A study of the accuracy of fine needle aspiration cytology in thyroid pathology Honored evaluation committee and students, distinguished guests, my name is Alexandra Contra and I am going to present you today a study of the accuracy of fine needle aspiration cytology in thyroid pathology. Author: Alexandra Contra 6th Grade MG Coordinator: Lecturer dr. Georgescu Rares

FNA cytology- summary data from literature Diagnosis procedure economical accurate efficient FNA cytology for the thyroid gland is considered to be the most efficient, economical and accurate diagnosis procedure for selecting the thyroid nodules which need to be referred for surgery. 2

FNA cytology – summary data from literature Sensitivity Specificity Overall accuracy PPV NPV FP FN 65-98% 72-100% 75-90% 94-99% 66-97% 0-8% 1-12% PPV: Positive predictive value NPV: Negative predictive value FP: False positive FN: False negative Statistical analysis conducted in various medical institutions around the world, showed a wide range of results but for a brief understanding, summary data from the literature is described as follows: a sensitivity and specificity ranging from 65-98% respectively from 72-100% and an overall accuracy which can reach 90% are very good indicators for the test. Of course, like any other test, it has it’s own diagnosis pitfalls and limitations. For example, the FP and FN rate which depend on many aspects: specimen adequacy, sampling techniques, the skill of the physician, the experience of the pathologist and many others. 3

Purpose of the study 2011 2013 Accuracy Of FNA Cytology Diagnosis patients diagnosed with thyroid nodules Surgery Department, Private Medical Clinic ‘’PULS’’ 2011 to 2013 FNA cytology The purpose of this study is to asses the accuracy of FNA cytology in the diagnosis of thyroid pathology of the patients who were referred to the Surgery Department of the Private Medical Clinic ‘’PULS’’, Târgu Mureş from 2011 to 2013. Diagnosis Accuracy Of FNA Cytology 4

Materials And Method Retrospective study 319 cases of thyroid nodules Ethical approval from UMF Târgu Mureş Written informed consent from the clinic Retrospective study 319 cases of thyroid nodules FNA cytology at the ‘’PULS’’ clinic Cytological diagnosis at ‘’SANTOMAR’’ private laboratory According to Bethesda We have been conducting a retrospective study on 319 cases of thyroid nodules which were further investigated through FNA cytology at the private medical clinic ‘’PULS’’. Cytology diagnosis was determined at ‘’SANTOMAR’’ private laboratory in Cluj Napoca and was established in conformity with the Bethesda classification. All the FNA procedures and cytological readings were made by the same physician respectively by the same pathologist, in order to reduce the diagnosis pitfall as much as possible. Ethical approval was obtained from the Ethics Commission of UMF Targu Mures and a written informed consent was waved by the review board of the clinic. All the FNA procedures - same surgeon All the cytological readings - same pathologist 5

Materials And Method FNA Cytology Telephonic questionnaire All of the FNA cytology cases gathered from 2011 to 2013 in the clinics archive were automatically selected. In order to obtain medical information afterwards the cytology test, we contacted the patients for a telephonic questionnaire. The most relevant part of the questionnaire was that were the patient informed us if surgical intervention OR only medical treatment followed. Patients where surgical intervention followed were asked for the histopathology results. The ones in which only medical treatment followed were questioned about the most recent ecographic review so we can confirm the stability of the nodule at least 6 months after FNA test. Medical treatment followed Thyroidectomy/ Lobectomy followed Ecographic follow-up at least 6 months after the FNA 6 Histopathology

The telephonic questionnaire 1. Accuses of painful sensations during the FNA procedure? 2. Accuses of local complications after the FNA procedure? 3. or treatment followed? Medical Surgical The telephonic questionnaire consisted in a few key questions which were developed depending on the cases so we can obtain the most accurate information. Ecographicaly followed-up nodule data Histopathology diagnosis 7

Criteria for excluding from the study NO contact details WERE NOT monitored by an endocrinologist after the FNA cytology DID NOT answer to the questionnaire The criteria for excluding from the study were: patients who couldn’t been contacted by phone patients who were not monitored after the FNA cytology test by an endocrinologist patients who refused to answer to the questionnaire The statistical calculations were made using MedCalc. 8 Statistical calculations were made using MedCalc

Median age and prevalence on gender Results Median age and prevalence on gender Variable Sex Female 289 (90,6%) Male 30 (9,4%) Variable Age Sample size 319 Lowest Value 17 Highest value 82 Arithmetic mean 53 The occurrence in female was 90,6% and the median age was 53 years, as reported in other literature. 9

Pain during the procedure Local complications and pain related questionnaire Pain during the procedure YES 19 NO 198 Total 217 Local complications Intensive pain 1 Hematoma 4 No 212 Total 217 Only 19 patients out of the 217 who answered the questionnaire accused pain during the procedure. Only 5 patients out of the 217 who answered the questionnaire accused local complications: intensive pain for a few days (1 case) and hematoma (4cases). 10

Cytology results FNAC results were interpreted as benign in 210 cases (69.30%), indeterminate in 46 cases, suspect in 4 cases, malignant in 1 case and inadequate in 42 cases (13,9%) – the last one, after excluding 11 cases of cystic lesions (? Worth mentioning? ) There is a quite remarking difference between the number of indeterminate cases and the number of suspicious or malignant cases which could be explained by the reduced number of smears read by the pathologist (only 2 instead of 6~10 smears)

Histology results and correlations with the cytology Benign 34 69,4% Malign 15 30,6% Total 49 Histology and cytology correlations Benign Indeterminate Malign Inadequate Suspect 14 13 6 1 34 4 2 15 Total 18 (36.7%) 17 (34.7%) 1 (2.0%) 10 (20.4%) 3 (6.1%) 49 Out of the 303 cases, we had histopathology data on 49 patients. This was the gold standard we used to correlate the correspondent FNAC results when possible. 34 cases (69,4%)out of 49, turned up to be benign and 15 of them (30,6%) had malignant results. The correlation made between the FNAC and the gold standard revealed some discordances. 4 out of 18 benign FNAC turned up to be malignant and 13 out of 17 indeterminate FNAC were benign. Also one suspicious FNAC case turned up to be benign. 12

Criterion values and coordinates of the ROC curve Our results Standard range worldwide Thyroid FNA cytology Sensitivity Specificity Overall accuracy PPV NPV FP FN 76,47% 83,1% 82,3% 35,1% 96,7% 16,9% 23,0% This being told, we obtained a sensitivity of 76,47%, a specificity of 83,1% and a total accuracy of 82,3%. All these results are in conformity with the literature data published so far. A high specificity test always comes in hand with a high NPV as you can see in our results. But FNAC to golden standard correlation discordances like those mentioned before affected the FP respectively the FN rate as you can see in the table. Thyroid FNA cytology Sensitivity Specificity Overall accuracy PPV NPV FP FN 65-98% 72-100% 75-90% 94-99% 66-97% 0-8% 1-12% 13

ROC Curve AUC = 0,798 AUC intervals: 0,9-1,0 excellent 0,8-0,9 very good 0,7-0,8 good 0,6-0,7 medium 0,5-0,6 weak <0,5 very weak p=0,0001 Despite the relatively high FP and FN rates, the AUC has a value of 0,798 and a statistically significant p value, which assures us that the procedure has a very good accuracy. 14

FNA cytology first line diagnostic test Conclusions FNA cytology first line diagnostic test Good accuracy Minor complications Reduces surgery Painless maneuver FNA cytology is a painless maneuver for the most of the patients. Therefore, local anesthesia is not compulsory. Local complications occur rarely and they are minor. FNA cytology has a good accuracy in the initial diagnosis of the patients with thyroid nodules or diffuse lesions avoiding unnecessary surgery in most of the cases. 15

Discussions Incidentalomas- worth puncturing? Optimal number of smear readings? PPV and FP interpretation? FN value interpretation? Like any other test, FNAC has it’s own diagnosis pitfalls which I believe that are worth mentioning. FNAC cytology on an incidentaloma (nodule <10mm) may increase the rate of inadequate results. A reduced number of smear readings/patient may influence the results increasing the number of indeterminate results which in histopathology may prove to be benign. This, translated into statistical terms, may mean a low PPV and high FP rates. As a last remark, increased FN value may be due to microfollicular type of papillary carcinoma which can be easily missed when puncturing. 16

Bibliography 1. Joe D. Jakowski, M.D, PathologyOutlines.com, Inc. 2013 2. American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidlines for clinical practice for the diagnosis and management of thyroid nodules, Endocrine Practice vol 12 No1 January/February 2006, 63. 3. Edmund S. Cibas, MD, Syed Z. Ali, MD, The Bethesda System for Reporting Thyroid Cytopathology, Am J Clin Pathol 2009;132:658-665. Thank you very much for your attention! 17