What can the final histology be in a thyroid nodule with a Thy3f (Thyroid 3f, atypia/follicular lesion of undetermined significance) cytology?

From the Guidelines

The final histology of a thyroid nodule with Thy3f cytology can be benign or malignant, with approximately 20-30% being malignant, most commonly follicular thyroid carcinoma or follicular variant of papillary thyroid carcinoma, as reported in the 2019 ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of thyroid cancer 1. The challenge with Thy3f cytology is that fine needle aspiration cannot distinguish between benign and malignant follicular lesions because this determination requires assessment of capsular or vascular invasion, which can only be evaluated on surgical specimens. Some key points to consider in the diagnosis and management of thyroid nodules with Thy3f cytology include:

• The estimated risk of malignancy is 15%–40% for Thy3f nodules, although this may vary by institution or cytopathologist 1.
• Molecular diagnostics may be useful to allow reclassification of follicular lesions as either more or less likely to be benign or malignant based on the genetic profile 1.
• The 2019 ESMO guidelines recommend that resected DTCs be histologically classified according to the World Health Organization (WHO) criteria, which includes the diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) 1.
• NIFTP is associated with an excellent prognosis, with no reports of cancer-related deaths and an estimated risk of recurrence of <1% 1.
• Other less common final histological diagnoses may include Hürthle cell adenoma, Hürthle cell carcinoma, or rarely, medullary thyroid carcinoma.
• Risk factors that increase the likelihood of malignancy include male gender, larger nodule size, younger age, and certain sonographic features such as hypoechogenicity and irregular margins. In summary, the management of thyroid nodules with Thy3f cytology should be individualized, taking into account the patient's clinical and sonographic features, as well as the results of molecular diagnostics and histological examination, as recommended by the 2019 ESMO guidelines 1.

From the Research

Final Histology in Thyroid Nodules with THY3f Cytology

The final histology in thyroid nodules with THY3f cytology can vary, with studies indicating the presence of both benign and malignant lesions.

• Benign tumors found in patients with THY3f cytology include follicular adenomas, Hurthle cell adenomas, multinodular goiter, adenomatoid nodules, colloid nodules, and thyroiditis 2, 3, 4.
• Malignant tumors found in patients with THY3f cytology include follicular carcinomas, papillary carcinomas, medullary thyroid carcinoma, poorly differentiated thyroid cancer, lymphoma, and metastatic renal carcinoma 2, 3, 4.
• The risk of malignancy in thyroid nodules with THY3f cytology has been reported to be around 20-30% 2, 3, with one study finding a malignancy rate of 43.8% in the THY3f group 4.
• Certain cytomorphologic features, such as high cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia, can be helpful in differentiating malignancy among follicular-patterned lesions 5.
• Next-generation sequencing assays, such as ThyroSeq v2, have been shown to provide highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology, with a sensitivity of 90% and specificity of 93% 6.

Factors Associated with Malignancy

Several factors have been associated with an increased risk of malignancy in thyroid nodules with THY3f cytology, including:

• Male gender 2
• Large tumor size (>4cm) 2, 3
• Age, with a higher risk in patients under 30 years and over 60 years 2
• Nodule size, with a higher risk in nodules over 40mm in diameter 2