title: Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features.
abstract: 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 BRAFV600Emutation 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 BRAFV600Emutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAFV600Emutation 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.
authors.affiliation: Department of Hospital Pathology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Uiju
authors.identifier: 0000-0002-6229-8418
authors.initials: U
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ja Seong
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Hospital Pathology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.|Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chan Kwon
authors.identifier: 0000-0001-6843-3708
authors.initials: CK
authors.lastname: Jung
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)