Problems in Diagnosis and Management of Follicular Neoplasm

Thyroid follicular adenoma and hyperplastic adenomatoid nodule may show overlapping cytologic pattern with thyroid follicular carcinoma and follicular variant of thyroid papillary carcinoma.Fine-needle aspiration cytology (FNAC) has limited role in differential diagnosis of those lesions showing high cellularity and absence of colloid.Those lesions are conventionally termed 'follicular neoplasm'.As diagnostic hallmarks of follicular carcinoma (vascular-and capsular invasion) cannot be detected by cytology, verification by histology after surgery is mandatory.However, only 20% of patients with thyroid nodules diagnosed cytologically as 'follicular neoplasm' are finally diagnosed as carcinoma after surgery.Therefore, there have been many trials to differentiate follicular adenoma (FA) from follicular carcinoma (FTC) in preoperative setting.Among those trials are 1) cell morphometry analysis by computer graphics, analysis of telomerase expression level, quantitation of specific protein markers, or intensive cytological analysis using FNAC specimens, 2) ultrasonographic evaluation, dynamic MRI, or MR spectroscopy for thyroid nodules and 3) gene expression profile analysis for thyroid nodules by microarray technique, all showing limited success or limitations hampering clinical application.Similarly, intra-operative frozen section analysis of thyroid nodule had been known to be of no diagnostic utility in a prospective, randomized trial.Current management strategy for 'follicular neoplasm' is initial surgery for diagnostic purpose to get pathologic diagnosis.If the nodule is diagnosed finally as FTC, completion thyroidectomy with or without radioactive iodine therapy is recommended in most cases.Minimally invasive FTC (without vascular invasion) is known to have excellent prognosis in most cases, so traditionally those patients had undergone unilateral operation without completion thyroidectomy.But, there had been reported cases showing distant metastasis and/or recurrence in patients with 'minimally invasive FTC'.One of problems in diagnosis of 'minimally invasive FTC' is lack of international standardization for pathologic diagnosis.Optimal surgical extent for cases with FTC is not known yet.It might have been due to lack of risk stratification of patients which is unique to FTC (not well differentiated thyroid cancer as a whole), lack of biomarker predicting prognosis of FTC, and lack of controlled trial for management of patients with FTC.In near future, application of molecular diagnostic markers is expected to improve our management strategy for thyroid nodules diagnosed as 'follicular neoplasm', if molecular pathogenesis of FA and of FTC are comprehensively understood.