Determining malignancy in thyroid nodules featuring anterior macrocalcifications with strong posterior acoustic shadowing: the combined utility of US-FNA and BRAF V600E mutation analysis

Background: Thyroid nodules with anterior macrocalcifications and strong posterior acoustic shadowing present diagnostic challenges due to uncertain malignancy risk. The diagnostic value of combining ultrasound-guided fine needle aspiration (US-FNA) with BRAF V600E mutation analysis in these nodules remains inadequately evaluated. This study aimed to determine the malignancy risk in such nodules and assess the efficacy of the combined diagnostic approach.

Methods: A retrospective study of 79 thyroid nodules exhibiting macrocalcifications at the anterior margin with strong posterior acoustic shadowing was performed. Based on sonographic features, we classified hyperechoic macrocalcifications into four subtypes: Type I (smooth arc-shaped eggshell-like), Type II (discontinuous arc-shaped, irregularly thickened), Type III (multiple macrocalcifications arranged as layers), and Type IV (multiple macrocalcifications stacked or clustered together). According to BRAF V600E mutation or surgical pathology results, the study determined the malignant risk for anteriorly macrocalcified nodules and assessed the diagnostic efficacy of both US-FNA and BRAF V600E mutation testing.

Results: The proportion of Type II macrocalcification was relatively high (70.0%) in the BRAF V600E mutation-positive cases. The malignant rate was 34.6% (18/52) for anteriorly macrocalcified nodules on US-FNA cytology and 25.3% (20/79) via BRAF V600E mutation testing. US-FNA yielded inconclusive results in 31.6% (25/79) of cases, predominantly 84.0% (21/25) with Type I/II macrocalcifications. The combination of US-FNA and BRAF V600E testing yielded a sensitivity of 100%, specificity of 75.0%, positive predictive value (PPV) of 94.7%, negative predictive value (NPV) of 100%, and diagnostic accuracy of 95.4%, compared to US-FNA alone (94.4%, 75.0%, 94.4%, 75.0%, and 90.9%, respectively).

Conclusions: Thyroid nodules featuring anterior macrocalcifications with strong posterior acoustic shadowing carry a significant moderate risk, and Type II calcification serves as a key imaging biomarker for malignancy. Combining US-FNA with BRAF V600E testing can enhance the diagnostic accuracy for thyroid nodules with anterior macrocalcifications.