What is the diagnosis and recommended management for a 59-year-old female with a 2.1 x 1.8 x 1.6 cm iso to slightly hyperechoic nodule in the right thyroid lobe, classified as Thyroid Imaging Reporting and Data System (TI-RADS) 4, with partially circumscribed borders, internal echogenic foci, shadowing calcifications, and posterior acoustic enhancement?

From the Guidelines

Based on the thyroid ultrasound findings, I strongly recommend proceeding with the ultrasound-guided fine needle aspiration (FNA) biopsy of the right thyroid nodule as suggested in the report, due to its TI-RADS 4 classification and concerning features such as size, partially circumscribed borders, internal echogenic foci, and shadowing calcifications, which are associated with a moderate suspicion for malignancy 1. The nodule's characteristics, particularly the calcifications, raise enough concern to warrant tissue sampling for definitive diagnosis. The FNA procedure is generally safe and performed as an outpatient procedure with local anesthesia, with mild discomfort during the procedure and possibly some minor bruising afterward, and no special preparation is typically needed beforehand 1. After the biopsy, results usually take 3-7 days, and follow-up with the doctor is necessary to discuss the findings and any further management needed. Additionally, the asymmetry of the thyroid (enlarged right lobe and diminutive left lobe) should be evaluated in the context of overall thyroid function, so thyroid blood tests would be appropriate if not already done, as recommended by recent guidelines 1. Some key points to consider include:

• The TI-RADS system is used for risk stratification of thyroid nodules detected on ultrasound, and a TI-RADS 4 classification indicates a moderate suspicion for malignancy 1.
• FNA is the gold standard for preoperative diagnosis of thyroid malignancy, and it can effectively distinguish between malignant and benign lesions, although inconclusive specimens remain a challenge 1.
• The treatment of differentiated thyroid carcinoma (DTC) can vary based on specific features, and the American Thyroid Association guidelines recommend classifying DTCs as low-, intermediate-, and high-risk, which helps determine the need for radioiodine treatment and tailor postoperative management for DTC 1.

From the Research

Thyroid Nodule Diagnosis and Treatment

• The patient's thyroid ultrasound shows an enlarged right thyroid lobe with a 2.1 x 1.8 x 1.6 cm iso to slightly hyperechoic nodule, partially circumscribed borders, internal echogenic foci, shadowing calcifications, and posterior acoustic enhancement 2.
• The TI-RADS classification is 4, indicating a moderate suspicion of malignancy, and ultrasound-guided FNA is recommended.
• Studies have shown that fine-needle aspiration biopsy (FNAB) is a recognized technique for the preoperative cytological diagnosis of thyroid nodules, with a high accuracy rate of around 95% 3.
• FNAB can help differentiate between benign and malignant thyroid nodules, and its results can guide the selection of patients for surgical excision 2, 4.

Fine-Needle Aspiration Biopsy (FNAB) Accuracy and Limitations

• The accuracy of FNAB in diagnosing thyroid cancer is high, especially for solitary thyroid nodules, with a predictive rate three times higher than for multiple nodules 2.
• However, FNAB can produce false-negative results, especially in patients with multiple malignant thyroid tumors, which may lead to reoperation 2.
• The use of ultrasound-guided FNAB can help reduce the rate of nondiagnostic and false-negative results, but its routine use is not necessary for all patients 5.
• Repeat FNAB can refine the selection of thyroid nodules for molecular testing, such as the Afirma Gene Expression Classifier, and can help avoid unnecessary diagnostic surgery for benign nodules 6.

Molecular Testing and Thyroid Nodule Management

• Molecular testing, such as the Afirma Gene Expression Classifier, can help refine the risk stratification of thyroid nodules that are indeterminate for cancer by FNAB cytology 6.
• The use of molecular testing can help guide the management of thyroid nodules, including the decision to perform surgical excision or to monitor the nodule with clinical and sonographic surveillance 6.
• The selection of thyroid nodules for molecular testing should be based on the results of repeat FNAB, with a restrictive approach using only nodules with two separate biopsies showing Bethesda III/IV cytology 6.