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BACKGROUND: Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. METHODS: Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. RESULTS: Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group-low, molecular risk group-intermediate, and molecular risk group-high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group-low, molecular risk group-intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group-intermediate, molecular risk group-high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group-high cancers than in molecular risk group-intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9-8.6; P < .001) and more likely in molecular risk group-intermediate than in molecular risk group-low (hazard ratio = 5.0; 95% confidence interval, 2.0-12.5; P < .001). CONCLUSION: Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.
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Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia/métodos , Biópsia por Agulha Fina , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
The diagnosis of "follicular neoplasm" (FN) in thyroid cytopathology has a long history that originated not long after the practice of fine-needle aspiration (FNA) of thyroid nodules. From the outset, this interpretive category was intended to convey a set of differential diagnoses rather than a precise diagnosis, as key diagnostic features, such as capsular and vascular invasion, were not detectable on cytology preparations. Cytologic-histologic correlation studies over the past several decades have shown that FN interpretation can be applied to the spectrum of nonneoplastic tumors to carcinomas. Most tumors classified as FN include follicular adenoma, follicular carcinoma, noninvasive follicular thyroid tumor with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma. Less common entities that may be classified as FN on FNA include hyalinizing trabecular tumor (HTT), poorly differentiated thyroid carcinoma, medullary carcinoma, and nonthyroidal lesions such as parathyroid tissue, paraganglioma, and metastatic tumors. Advances in our ability to detect characteristic molecular alterations (eg, GLIS gene rearrangements for hyalinizing trabecular tumor) in FNA samples may assist in the identification of some of these entities. In this review, we summarize the pathophysiology, history, and evolution of the terminology and the current differential diagnosis according to the recently published 2022 World Health Organization classification, molecular testing, and management of nodules classified as FN.
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Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Diagnóstico Diferencial , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Técnicas de Diagnóstico Molecular , Carcinoma Neuroendócrino/diagnósticoRESUMO
OBJECTIVES: Computed tomography-guided fine needle aspiration (CT-FNA) biopsy is a well-established diagnostic technique in the evaluation of lung nodules that is performed by radiologists in most centers. In this series, we analyzed the diagnostic and perioperative outcomes following CT-FNA performed by a dedicated group of thoracic surgeons. METHODS: We conducted a retrospective analysis of 955 patients undergoing CT-FNA by the thoracic surgery service. Primary outcome variables included diagnostic yield and accuracy, number of needle passes, complication rates, and adequacy of specimen for molecular testing. RESULTS: A satisfactory diagnostic specimen was obtained in 94.1% of cases. The average number of needle passes was 3.2 ± 1.5 (range, 1-10 passes). Diagnostic yield was significantly improved by increasing the number of passes from 1 to 2 to 3 passes (P = .0003). CT-FNA diagnostic accuracy was 88.8%. Diagnostic accuracy did not significantly improve with ≥4 passes (P = .20). Molecular testing was successful in 43.1%, and did not improve with ≥4 passes (P = .5). Molecular testing success did improve with the addition of core needle biopsy (P = .005). The pneumothorax rate for CT-FNA alone was 26.4%, and increased with ≥4 passes (P = .009). The median length of stay for CT-FNA alone was 0 days (range, 0-74 days), with same-day discharge in 67.5% of patients. CONCLUSIONS: Thoracic surgeons can perform CT-FNA with excellent diagnostic yield and accuracy. Diagnostic yield, accuracy, and success in molecular testing do not improve with ≥4 CT-FNA passes. Pneumothorax rates do increase with ≥4 passes. The addition of core needle biopsy enhances success with molecular testing.
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BACKGROUND: Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines. METHODS: We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy. RESULTS: Among 447 patients, high-risk features necessitating total thyroidectomy were present in 19% (72/380) of positive and 15% (10/67) of suspicious for malignancy patients (P = .5). Intermediate-risk features on histology were identified postoperatively in 46% (175/380) with positive and 15% (18/67) with suspicious for malignancy fine-needle aspiration results. In multivariable analysis, preoperative factors associated with intermediate-risk disease included age ≥45 years, women, larger tumor size, positive fine-needle aspiration cytology, and BRAF V600E or RET/PTC positivity. CONCLUSION: When patients are considered for lobectomy under the 2015 American Thyroid Association guidelines, ~ 60% with positive and 30% with suspicious for malignancy cytology would need completion thyroidectomy based on intermediate-risk disease. The cost and risk implications of the new American Thyroid Association strategy were substantial and better tools are needed to improve preoperative risk stratification.
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Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/normas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Medição de Risco , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy. METHODS: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay. RESULTS: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease. CONCLUSION: Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.
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Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Idoso , Biópsia por Agulha Fina , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 ± 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery.
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Carcinoma/genética , Carcinoma/mortalidade , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Estadiamento de Neoplasias , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados/genética , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Estudos Retrospectivos , Análise de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Tireoidectomia/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVES: Molecular testing of lung adenocarcinomas for epidermal growth factor (EGFR) mutations and an anaplastic lymphoma kinase (ALK) translocation is important to guide directed therapy with tyrosine kinase inhibitors. The goal of this study was to determine whether transthoracic computed tomography-guided core needle biopsy (CNB) and fine-needle aspiration (FNA) biopsy specimens were equally suitable for molecular testing. METHODS: We determined the percentage of 52 CNB and 120 FNA specimens that contained sufficient paraffin-embedded tumor tissue for EGFR, KRAS, and ALK testing over a period of 2 years. We correlated sample sufficiency with the sampling method, tumor size, biopsy operator, pathologist assessing the adequacy of the sample, and the number of FNA passes performed. RESULTS: Univariate analysis showed that CNB specimens provided a significantly higher number of samples sufficient for molecular testing than did FNA specimens (67% vs 46%; P = .007) and that one operator achieved a significantly higher percentage of sufficient FNA specimens. Binomial logistic regression found sufficiency of FNA samples to correlate with tumor size (P = .015) but not operator. CONCLUSIONS: When paraffin-embedded tissue is used for molecular testing of lung cancer, CNB specimens are more likely than FNA specimens to provide adequate tissue for molecular testing. Obtaining a sufficient FNA specimen depends on the tumor size and the individual performing the biopsy.
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Adenocarcinoma/diagnóstico , Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Neoplasias Pulmonares/diagnóstico , Patologia Cirúrgica/métodos , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Biópsia por Agulha Fina/normas , Biópsia com Agulha de Grande Calibre/normas , Citodiagnóstico/métodos , Citodiagnóstico/normas , Receptores ErbB/análise , Receptores ErbB/genética , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Patologia Cirúrgica/normas , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/análise , Proteínas ras/genéticaRESUMO
BACKGROUND: In thyroid nodule fine-needle aspiration (FNA) cytology, the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category has a 5-15% malignancy risk that increases to 85-99% when mutation testing for BRAF, RAS, RET/PTC, or PAX8/PPARγ is positive. However, negative testing does not exclude malignancy. The study objective was to identify clinical and imaging features that predict cancer in mutation-negative AUS/FLUS thyroid nodules. METHODS: All patients were reviewed (April 2007 to April 2009) who had AUS/FLUS cytology, negative prospective molecular testing of FNA, and histopathology. RESULTS: Of the 230 nodules, 12 (5.2%) were malignant in 11 of 190 patients, and known clinical risk factors for thyroid cancer did not predict malignancy. On preoperative imaging, ≥1 suspicious ultrasound feature was identified in 33% of nodules and occurred regardless of histology (P = .23). Malignant mutation-negative AUS/FLUS nodules were larger than benign nodules (mean maximum diameter, 33.6 vs 24.0 mm; P = .007). On multivariate analysis, nodule size remained an independent predictor of malignancy (odds ratio, 1.043; P = .018). We observed no malignancies in 88 mutation-negative AUS/FLUS nodules <18.5 mm. CONCLUSION: Size is an independent predictor of malignancy in mutation-negative AUS/FLUS nodules and the risk increased 4.3% with every millimeter increase in nodule size. Selected patients with small, mutation-negative AUS/FLUS thyroid nodules may be managed with ultrasound surveillance in lieu of thyroidectomy.