WORLD JOURNAL OF ADVANCE
HEALTHCARE RESEARCH

Alaa Al-Maaitah*, Moaath Alsmady, Mira Younis, Ahmad Al-Alwan, Dana Alsmady, Shatha Dmour, Handan Ankaralı, Malek Zihlif, Mohammad Al-Shehab, Heyam Awad, Nader Albsoul, Orhan Alimoglu

ABSTRACT

Background: Fine needle aspiration biopsies of thyroid nodules are indeterminate in approximately 30% of the cases, so several preoperative molecular markers have been studied to improve the diagnostic utility of such nodules. We aimed to study the role of BRAF V600E mutation and ultrasonography to predict malignancy preoperatively for indeterminate thyroid nodules. Methods: This is a retrospective study that included 78 indeterminate nodules. DNA was extracted from formalin-fixed paraffin-embedded tissues and BRAFV600E mutation was analyzed by direct sequencing. Neck ultrasound records were evaluated for the major sonographic features including size, margin, halo, echogenicity, calcifications, vascularity and cervical lymphadenopathy. A “p” value less than 0.05 was considered statistically significant. Results: Seventy-eight indeterminate nodules were distributed in Bethesda categories III, IV and V as 38, 17, 23, respectively. Malignant cases in each category were 6/38, 5/17, 12/23, respectively. All of them were diagnosed with papillary thyroid cancer. Four cases out of 78 harbored BRAFV600E mutation (1 in category III, 3 in category V). Accordingly, malignancy was significantly predicted by cytology (p=0.009) and BRAFV600E mutation (p=0.001). The latter exhibited 100% specificity. However, the overall sensitivity of BRAFV600E mutation was 17.4% and increased only to 25% in category V. Sonographic features that corresponded significantly to malignancy were microcalcifications and cervical lymphadenopathy (p=0.026 and p=0.017, respectively). But only ill-defined margin was associated with BRAFV600E mutation (p= 0.032). Ultrasound features had low sensitivity (15.4%-84.6%), but higher specificity (9.7%-93.9%) of which microcalcifications and ill-defined margin were the most specific signs. Conclusions: BRAFV600E mutation was a significant predictor of malignancy for indeterminate thyroid nodules. However, it was most useful in Bethesda category V. Microcalcifications, ill-defined margin and cervical lymphadenopathy were the most suspicious sonographic features of malignancy.

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