How should I manage a sub‑centimeter thyroid nodule with a wider‑than‑tall sonographic shape in a patient with a history of melanoma and prior radioactive iodine treatment for Graves disease?

Management of Sub-Centimeter Thyroid Nodule with Wider-Than-Tall Shape in High-Risk Patient

For this sub-centimeter thyroid nodule with a wider-than-tall orientation, you should proceed directly to ultrasound-guided fine-needle aspiration (FNA) because the patient's history of prior radioactive iodine treatment for Graves' disease constitutes a high-risk clinical factor that lowers the threshold for biopsy, even though the nodule is <1 cm. 1

Rationale for FNA Despite Size <1 cm

• Prior radioactive iodine (RAI) treatment for hyperthyroidism is a recognized risk factor that modifies standard management algorithms for thyroid nodules, particularly when combined with suspicious ultrasound features. 2

• The National Comprehensive Cancer Network explicitly recommends FNA for nodules <1 cm when high-risk clinical factors are present, including history of head and neck irradiation (which RAI treatment represents), family history of thyroid cancer, suspicious cervical lymphadenopathy, or subcapsular location. 1

• The history of melanoma adds additional concern, as patients with one malignancy have heightened surveillance needs and any new lesion warrants thorough evaluation to exclude metastatic disease or second primary malignancy. 1

Critical Ultrasound Re-Assessment Required

Before proceeding to FNA, perform a comprehensive ultrasound evaluation documenting:

• Confirm the wider-than-tall shape (anteroposterior-to-transverse ratio <1), which is generally reassuring but does not exclude malignancy in the context of other risk factors. 3, 4

• Assess for additional suspicious features including marked hypoechogenicity, microcalcifications, irregular or microlobulated margins, absence of peripheral halo, solid composition, and central hypervascularity. 1, 5

• Evaluate cervical lymph nodes for pathologic features, as suspicious lymphadenopathy is an absolute indication for FNA regardless of nodule size. 1

• Document nodule size precisely to establish baseline for surveillance, as growth ≥3 mm in any dimension during follow-up is considered significant progression. 1

Why the Wider-Than-Tall Shape Alone Is Insufficient to Defer FNA

• While a taller-than-wide shape (anteroposterior-to-transverse ratio >1) is highly specific for papillary thyroid carcinoma in small nodules (specificity 96.8% in nodules ≤0.5 cm), the absence of this feature does not reliably exclude malignancy when high-risk clinical factors are present. 4, 5

• Studies show that male gender and taller-than-wide shape are independent predictors of nondiagnostic FNA (not malignancy per se), but this should not deter biopsy in high-risk patients. 3

• In patients with prior RAI treatment, thyroid nodules with suspicious features—particularly hypoechoic appearance and macrocalcification—should undergo FNA irrespective of time elapsed after treatment. 2

Procedural Approach

• Perform ultrasound-guided FNA rather than palpation-guided biopsy, as ultrasound guidance provides real-time needle visualization, improves sampling accuracy, and allows marker clip placement if needed. 1

• Measure serum TSH before FNA to assess functional status, though most thyroid cancers present with normal thyroid function. 1, 6

• Consider measuring serum calcitonin as part of the diagnostic workup to screen for medullary thyroid cancer (5-7% of thyroid cancers), which has higher sensitivity than FNA alone for this specific malignancy. 1, 6

Management Based on FNA Results

• Bethesda II (benign): Surveillance with repeat ultrasound at 12-24 months is appropriate, with malignancy risk only 1-3%. However, a reassuring FNA should not override concerns when worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases. 1

• Bethesda III (AUS/FLUS) or IV (follicular neoplasm): Consider molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations to refine malignancy risk and guide surgical decision-making. 1, 6

• Bethesda V (suspicious) or VI (malignant): Immediate referral to an endocrine surgeon for total or near-total thyroidectomy with pre-operative assessment of lymph node compartments. 1

• Nondiagnostic/inadequate sample: Repeat FNA under ultrasound guidance is mandatory, as inadequate samples occur in 5-20% of cases. 1

Common Pitfalls to Avoid

• Do not defer FNA based solely on the wider-than-tall shape when high-risk clinical factors (RAI treatment, melanoma history) are present—these factors override standard size-based algorithms. 1, 2

• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function. 1, 6

• Do not perform radionuclide scanning in euthyroid patients, as ultrasound features are far more predictive of malignancy risk. 1

• Do not assume benignity based on size alone—the combination of RAI exposure and melanoma history creates a clinical context where aggressive evaluation is warranted even for small nodules. 1, 2

Alternative Consideration: Active Surveillance

If the patient strongly prefers to avoid FNA and the nodule demonstrates no other suspicious ultrasound features beyond size, active surveillance with repeat ultrasound at 6 months could be considered, but this approach carries risk given the high-risk clinical context. 1 However, this is not the recommended approach given the RAI and melanoma history. 1, 2