What is the diagnostic and treatment approach for follicular nodular disease, follicular adenoma, and follicular neoplasm of the thyroid gland?

From the Guidelines

The diagnostic and treatment approach for follicular thyroid lesions begins with a thorough clinical evaluation, laboratory testing, and ultrasound imaging, with fine needle aspiration (FNA) biopsy being the cornerstone diagnostic procedure, as recommended by the NCCN guidelines 1. The FNA biopsy results are categorized based on the 2017 Bethesda System for Reporting Thyroid Cytopathology, which includes six categories: nondiagnostic or unsatisfactory, benign, atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), follicular neoplasm or suspicious for follicular neoplasm, suspicious for malignancy, and malignancy. For indeterminate nodules classified as follicular neoplasms (Bethesda category III or IV), molecular testing such as ThyroSeq or Afirma may help stratify malignancy risk, as suggested by the ESMO clinical practice guidelines 1. Treatment depends on risk assessment:

• observation with periodic ultrasound monitoring is appropriate for small, low-risk nodules,
• while surgical management typically involves thyroid lobectomy for most follicular lesions,
• and total thyroidectomy may be considered for larger nodules (>4cm), those with suspicious features, or when molecular testing suggests higher malignancy risk, as recommended by the Annals of Oncology guidelines 1 and 1. Following surgery, thyroid hormone replacement with levothyroxine is necessary after total thyroidectomy (typically starting at 1.6 mcg/kg/day) and may be required after lobectomy depending on postoperative thyroid function. Patients require lifelong monitoring of thyroid function with TSH measurements every 6-12 months. The management approach balances cancer risk against surgical complications, as approximately 80% of follicular neoplasms are ultimately benign, but preoperative distinction between benign and malignant follicular lesions remains challenging due to their similar cytological appearance, necessitating surgical excision for definitive diagnosis in many cases. Some key points to consider in the management of follicular thyroid lesions include:
• The use of ultrasound-guided FNA biopsy to evaluate suspicious thyroid nodules, as recommended by the NCCN guidelines 1.
• The consideration of molecular testing for indeterminate nodules, as suggested by the ESMO clinical practice guidelines 1.
• The importance of risk assessment in determining the appropriate treatment approach, as recommended by the Annals of Oncology guidelines 1 and 1.
• The need for lifelong monitoring of thyroid function in patients with follicular thyroid lesions, as emphasized by the ESMO clinical practice guidelines 1.

From the Research

Diagnostic Approach

• The diagnostic approach for follicular nodular disease, follicular adenoma, and follicular neoplasm of the thyroid gland typically involves fine-needle aspiration (FNA) cytology 2, 3, 4.
• FNA cytology can help identify the risk of malignancy, but it may not always provide a definitive diagnosis 2, 3.
• The National Cancer Institute (NCI) recommends dividing follicular patterned lesions into two diagnostic categories: follicular lesion of undetermined significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for follicular neoplasm/follicular neoplasm (SFON/FON) 4.

Treatment Approach

• The treatment approach for follicular adenoma and follicular neoplasm typically involves surgical excision, as the diagnosis of follicular carcinoma cannot be made based on cytologic, sonographic, or clinical features alone 5, 6.
• A diagnostic thyroid lobectomy and isthmusectomy is often recommended, which is definitive treatment for a benign follicular adenoma or a minimally invasive follicular cancer 6.
• Additional therapy, such as completion thyroidectomy, postoperative radioactive iodine ablation, and whole body scanning, may be necessary for invasive follicular carcinoma 6.

Risk of Malignancy

• The risk of malignancy in follicular neoplasms is estimated to be around 20-30% 3, 5, 4.
• Clinical features, such as gender, nodule size, and age, can help predict the risk of malignancy in patients with an FNA diagnosis of follicular neoplasm 3.
• Repeat FNA (RFNA) can be effective in managing thyroid nodules diagnosed as FLUS/AUS, as it can help achieve a more definitive diagnosis and reduce the risk of malignancy 4.

Follow-up and Management

• Regular follow-up is essential for patients with follicular adenoma and follicular neoplasm, and includes history and physical examination, cervical ultrasound, and serum TSH, thyroglobulin, and antithyroglobulin antibody levels 6.
• Other imaging studies, such as whole body scanning, may be reserved for patients with an elevated serum thyroglobulin level and a negative cervical ultrasound 6.
• Systemic metastases, if present, can be treated with high doses of radioactive iodine, and isolated macroscopic metastases can be resected to improve survival 6.