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Krzentowska A, Gołkowski F, Broniatowska E, Konturek A, Barczyński M. Risk Factors for Malignancy of Thyroid Nodules in Patients Undergoing Thyroid Resection. J Clin Med 2024; 13:7559. [PMID: 39768482 PMCID: PMC11728177 DOI: 10.3390/jcm13247559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 12/07/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025] Open
Abstract
Background: An accurate diagnosis of thyroid nodules is crucial for avoiding unnecessary surgical procedures and making timely treatment possible. The objective of the present study was to evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) using histopathological findings as the reference standard. Patients with the diagnostic categories (DCs) III, IV, and V were subjected to special analysis. In addition, the authors assessed whether other factors, including age, gender, body mass index (BMI), obesity, and histopathologically confirmed lymphocytic thyroiditis, had an impact on the occurrence of malignant tumors. Methods: We performed a retrospective analysis of 535 patients (with a mean age of 52.3) who underwent thyroid surgery between October 2022 and September 2023 at the Department of Endocrine Surgery at the University Hospital in Krakow. To assess the reliability of FNAB, the results obtained using the Bethesda classification were compared with the histopathological results. Results: The risk of malignancy (ROM) values for DCs I-VI were 38.1%, 15.6%, 29.8%, 18.6%, 91.0%, and 93.2%, respectively. DC V (OR 62.34, p < 0.0001) and an age ≤ 50 (OR = 2.31, p < 0.006) had statistically significant effects on the risk of thyroid cancer. DCs III and IV were not statistically significantly associated with the risk of malignancy (OR = 1.68, p = 0.16; OR = 1.51, p = 0.3, respectively). There were no statistically significant differences in sex, BMI, or obesity between the patients with benign and malignant lesions. Conclusions: DC V is associated with a high likelihood of malignancy, especially in patients under 50 years of age, and, therefore, surgery is indicated in this category of subjects. In DCs III and IV, the risk of malignancy is lower, and conservative management with active clinical and ultrasound surveillance can be considered. In patients < 50 years of age, with Bethesda categories III and IV, surgical treatment should be considered.
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Affiliation(s)
- Anna Krzentowska
- Department of Endocrinology and Internal Medicine, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland;
| | - Filip Gołkowski
- Department of Endocrinology and Internal Medicine, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland;
| | - Elżbieta Broniatowska
- Faculty of Medicine and Health Sciences, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland;
| | - Aleksander Konturek
- Department of Endocrine Surgery, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Kraków, Poland; (A.K.); (M.B.)
| | - Marcin Barczyński
- Department of Endocrine Surgery, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Kraków, Poland; (A.K.); (M.B.)
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Lee WY, Wang HC, Huang LE, Tseng MH, Chiang SH, Lee CC. Diagnostic values of SurePath liquid-based cytology versus conventional smear in thyroid aspiration samples: A 13-year experience at a single institution. Diagn Cytopathol 2024; 52:369-376. [PMID: 38595067 DOI: 10.1002/dc.25319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/06/2024] [Accepted: 03/29/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Fine needle aspiration cytology (FNAC) is the most useful tool in the diagnosis of thyroid nodules. Liquid-based cytology (LBC) is replacing the conventional smear (CS) for evaluation of thyroid FNAC. In our institution, thyroid FNAC preparation was changed from CS to LBC SurePath in July 2016. This study aimed to compare the diagnostic value of SurePath with that of CS in thyroid lesions. METHODS A total of 35,406 samples of thyroid FNAC (11,438 CS and 23,968 SurePath), collected from January 2010 to December 2022, were included in this study. We also examined the malignant rate using the surgical pathology diagnosis as the gold standard. RESULTS The distribution of TBSRTC cytological categories was equivalent between CS and SurePath. The rate of nondiagnostic/unsatisfactory category was higher in CS compared to SurePath (43.4% vs. 22.3%; p < .05). After routine use of SurePath, the surgical resection rate was reduced from 12.0% to 8.6% (p < .05) and the malignant rate increased from 32.2% to 41.5% (p < .05). The sensitivities of CS and SurePath were 71.0% and 82.0%, respectively, and the specificities were 99.0% and 97.3%, respectively, whereas the positive predictive values were 97.8% and 96.8%, respectively, and the negative predictive values were 85.0% and 84.6%, respectively. Diagnostic accuracy of CS and SurePath were 88.5% and 89.7% respectively. CONCLUSION SurePath can increase the sample adequacy, increase the sensitivity and reduce the workload and avoid unnecessary surgeries with similar accuracy to CS.
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Affiliation(s)
- Wen-Ying Lee
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Hsiu-Chu Wang
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Lee-E Huang
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Min-Hui Tseng
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Shu-Hui Chiang
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ching-Chien Lee
- Division of Cytopathology, Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
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Osseis M, Jammal G, Kazan D, Noun R. Comparison between Fine Needle Aspiration Cytology with Histopathology in the Diagnosis of Thyroid Nodules. J Pers Med 2023; 13:1197. [PMID: 37623448 PMCID: PMC10455374 DOI: 10.3390/jpm13081197] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 07/22/2023] [Accepted: 07/24/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Accurate diagnosis of thyroid nodules is crucial for avoiding unnecessary surgeries and enabling timely treatment. Fine needle aspiration cytology (FNAC) and ultrasound are commonly employed diagnostic techniques, but their reliability is debated. This study aimed to compare the diagnostic accuracy of FNAC and ultrasounds using histopathology as the reference standard. METHODS A retrospective review was conducted on 344 patients who underwent thyroidectomy between January 2017 and May 2022. An ultrasound and FNAC were performed before surgery, and histopathological findings were compared. Statistical analyses were conducted to calculate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false positive rate, false negative rate, and overall accuracy for each diagnostic method. RESULTS Among the study population, 38.67% of thyroid tumors were malignant. Ultrasound showed a sensitivity of 68.18%, specificity of 76.55%, PPV of 64.74%, NPV of 79.20%, and overall accuracy of 73.31%. FNAC had a sensitivity of 89.31%, specificity of 48.44%, PPV of 78%, NPV of 68.89%, and accuracy of 75.89%. The correlation coefficient between ultrasound and FNAC was 0.512 (p < 0.0000001). Ultrasound correlated with histopathology with a coefficient of 0.408 (p < 0.0000001), while FNAC with histopathology had a coefficient of 0.304 (p < 0.00001). The correlation coefficient between these three diagnostic methods was 0.423 (p < 0.0001). CONCLUSION In the diagnosis of thyroid nodules, both FNAC and ultrasound demonstrated moderate diagnostic accuracy. Ultrasound showed a higher specificity, while FNAC exhibited a higher sensitivity. Combining these techniques may improve diagnostic accuracy. Further research and the development of more reliable diagnostic methods are warranted to optimize the management of thyroid nodules and avoid unnecessary surgeries.
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Sen A, Sarkar M, Das RN, Paul SS, Chatterjee U. The Bethesda system for reporting thyroid fine needle aspirates: A study of 1763 patients; with histopathological correlations, in eastern India. Diagn Cytopathol 2023; 51:174-181. [PMID: 36409469 DOI: 10.1002/dc.25080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 11/02/2022] [Accepted: 11/02/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Fine-needle aspiration cytology (FNAC) is an important test for triaging patients with thyroid nodules. The 2007 National Cancer Institute Thyroid Fine-Needle Aspiration State-of-the-Science Conference helped instigate the recent publication of The Bethesda System for Reporting Thyroid Cytopathology (TBS). AIMS AND OBJECTIVES Terminology and therefore the probability of malignancy vary between pathologists and institutions. The purpose of this study was to evaluate a single institution's experience to determine if sub-classification (neoplasm versus lesion) aids in identifying patients at higher risk for malignancy. Also, an effort in regional and worldwide variation of significance of adoption of Bethesda classification has been evaluated. MATERIALS AND METHODS From 2018 to 2021, all patients with thyroid lesions' were evaluated for FNAC correlation with the surgical diagnosis. During this period, 1763 thyroid FNACs were reported. Histopathological examination (HPE) outcome data was available in 444 (25.2%) cases. RESULTS The cytologic-histologic diagnostic discrepancy rate was 11.5%. The sensitivity and specificity of thyroid FNA for the diagnosis of malignancy were 71.4% and 49.5%, respectively. In our study, the maximum cases were benign (84.5%). The malignancy risk for the different categories in our study, as seen by follow-up HPE, has corroborated well with the Bethesda System. CONCLUSION The current results indicated that FNAC provides an accurate diagnosis of thyroid malignancy. The classification is directly related to the risk of malignancy in each category and this helps in accurate clinical management of that category.
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Affiliation(s)
- Ankita Sen
- Department of Hematology, NRS Medical College, Kolkata, India
| | - Manisha Sarkar
- Department of Pathology, Dr. B C Roy PGIPS, Kolkata, India
| | - Ram Narayan Das
- Department of Pathology, MJN Medical College & Hospital, Cooch Behar, India
| | - Shib Shankar Paul
- Department of ENT, Eves Clinic Nursing Home & Polyclinic, Kolkata, India
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Aboudi N, Khachnaoui H, Moussa O, Khlifa N. Bilinear Pooling for Thyroid Nodule Classification in Ultrasound Imaging. ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING 2023. [DOI: 10.1007/s13369-023-07674-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
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Panda S, Nayak M, Pattanayak L, Behera PK, Samantaray S, Dash S. Reproducibility of Cytomorphological Diagnosis and Assessment of Risk of Malignancy of Thyroid Nodules Based on the Bethesda System for Reporting Thyroid Cytopathology: A Tertiary Cancer Center Perspective. J Microsc Ultrastruct 2022; 10:174-179. [PMID: 36687323 PMCID: PMC9846927 DOI: 10.4103/jmau.jmau_88_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was introduced for unifying the terminology and morphologic criteria along with the corresponding risk of malignancy, leading to more consistent management approaches. The aim of this study was to study the utility and reproducibility of TBSRTC in reporting thyroid cytology in a referral cancer center. Methods The fine-needle aspiration (FNA) of all thyroid nodules were included for a period of 5 years, from January 2016 to December 2021, in this cancer center. They were retrospectively reviewed and recategorized according to TBSRTC by two experienced pathologists. Cytohistopathological correlation was done for the cases which underwent surgical resection. Results 522 fine-needle aspiration cytology (FNAC) of thyroid swellings were evaluated and categorized according to TBSRTC. There was agreement in the cytological diagnosis of 512 cases, of which 260 (50.78%) were benign lesions, 189 (36.91%) were malignant, 5 (0.97%) were unsatisfactory/nondiagnostic, 41 (8.01%) were follicular neoplasm/suspicious for neoplasm, 13 (2.53%) were suspicious for malignancy, and 4 (0.78%) cases were reported as atypia of undetermined significance. Two cytopathologists were in agreement in 512 cases (98%) of cases. Almost complete concordance was noted in the malignant (99%) and benign categories (98%). Disagreement was seen in 10 cases. Histological follow-up was available in 201 cases with an overall malignancy rate of 62.68% (126/201). Conclusion TBSRTC proved to be a very simple and effective reporting system for thyroid FNAC, especially in the setting of a cancer center. This enables proper triaging of cases with thyroid masses into those who require surgical intervention and those who can avoid it, thereby preventing unnecessary morbidity.
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Affiliation(s)
- Sasmita Panda
- Department of Oncopathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India
| | - Mamita Nayak
- Department of Oncopathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India,Address for correspondence: Dr. Mamita Nayak, Department of Oncopathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India. E-mail:
| | - Lucy Pattanayak
- Department of Radiation Oncology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India
| | - Paresh Kumar Behera
- Department of Head and Neck Oncology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India
| | - Sagarika Samantaray
- Department of Oncopathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India
| | - Sashibhusan Dash
- Department of Oncopathology, Acharya Harihar Postgraduate Institute of Cancer, Cuttack, Odisha, India
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Stewardson P, Eszlinger M, Paschke R. DIAGNOSIS OF ENDOCRINE DISEASE: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer. Eur J Endocrinol 2022; 187:R41-R52. [PMID: 35900312 DOI: 10.1530/eje-21-1293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 07/04/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Genetic testing is increasingly used to diagnose or rule out thyroid cancer in indeterminate fine-needle aspirations. This review evaluates the usefulness of these methods with considerations of advantages and limitations. DESIGN Given the diagnostic problem associated with the increasing incidental detection of indeterminate thyroid nodules in the context of thyroid cancer overtreatment, we consider the conditions and respective necessary settings for the role of genetic testing to improve presurgical malignancy risk stratification. METHODS We review diagnostic pathway requirements and commercially available molecular tests with their respective advantages and disadvantages and discuss the prerequisites required for local application and implementation including quality assurance for local ultrasound and cytopathology practices. RESULTS Recent improvements in available molecular diagnostic tests have brought high sensitivity and specificity in initial validation studies, but whether these promising results translate to other clinical settings depends on the quality of the local thyroid nodule diagnostic pathway. CONCLUSIONS Genetic testing can meaningfully improve presurgical malignancy risk assessment, but more work is needed to implement and use genetic testing effectively in local settings.
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Affiliation(s)
- Paul Stewardson
- Arnie Charbonneau Cancer Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Markus Eszlinger
- Departments of Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, University of Calgary Cumming School of Medicine, Universitätsklinikum Halle, Institute of Pathology
| | - Ralf Paschke
- Departments of Medicine, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
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Ghaznavi SA, Clayton H, Eszlinger M, Khalil M, Symonds CJ, Paschke R. Accuracy of Thyroid Fine-Needle Aspiration Cytology: A Cyto-Histologic Correlation Study in an Integrated Canadian Health Care Region with Centralized Pathology Service. Acta Cytol 2022; 66:171-178. [PMID: 35108713 DOI: 10.1159/000521562] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 12/13/2021] [Indexed: 01/21/2023]
Abstract
INTRODUCTION The reported ROM within TBSRTC categories varies widely and depends on several factors in the clinical care pathway for thyroid nodules, including sonographic risk stratification, cytology expertise, selection criteria for surgical resection, and definitions of malignancy used. METHODS We present 5,867 consecutive thyroid FNAC and corresponding surgical pathology in the context of a comprehensive, single-payer health care system with centralized cytology and surgical pathology services for over 1.5 million inhabitants. RESULTS We report higher usage of ND and AUS/FLUS categories than the literature (19% vs. <10% and 15% vs. <10%, respectively). Our surgical resection rate for malignant cytology is substantially higher than the literature (94% vs. 50%, respectively). The ROM by the TBSRTC category in our cohort was similar to the literature. The overall diagnostic accuracy of thyroid FNAC was 92%, which is similar to other studies. Inclusion of incidental PMC as histologically malignant raised the ROM in the ND, benign, and AUS/FLUS categories. DISCUSSION The diagnostic performance of thyroid FNAC in our study is similar to the reported literature. Differences in TBSRTC category usage likely arise from cytologist variability and expertise. Our higher surgical resection rate in the malignant cytology category reflects the greater capture of surgical follow-up within our healthcare region with centralized pathology and a single EMR system. Keeping in mind the method of calculation of ROM, the malignancy rate by TBSRTC is similar to previous reports.
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Affiliation(s)
- Sana A Ghaznavi
- Division of Endocrinology & Metabolism, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
| | - Hailey Clayton
- Faculty of Science, University of Calgary, Calgary, Alberta, Canada
| | - Markus Eszlinger
- Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Moosa Khalil
- Department of Pathology & Laboratory Medicine and Calgary Laboratory Services, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
| | - Christopher J Symonds
- Division of Endocrinology & Metabolism, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
| | - Ralf Paschke
- Division of Endocrinology & Metabolism, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada
- Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Mascarella MA, Peeva M, Forest VI, Pusztaszeri MP, Avior G, Tamilia M, Mlynarek AM, Hier MP, Payne RJ. Association of Bethesda category and molecular mutation in patients undergoing thyroidectomy. Clin Otolaryngol 2021; 47:75-80. [PMID: 34510770 DOI: 10.1111/coa.13859] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 07/22/2021] [Accepted: 08/28/2021] [Indexed: 01/21/2023]
Abstract
OBJECTIVES The aim of this study was to ascertain the relationship between Bethesda category and molecular mutation of thyroid nodules in patients undergoing thyroidectomy. DESIGN A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed. SETTING Two tertiary care academic hospitals. PARTICIPANTS Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study. MAIN OUTCOME AND MEASURES The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and chi-square testing. RESULTS Four hundred fifty-one patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (p < .001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (p ≤ .01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs. 44.3%, p < .01). CONCLUSION BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive whereas RAS and EIF1AX mutations, copy number alterations, and GEP were related to Bethesda categories III and IV. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories.
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Affiliation(s)
- Marco Antonio Mascarella
- Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, QC, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, QC, Canada.,Department of Biomedical Sciences, University of Montreal, Montreal, QC, Canada
| | - Magdalena Peeva
- Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, QC, Canada
| | | | | | - Galit Avior
- Department of Otolaryngology - Head and Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel
| | - Michael Tamilia
- Division of Endocrinology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Alex M Mlynarek
- Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, QC, Canada
| | - Michael P Hier
- Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, QC, Canada
| | - Richard J Payne
- Department of Otolaryngology - Head and Neck Surgery, McGill University, Montreal, QC, Canada
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Bhartiya R, Mallik M, Kumari N, Prasad BN. Evaluation of thyroid lesions by fine-needle aspiration cytology based on Bethesda system for reporting thyroid cytopathology classification among the population of South Bihar. Indian J Med Paediatr Oncol 2021; 37:265-270. [PMID: 28144094 PMCID: PMC5234164 DOI: 10.4103/0971-5851.195742] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Background: Fine-needle aspiration (FNA) of the thyroid gland has proven to be an important and widely accepted, cost-effective, simple, safe, and accurate method triaging patients with thyroid nodules. Awareness and understanding of wide spectrum thyroid disorders are of great value because most lesions are treatable by medical or surgical management. Aim: The aim of this study is to determine the accuracy of FNA cytology (FNAC) in the diagnosis of thyroid lesion using the Bethesda system for reporting thyroid cytopathology nomenclature (BSRTC) and to correlate these with histopathological findings. Materials and Methods: FNA was performed in 238 patients from January 2014 to October 2015 at a Tertiary Teaching Hospital in Bihar presenting with the thyroid swelling and its histopathological correlation was done in 105 patients. Results and Observations: Out of 238 patients with thyroid swelling, majority were females (196) and in younger age group (n = 104 [43.6%], 21–40 years). In 224 cases, adequate smears for cytological interpretation were obtained. Among them, colloid goiter was the most common lesion. Of these, 105 cases were surgically treated, and tissue was submitted for histopathological examination, which showed 97 nonneoplastic lesions and eight neoplastic lesions. Conclusion: FNAC is rapid, simple, safe, and cost-effective diagnostic modality in the investigation of thyroid disease with high sensitivity, specificity, and accuracy. It can be used as an excellent first-line method for investigating the nature of lesion. Bethesda system is very useful as it is simplified, systematic, standardized system for reporting thyroid cytopathology, which provides better communication between cytopathologist and clinicians, leading to more consistent management approach.
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Affiliation(s)
- Richa Bhartiya
- Department of Pathology, Patna Medical College and Hospital, Patna, Bihar, India
| | - Mahasweta Mallik
- Department of Pathology, Patna Medical College and Hospital, Patna, Bihar, India
| | - Nawanita Kumari
- Department of Pathology, Patna Medical College and Hospital, Patna, Bihar, India
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Ng DL, van Zante A, Griffin A, Hills NK, Ljung BM. A Large Thyroid Fine Needle Aspiration Biopsy Cohort with Long-Term Population-Based Follow-Up. Thyroid 2021; 31:1086-1095. [PMID: 33371796 PMCID: PMC9469749 DOI: 10.1089/thy.2020.0689] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background: Prior studies evaluating thyroid fine needle aspiration biopsies (FNABs) have limited the calculation of risk of malignancy (ROM) to cytologic specimens with corresponding histologic specimens, and clinical follow-up for those patients who do not undergo immediate surgery has been largely disregarded. Moreover, there is marked variability in how researchers have approached thyroid FNAB statistical analyses. This study addresses the urgent need for information from a large cohort of patients with long-term clinical follow-up to more accurately determine the performance of thyroid FNAB and ROM for each diagnostic category. Methods: A retrospective review of the University of California, San Francisco (UCSF), pathology database for thyroid FNABs from January 1, 1997, to December 31, 2004, was performed. Diagnoses were coded using the 2017 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and patients were matched to both the UCSF cancer registry and California Cancer Registry. Data were analyzed using the Kaplan-Meier method, and stratified by TBSRTC diagnostic category. Kaplan-Meier curves were used to estimate incidence rates of malignancy, stratified by FNAB category. Cox proportional hazards models were used to determine the instantaneous ROM. Results: Initial FNABs from 2207 patients were included. Median follow-up period after the first thyroid FNAB was 13.9 years (range: 10.5-18.4 years). During follow-up, there were 279 confirmed diagnoses of thyroid malignancy. Estimates derived from Kaplan-Meier curves demonstrated that the risk of having a thyroid malignancy was low for nondiagnostic and benign categories, intermediate for atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), AUS/FLUS combined, and follicular neoplasm, and high for suspicious and malignant categories. A total of 52/1575 false-negative cases (3.2%) were identified. Excluding papillary microcarcinomas, the false-negative rate was 1.5% (23/1575). No patients with a false-negative diagnosis died of thyroid cancer during the follow-up period. Conclusions: Asymptomatic patients with low-risk clinical and radiologic features and initially benign or unsatisfactory biopsy are unlikely to develop thyroid malignancy and highly unlikely to die of thyroid cancer. FNAB is highly accurate in detecting malignancy. Additional studies evaluating similar large data sets after the adoption of TBSRTC and the integration of molecular testing are needed.
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Affiliation(s)
- Dianna L. Ng
- Department of Pathology, University of California, San Francisco, San Francisco, California, USA
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Annemieke van Zante
- Department of Pathology, University of California, San Francisco, San Francisco, California, USA
| | - Ann Griffin
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA
| | - Nancy K. Hills
- Department of Epidemiology and Biostatistics, and University of California, San Francisco, San Francisco, California, USA
- Department of Neurology, University of California, San Francisco, San Francisco, California, USA
| | - Britt-Marie Ljung
- Department of Pathology, University of California, San Francisco, San Francisco, California, USA
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA
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12
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Madgar O, Avior G, Shochat I, Joshua BZ, Baraf L, Avidor Y, Avi Khafif, Assadi N, Alon EE. Thyroid malignancy rates according to the Bethesda reporting system in Israel - A multicenter study. Eur J Surg Oncol 2021; 47:1370-1375. [PMID: 33745793 DOI: 10.1016/j.ejso.2021.03.237] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/01/2021] [Accepted: 03/09/2021] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION The Bethesda System for Reporting Thyroid Cytopathology was developed in 2007 to facilitate an accurate, reproducible communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists and to serve as a guide for treatment. Based on large patient series, the system details the risk of malignancy for each category as well as a suggested management for each FNA result. Though this system has been widely adopted, there are only few studies to determine whether results are applicable for Israel. METHODS A multicenter, retrospective analysis of medical charts of all patients who underwent thyroid surgery between January 1st, 2012 and December 31st, 2016 in four medical centers in Israel was performed. Data was analyzed for the overall risk of malignancy for the Bethesda system groups as well as comparison between the different laboratories performing the test. RESULTS Records of 810 thyroidectomies in which preoperative cytological reports and final pathology were available and reviewed. The malignancy rates according to the Bethesda groups' I-VI for our cohort were: 27.8%, 17.6%, 41.4%, 41.4%, 86.9%, and 98.1% respectively. Similar results were seen when results were analyzed according to the different laboratories performing the tests. CONCLUSIONS Post-surgical review of all Bethesda groups had higher malignancy rates than those reported in the original report. These results indicate a difference in the malignancy rates for the different Bethesda system groups in Israel compared to those reported. Physicians are encouraged to use data validated for their own country or patients' community in addition to published values.
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Affiliation(s)
- Ory Madgar
- Department of Otolaryngology, Head and Neck Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
| | - Galit Avior
- Otolaryngology - Head and Neck Surgery Unit, The Hillel Yaffe Medical Center, Hadera, Israel; Faculty of Medicine, Technion, Haifa, Israel
| | - Isaac Shochat
- Otolaryngology - Head and Neck Surgery Unit, The Hillel Yaffe Medical Center, Hadera, Israel
| | - Ben-Zion Joshua
- Department of Otolaryngology, Head and Neck Surgery, Soroka University Medical Center, Beer-Sheva, Israel. Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Lior Baraf
- Endocrinology Unit, Soroka University Medical Center, Beer-Sheva, Israel
| | - Yuval Avidor
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Avi Khafif
- ARM Center for Advanced Otolaryngology Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel; Faculty of Medicine, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Niddal Assadi
- ARM Center for Advanced Otolaryngology Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel
| | - Eran E Alon
- Department of Otolaryngology, Head and Neck Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
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Avior G, Dagan O, Shochat I, Frenkel Y, Tessler I, Meir A, Jaffe A, Cohen O. Outcomes of the Bethesda system for reporting thyroid cytopathology: Real-life experience. Clin Endocrinol (Oxf) 2021; 94:521-527. [PMID: 32981060 DOI: 10.1111/cen.14341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/08/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The 2017 revised Bethesda System for Reporting Thyroid Cytopathology (BSRTC) included new malignancy rates for each category as well as new management recommendations. Here, we evaluate the malignancy rate and test performance for BSRTC categories in a middle-sized institution outside the United States (US). DESIGN Retrospective single centre case series with chart review. PATIENTS All patients who underwent thyroid surgery with a preoperative BSRTC between the years 2010 and 2018 at our institution. MEASUREMENTS In order to assess the malignancy rate for each BSRTC, all medical records were reviewed to collect demographics, nodule's size, BSRTC and final pathology. RESULTS Three hundred and sixty-four patients were included, with an overall malignancy rate of 34.3%. The malignancy rate for BSRTC categories I-VI was as follows: 13.3%, 5.1%, 25.0%, 24.4%, 91.3% and 95.2%, respectively. The most sensitive test was when BSRTC III-VI were evaluated (91%). Overall best performance (sensitivity, specificity, PPV, NPV and accuracy) was obtained when BSRTC V-VI were grouped together with a substantial decrease when adding BSRTC III-IV (90%, 97%, 94%, 95%, 95% vs, respectively, 91%, 73%, 62%, 95%, 79%, respectively). CONCLUSIONS Despite differences from the reported 2017 BSRTC malignancy rates, we demonstrated that the revised 2017 BSRTC management recommendations for thyroid nodules are also valid in smaller non-US centre, supporting its use globally.
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Affiliation(s)
- Galit Avior
- Otorhinolaryngology and Head & Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel
- Faculty of Medicine, Technion, Haifa, Israel
| | - Or Dagan
- Otorhinolaryngology and Head & Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel
| | - Isaac Shochat
- Otorhinolaryngology and Head & Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel
| | - Yulia Frenkel
- Otorhinolaryngology and Head & Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel
| | - Idit Tessler
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
| | - Alona Meir
- Department of Pathology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Anat Jaffe
- Endocrinology and Diabetes Unit, Hillel Yaffe Medical Center, Hadera, Israel
| | - Oded Cohen
- Faculty of Medicine, Hebrew University, Jerusalem, Israel
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Raveh Gildin N, Cohen H, Ronen O. Not All Bethesda 1 Thyroid Nodules Were Created Equal: Different B1 Subgroups. Endocr Pract 2020; 27:223-227. [PMID: 33779555 DOI: 10.1016/j.eprac.2020.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/09/2020] [Accepted: 09/21/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The Bethesda System for Reporting Thyroid Cytopathology is a uniform method used worldwide to report thyroid fine-needle aspiration (FNA) outcomes. This study focuses on the Nondiagnostic/Unsatisfactory category, designated as Bethesda1 (B1). The documented risk of malignancy for B1 nodules can vary significantly, implying this category is not homogenous and might be composed of different subtypes. Our hypothesis was that B1 subgroups (blood only, insufficient thyrocytes, cyst content) will vary in their malignancy rate. METHODS The study design was observational and retrospective. The study population included 154 patients in the Galilee Medical Center who underwent FNA examination of the thyroid gland from 2013-2018 and had a B1 result. We looked at the final diagnosis of malignant or benign for patients who underwent surgery and calculated the malignancy rate for each subgroup. RESULTS Malignancy rates were higher in the Blood subgroup than in the other subgroups, and higher in the Thyrocytes subgroup than in the Cyst subgroup (P < .05). All malignancies were papillary thyroid carcinomas. There was no significant difference in the malignancy rate when we further divided the B1 samples into 2 groups based on the presence of epithelial cells. Many repeat FNA tests resulted in a different B1 subgroup. CONCLUSION The different malignancy rates suggest that individual management approaches should be considered for each B1 subgroup.
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Affiliation(s)
| | - Hector Cohen
- Department of Pathology, Galilee Medical Center, Nahariya, Israel affiliate with Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Ohad Ronen
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Department of Otolaryngology - Head and Neck Surgery, Galilee Medical Center, Nahariya, Israel affiliate with Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
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Shi G, Wang J, Qiang Y, Yang X, Zhao J, Hao R, Yang W, Du Q, Kazihise NGF. Knowledge-guided synthetic medical image adversarial augmentation for ultrasonography thyroid nodule classification. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2020; 196:105611. [PMID: 32650266 DOI: 10.1016/j.cmpb.2020.105611] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 06/14/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND AND OBJECTIVE Image classification is an important task in many medical applications. Methods based on deep learning have made great achievements in the computer vision domain. However, they typically rely on large-scale datasets which are annotated. How to obtain such great datasets is still a serious problem in medical domain. METHODS In this paper, we propose a knowledge-guided adversarial augmentation method for synthesizing medical images. First, we design Term and Image Encoders to extract domain knowledge from radiologists, then we use domain knowledge as novel condition to constrain the Auxiliary Classifier Generative Adversarial Network (ACGAN) framework for the synthesis of high-quality thyroid nodule images. Finally, we demonstrate our method on the task of classifying ultrasonography thyroid nodule. Our method can make effective use of the high-quality diagnostic experience of advanced radiologists. In addition, we creatively choose to extract domain knowledge from standardized terms rather than ultrasound images. RESULTS Our novel method is demonstrated on a limited dataset of 1937 clinical thyroid ultrasound images and corresponding standardized terms. The accuracy of the proposed model for thyroid nodules is 91.46%, the sensitivity is 90.63%, the specificity is 92.65%, and the AUC is 95.32%, which is better than the current classification methods for thyroid nodules. The experimental results show the model has better generalization and robustness. CONCLUSIONS We believe that the proposed method can alleviate the problem of insufficient data in the medical domain, and other medical problems can benefit from using synthetic augmentation.
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Affiliation(s)
- Guohua Shi
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Jiawen Wang
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Yan Qiang
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China.
| | - Xiaotang Yang
- Department of Radiology, Shanxi Province Cancer Hospital, Shanxi Medical University, Taiyuan, China.
| | - Juanjuan Zhao
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Rui Hao
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Wenkai Yang
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
| | - Qianqian Du
- College of Information and Computer, Taiyuan University of Technology, Taiyuan, China
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Ciarletto AM, Narick C, Malchoff CD, Massoll NA, Labourier E, Haugh K, Mireskandari A, Finkelstein SD, Kumar G. Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine-needle aspiration samples. Cancer Cytopathol 2020; 129:239-249. [PMID: 33017868 PMCID: PMC7984450 DOI: 10.1002/cncy.22365] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/28/2020] [Accepted: 09/04/2020] [Indexed: 12/24/2022]
Abstract
Background Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine‐needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one‐half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single‐stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy. In the current study, the authors hypothesized that differential pairwise (diff‐pair) analysis of miRNA expression levels would reliably identify MTC in FNA samples. Methods The relative abundance of 10 different miRNAs in total nucleic acids was obtained from ThyraMIR test results. Diff‐pair analysis was performed by subtracting the critical threshold value of one miRNA from the critical threshold values of other miRNAs. Next‐generation sequencing with the ThyGeNEXT panel identified oncogenic gene alterations. The discovery cohort consisted of 30 formalin‐fixed, paraffin‐embedded benign and malignant thyroid neoplasms, including 4 cases of MTC. After analytical validation, clinical validation was performed using 3 distinct cohorts (total of 7557 specimens). Results In the discovery cohort, 9 diff‐pairs were identified as having significant power using the Kruskal‐Wallis test (P < .0001) to distinguish MTC samples from non‐MTC samples. The assay correctly classified all MTC and non‐MTC samples in the analytical validation study and in the 3 clinical validation cohorts. The overall test accuracy was 100% (95% confidence interval, 99%‐100%). In indeterminate FNAC samples, the sensitivity of the diff‐pair analysis was greater than that of the MTC‐specific mutation analysis (100% vs 25%; P = .03). Conclusions Pairwise miRNA expression analysis of ThyraMIR results were found to accurately predict MTC in thyroid FNA samples, including those with indeterminate FNAC findings. The authors have developed and validated a microRNA (miRNA) test for the detection of medullary thyroid cancer (MTC) in preoperative thyroid nodule samples. The method, based on differential pairwise analysis of miRNA expression data generated using the ThyraMIR Thyroid miRNA Classifier, accurately predicts MTC with 100% sensitivity and 100% specificity in thyroid fine‐needle aspiration biopsies.
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Affiliation(s)
- Andrea M Ciarletto
- Interpace Diagnostics Laboratory, Interpace Biosciences Inc, New Haven, Connecticut
| | - Christina Narick
- Interpace Diagnostics, Interpace Biosciences Inc, Pittsburgh, Pennsylvania, United States
| | - Carl D Malchoff
- Carole and Ray Neag Comprehensive Cancer Center, UConn Health, Farmington, Connecticut
| | - Nicole A Massoll
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
| | | | - Keith Haugh
- Interpace Diagnostics, Interpace Biosciences Inc, Pittsburgh, Pennsylvania, United States
| | - Alidad Mireskandari
- Interpace Diagnostics Laboratory, Interpace Biosciences Inc, New Haven, Connecticut
| | - Sydney D Finkelstein
- Interpace Diagnostics Laboratory, Interpace Biosciences Inc, New Haven, Connecticut.,Interpace Diagnostics, Interpace Biosciences Inc, Pittsburgh, Pennsylvania, United States
| | - Gyanendra Kumar
- Interpace Diagnostics Laboratory, Interpace Biosciences Inc, New Haven, Connecticut
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Yoon JH, Lee HS, Kim EK, Moon HJ, Park VY, Kwak JY. Follow-Up Strategies for Thyroid Nodules with Benign Cytology on Ultrasound-Guided Fine Needle Aspiration: Malignancy Rates of Management Guidelines Using Ultrasound Before and After the Era of the Bethesda System. Thyroid 2019; 29:1227-1236. [PMID: 31359839 DOI: 10.1089/thy.2018.0769] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Background: To evaluate differences in malignancy rates and consequent follow-up strategies for cytologically benign thyroid nodules before and after the introduction of the Bethesda system according to the risk stratification categories of four thyroid management guidelines. Methods: This retrospective study was approved by our institutional review board. In this study, 1716 thyroid nodules with initially benign cytologic diagnosis at ultrasound-guided fine needle aspiration (US-FNA) in 1695 patients were included: 1187 nodules from the pre-Bethesda period and 529 nodules from the post-Bethesda period. Based on US features, the thyroid nodules were categorized into the final assessment categories of the 2015 American Thyroid Association (ATA), the 2016 American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), and the European Thyroid Association guidelines for Ultrasound Malignancy Risk Stratification systems. Estimated malignancy rates before and after propensity score matching according to follow-up intervals were obtained. Results: Of the 1716 thyroid nodules benign on initial US-FNA, the malignancy rate was 3.2% (38 of 1187) in the pre-Bethesda period and 2.6% (14 of 529) in the post-Bethesda period (p = 0.641). The 2015 ATA high suspicion pattern and the ACR-TIRADS category 5 had high estimated malignancy rates of >5% in the post-Bethesda period (6.52 and 8.57, respectively). Positive findings that indicated US-FNA in the ACR-TIRADS had estimated malignancy rates of 5.26 and 5.67, respectively, while the remaining guidelines had estimated malignancy rates of <5% in both periods. Conclusions: Immediate diagnostic intervention after benign cytologic diagnosis may not be necessary regardless of the cytologic criteria applied, but it can be considered for the highly suspicious categories in the 2015 ATA or the ACR-TIRADS for benign cytologic diagnosis of the Bethesda system.
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Affiliation(s)
- Jung Hyun Yoon
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
| | - Eun-Kyung Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Hee Jung Moon
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Vivian Youngjean Park
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Young Kwak
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
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Ferris RL, Nikiforov Y, Terris D, Seethala RR, Ridge JA, Angelos P, Duh Q, Wong R, Sabra MM, Fagin JA, McIver B, Bernet VJ, Harrell RM, Busaidy N, Cibas ES, Faquin WC, Sadow P, Baloch Z, Shindo M, Orloff L, Davies L, Randolph GW. AHNS Series: Do you know your guidelines? AHNS Endocrine Section Consensus Statement: State-of-the-art thyroid surgical recommendations in the era of noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Head Neck 2018; 40:1881-1888. [PMID: 29947030 PMCID: PMC6175359 DOI: 10.1002/hed.25141] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 02/02/2018] [Indexed: 01/31/2023] Open
Abstract
The newly introduced pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) will result in less bilateral thyroid surgery as well as deescalation in T4 suppressive and radioactive iodine treatment. Although, NIFTP is a nonmalignant lesion that has nuclear features of some papillary malignancies, the challenge for the surgeon is to identify a lesion as possibly NIFTP before the pathologic diagnosis. NIFTP, due to its reduction of overall rates of malignancy, will result in the initial surgical pendulum swinging toward lobectomy instead of initial total thyroidectomy. This American Head and Neck Society endocrine section consensus statement is intended to inform preoperative evaluation to attempt to identify those patients whose final pathology report may ultimately harbor NIFTP and can be offered a conservative surgical plan to assist in cost-effective, optimal management of patients with NIFTP.
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Affiliation(s)
- Robert L. Ferris
- Department of Otolaryngology ‐ Head and Neck SurgeryUniversity of Pittsburgh Medical CenterPittsburghPennsylvania
| | - Yuri Nikiforov
- Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghPennsylvania
| | - Davis Terris
- Department of Otolaryngology ‐ Head and Neck SurgeryAugusta UniversityAugustaGeorgia
| | - Raja R. Seethala
- Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghPennsylvania
| | - J. Andrew Ridge
- Department of Surgical OncologyFox Chase Cancer CenterPhiladelphiaPennsylvania
| | - Peter Angelos
- Department of SurgeryUniversity of Chicago Medical CenterChicagoIllinois
| | - Quan‐Yang Duh
- Department of SurgeryUniversity of California San FranciscoSan FranciscoCalifornia
| | - Richard Wong
- Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkNew York
| | - Mona M. Sabra
- Department of EndocrinologyMemorial Sloan Kettering Cancer CenterNew YorkNew York
| | - James A. Fagin
- Department of EndocrinologyMemorial Sloan Kettering Cancer CenterNew YorkNew York
| | - Bryan McIver
- Department of Head and Neck ‐ Endocrine OncologyMoffitt Cancer CenterTampaFlorida
| | - Victor J. Bernet
- Department of EndocrinologyMayo Clinic JacksonvilleJacksonvilleFlorida
| | - R. Mack Harrell
- Department of EndocrinologyMemorial Regional HospitalHollywoodFlorida
| | - Naifa Busaidy
- Department of Endocrine NeoplasiaMD Anderson Cancer Center; HoustonTexas
| | - Edmund S. Cibas
- Department of PathologyBrigham and Women's HospitalBostonMassachusetts
| | - William C. Faquin
- Department of PathologyMassachusetts General HospitalBostonMassachusetts
- Department of Otolaryngology Head and Neck SurgeryHarvard Medical SchoolBostonMassachusetts
| | - Peter Sadow
- Department of PathologyMassachusetts General HospitalBostonMassachusetts
- Department of Otolaryngology Head and Neck SurgeryHarvard Medical SchoolBostonMassachusetts
| | - Zubair Baloch
- Department of PathologyUniversity of PennsylvaniaPhiladelphiaPennsylvania
| | - Maisie Shindo
- Department of OtolaryngologyOregon Health Science UniversityPortlandOregon
| | - Lisa Orloff
- Department of OtolaryngologyStanford UniversityStanfordCalifornia
| | - Louise Davies
- Department of Otolaryngology and AudiologyDartmouth‐Hitchcock Medical CenterLebanonNew Hampshire
| | - Gregory W. Randolph
- Department of Otolaryngology Head and Neck SurgeryHarvard Medical SchoolBostonMassachusetts
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Eszlinger M, Ullmann M, Ruschenburg I, Böhme K, Görke F, Franzius C, Adam S, Molwitz T, Landvogt C, Amro B, Hach A, Feldmann B, Graf D, Wefer A, Niemann R, Bullmann C, Klaushenke G, Santen R, Tönshoff G, Ivancevic V, Kögler A, Bell E, Lorenz B, Kluge G, Hartenstein C, Paschke R. Low Malignancy Rates in Fine-Needle Aspiration Cytologies in a Primary Care Setting in Germany. Thyroid 2017; 27:1385-1392. [PMID: 28982301 DOI: 10.1089/thy.2017.0167] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings. METHODS In a primary care setting, 9460 FNAs of thyroid nodules were retrospectively analyzed from 8380 patients evaluated by one cytologist (I.R.) during a period of two years. The 8380 FNA cytologies were performed by 64 physicians in different private practices throughout Germany in primary care settings. RESULTS The cytopathologic results were classified according to the Bethesda System as non-diagnostic in 19%, cyst/cystic nodule in 21%, benign (including thyroiditis) in 48%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 6%, follicular neoplasms/suspicious for follicular neoplasm (FN/SFN) in 4%, suspicious for malignancy (SFM) in 1%, and malignant in 1%. The proportion of patients proceeding to surgery or with a follow-up of at least one year and the observed risks of malignancy were 22%/8% for AUS/FLUS, 69%/17% for FN/SFN, 78%/86% for SFM, and 71%/98% for malignant. For 112 cytologically suspicious and malignant FNAs, there were 102 true positives and 10 false positives, considering histology as gold standard. CONCLUSION At variance with other data mostly originating from tertiary centers, these data demonstrate low percentages for malignant, SFM, FN/SFN, and AUS/FLUS, and high percentages for cysts/cystic nodules in this primary care setting in Germany. The risks of malignancy for malignant, SFM, AUS/FLUS, and FN/SFN FNA cytologies are according to Bethesda recommendations.
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Affiliation(s)
- Markus Eszlinger
- 1 Departments of Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Maha Ullmann
- 2 Divisions of Endocrinology and Nephrology, Department of Internal Medicine, Neurology, and Dermatology, University of Leipzig, Leipzig, Germany
| | - Ilka Ruschenburg
- 3 MVZ wagnerstibbe für Gynäkologie, Reproduktionsmedizin, Zytologie, Pathologie, und Innere Medizin GmbH , Einbeck, Germany
| | - Katharina Böhme
- 2 Divisions of Endocrinology and Nephrology, Department of Internal Medicine, Neurology, and Dermatology, University of Leipzig, Leipzig, Germany
| | - Fabian Görke
- 2 Divisions of Endocrinology and Nephrology, Department of Internal Medicine, Neurology, and Dermatology, University of Leipzig, Leipzig, Germany
| | | | | | | | | | - Bassam Amro
- 8 Praxis für Nuklearmedizin , Oldenburg, Germany
| | - Anja Hach
- 9 Institut für Radiologie und Nuklearmedizin , Bremerhaven, Germany
| | - Berit Feldmann
- 10 Endokrinologie und Diabetologie im Zentrum , Stuttgart, Germany
| | - Dieter Graf
- 11 Praxisgemeinschaft Auf dem Meere , Lüneburg, Germany
| | - Antje Wefer
- 12 Radiologie und Nuklearmedizin in der Gottorpstraße , Oldenburg, Germany
| | - Rainer Niemann
- 13 Radiologie Oldenburg, Praxis Stehen und Partner GbR , Oldenburg, Germany
| | | | | | - Reinhard Santen
- 16 Endokrinologische Gemeinschaftspraxis, Zentrum für Hormon- und Stoffwechselstörungen , Frankfurt/Main, Germany
| | | | - Velimir Ivancevic
- 18 Radiologisch-Nuklearmedizinische Gemeinschaftspraxis , Celle, Germany
| | - Andreas Kögler
- 18 Radiologisch-Nuklearmedizinische Gemeinschaftspraxis , Celle, Germany
| | | | - Bernd Lorenz
- 20 Schilddrüsen- und Hormon-Praxis , Gera, Germany
| | - Gerald Kluge
- 21 Diagnostisches Zentrum Göttingen, Gemeinschaftspraxis für Radiologie und Nuklearmedizin , Göttingen, Germany
| | - Christoph Hartenstein
- 22 Schilddrüse Stuttgart, Fachärzte für Innere Medizin und Nuklearmedizinische Schilddrüsendiagnostik , Stuttgart, Germany
| | - Ralf Paschke
- 1 Departments of Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada
- 23 Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
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[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses]. DER PATHOLOGE 2017; 37:465-72. [PMID: 27350133 DOI: 10.1007/s00292-016-0172-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. OBJECTIVES Investigation of causes and relevance of discrepant diagnoses. MATERIALS AND METHOD The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. RESULTS Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. CONCLUSIONS Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.
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Eszlinger M, Lau L, Ghaznavi S, Symonds C, Chandarana SP, Khalil M, Paschke R. Molecular profiling of thyroid nodule fine-needle aspiration cytology. Nat Rev Endocrinol 2017; 13:415-424. [PMID: 28361927 DOI: 10.1038/nrendo.2017.24] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The differential diagnosis and malignancy risk stratification of thyroid nodules requires multidisciplinary expertise and knowledge of both local ultrasonography practices and the local malignancy rates for a given fine-needle aspiration (FNA) result. Even in such a multidisciplinary setting, FNA cytology has the inherent limitation that indeterminate cytology results cannot distinguish between follicular adenomas, follicular thyroid carcinomas or follicular variant papillary thyroid carcinomas. Accumulating evidence suggests that this limitation can be overcome by using molecular diagnostic approaches. In this Review, we present the advantages and disadvantages of the different molecular diagnostic methodologies, which can be divided into two approaches: those that 'rule out' malignancy (to reduce the overtreatment of benign nodules) and those that 'rule in' malignancy (to optimize surgical planning). We identify microRNA classifiers as potential additional markers for use in a two-step diagnostic approach, consider the potential implications of the reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinomas to noninvasive follicular thyroid neoplasms with papillary-like nuclear features and discuss the cost-effectiveness of molecular testing. Molecular FNA diagnostics is an important complementary addition to FNA cytology that could substantially reduce unnecessary surgery and better define the need for appropriate surgery in patients who have thyroid nodules with indeterminate FNA cytology.
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Affiliation(s)
- Markus Eszlinger
- Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada
- Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2T 4Z6, Canada
| | - Lorraine Lau
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada
| | - Sana Ghaznavi
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada
| | - Christopher Symonds
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada
| | - Shamir P Chandarana
- Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada
- Department of Surgery, Cumming School of Medicine, University of Calgary, Foothills Medical Centre, North Tower 1012, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada
| | - Moosa Khalil
- Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Centre, McCaig Tower, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada
| | - Ralf Paschke
- Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada
- Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2T 4Z6, Canada
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada
- Department of Medicine, Cumming School of Medicine, University of Calgary, North Tower 9th floor, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2N 4Z6, Canada
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Al Dawish MA, Robert AA, Muna A, Eyad A, Al Ghamdi A, Al Hajeri K, Thabet MA, Braham R. Bethesda System for Reporting Thyroid Cytopathology: A three-year study at a tertiary care referral center in Saudi Arabia. World J Clin Oncol 2017; 8:151-157. [PMID: 28439496 PMCID: PMC5385436 DOI: 10.5306/wjco.v8.i2.151] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 12/01/2016] [Accepted: 12/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To stratify the malignancy risks in thyroid nodules in a tertiary care referral center using the Bethesda system.
METHODS From January, 2012 to December, 2014, a retrospective analysis was performed among 1188 patients (15-90 years) who had 1433 thyroid nodules and fine-needle aspiration at Prince Sultan Military Medical City, Saudi Arabia. All thyroid cyto-pathological slides and ultra sound reports were reviewed and classified according to the Bethesda System for Reporting Thyroid Cytopathology. Age, gender, cytological features and histological types of the thyroid cancer were collected from patients’ medical chart and cytopathology reports.
RESULTS There were 124 total cases of malignancy on resection, giving an overall surgical yield malignancy of 33.6%. Majority of the thyroid cancer nodules (n = 57, 46%) in Bethesda VI category followed by Bethesda IV (n = 25, 20.2%). Almost 40% of the cancer nodules in 31-45 age group in both sex. Papillary thyroid carcinoma (PTC) was the most common form of thyroid cancer among the study population (111, 89.6%) followed by 8.9% of follicular thyroid carcinoma (FTC), 0.8% of medullary carcinoma and 0.8% of anaplastic carcinoma. Among the Bethesda IV category 68% thyroid nodules were PTC and 32% FTC.
CONCLUSION The malignancy values reported in our research were constant and comparable with the results of other published data with respect to the risk of malignancy. Patients with follicular neoplasm/suspicious for follicular neoplasm and suspicious of malignancy categories, total thyroidectomy is indicted because of the substantial risk of malignancy.
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Na CH, Kim DJ, Kim MS, Shin BS. Cutaneous Implantation Metastasis of Papillary Thyroid Carcinoma Following Fine Needle Aspiration Biopsy. Ann Dermatol 2017; 29:123-125. [PMID: 28223766 PMCID: PMC5318514 DOI: 10.5021/ad.2017.29.1.123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 01/14/2016] [Accepted: 01/25/2016] [Indexed: 01/27/2023] Open
Affiliation(s)
- Chan Ho Na
- Department of Dermatology, Chosun University Medical School, Gwangju, Korea
| | - Dong Jin Kim
- Department of Dermatology, Chosun University Medical School, Gwangju, Korea
| | - Min Sung Kim
- Department of Dermatology, Chosun University Medical School, Gwangju, Korea
| | - Bong Seok Shin
- Department of Dermatology, Chosun University Medical School, Gwangju, Korea
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Kloos RT. Molecular Profiling of Thyroid Nodules: Current Role for the Afirma Gene Expression Classifier on Clinical Decision Making. Mol Imaging Radionucl Ther 2017; 26:36-49. [PMID: 28117288 PMCID: PMC5283710 DOI: 10.4274/2017.26.suppl.05] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Thyroid fine-needle aspiration biopsy results are cytologically indeterminate in 15-30% of cases. When these nodules undergo diagnostic surgery, approximately three-quarters are histologically benign. These unnecessary surgeries diminish quality of life, generate complications, and increase healthcare costs. The Afirma gene expression classifier (GEC) is validated to pre-operatively identify cytologically indeterminate nodules likely to be truly benign so that surgery can be avoided. Its performance is supported by robust multicenter prospective and blinded clinical validation studies, and supported by extensive independent clinical utility publications which show a marked reduction in surgery among patients with benign Afirma GEC results. To rule-out cancer and avoid unnecessary diagnostic surgery, Afirma’s quality and depth of validation stand alone. The accuracy of a benign result is the negative predictive value (NPV). Afirma achieves an NPV ≥94% among cytologically indeterminate nodules (Bethesda III or IV). Thirteen clinical utility studies describing 1468 GEC benign patients demonstrate that few Afirma GEC benign nodules undergo surgery, including after 3 years of follow-up. With a specificity of 52%, over half of the truly benign nodules with indeterminate cytology receive a benign GEC result. High test sensitivity is critical to safely rule out cancer. The Afirma GEC’s 90% sensitivity means that regardless of the pre-test risk of malignancy, 90% of all malignant nodules are GEC suspicious. The Afirma GEC has transformed patient care. Where the majority of cytologically indeterminate patients were once operated to determine if the nodule was benign or malignant, now nearly half of these surgeries can be avoided.
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Affiliation(s)
- Richard T Kloos
- Veracyte, Inc., Department of Medical Affairs, Senior Medical Director-Endocrinology, California, USA, Phone: +1(650)243-6300, E-mail:
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Ma J, Wu F, Zhu J, Xu D, Kong D. A pre-trained convolutional neural network based method for thyroid nodule diagnosis. ULTRASONICS 2017; 73:221-230. [PMID: 27668999 DOI: 10.1016/j.ultras.2016.09.011] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 07/26/2016] [Accepted: 09/11/2016] [Indexed: 05/22/2023]
Abstract
In ultrasound images, most thyroid nodules are in heterogeneous appearances with various internal components and also have vague boundaries, so it is difficult for physicians to discriminate malignant thyroid nodules from benign ones. In this study, we propose a hybrid method for thyroid nodule diagnosis, which is a fusion of two pre-trained convolutional neural networks (CNNs) with different convolutional layers and fully-connected layers. Firstly, the two networks pre-trained with ImageNet database are separately trained. Secondly, we fuse feature maps learned by trained convolutional filters, pooling and normalization operations of the two CNNs. Finally, with the fused feature maps, a softmax classifier is used to diagnose thyroid nodules. The proposed method is validated on 15,000 ultrasound images collected from two local hospitals. Experiment results show that the proposed CNN based methods can accurately and effectively diagnose thyroid nodules. In addition, the fusion of the two CNN based models lead to significant performance improvement, with an accuracy of 83.02%±0.72%. These demonstrate the potential clinical applications of this method.
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Affiliation(s)
- Jinlian Ma
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, China
| | - Fa Wu
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, China
| | - Jiang Zhu
- Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China
| | - Dong Xu
- Department of Ultrasound, Zhejiang Cancer Hospital, Hangzhou 310022, China
| | - Dexing Kong
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, China.
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Abstract
Next-generation sequencing (NGS) in thyroid cancer allows for simultaneous high-throughput sequencing analysis of variable genetic alterations and provides a comprehensive understanding of tumor biology. In thyroid cancer, NGS offers diagnostic improvements for fine needle aspiration (FNA) cytology of thyroid with indeterminate features. It also contributes to patient management, providing risk stratification of patients based on the risk of malignancy. Furthermore, NGS has been adopted in cancer research. It is used in molecular tumor classification, and molecular prediction of recurrence and metastasis in papillary thyroid carcinoma. This review covers previous NGS analyses in variable types of thyroid cancer, where samples including FNA cytology, fresh frozen tissue, and formalin-fixed, paraffin-embedded tissues were used. This review also focuses on the clinical and research implications of using NGS to study and treat thyroid cancer.
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Affiliation(s)
- Yoon Jin Cha
- Department of Pathology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 South Korea
| | - Ja Seung Koo
- Department of Pathology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 South Korea
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Evranos B, Polat SB, Baser H, Ozdemir D, Kilicarslan A, Yalcin A, Ersoy R, Cakir B. Bethesda classification is a valuable guide for fine needle aspiration reports and highly predictive especially for diagnosing aggressive variants of papillary thyroid carcinoma. Cytopathology 2016; 28:259-267. [PMID: 27666595 DOI: 10.1111/cyt.12384] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND A fine needle aspiration biopsy (FNAB) is the most valuable diagnostic procedure for pre-operative discrimination of benign and malignant nodules. The Bethesda System for Reporting Thyroid Cytopathology provides standardised reporting and cytomorphological criteria in aspiration smears. The aim of the present study was to determine malignancy rates in nodules with different cytology results and evaluate the diagnostic value of Bethesda for variants of papillary thyroid carcinoma (PTC). MATERIALS AND METHODS A retrospective analysis of 2534 cases with 5784 thyroid nodules, who underwent FNAB followed by surgery, were included in this study. FNAB was performed with ultrasonography guidance. Cytological diagnoses were classified as: non-diagnostic (ND), benign, atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SUS) and malignant. Histopathological diagnoses were classified into four groups: benign, PTC, follicular thyroid cancer and other types of thyroid cancer (including medullary thyroid cancer, undifferentiated thyroid cancer and thyroid tumours of uncertain malignant potential). Cases with PTC were further divided into four categories: conventional variant, follicular variant, aggressive variants (tall cell, diffuse sclerosing and columnar variant) and other variants (oncocytic, solid/trabecular and warthin-like variants). FNAB results were compared with histopathological results. RESULTS Malignancy rates were 6.3%, 3.2%, 20.7%, 33.3%, 74.2% and 95.6% in the nodules with ND, benign, AUS/FLUS, FN/SFN, SUS and malignant cytology results, respectively. Pre-operative cytology was malignant or SUS in 56.6% of conventional, 24.3% of follicular, 92% of aggressive and 41.7% of other variants of histopathologically confirmed PTC. The difference between the groups was significant (P < 0.001). CONCLUSION The Bethesda classification is a reliable indicator of malignancy in nodules with different cytology results and seems to be very effective in predicting the malignancy for the nodules diagnosed with aggressive variant PTC on the final histological examination.
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Affiliation(s)
- B Evranos
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - S B Polat
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - H Baser
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - D Ozdemir
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - A Kilicarslan
- Department of Pathology, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - A Yalcin
- Department of Surgery, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - R Ersoy
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
| | - B Cakir
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Yildirim Beyazit University, Ankara, Turkey
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Glynn N, Hannon MJ, Lewis S, Hillery P, Al-Mousa M, Hill ADK, Keeling F, Morrin M, Thompson CJ, Smith D, Royston D, Leader M, Agha A. Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre. BMC Endocr Disord 2016; 16:45. [PMID: 27485324 PMCID: PMC4969652 DOI: 10.1186/s12902-016-0125-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 07/25/2016] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients. METHODS We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables. RESULTS Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase. CONCLUSIONS The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified.
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Affiliation(s)
- Nigel Glynn
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Mark J. Hannon
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Sarah Lewis
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Patrick Hillery
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Mohammed Al-Mousa
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Arnold D. K. Hill
- Department of Surgery, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Frank Keeling
- Department Radiology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Martina Morrin
- Department Radiology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | | | - Diarmuid Smith
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Derval Royston
- Department of Pathology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Mary Leader
- Department of Pathology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
| | - Amar Agha
- Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland
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Arul P, Akshatha C, Masilamani S. A study of malignancy rates in different diagnostic categories of the Bethesda system for reporting thyroid cytopathology: An institutional experience. Biomed J 2016; 38:517-22. [PMID: 27013451 PMCID: PMC6138258 DOI: 10.1016/j.bj.2015.08.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 08/07/2015] [Indexed: 01/21/2023] Open
Abstract
Background The Bethesda system for reporting thyroid cytopathology (TBSRTC) was introduced to standardize the communication of fine-needle aspiration cytology (FNAC) interpretation between clinicians and pathologists. This study was undertaken to evaluate the diagnostic utility of TBSRTC for reporting thyroid FNACs and rate of malignancy in each diagnostic category of TBSRTC. Methods A total of 603 thyroid FNAC results were retrieved retrospectively between July 2012 and January 2015 and reclassified according to TBSRTC. Of these, 392 cases had a histopathological follow-up. The FNACs results were compared to the histopathological diagnoses and the malignancy rates of each diagnostic categories of TBSRTC were calculated. Results Of the 603 FNACs, nondiagnostic were 16 (2.7%), benign were 393 (65.2%), atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) were 60 (10%), follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) were 64 (10.6%), suspicious for malignancy (SM) were 32 (5.3%), and malignant were 38 (6.3%). In 392 cases, there was follow-up histopathology. The malignancy rate for nondiagnostic, benign, AUS/FLUS, FN/SFN, SM, and malignant categories were 0%, 0.8%, 24.4%, 28.9%, 70.8%, and 100%, respectively. Conclusion Our study validated the efficacy of TBSRTC. In conclusion, the malignancy rate of AUS/FLUS in this study was higher than the risk mentioned in TBSRTC and other published studies. Hence, AUS/FLUS category patients in our setup warrant further workup including ultrasound and/or thyroid scan in addition to immediate repeat FNAC.
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Affiliation(s)
- P Arul
- Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur, Tamil Nadu, India.
| | - C Akshatha
- Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur, Tamil Nadu, India
| | - Suresh Masilamani
- Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur, Tamil Nadu, India
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Liu CC, Jethwa AR, Khariwala SS, Johnson J, Shin JJ. Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle Aspiration: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg 2016; 154:9-23. [PMID: 26428476 PMCID: PMC4896151 DOI: 10.1177/0194599815607841] [Citation(s) in RCA: 135] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 09/02/2015] [Indexed: 12/23/2022]
Abstract
OBJECTIVES (1) To analyze the sensitivity and specificity of fine-needle aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To determine the anticipated posttest probability of malignancy and probability of nondiagnostic and indeterminate cytology with parotid FNA. DATA SOURCES Independently corroborated computerized searches of PubMed, Embase, and Cochrane Central Register were performed. These were supplemented with manual searches and input from content experts. REVIEW METHODS Inclusion/exclusion criteria specified diagnosis of parotid mass, intervention with both FNA and surgical excision, and enumeration of both cytologic and surgical histopathologic results. The primary outcomes were sensitivity, specificity, and posttest probability of malignancy. Heterogeneity was evaluated with the I(2) statistic. Meta-analysis was performed via a 2-level mixed logistic regression model. Bayesian nomograms were plotted via pooled likelihood ratios. RESULTS The systematic review yielded 70 criterion-meeting studies, 63 of which contained data that allowed for computation of numerical outcomes (n = 5647 patients; level 2a) and consideration of meta-analysis. Subgroup analyses were performed in studies that were prospective, involved consecutive patients, described the FNA technique utilized, and used ultrasound guidance. The I(2) point estimate was >70% for all analyses, except within prospectively obtained and ultrasound-guided results. Among the prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI], 0.509-0.982) and a specificity of 0.995 (95% CI, 0.960-0.999). The probabilities of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030-0.075) and 0.147 (95% CI, 0.106-0.188), respectively. CONCLUSION FNA has moderate sensitivity and high specificity in differentiating malignant from benign parotid lesions. Considerable heterogeneity is present among studies.
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Affiliation(s)
- C Carrie Liu
- Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Canada
| | - Ashok R Jethwa
- Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Samir S Khariwala
- Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jonas Johnson
- Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Jennifer J Shin
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA
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Abstract
This article reviews the most current literature on thyroid nodule evaluation, with particular attention to the problem of the incidentally identified thyroid nodule. Although traditional risk factors for thyroid cancer, such as age, gender, and familial syndromes, are still important, the manner in which a thyroid nodule comes to attention is of great importance these days when considering how to proceed in a workup. Most thyroid nodules today are discovered through radiologic imaging tests performed for other reasons. This article covers the key considerations that are vital in balancing the risks and benefits of thyroid nodule workup and treatment.
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Affiliation(s)
- Louise Davies
- Department of Veterans Affairs Medical Center, VA Outcomes Group, 111B, 215 North Main Street, White River Junction, VT 05009, USA; Section of Otolaryngology, Geisel School of Medicine at Dartmouth, Rope Ferry Road, Hanover, NH 03755, USA; The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA.
| | - Gregory Randolph
- Division of Thyroid and Parathyroid Surgery, Department Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA; Division of Surgical Oncology, Massachusetts General Hospital, 55 Fuit Street, Boston, MA 02114, USA
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Abdelrahman SF, Ali FH, El-Sayed Khalil M, El Masry MR. Ultrasound elastography in the diagnostic evaluation of indeterminate thyroid nodules. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2015. [DOI: 10.1016/j.ejrnm.2015.05.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Mayooran N, Waters PS, Kaim Khani TY, Kerin MJ, Quill D. FNAC and frozen section correlations with definitive histology in thyroid diseases. Eur Arch Otorhinolaryngol 2015; 273:2181-4. [DOI: 10.1007/s00405-015-3742-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2015] [Accepted: 07/28/2015] [Indexed: 10/23/2022]
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Sharma C. Diagnostic accuracy of fine needle aspiration cytology of thyroid and evaluation of discordant cases. J Egypt Natl Canc Inst 2015; 27:147-53. [PMID: 26185872 DOI: 10.1016/j.jnci.2015.06.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 05/30/2015] [Accepted: 06/01/2015] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION The main role of fine needle aspiration cytology (FNAC) lies in differentiating between a malignant and benign thyroid nodule. It greatly influences the treatment decision. The current study was undertaken to evaluate the cytology-histopathology correlation and to analyze the cause of diagnostic errors with an eventual aim to improve diagnostic accuracy. MATERIALS AND METHODS This is a retrospective study comparing cytology and corresponding histopathology report in 724 thyroid cases. The statistical analysis included false positive rate, false negative rate, sensitivity, specificity, positive predictive value, negative predictive value and accuracy. RESULTS On cytological examination, 635/724 were reported as benign, 68 malignant and 21 suspicious. On histopathological examination, 626/635 cases were confirmed as benign but there were 9 discordant cases. Among the other cases histopathology diagnosis of malignancy matched in 66/68 and 11/21 cases. Diagnosis correlated in 703/724 cases (97%) [p<0.001]. False positive and false negative rates were 1.9% and 10.5%, respectively. The sensitivity and specificity were 89.5% and 98%, respectively. The positive predictive value was 84.6% and negative predictive value was 98.6%. Accuracy of FNA was 97%. CONCLUSION In spite of high accuracy of FNAC in differentiating between a benign and malignant lesion, certain pitfalls should be kept in mind. The common false negative diagnoses were follicular pattern cases which constitute a 'gray zone', cystic papillary thyroid carcinoma (PTC) and papillary microcarcinoma. The reason for false positive diagnoses was the occurrence of nuclear features characteristic of PTC in other thyroid lesions. Awareness of pathologist regarding these pitfalls can minimize false negative/positive diagnoses.
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Affiliation(s)
- Chetna Sharma
- Department of Pathology, PSG Institute of Medical Sciences, Coimbatore, India.
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Ultrasound-guided core-needle biopsy in thyroid nodules. A study of 676 consecutive cases with surgical correlation. Eur Radiol 2015; 26:1-8. [PMID: 25956937 DOI: 10.1007/s00330-015-3821-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Revised: 04/19/2015] [Accepted: 04/22/2015] [Indexed: 12/29/2022]
Abstract
OBJECTIVES To analyze the diagnostic accuracy of ultrasound-guided core-needle biopsy (CNB) of thyroid nodules. METHODS Of 3517 CNBs performed using an 18G spring-loaded device in one institution, we retrospectively reviewed 676 nodules in 629 consecutive patients who underwent surgery. CNB and pathological examination were compared. CNB diagnosis was standardized in four categories: insufficient (I), benign (B), follicular lesion (FOL), and malignant (M). Main outcome measures were predictive positive values (PPV), false positives (FP), and false negatives (FN). RESULTS CNB showed a low rate of insufficient and FOL diagnoses (5.8 % and 4.5 %). On surgery, there were eight FNs in 374 benign CNBs and three FPs in 148 malignant CNBs. The 154 nodules classified as FOL in CNB included, at surgery, 122 neoplasms; 28 of them malignant. PPV for malignancy of a malignant CNB was 98 %, and for a CNB diagnosis of FOL 18.2 %. Sensitivity for malignancy if CNB of FOL and M are considered positive was 95.6. Only one major complication was observed. CONCLUSIONS CNB is reliable, safe, and accurate to evaluate thyroid nodules and can be an alternative technique to FNA. It has low rate of non-diagnostic and undetermined cases, with high sensitivity and PPV. KEY POINTS Thyroid core-needle biopsy (CNB) has high sensitivity and PPV. Pitfalls of CNB are rare. Pitfalls are due to cystic cancer, histological heterogeneity, and mistakes in analysis. CNB is a reliable, safe, and accurate method to approach thyroid nodules. CNB can be used primarily or after insufficient or indeterminate FNA.
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Ucler R, Usluogulları CA, Tam AA, Ozdemir D, Balkan F, Yalcın S, Kıyak G, Ersoy PE, Guler G, Ersoy R, Cakır B. The diagnostic accuracy of ultrasound-guided fine-needle aspiration biopsy for thyroid nodules three centimeters or larger in size. Diagn Cytopathol 2015; 43:622-8. [PMID: 25914194 DOI: 10.1002/dc.23289] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 02/05/2015] [Accepted: 03/30/2015] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND PURPOSE Whether under ultrasonography (US) guidance or not, fine-needle aspiration biopsy (FNAB) has some limitations, particularly in larger nodules. In this study, we aimed to evaluate the diagnostic value of US-guided fine-needle aspiration biopsy (US-FNAB) in thyroid nodules equal to or larger than 3 cm. MATERIALS AND METHODS Data of 267 patients operated for nodular goiter in the period of January 2006 and March 2012 were reviewed retrospectively. The study group (40 males, 104 females; mean age 42.3 ± 12.3, between 17 and 71) consisted of patients with nodules with a diameter of 3 cm or larger. Patients with nodules less than 3 cm in diameter were considered as the control group (27 males, 96 females; mean age 44.4 ± 11.9, between 18 and 71). RESULTS For nodules smaller than 3 cm, US-FNAB had an accuracy rate of 60% and a false negativity rate of 21.9%. In nodules equal to or larger than 3 cm, the accuracy rate of US-FNAB was 80%, with a false negativity rate of 6.7%. Malignancy was observed in 16% of the study group and 42.3% of the control group. CONCLUSION This study showed that increased nodule diameter is not associated with limitations in the diagnostic value of US-FNAB. We also found that the malignancy rate was smaller for larger nodules. This finding reflects the importance of accurate and rational diagnostic work-up and clinical management for detecting malignancy and surgical decision-making.
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Affiliation(s)
- Rıfkı Ucler
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Celil Alper Usluogulları
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Abbas Ali Tam
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Didem Ozdemir
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Fevzi Balkan
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Samet Yalcın
- Department of General Surgery, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Gulten Kıyak
- Department of General Surgery, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Pamir Eren Ersoy
- Department of General Surgery, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Gulnur Guler
- Department of Pathology, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Reyhan Ersoy
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
| | - Bekir Cakır
- Department of Endocrinology and Metabolism, Ataturk Education and Research Hospital, Ankara, Turkey
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Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, Gooding WE, Hodak SP, LeBeau SO, Ohori NP, Seethala RR, Tublin ME, Yip L, Nikiforova MN. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer 2014; 120:3627-34. [PMID: 25209362 PMCID: PMC7737376 DOI: 10.1002/cncr.29038] [Citation(s) in RCA: 371] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 08/18/2014] [Accepted: 08/19/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. METHODS The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. RESULTS In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). CONCLUSIONS The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.
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Affiliation(s)
- Yuri E. Nikiforov
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sally E. Carty
- Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Simon I. Chiosea
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Christopher Coyne
- Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Umamaheswar Duvvuri
- Department of Otolaryngology, Head Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Robert L. Ferris
- Department of Otolaryngology, Head Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - William E. Gooding
- Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
| | - Steven P. Hodak
- Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Shane O. LeBeau
- Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - N. Paul Ohori
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Raja R. Seethala
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Mitchell E. Tublin
- Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Linwah Yip
- Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
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The role of elastosonography, gray-scale and colour flow Doppler sonography in prediction of malignancy in thyroid nodules. Radiol Oncol 2014; 48:348-53. [PMID: 25435847 PMCID: PMC4230554 DOI: 10.2478/raon-2014-0007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Accepted: 01/27/2014] [Indexed: 12/03/2022] Open
Abstract
Background Ultrasound is as a noninvasive method commonly used in the work-up of thyroid nodules. This study aimed to evaluate the usefulness of sonographic and elastosonographic parameters in the discrimination of malignancy. Patients and methods. 150 thyroid nodules were evaluated by gray-scale, Doppler and elastosonography. The cytological analysis revealed that 141 nodules were benign and 9 were malignant. Results Orientation of the nodule was the only sonographic parameter associated with malignancy (p = 0.003). In the strain ratio analysis the best cut-off point was 1.935 to discriminate malignancy (p = 0.000), with 100% sensitivity, 76% specificity, 100% negative predictive value, 78.5% positive predictive value and 78% accuracy rate. There was a statistically significant correlation between the elasticity score and malignancy (p = 0.001). Most of the benign nodules had score 2 and 3, none of them displayed score 5. On the other hand, none of the malignant nodules had score 1 and 2, most of them displaying score 5. Conclusions A change in the diagnostic algorithm of the thyroid nodules should be considered integrating the elastosonographic analysis.
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Armstrong MJ, Yang H, Yip L, Ohori NP, McCoy KL, Stang MT, Hodak SP, Nikiforova MN, Carty SE, Nikiforov YE. PAX8/PPARγ rearrangement in thyroid nodules predicts follicular-pattern carcinomas, in particular the encapsulated follicular variant of papillary carcinoma. Thyroid 2014; 24:1369-74. [PMID: 24798894 PMCID: PMC4148057 DOI: 10.1089/thy.2014.0067] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND PAX8/PPARγ rearrangement is a common genetic alteration in follicular thyroid carcinoma (FTC) and has been reported with variable frequency in papillary thyroid carcinoma (PTC). The diagnostic and phenotypic features of thyroid nodules positive for PAX8/PPARγ on preoperative examination are not well understood. METHODS The prevalence of PAX8/PPARγ rearrangement was analyzed in a series of 2015 consecutive thyroid nodules that underwent molecular analysis on cytology specimens and in 446 surgically removed PTCs. For all PAX8/PPARγ positive cases, cytology and surgical pathology slides were examined and the available clinical records were reviewed. RESULTS Twenty-two PAX8/PPARγ rearrangements were identified, including 16 detected preoperatively and 6 postoperatively. The incidence of PAX8/PPARγ in PTC was 1.1%. Cytologically, most of these nodules were diagnosed as a follicular neoplasm (73%), followed by the diagnosis of atypia of undetermined significance (19%), and none of the cases was diagnosed as cytologically malignant. All nodules with PAX8/PPARγ detected preoperatively and surgical follow-up available were found to be malignant, among which the most common diagnosis was the encapsulated follicular variant of PTC. Overall, among 20 PAX8/PPARγ-positive tumors that were surgically excised, 17 (85%) were PTC and 3 (15%) were FTC. On follow-up available for 17 patients (mean, 22.4 months), 16 PAX8/PPARγ-positive cancers showed no evidence of biochemical or structural recurrence, whereas 1 patient with FTC developed bone metastasis. CONCLUSIONS In this series, PAX8/PPARγ rearrangement found in thyroid nodules had a 100% predictive value for differentiated thyroid cancer, and was more predictive of PTC than FTC. However, almost all PTC carrying PAX8/PPARγ were encapsulated follicular-pattern tumors, distinguished from FTC only by nuclear features. Although most tumors carrying this mutation appear to be clinically indolent, at least on short-term follow-up, distant metastasis can develop from FTC positive for PAX8/PPARγ.
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Affiliation(s)
- Michaele J. Armstrong
- Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Huaitao Yang
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Linwah Yip
- Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - N. Paul Ohori
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Kelly L. McCoy
- Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Michael T. Stang
- Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Steven P. Hodak
- Division of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Marina N. Nikiforova
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Sally E. Carty
- Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Yuri E. Nikiforov
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Tuluc M, Solomides C. Thyroid cytology. Otolaryngol Clin North Am 2014; 47:475-89. [PMID: 25041952 DOI: 10.1016/j.otc.2014.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
This article covers, in a comprehensive way, thyroid cytopathology. The Bethesda System for Reporting Thyroid Cytology is reviewed, with emphasis on the atypical and indeterminate diagnostic categories. Immunohistochemistry stains and molecular tests panels applicable to cytology specimens are described.
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Affiliation(s)
- Madalina Tuluc
- Department of Pathology, Jefferson University Hospital, 132S 10th Street, Main Building, Philadelphia, PA 19107, USA.
| | - Charalambos Solomides
- Department of Pathology, Jefferson University Hospital, 132S 10th Street, Main Building, Philadelphia, PA 19107, USA
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Shin JJ, Caragacianu D, Randolph GW. Impact of thyroid nodule size on prevalence and post-test probability of malignancy: a systematic review. Laryngoscope 2014; 125:263-72. [PMID: 24965892 DOI: 10.1002/lary.24784] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 04/26/2014] [Accepted: 05/27/2014] [Indexed: 12/21/2022]
Abstract
OBJECTIVES/HYPOTHESIS Large thyroid nodules may be associated with higher risk of malignancy and less-accurate fine-needle aspiration (FNA) results, but there is currently no overarching consensus. We therefore tested two null hypotheses: 1) thyroid nodule size >3 to 4 cm is not associated with a higher baseline prevalence of malignancy (i.e., the associated pretest probability is the same, regardless of size), and 2) thyroid nodule size >3 to 4 cm is not associated with worse diagnostic accuracy (i.e., the associated sensitivity, false-negative rate, and post-test probability of malignancy is not affected by nodule diameter). STUDY DESIGN Computerized searches of PubMed, Embase, and The Cochrane Library through July 2013 were performed, supplemented with manual searches. METHODS A priori criteria were defined to determine inclusion and exclusion of studies. Searches and data extraction were performed by independent reviewers and focused on FNA histopathologic findings and their relationship to nodule size, study design, and potential confounders. RESULTS Criterion-meeting studies (n = 15) included a total of 13,180 participants. The preponderance of prospective comparative studies showed a statistically significantly higher prevalence of malignancy in large nodules. Although data are mixed, evidence from the best-reported studies suggests sensitivity, false-negative rates, and frequency of true negatives among benign FNA results are worse in large nodules. CONCLUSIONS Large nodules have a higher pretest probability of malignancy. Data from larger studies suggest reduced FNA diagnostic accuracy in nodules >3 to 4 cm in diameter. Surgery represents a reasonable clinical option for nodules >3 cm.
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Proietti A, Borrelli N, Giannini R, Romani R, Di Coscio G, Quilici F, Rago T, Miccoli P, Vitti P, Basolo F. Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1347 papillary thyroid carcinomas. Cancer Cytopathol 2014; 122:751-9. [PMID: 24913568 DOI: 10.1002/cncy.21454] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 05/12/2014] [Accepted: 05/27/2014] [Indexed: 11/11/2022]
Abstract
BACKGROUND Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated. METHODS In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both cytological and histological diagnoses were collected from the same center. A blinded revision of the false-negative cases was performed. An analysis of the BRAF and Ras genes in the false-negative cases was then performed. RESULTS The false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347 cases). False-negative cases were 15 follicular variant PTCs, 2 classical variant, and 1 solid variant that lacked peculiar PTC cytomorphological features. Adequate cellular material for molecular analysis was available only in 54 of the 65 false-negative cases. Mutations were found in 6 cases (11%), and Ras alterations were present in 16 cases (29.6%). The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases). CONCLUSIONS The results of the current study confirm the feasibility of BRAF and Ras analysis in routine FNA. However, when the false-negative FNA rate is low, the cost-benefit analysis of the detection of BRAF and Ras mutations should be carefully evaluated. Consequently, the authors suggest that preoperative molecular assessment could be helpful for benign nodules, but only in the presence of clinical suspicion of malignancy.
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Affiliation(s)
- Agnese Proietti
- Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathological Anatomy, University of Pisa, Pisa, Italy
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Mon SY, Hodak SP. Molecular diagnostics for thyroid nodules: the current state of affairs. Endocrinol Metab Clin North Am 2014; 43:345-65. [PMID: 24891166 DOI: 10.1016/j.ecl.2014.02.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Molecular diagnostics offers great promise for the evaluation of cytologically indeterminate thyroid nodules. Numerous molecular genetic and immunohistochemical tests have been developed that may be performed on thyroid specimens obtained during standard fine-needle aspiration, some of which may greatly improve diagnostic yield. A sound understanding of the diagnostic performance of these tests, and how they can enhance clinical practice, is important. This article reviews the diagnostic utility of immunohistochemical and molecular testing for the clinical assessment of thyroid nodules, and makes recommendations about how these tests can be integrated into clinical practice for patients with cytologically indeterminate thyroid nodules.
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Affiliation(s)
- Sann Yu Mon
- Division of Endocrinology, University of Pittsburgh School of Medicine, 200 Lothrop Street, BST 1140, Pittsburgh, PA 15213, USA
| | - Steven P Hodak
- Division of Endocrinology, Center for Diabetes and Endocrinology, University of Pittsburgh School of Medicine, 3601 Fifth Avenue, Suite 587, Pittsburgh, PA 15213, USA.
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Güneş P, Demirtürk P, Aker F, Tanrıöver Ö, Gönültaş A, Akkaynak Ş. Evaluation of Fine-Needle Aspiration of Thyroid Nodules in a Series of 1,100 Patients: Correlation Between Cytology and Histopathology Original Article. Indian J Surg 2014; 77:990-5. [PMID: 27011496 DOI: 10.1007/s12262-014-1102-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Accepted: 05/08/2014] [Indexed: 01/21/2023] Open
Abstract
In this study, our aim was to test the usefulness of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in indeterminate lesions in which cytological and histological diagnosis discordance was high and to investigate the contribution of TBSRTC in this indeterminate diagnostic group. The medical records of the patients who presented to the Haydarpasa Numune Training and Research Hospital in Istanbul, Turkey, between October of 1999 and September of 2010, for the cytological and histological diagnosis of thyroid nodules, were reviewed retrospectively. We reclassified these patients according to the Bethesda method, which features well-defined cytological criteria for each category within a six-tiered system. For each patient, the diagnosis and reasons for discordance were discussed and a final decision was made for each discordant case. The overall distribution of the cytological diagnoses using an in-house system was as follows: 811 benign (73.7 %), 87 suspicious follicular cell/follicular neoplasia (7.9 %), 52 suspicious for malignancy (4.7 %), and 45 malignant (4.1 %). We reclassified the diagnoses using the Bethesda system and the results are as follows: 797 benign (73.7 %), 48 follicular lesion of undetermined significance (4.3 %), 68 follicular neoplasia (7.9 %), 40 suspicious for malignancy (3.6 %), and 44 malignant (4 %). Our results showed that using TBRSTC for the lesions in the indeterminate category decreased the ratios of false-positive and false-negative diagnoses.
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Affiliation(s)
- Pembegül Güneş
- Department of Pathology, Haydarpasa Numune Training and Research Hospital, 34668 İstanbul, Turkey
| | - Pelin Demirtürk
- Department of Pathology, Haydarpasa Numune Training and Research Hospital, 34668 İstanbul, Turkey
| | - Fügen Aker
- Department of Pathology, Haydarpasa Numune Training and Research Hospital, 34668 İstanbul, Turkey
| | - Özlem Tanrıöver
- Department of Family Medicine, Yeditepe University Faculty of Medicine, İstanbul, Turkey
| | - Aylin Gönültaş
- Department of Pathology, Haydarpasa Numune Training and Research Hospital, 34668 İstanbul, Turkey
| | - Şerike Akkaynak
- Department of Pathology, Haydarpasa Numune Training and Research Hospital, 34668 İstanbul, Turkey
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Thyroid nodules in childhood: indications for biopsy and surgery. Ital J Pediatr 2014; 40:48. [PMID: 24887308 PMCID: PMC4046031 DOI: 10.1186/1824-7288-40-48] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 04/29/2014] [Indexed: 11/10/2022] Open
Abstract
Aims of this commentary is to report the most recent views about epidemiology, diagnostic procedures, malignancy risk factors and clinical management of thyroid nodules in children. On the basis of our personal experiences and recent literature evidences, we conclude that: a) if nodule is accompanied by lymphadenopathy and/or other alert findings, fine-needle aspiration biopsy (FNAB) should be recommended; b) if no lymphadenopathy and no other clinical and ultrasonographic alert signs are observed, work-up can progress to FNAB only if nodule persists or grows over time, even under levo-thyroxine therapy.
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Pathak P, Srivastava R, Singh N, Arora VK, Bhatia A. Implementation of the bethesda system for reporting thyroid cytopathology: Interobserver concordance and reclassification of previously inconclusive aspirates. Diagn Cytopathol 2014; 42:944-9. [DOI: 10.1002/dc.23162] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 02/19/2014] [Accepted: 03/18/2014] [Indexed: 12/30/2022]
Affiliation(s)
- Priya Pathak
- Department of Pathology; University College of Medical Sciences and GTB Hospital; Delhi 110095 India
| | - Ruchi Srivastava
- Department of Pathology; University College of Medical Sciences and GTB Hospital; Delhi 110095 India
| | - Navjeevan Singh
- Department of Pathology; University College of Medical Sciences and GTB Hospital; Delhi 110095 India
| | - Vinod K. Arora
- Department of Pathology; University College of Medical Sciences and GTB Hospital; Delhi 110095 India
| | - Arati Bhatia
- Department of Pathology; University College of Medical Sciences and GTB Hospital; Delhi 110095 India
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Sheffield BS, Masoudi H, Walker B, Wiseman SM. Preoperative diagnosis of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology: a comprehensive review and meta-analysis. Expert Rev Endocrinol Metab 2014; 9:97-110. [PMID: 30743753 DOI: 10.1586/17446651.2014.887435] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Fine-needle aspiration biopsy (FNAB) is the test of choice for the evaluation of nodules, arriving at a cancer diagnosis, and guiding surgical management. This review and meta-analysis aims to objectively evaluate the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) based upon literature reports of histopathological outcomes following cytopathological diagnoses. Thirteen studies were reviewed and the risk of malignancy (ROM) for each of the BSRTC diagnostic categories were calculated as: Non-diagnostic 11-26%, Benign 4-9%, AUS/FLUS 19-38%, FN/SFN 27-40%, SFM 50-79%, and Malignant 98-100%. In typical clinical utilization, the sensitivity and specificity of thyroid FNAB diagnosis using the BSRTC were 96% and 46%, respectively. The BSRTC represents an important advance in standardizing thyroid FNAB cytopathological reporting. Close attention should be paid to the observation that the AUS-FLUS and FN-SFN DCs have overlapping ROMs, and the potential clinical implications of this finding on patient management.
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Affiliation(s)
- Brandon S Sheffield
- a Department of Pathology and Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
| | - Hamid Masoudi
- a Department of Pathology and Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
| | - Blair Walker
- a Department of Pathology and Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
| | - Sam M Wiseman
- b Department of Surgery, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada
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Molecular Markers: From Diagnosis to Prognosis in 2013. CURRENT OTORHINOLARYNGOLOGY REPORTS 2014. [DOI: 10.1007/s40136-013-0031-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Ward LS, Kloos RT. Molecular markers in the diagnosis of thyroid nodules. ACTA ACUST UNITED AC 2014; 57:89-97. [PMID: 23525286 DOI: 10.1590/s0004-27302013000200001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2013] [Accepted: 02/03/2013] [Indexed: 01/21/2023]
Abstract
An indeterminate thyroid nodule cytology result occurs about every sixth fine-needle aspiration. These indeterminate nodules harbor a 24% risk of malignancy (ROM); too high to ignore, but driving surgery where most nodules are benign. Molecular diagnostics have emerged to ideally avoid surgery when appropriate, and to trigger the correct therapeutic surgery when indicated, as opposed to an incomplete diagnostic surgery. No current molecular test offers both high sensitivity and high specificity. A molecular diagnostic test with high sensitivity (e.g. Afirma Gene Expression Classifier sensitivity 90%) offers a high Negative Predictive Value when the ROM is relatively low, such as < 30%. Only such tests can "rule-out" cancer. In this setting, a molecularly benign result suggests the same ROM as that of operated cytologically benign nodules (~6%). Thus, clinical observation can replace diagnostic surgery; increasing quality of life and decreasing medical costs. However, its low specificity cannot "rule-in" cancer as a suspicious result has a Positive Predictive Value (PPV) of ~40%, perhaps too low to routinely reflex to definitive cancer surgery. Conversely, high specificity tests (BRAF, RAS, PPAR/PAX-8, RET/PTC, PTEN) offer high PPV results, and only these tests can "rule-in" cancer. Here a positive molecular result warrants definitive therapeutic surgery. However, their low sensitivity cannot "rule-out" cancer and a negative molecular result cannot dissuade diagnostic surgery; limiting their cost-effectiveness. Whether or not there is a useful and cost-effective role to sequentially combine these approaches, or to modify existing approaches, is under investigation.
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Affiliation(s)
- Laura S Ward
- Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
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