Cancer Treatment Today

Guidelines from the National Comprehensive Cancer Network (NCCN) indicate that molecular diagnostic approaches may be useful in the evaluation of thyroid FNA samples that are indeterminate to assist in patient management, including identifying patients who are appropriate candidates for surgery and those for whom surveillance is appropriate (NCCN, 2017).

Approximately 525,000 thyroid nodule fine needle aspiration (FNA) procedures are performed each year in the United States. Prevalence of thyroid cancer in the clinical setting is often not known and varies between institutions. According to Gharib et al. (2016), “Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones… A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions.”

National Comprehensive Cancer Network (NCCN) and American Thyroid Association (ATA) guidelines currently recommend consideration of molecular testing on these indeterminate cases to help inform treatment decisions and to help avoid unnecessary surgery on benign nodules, which may occur in 70% to 80% of the cases.

According to Labourier et al. (2015), “Cytopathology on ultrasound-guided fine-needle aspiration (FNA) biopsies has dramatically improved the clinical management of patients with solid thyroid nodules greater than 1 cm. In routine clinical practice, this procedure can identify approximately 50% of malignant nodules (50% sensitivity) and 70% of benign nodules (70% specificity) without the need to perform a diagnostic surgery. Because cytology has both high positive predictive value (PPV) (PPV > 98%) and high negative predictive value (NPV) (NPV > 95%), it allows accurate, preoperative, risk-based classification of thyroid nodules. However, the relatively low diagnostic yield of cytology also results in a large fraction of nodule aspirates, up to 35%, without a definitive benign or malignant diagnosis (Bethesda categories II or VI). In addition, the residual risk of thyroid cancer in nodules with indeterminate cytology varies significantly across institutions, in particular for nodules with a preoperative diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, Bethesda category III) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, Bethesda category IV).” Labourier et al. conclude, “Multiplatform testing for DNA, mRNA, and miRNA can accurately classify benign and malignant thyroid nodules, increase the diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFN cytology.”

Further, according to Tamhane and Gharib (2016), “For nodules with the cytology reported as suspicious for malignancy, after consideration of clinical and US risk factors and patient preference, molecular tests (seven-gene mutation and rearrangement panel) can be considered if it would alter the surgical decision making, which is the recommended modality of management.”

ThyraMIR™ is a novel microRNA gene expression classifier combined with ThyGenX™ By combining it with ThyGenx, a better specificity and sensitivity may result in a genetic mutation panel to increase accuracy. Performing the tests together will in many cases eliminate the need for patients to undergo a second fine needle biopsy to collect the specimen typically needed for further tests. TyoaMIR™ can identify malignancy in nodules that are negative for ThyGenX®, thereby improving overall sensitivity and ability to detect malignancy. Whereas ThyGen is well supported, most of the literature on ThyraMIR is about the test alone and not in combination with ThyGen, but medicare covers both tests.

1. Labourier E, Shifrin A, Busseniers AE, Lupo MA, Manganelli ML, Andruss B, Wylie D, Beaudenon-Huibreqtse S.  Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules with Indeterminate Cytology.  J Clin Endocrinol Metab.  2015 Jul; 100(7): 2743-50.

2. Tamhane S, Gharib H.  Thyroid nodule update on diagnosis and management.  Clinical Diabetes and Endocrinology.  2016; 2(17).

3. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules – 2016 Update.  Endocr Pract.  2016 May; 22(5): 622-39.

4. National Comprehensive Cancer Network.  NCCN Clinical Practice Guidelines in Oncology:  Thyroid Carcinoma.  2017

5. Labourier E, Beaudenon A, Wylie D, Giordano TJ. Multi-categorical testing for miRNA, mRNA and DNA on fine needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. ENDO 2015. Presented at the 97th Meeting and Expo of the Endocrine Society March 5-8, 2015. SAT-344.