CONTEXT: Thyroid nodules are common in adults, but only a small fraction of them is malignant. Fine-needle aspiration (FNA) cytology provides a definitive diagnosis of benign or malignant disease in many cases, whereas about 25% of nodules are indeterminate, hindering most appropriate management. OBJECTIVE: The objective of the investigation was to study the clinical utility of molecular testing of thyroid FNA samples with indeterminate cytology. DESIGN: Residual material from 1056 consecutive thyroid FNA samples with indeterminate cytology was used for prospective molecular analysis that included the assessment of cell adequacy by a newly developed PCR assay and testing for a panel of mutations consisted of BRAF V600E, NRAS codon 61, HRAS codon 61, and KRAS codons 12/13 point mutations and RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. RESULTS: The collected material was adequate for molecular analysis in 967 samples (92%), which yielded 87 mutations including 19 BRAF, 62 RAS, 1 RET/PTC, and five PAX8/PPARγ. Four hundred seventy-nine patients who contributed 513 samples underwent surgery. In specific categories of indeterminate cytology, i.e. atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignant cells, the detection of any mutation conferred the risk of histologic malignancy of 88, 87, and 95%, respectively. The risk of cancer in mutation-negative nodules was 6, 14, and 28%, respectively. Of 6% of cancers in mutation-negative nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology, only 2.3% were invasive and 0.5% had extrathyroidal extension. CONCLUSION: Molecular analysis for a panel of mutations has significant diagnostic value for all categories of indeterminate cytology and can be helpful for more effective clinical management of these patients.
CONTEXT: Thyroid nodules are common in adults, but only a small fraction of them is malignant. Fine-needle aspiration (FNA) cytology provides a definitive diagnosis of benign or malignant disease in many cases, whereas about 25% of nodules are indeterminate, hindering most appropriate management. OBJECTIVE: The objective of the investigation was to study the clinical utility of molecular testing of thyroid FNA samples with indeterminate cytology. DESIGN: Residual material from 1056 consecutive thyroid FNA samples with indeterminate cytology was used for prospective molecular analysis that included the assessment of cell adequacy by a newly developed PCR assay and testing for a panel of mutations consisted of BRAFV600E, NRAS codon 61, HRAS codon 61, and KRAS codons 12/13 point mutations and RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. RESULTS: The collected material was adequate for molecular analysis in 967 samples (92%), which yielded 87 mutations including 19 BRAF, 62 RAS, 1 RET/PTC, and five PAX8/PPARγ. Four hundred seventy-nine patients who contributed 513 samples underwent surgery. In specific categories of indeterminate cytology, i.e. atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignant cells, the detection of any mutation conferred the risk of histologic malignancy of 88, 87, and 95%, respectively. The risk of cancer in mutation-negative nodules was 6, 14, and 28%, respectively. Of 6% of cancers in mutation-negative nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology, only 2.3% were invasive and 0.5% had extrathyroidal extension. CONCLUSION: Molecular analysis for a panel of mutations has significant diagnostic value for all categories of indeterminate cytology and can be helpful for more effective clinical management of these patients.
Authors: F Basolo; F Pisaturo; L E Pollina; G Fontanini; R Elisei; E Molinaro; P Iacconi; P Miccoli; F Pacini Journal: Thyroid Date: 2000-01 Impact factor: 6.568
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Authors: Guido M Sclabas; Gregg A Staerkel; Suzanne E Shapiro; Bruno D Fornage; Steven I Sherman; Rena Vassillopoulou-Sellin; Jeffrey E Lee; Douglas B Evans Journal: Am J Surg Date: 2003-12 Impact factor: 2.565
Authors: Ginesa Garcia-Rostan; Hongyu Zhao; Robert L Camp; Marina Pollan; Agustin Herrero; Javier Pardo; Ran Wu; Maria Luisa Carcangiu; Jose Costa; Giovanni Tallini Journal: J Clin Oncol Date: 2003-09-01 Impact factor: 44.544
Authors: Rebecca J Leeman-Neill; Lindsey M Kelly; Pengyuan Liu; Alina V Brenner; Mark P Little; Tetiana I Bogdanova; Viktoria N Evdokimova; Maureen Hatch; Liudmyla Y Zurnadzy; Marina N Nikiforova; Ning J Yue; Miao Zhang; Kiyohiko Mabuchi; Mykola D Tronko; Yuri E Nikiforov Journal: Cancer Date: 2013-12-10 Impact factor: 6.860