Cytomorphologic features in thyroid nodules read as “suspicious for malignancy” on cytology may predict thyroid cancers with the BRAF mutation

Larocca

Pantanowitz

2018

Cancer Cytopathology

Cytological specimens from thyroid nodules are increasingly being adopted as the first available material for cost effectively managing patients in the era of personalized medicine. Cytology aspirates not only play a central role in providing accurate diagnoses, but are also being collected for ancillary molecular testing. Molecular analysis, including the evaluation of somatic mutations and other genomic alterations, has accordingly become well integrated in the cytological workup of thyroid lesions. Appropriately handled thyroid cytology preparations provide well-preserved and adequately cellular material with improved DNA/RNA quantity. The recent publication of the 2nd edition of The Bethesda System for Reporting Thyroid Cytopathology and the American Thyroid Association guidelines confirm the relevant role of molecular testing in the management of the different subcategories of indeterminate thyroid lesions. This review discusses the role of molecular testing for indeterminate thyroid nodules, including the recent introduction of the noninvasive, encapsulated follicular variant of papillary thyroid carcinoma (FVPTC), known also as noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP).

Section: Sfm and Molecular Testingmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ancillary molecular testing of indeterminate thyroid nodules

Larocca

Pantanowitz

2018

Cancer Cytopathology

“…In fact, these authors demonstrated the presence of mutated cancer cells characterized by nuclei which tended to be smaller, pleomorphic and eccentrically located with a particular sickle shape, which was absent in wild-type cases [24,25]. However, the presence of these plump cells with sickle-shaped nuclei has recently been confirmed by Kwon et al [26] in a series of 142 thyroid lesions diagnosed as suspicious for malignancy and performed with conventional cytology. …”

Section: The New Perspective Of Morphological Findings Of Mutationmentioning

confidence: 89%

When Morphology Meets Somatic Mutations: The New Possible Scenario in Thyroid Fine-Needle Aspiration

Schmitt²

2016

Acta Cytologica

This study points to the analysis of the morphological features suggestive of somatic mutations, mostly the BRAF^V600E mutation, on cytological samples of thyroid carcinomas. According to the literature, the application of ancillary techniques on cytology comes in handy as a challenging aid in ruling out a malignant outcome on both conventional and liquid-based cytological preparations. However, the evaluation of somatic mutations, including BRAF^V600E, usually performed by DNA techniques, may have some limitations in a worldwide diffusion. In this perspective, few authors emphasized the morphological search for BRAF^V600E mutations harbored in papillary thyroid carcinoma (PTC) and characterized by specific architectural and cellular findings (i.e. eosinophilic cells defined as ‘plump cells' and sickle-shaped nuclei). Hence, the detection of eosinophilic cytoplasm of mutated PTC cells seems to suggest the possible involvement of the ‘Warburg effect' pioneering the ability of cancer cells to convert glucose into lactic acid. The recent yields of immunohistochemical expression of monocarboxylate transporters in mutated PTCs may suggest the accumulation of lactate in these plump cells. Equally importantly, the detection of these morphological findings using fine-needle aspiration cytology may be helpful in triaging thyroid lesions and limiting costs. Additionally, it may lead to the stratification of the malignant risk and personalized management in cases with multifocal lesions.

“…[19]. Familiarity with molecular testing options available for thyroid cytopathology as well as their indications, significance, and limitations is an important aspect of thyroid cytopathology, and may have implications for NIFTP [47,48,49,50,51,52,53,54,55,56,57,58,59,60].…”

Section: Molecular Testing and The Indeterminate Categories Of Thementioning

confidence: 99%

The Role of Molecular Testing for the Indeterminate Thyroid FNA

Pantanowitz

Faquin

2019

Genes

Thyroid nodules are common in the adult population where a majority are benign and only 4.0% to 6.5% are malignant. Fine needle aspiration (FNA) is a key method used in the early stages to evaluate and triage patients with thyroid nodules. While a definitive cytological diagnosis is provided in more than 70–75% of all thyroid FNA cases, the group of indeterminate lesions offers a challenge in terms of interpretation and clinical management. Molecular testing platforms have been developed, are recognized as an option by the 2015 American Thyroid Association Guidelines, and are frequently used in conjunction with FNA as an integral part of the cytologic evaluation. In this review, the utility of molecular testing options for nodules assigned to the group of indeterminate thyroid FNAs is described.