Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma

Chiosea, Simion I.; Sylvia, L.; Berman, Michael A.; Carty, Sally E.; Currence, Louanne; Hodak, Steven P.; Nikiforov, Yuri E.; Richardson, Mary S.; Seethala, Raja R.; Sholl, Lynette M.; Thompson, Lester D.�R.; Wenig, Bruce M.; Worden, Frank

doi:10.5858/arpa.2016-0326-cp

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…A recently published template for reporting results of biomarker testing for patients with suspected thyroid carcinoma produced by the College of American Pathologists gives a series of practical explanatory notes on the clinical significance of identified mutations; BRAF V600E, RAS , PIK3A , AKT1 , TP53 , CTNNB1 , RET , ALK , NTRK1 , NTRK3 and PPARG . Between 5% and 10% of thyroid cancers do not appear to have a specifically identifiable driver gene mutation that can be identified using existing molecular techniques.…”

Section: Approaches To Molecular Diagnosis Of Thyroid Fnamentioning

confidence: 99%

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Molecular pathology and thyroid FNA

Poller

Glaysher

2017

Cytopathology

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This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer.

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Section: Approaches To Molecular Diagnosis Of Thyroid Fnamentioning

confidence: 99%

“…RAS, PIK3A, AKT1, TP53, CTNNB1, RET, ALK, NTRK1, NTRK3 and PPARG 42. Between 5% and 10% of thyroid cancers do not appear to have a specifically identifiable driver gene mutation that can be identified using existing molecular techniques.…”

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confidence: 99%

Molecular pathology and thyroid FNA

Poller

Glaysher

2017

Cytopathology

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“…The final histological diagnoses were made in accordance with the fifth WHO classification of thyroid neoplasms 22 and Protocol for the Examination of Specimens From Patients With Carcinomas of the Thyroid Gland. 24 Patients with cancer were further stratified as having low, intermediate, or high risk of recurrence based on the 2015 American Thyroid Association guidelines. 25 …”

Section: Methodsmentioning

confidence: 99%

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer

Fu,

Chazen,

MacMillan

et al. 2024

JAMA Netw Open

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ImportanceInterpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals.ObjectivesTo delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules.Design, Setting, and ParticipantsThis prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023.ExposuresQuantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays.Main Outcomes and MeasuresInterpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated.ResultsA total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P &lt; .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P &lt; .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy.Conclusions and RelevanceThis diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.

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“…The most specific single molecular diagnostic test is BRAF V600E mutation, which, if present, indicates with 99% certainty the presence of thyroid carcinoma. 44 However, as a screening test, the sensitivity of BRAF V600E mutation is too low to reliably rule out thyroid carcinoma. 45 Other gene mutations may be useful and suggest adverse prognosis (eg, TERT promoter mutation, PIK3CA, TP53, and AKT1).…”

Section: Molecular Techniquesmentioning

confidence: 99%

“…The use of molecular techniques for thyroid lesions is now common, particularly in North America, where various proprietary systems are marketed. The most specific single molecular diagnostic test is BRAF V600E mutation, which, if present, indicates with 99% certainty the presence of thyroid carcinoma 44 . However, as a screening test, the sensitivity of BRAF V600E mutation is too low to reliably rule out thyroid carcinoma 45 .…”

Section: Molecular Techniquesmentioning

confidence: 99%

Measures to reduce diagnostic error and improve clinical decision making in thyroid FNA aspiration cytology: A proposed framework

Poller¹,

Johnson

Bongiovanni

2020

Cancer Cytopathology

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Thyroid fine-needle aspiration cytology (FNA) and histopathology can be subjective areas of medical diagnosis and subject to different interpretations. On the basis of the authors' personal experience, 12 recommendations with potential to improve clinical decision making, ensure quality, and reduce diagnostic error in thyroid FNAC and histopathology are presented. 1) use a standardized reporting terminology for thyroid FNAC; 2) understand and explain to service users the limitations of cytology and the standardized thyroid FNAC reporting terminology used; 3) the cytopathologist should review all relevant clinical and ultrasound findings, if feasible; 4) include the risk of malignancy in all FNAC reports if feasible; 5) collect data to calculate the local institutional risk of malignancy for FNAC if feasible; 6) accept that nondiagnostic FNAC will include small numbers of carcinomas; 7) use rapid on-site evaluation and/or educational sessions for aspirators if the nondiagnostic aspiration rate is high; 8) know the diagnostic pitfalls of both cytology and histopathology; 9) use special immunohistochemical and molecular techniques that are evidence-based; 10) make use of second opinions, either in-house or interinstitutional; 11) multidisciplinary discussion of cases before surgery or therapy is invaluable; and, finally, 12) manage patient and clinician expectations of thyroid cytology and histopathology. These 12 recommendations may assist in quality-improvement initiatives and may reduce diagnostic errors in thyroid cytology and histopathology. Thyroid multidisciplinary case discussion remains the principal, overarching method for error reduction and for providing high-quality clinical decision making.

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Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma

Cited by 8 publications

References 28 publications

Molecular pathology and thyroid FNA

Molecular pathology and thyroid FNA

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer

Measures to reduce diagnostic error and improve clinical decision making in thyroid FNA aspiration cytology: A proposed framework

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