Molecular Diagnosis for Cytologically Indeterminate Thyroid Nodules

Tae Sook Hwang

doi:10.11106/ijt.2015.8.2.153

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Hwang: Molecular Diagnosis for Cytologically Indeterminate Thyroid Nodules

Review Article

Int J Thyroidol 2015;8(2):153-160.

Published online: 20 November 2015

DOI: https://doi.org/10.11106/ijt.2015.8.2.153

Molecular Diagnosis for Cytologically Indeterminate Thyroid Nodules

Tae Sook Hwang

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea

Correspondence: Tae Sook Hwang, MD, PhD, Department of Pathology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea Tel: 82-2-2030-5641, Fax: 82-2-2030–5629, E-mail: tshwang@kuh.ac.kr

Received 13 July 2015 Revised 5 August 2015 Accepted 6 August 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

An accurate diagnosis of cancer or benign disease is important for the effective clinical management of the patients. Thyroid fine needle aspiration cytology (FNAC) is a safe and cost effective technic for evaluating thyroid nodules. However, 20–30% of thyroid FNAC specimens are indeterminate and fall into one of the following categories; AUS/FLUS (atypical ceils of undetermined significance/follicular cells of undetermined significance), FN/SFN (follicular neoplasm/suspicious for follicular neoplasm), and SMC (suspicious for malignant cells). The AUS/FLUS, FN/SFN, and SMC diagnostic category is associated with a 5–15%, 15–30%, and 60–75% risk of malignancy, respectively. Of the indeterminate thyroid nodules that are surgically resected, 10–40% were confirmed to be malignant. A significant progress has been made in the development of molecular tests for cancer diagnosis in thyroid nodules. Most common molecular alteration in thyroid cancer is the activation of mitogen-activated protein kinase (MAPK) pathway. Activation of this pathway in thyroid cells results from point mutation of BRAF and RAS genes and rearrangement of RET/PTC and NTRK genes and these genetic alterations are mutually exclusive. Preoperative molecular diagnostic techniques could be applied in FNAC specimen when optimum dissection techniques are provided to collect sufficient numbers of target cells without contamination of blood cells, inflammatory cells including histiocytes, and stromal cells. The optimum number of cells for PCR is about 100 although as few 50 cells has been successful. To obtain a good DNA yield from a very limited number of target cells, avoid DNA loss as much as possible.

Keywords: Molecular diagnosis, FNAC, Indeterminate nodule, Thyroid cancer

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