The Impact of Molecular Testing on the Surgical Management of Patients with Thyroid Nodules

AbstractWhether molecular testing adds diagnostic value to the evaluation of thyroid nodules 4-cm or larger is unknown. The impact of molecular testing on cytopathologic-histopathologic diagnosis of neoplasm (adenoma or malignant), stratified by nodule size <or≥ 4-cm, was analyzed from a surgical series. Of 490 index nodules, molecular testing was performed on 18% of 353 nodules <4-cm and 8.8% of 137 nodules ≥4-cm (p = 0.0118). Adenoma was higher (30% vs 14%) and malignancy lower in nodules ≥4-cm vs <4-cm (p < 0.0001). Molecular testing impacted the finding of malignancy in the <4-cm group. Molecular testing of the ≥4-cm AUS and FN cytology subcategory impacted neoplasm discovery (combining adenoma and malignancy), with mutation positive 100% (3/3), mutation negative 38% (3/8), no mutation testing 88% (21/24), p = 0.0122. In conclusion, more adenoma was found in nodules ≥4-cm, including those with benign cytology, which was not explained by available molecular testing results. Molecular testing impacted the finding of malignancy in thyroid nodules <4-cm. The overall number of ≥4-cm nodules with molecular testing in this study was too low to exclude its diagnostic value in this setting. Further study is recommended to include molecular testing in nodules ≥4-cm, including those with benign cytology, to identify follicular adenoma.

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Molecular genetic markers for thyroid FNAB

Nuklearmedizin ◽

10.1055/s-0037-1616610 ◽

2015 ◽

Vol 54 (03) ◽

pp. 94-100 ◽

Cited By ~ 4

Author(s):

P. B. Musholt ◽

T. J. Musholt

Keyword(s):

Genetic Markers ◽

Thyroid Nodules ◽

Molecular Genetic ◽

Genetic Alterations ◽

Diagnostic Tools ◽

Ultrasound Screening ◽

Thyroid Malignancy ◽

Thyroid Carcinomas ◽

Molecular Genetic Markers ◽

The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

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Contemporary Surgical Management of Juvenile Nasopharyngeal Angiofibroma

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0041-1725031 ◽

2021 ◽

Author(s):

Salomon Cohen-Cohen ◽

Kristen M. Scheitler ◽

Garret Choby ◽

Jeffrey Janus ◽

Eric J. Moore ◽

...

Keyword(s):

Surgical Management ◽

Intracranial Extension ◽

Preoperative Embolization ◽

Tumor Diameter ◽

Historical Cohort ◽

Nasopharyngeal Angiofibroma ◽

Estimated Blood Loss ◽

The Impact ◽

Previous Series

Abstract Objectives Juvenile nasopharyngeal angiofibromas (JNAs) are uncommon tumors with an evolving treatment paradigm. The objective of this study was to compare our prior experience reported in 2005 with our most contemporary series to compare practice improvements and the impact of expanded endonasal procedures. Design Retrospective review comparing a contemporary 22 patients with JNA who underwent surgical management between 2005 and 2019, compared with a historical cohort of 65 patients from the same center. Results The most common presenting symptom was epistaxis (68%). The median maximum tumor diameter was 4.4 cm. All patients underwent preoperative embolization. An endoscopic endonasal approach (EEA) was used in 18 patients (82%), compared with 9% in the series prior to 2005. Gross total resection was achieved in all patients. The median estimated blood loss was 175 and 350 mL for EEA and open (transfacial) cases, respectively. Only two patients (9%) required a blood transfusion compared with 52% on the previous series. The median follow-up was 19 months. The overall recurrence rate was 9% in this series and 24% in the previous series. No patient required radiation therapy in follow-up compared with 3% in our historical cohort. Conclusion There have been significant changes regarding the management of patients with JNA compared with the previous Mayo Clinic experience. The EEA has become the preferred route over the transfacial approaches to treat JNA in selected patients who do not have intracranial extension. Preoperative embolization has aided in reducing the postoperative transfusion rates.

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Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine-needle aspiration

Diagnostic Cytopathology ◽

10.1002/dc.24250 ◽

2019 ◽

Vol 47 (9) ◽

pp. 853-862 ◽

Cited By ~ 2

Author(s):

Kristen L. Partyka ◽

Karen Trevino ◽

Melissa L. Randolph ◽

Harvey Cramer ◽

Howard H. Wu

Keyword(s):

Fine Needle Aspiration ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Molecular Testing ◽

Fine Needle ◽

Risk Of Malignancy

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Molecular Testing Has Limited Utility in the Surgical Evaluation of Bethesda III Thyroid Nodules

Journal of Surgical Research ◽

10.1016/j.jss.2021.06.026 ◽

2021 ◽

Vol 268 ◽

pp. 209-213

Author(s):

William H. Scola ◽

Samantha M. Linhares ◽

Rachel S. Handelsman ◽

Omar Picado ◽

Zahra F. Khan ◽

...

Keyword(s):

Thyroid Nodules ◽

Molecular Testing ◽

Surgical Evaluation

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Thyroid and Molecular Testing. Advances in Thyroid Molecular Cytopathology

Journal of Molecular Pathology ◽

10.3390/jmp2020008 ◽

2021 ◽

Vol 2 (2) ◽

pp. 77-92

Author(s):

Esther Diana Rossi ◽

Philippe Vielh

Keyword(s):

Thyroid Nodules ◽

Adult Population ◽

Needle Aspiration ◽

Common Finding ◽

Molecular Testing ◽

Additional Tool ◽

Thyroid Cytology ◽

Hürthle Cell ◽

Cell Neoplasm ◽

Undetermined Significance

Thyroid nodules are a common finding in the adult population including the fact that more than 50% of individuals, over the age of 60, have thyroid nodules. The majority have been mostly detected with ultrasonography and 10% by palpation. The majority of these nodules are benign, whereas 5–15% of them are malignant. The pre-operative diagnosis of cancer is a critical challenge in order to ensure that each patient can be treated with the best tailored management with a reduction of unnecessary surgery for benign lesions. Fine needle aspiration cytology (FNAC) represents the first and most important diagnostic tool for the evaluation of thyroid lesions. According to the literature, FNAC is able to render a conclusive diagnosis in up to 70–80% of all cases. For the remaining 20–30% of nodules, cytological diagnoses fall into the category of indeterminate lesions mostly due to the lack of specific morphological features. According to the Bethesda system for reporting thyroid cytopathology (TBSRTC), indeterminate lesions can be sub-stratified into three different subcategories including “atypia of undetermined significance/follicular lesion of undetermined significance-AUS/FLUS”; “follicular or Hürthle cell neoplasm/suspicious for follicular or Hürthle cell neoplasm-FN/SFN”; and “suspicious for malignancy-SFM”. Many of these indeterminate lesions undergo repetition or diagnostic lobectomy. Nonetheless, the majority of these cases will have a benign diagnosis due to the fact that the rate of cancer ranges between 6 and 30%. It stands to reason that the application of ancillary technique, mostly molecular testing, emerged as a critical additional tool for those thyroid indeterminate lesions. Since the early 1990s, material collected from cytological samples yields sufficient and adequate cells for the detection of point mutation or gene fusions. Nonetheless, the further availability of new sequencing technologies such as next-generation sequencing (NGS) has led to more comprehensive molecular applications adopted now in clinical use. The current review investigates the multiple advances in the field of molecular testing applied in thyroid cytology.

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Contemporary Management of Thyroid Nodules

Annual Review of Medicine ◽

10.1146/annurev-med-042220-015032 ◽

2021 ◽

Vol 73 (1) ◽

Author(s):

Kristen Kobaly ◽

Caroline S. Kim ◽

Susan J. Mandel

Keyword(s):

Thyroid Nodules ◽

Cervical Lymphadenopathy ◽

Standard Technique ◽

Clinical History ◽

Needle Aspiration ◽

Annual Review ◽

Publication Date ◽

Molecular Testing ◽

Risk Of Malignancy ◽

Indeterminate Cytology

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Incorporation of plasma-based next-generation sequencing to improve guideline-concordant molecular testing in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.14 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 14-14

Author(s):

Charu Aggarwal ◽

Melina Elpi Marmarelis ◽

Wei-Ting Hwang ◽

Dylan G. Scholes ◽

Aditi Puri Singh ◽

...

Keyword(s):

Clinical Practice ◽

Practice Change ◽

Molecular Testing ◽

Tier 2 ◽

Newly Diagnosed ◽

Next Generation ◽

First Line ◽

Tier 1 ◽

Tier 3 ◽

The Impact

14 Background: Current NCCN guidelines recommend comprehensive molecular profiling for all newly diagnosed patients with metastatic non-squamous NSCLC to enable the delivery of personalized medicine. We have previously demonstrated that incorporation of plasma based next-generation gene sequencing (NGS) improves detection of clinically actionable mutations in patients with advanced NSCLC (Aggarwal et al, JAMA Oncology, 2018). To increase rates of comprehensive molecular testing at our institution, we adapted our clinical practice to include concurrent use of plasma (P) and tissue (T) based NGS upon initial diagnosis. P NGS testing was performed using a commercial 74 gene assay. We analyzed the impact of this practice change on guideline concordant molecular testing at our institution. Methods: A retrospective cohort study of patients with newly diagnosed metastatic non-squamous NSCLC following the implementation of this practice change in 12/2018 was performed. Tiers of NCCN guideline concordant testing were defined, Tier 1: complete EGFR, ALK, BRAF, ROS1, MET, RET, NTRK testing, Tier 2: included above, but with incomplete NTRK testing, Tier 3: > 2 genes tested, Tier 4: single gene testing, Tier 5: no testing. Proportion of patients with comprehensive molecular testing by modality (T NGS vs. T+P NGS) were compared using one-sided Fisher’s exact test. Results: Between 01/2019, and 12/2019, 170 patients with newly diagnosed metastatic non-Sq NSCLC were treated at our institution. Overall, 98.2% (167/170) patients underwent molecular testing, Tier 1: n = 100 (59%), Tier 2: n = 39 (23%), Tier 3/4: n = 28 (16.5%), Tier 5: n = 3 (2%). Amongst these patients, 43.1% (72/167) were tested with T NGS alone, 8% (15/167) with P NGS alone, and 47.9% (80/167) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS: 95.7% (79/80) compared to T alone: 62.5% (45/72), p < 0.0005. Prior to the initiation of first line treatment, 72.4% (123/170) patients underwent molecular testing, Tier 1: n = 73 (59%), Tier 2: n = 27 (22%) and Tier 3/4: n = 23 (18%). Amongst these, 39% (48/123) were tested with T NGS alone, 7% (9/123) with P NGS alone and 53.6% (66/123) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS, 100% (66/66) compared to 52% (25/48) with T NGS alone (p < 0.0005). Conclusions: Incorporation of concurrent T+P NGS testing in treatment naïve metastatic non-Sq NSCLC significantly increased the proportion of patients undergoing guideline concordant molecular testing, including prior to initiation of first-line therapy at our institution. Concurrent T+P NGS should be adopted into institutional pathways and routine clinical practice.

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