of Pathology, Beijing Hospital. The cases were evaluated by cyclin D1 immunocytochemistry and molecular testing of BRAF^V600E or a small panel of markers (BRAF, N-RAS, H-RAS, K-RAS and TERT) in the FNA specimens. The identification of the optimal cut-off point of cyclin D1 for the diagnosis of malignancy was evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of all these markers were evaluated with the crosstabs and significance was calculated. Results: Ninty-six patients with 96 thyroid nodules were enrolled, including 42 cases of TBSRTC-III, 10 cases of TBSRTC-IV and 44 cases of TBSRTC-V. There were 79 females and 17 males with a median age of 47 years (range, 25 to 75 years). A 7.5% cut-off value for positive cyclin D1 nuclear immunostaining in thyroid cells demonstrated 100% PPV, 57.1% NPV, 81.0% sensitivity and 100% specificity for thyroid malignancy diagnosis. The sensitivity of the BRAF^V600E mutation test or combined with a small panel test alone for thyroid malignancy diagnosis were 65.5% and 69.0% respectively. The sensitivity for thyroid malignancy diagnosis increased to 94.0% and 95.2% respectively when combining the cyclin D1 immunocytochemistry with the molecular test, and the specificities remained 100% and 91.7% respectively.The accuracy of cyclin D1 immunocytochemistry combined with a small panel of molecular test in detecting thyroid malignancy increased to 94.8% compared to using these markers alone. Conclusions: The addition of cyclin D1 immunocytochemistry and a small panel of molecular testing to FNA cytology can increase the sensitivity and NPV of cytology in indeterminate categories, and this supplementary approach provides a simple, accurate and convenient diagnostic method for reducing unnecessary thyroidectomies.