Thyroid
tumors formerly classified as non-invasive encapsulated follicular variant of
papillary thyroid carcinoma were recently renamed 'non-invasive follicular
thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of
lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central
neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such
tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269
papillary thyroid carcinomas, 152
tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of
lymph node metastasis and BRAFV600E mutation were 3% and 10% in non-invasive
tumors and 9% and 4% in invasive
tumors, respectively. Despite the lack of invasive growth, one patient with BRAFV600E mutant-
tumor displaying predominant follicular growth and subtle papillae developed a bone
metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAFV600E mutation was found in all
tumors. However, central lymph node
micrometastasis still occurred in 3% of non-invasive
tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive
tumors, respectively. Our findings suggest that non-invasive follicular
thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign
thyroid neoplasm as it can present with lymph node
micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk
thyroid cancers. Clinical surveillance similar to low risk differentiated
thyroid cancers and capture of this diagnostic category by
Cancer Registries should be considered.