Fig 1: Confusion matrices assessing the diagnostic performance of specific immunohistochemical markers compared to the molecular gold standard method. (A) BRAFV600E VE1 clone compared to Sanger sequencing; (B) TERT polyclonal compared to Sanger sequencing for C228T and C250T mutations.
Fig 2: Example of histologic and immunohistochemical expression. (Left panel)—expression of markers on normal thyroid tissue: HE (top) shows normal follicular architecture. BRAFV600E is negative; BRAF is negative; TERT is negative in follicular cell nuclei; TTF1 positive; PAX8 positive; P53 wild-type pattern; Ki-67 negative. (Middle panel)—photomicrographs of a case of PDTC: HE (top) shows prominent trabecular proliferation with thin fibrovascular septa, cells present minimal pleomorphism and round heterochromatic nuclei without nucleoli. BRAFV600E diffused cytoplasmic staining (+3); B-RAF diffused cytoplasmic staining (+3); K-RAS diffused strong cytoplasmic staining (+3); PAX8 retained nuclear staining; TERT diffused nuclear staining in tumoral cells (3+); TTF1 diffused strong nuclear staining (3+); P53 wild-type pattern: nuclear staining in rare tumoral cells (+0); Ki-67 normal nuclear staining in very rare tumoral cells (+0). (Right panel)—photomicrographs of a case of ATC: HE (top) shows spindle cell proliferation (sarcomatoid) with marked nuclear atypia and bizarre hyperchromic nuclei and frequent mitoses; BRAFV600E zonal cytoplasmic staining (+2); B-RAF negative (+0); K-RAS diffused strong cytoplasmic staining (3+); PAX8 rare positive nuclei still retaining expression; TERT zonally positive perinuclear staining (+2); TTF1 negative (+0); P53 mutant-type pattern: positive strong nuclear stain in all tumoral cells (+3); Ki-67 high expression in >10% of tumoral cells (+2). Scale bar = 50 μm.
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