Positive predictive value and inter-observer agreement of TIRADS for ultrasound features of thyroid nodules

Transcription

1 Positive predictive value and inter-observer agreement of TIRADS for ultrasound features of thyroid nodules Poster No.: C-0594 Congress: ECR 2014 Type: Scientific Exhibit Authors: C. Anuradha, K. Abhishek, B. Pushpa, A. Deepak, P. Mj ; , Ta/IN, Vellore, Ta/IN Keywords: Cancer, Observer performance, Ultrasound, Thyroid / Parathyroids, Head and neck DOI: /ecr2014/C-0594 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 29

2 Aims and objectives Palpable goiter is a very common condition and around 12 % of adult Indians have a palpable thyroid nodule in recent population based study.(1) When assessed by ultrasound the prevalence of thyroid nodule was as high as 80% among children in iodine deficient part of India.(2) However the incidence of thyroid cancer is low (1-1.8 per 100,000).(3) Ultrasound is a widely accepted imaging modality for the initial assessment of thyroid nodules. There are well established ultrasound findings that differentiate benign and malignant thyroid nodules (4-11) and there are several classification systems which categorize thyroid nodules according to the risk of cancer.(8, 12-14) Of the various classification system described, thyroid imaging reporting and data system (TIRADS) described by Kwak JY et al(12) is a relatively simple system which can be easily adopted in a teaching hospital which has radiologists of varying experience performing thyroid ultrasound. We aimed at assessing the positive predictive value and the interobserver variability of TIRADS for ultrasound features of thyroid nodules as described by Kwak JY et al.(12) Methods and materials Study population: This is an institutional review board approved prospective study conducted in the department of Radiology of a 2800 bedded tertiary care teaching hospital in South India. From January to November 2012, 520 patients underwent thyroid ultrasound. Patients with solitary thyroid nodule and dominant nodules of multi-nodular goiter with maximum size greater than 1 cm were included in the study. Out of 526 patients, 307 consecutive patients with a total of 346 nodules satisfied above size criteria and participated in the study. Fig. 1 on page 5 shows the study population. Patients were included for final analysis if they had (a) fine needle aspiration cytology (FNAC) result showing benign or malignant lesion (b) underwent surgery for treatment of thyroid nodule with initial FNAC reported as nodule suspicious for malignancy, indeterminate or inadequate. Informed consent was obtained from all participants. Among 307 patients who participated in the study, 69 patients (9 males, 60 female) with 74 nodules were excluded from the study. They had non-diagnostic FNAC results such as inadequate cytology (n=22), indeterminate (n=14), follicular neoplasm (n=9), suspicious for malignancy (n=5), did not undergo surgery or FNAC (n=24). 238 patients (68 males, 170 females) with 272 nodules were included for the final analysis. Mean age was / years with a range of Page 2 of 29

3 16-82 years. Mean age of male patients was / years (range of years) and mean age of female patients was / years (range of years). Out of 238 patients, 207 patients had single nodule, 28 patients had two nodules and 3 patients had three nodules. Mean nodule size was 2.9 +/- 1.7 cm (range of 1 to 9.2 cm). Thyroid ultrasound: Ultrasound of the neck and thyroid gland was performed in two ultrasound machines TM TM (ACUSON S2000, Siemens and ACUSON Antares, Siemens) using a high frequency probe (7-11 MHz). Conventional and compound ultrasound was performed in all patients. Ultrasonography was performed by two radiologists with 8 years (A.C reader1) and 4 years (A.K - reader 2) experience, one after the other, blind to the findings of the other radiologist. Ultrasound features assessed for each nodule were composition (solid, cystic, mixed) Fig. 2 on page 6, echogenicity (hyperechoic, isoechoic, hypoechoic, markedly hypoechoic) Fig. 3 on page 7, margins (well defined with or without halo sign, microlobulated, ill-defined, irregular) Fig. 4 on page 7, presence of calcification (microcalcification, macrocalcification) Fig. 5 on page 9 and shape of the nodule (round, oval) Fig. 6 on page 8. Nodule with > 75% solid component were labeled as solid; cystic nodules had no solid components, mixed nodules had both solid and cystic areas with solid component constitution <75% of the size of the lesion. For mixed lesions echogenicity, margin, shape and presence of calcification was assessed for the solid component. Fig. 2 on page 6 Echogenicity was described in comparison with the thyroid gland and strap muscles. Lesion was considered hyperechoic if the echogenicity was more than thyroid gland; isoechoic if the echogenicity was equal to thyroid gland; hypoechoic if the echogenicity was equal to strap muscle and markedly hypoechoic if the echogenicity was lower than the stap muscle. Fig. 3 on page 7 Hypoechoic smooth rim around the nodule was considered as positive halo sign. Short cycle undulations of >3 along the margin was considered as microlobulated margin. Spiculated margin was considered as irregular while fussy margins were considered ill-defined. Calcification measuring less than 1 mm was defined as microcalcification and calcification more than 1mm was labeled as macrocalcification. Fig. 5 on page 9 Shape was described as round if anterio-posterior dimension was equal to greater than transverse dimension and nodule which is wider than tall was described as oval nodule. Fig. 6 on page 8 Findings that were considered to be favoring malignancy were hypoechoic Page 3 of 29

4 or markedly hypoechoic echogenicity; irregular, microlobulated or ill-defined margins; presence of microcalcification and round shape. In addition to describing the ultrasound features, a TIRADS category was assigned to the thyroid nodule as described by Kwak JY et al(12) by both the observers. Fig. 7 on page 9, Fig. 8 on page 10, Fig. 9 on page 11 shows examples of nodules in each TIRADS category. Another radiologist with 3 years experience (P.P - reader 3) retrospectively reviewed the images of the thyroid stored in picture archiving and communication system (PACS) and documented ultrasound features and TIRADS final assessment category for each thyroid nodule blind to the findings of other two radiologists, FNAC and histopathology reports. A common consensus was arrived after discussion among each other for nodules with discrepancy in the interpretation of the findings or assigned TIRADS category. Thyroid FNAC: FNAC was performed after thyroid ultrasound and time period between the ultrasound and the FNAC was 12 hours to 2 days. FNAC was performed by the surgeon for solid palpable thyroid nodules. In patients with dominant nodule of multi-nodular goiter, nodules to be subjected for FNAC were marked by the radiologist. Radiologists performed ultrasound guided FNAC for cystic, mixed solid and cystic nodules, non palpable nodules with suspicious ultrasound features and palpable thyroid nodule in which part of the nodule had features suspicious for malignancy. Aspiration was performed using 23 gauge needle attached to 5 ml syringe. Two to three aspirations were performed on each nodule. Cytology smears were prepared in three to six slides. Slides were fixed immediately in 95% alcohol and stained with Papinicolaou stain. Cytology technician was available to prepare the slides and to confirm adequacy of specimen. Cytology was reported by cytopathologists according to Bethesda system for reporting thyroid cytology. (15) Bethesda class II (benign) and Bethesda class VI (malignant) were considered as diagnostic cytology reports. Rest of the categories was considered non-diagnostic. Cytology was reported inadequate (Bethesda class I) if there were less than six clusters of cells with each cluster comprising of less than 10 cells. Cytology reported as atypical cells or follicular cells of indeterminate significance was classified as indeterminate cytology (Bethesda class III). Specimen rich in follicular cells or hurthle cells were classified as follicular neoplasm (Bethesda class IV). FNAC of nodules showing few abnormalities of carcinoma however did not fulfill criteria for diagnosis of carcinoma were classified as suspicious for malignancy (Bethesda class V). Page 4 of 29

5 Imaging findings and TIRADS category were compared with FNAC and surgical histopathology when available. Patients with non-diagnostic FNAC and not being planned for surgery had follow up ultrasound every 6 months. A nodule in which temporal stability was demonstrated with ultrasound follow up at one year follow up was considered benign even if FNAC was non diagnostic and patient did not undergo surgery. Total of nine nodules (six cystic and three hyperechoic nodules) were considered benign using temporal stability of ultrasound appearance of the nodules with no features suspicious for malignancy as a criteria for inclusion. Of these four nodules (2 hyperechoic and one cystic nodule) had non diagnostic cytology (bethesda class I - inadequate). Other five nodules, all cystic neither had cytology nor surgery, but were unchanged at 12 months follow up ultrasound. Statistical methods: IBM SPSS Analytics 16.0 software (Chicago, Ill., USA) and MedCalc - version was used for statistical analysis. The positive predictive value, likelihood ratio and odds ratio for malignancy for ultrasound features of thyroid nodules and final assessment categories was determined by using data from the assessments of all readers combined. Inter-rater reliability was measured using the kappa coefficient, and reported using a bootstrapped, bias-corrected method with 95% confidence interval (Reichenheim, 2004; Carpenter and Bithell, 2000). Kappa is scaled such that zero is the amount of agreement that would be expected by chance and one is perfect agreement. Kappa was interpreted according to guidelines laid by Landis and Koch.(16) Images for this section: Page 5 of 29

6 Fig. 1: Study population Page 6 of 29

7 Fig. 2: Ultrasound of thyroid demonstrating nodules of different composition a. Cystic nodule b. Solid nodule c. Mixed solid and cystic nodule. Fig. 3: Ultrasound of thyroid demonstrating nodules of different echogenecity. a. Hyperechoic when nodule more echogenic than thyroid gland b. Isoechoic when echogenecity is same as thyroid gland c. Hypoechoic when nodule is isoechoic to adjacent strap muscle d. Markedly hypoechoic when nodule is hypoechoic compared to strap muscle Page 7 of 29

8 Fig. 4: Ultrasound of thyroid demonstrating nodules of different margins. a. Nodule with well defined margin and hypoechoic halo b. Nodule with well defined margin and without a hypoechoic halo c. Ill-defined margin d. Irregular margin Page 8 of 29

9 Fig. 6: Ultrasound of thyroid demonstrating nodule of a. Oval shape and b. Round shape. Fig. 5: Ultrasound macrocalcification. of thyroid demonstrating a. microcalcification and b. Page 9 of 29

10 Fig. 7: TIRADS 2 - benign thyroid nodules. (a) Well defined, oval, solid, hyperechoic nodule with seeve or honey comb like pattern (b) Cystic nodule with comet tail artifacts (c) Simple cystic nodule (d,e) cystic nodule with thin internal septa (f) Hyperechoic oval nodule with positive halo sign Page 10 of 29

11 Fig. 8: TIRADS 3 - probably benign nodules. (a,b) Homogeneous isoechoic, solid, oval thyroid nodules with well defined margins and no calcification which were nodular hyperplasia on histology. (c-e) Isoechoic, solid, oval nodules with heterogeneous echotexture and no calcification. (c and d) were nodular hyperplasia while nodule displayed in panel (e) was a follicular variant of papillary carcinoma. Page 11 of 29

12 Fig. 9: TIRADS 5 - highly suggestive of malignancy. These nodules demonstrate more than three features of malignancy (hypoechoic or markedly hypoechoic, ill-defined or irregular margins, microcalcification, taller than wide shape). Page 12 of 29

13 Table 1: Histopathology of 168 nodules treated with surgery. Page 13 of 29

14 Results Results Out of 272 nodules (right lobe- 134, isthmus - 11, left lobe -127) in 238 patients, 154 nodules were benign (119 nodules in females, 35 nodules in males) and 118 nodules were malignant (75 nodules in females, 43 nodules in males). Malignancy was more common among male patients presenting with thyroid nodule (p=0.01). There was no significant difference in the mean age of patients with benign (mean age was /12.7 years) and malignant thyroid nodules (mean age was / years), p= There was no significant difference in the age of male and female patients with benign nodules (p=0.712). However among patient with malignant thyroid nodules, men (mean age was / years) were significantly older than women (mean age was /- 12 years), p=0.01. Size of the benign nodules (mean of 4.2 +/- 2.7 cm range of cm) were significantly larger than the malignant nodules (mean of 2.3 +/-1.9 cm, range of cm), p = Total of 168 (56 benign and 112 malignant) nodules were treated with surgery and Table 1 on page 15 gives the histopathology of these nodules. Out of a total of 282 nodules which were subjected to FNAC, surgical histopathology was available in 141 nodules. Table 2 on page 16 shows the performance of FNAC when compared to surgical histopathology. Frequency of ultrasound findings in thyroid nodules according to TIRADS descriptors is given in Table 3 on page 17. Vascularity was assessed in 182 nodules, 40 had central vascularity and rest showed peripheral vascularity. Of them 10 (0.3%) of benign nodules and 30 (16.4%) malignant nodules showed central vascularity; 95 (52.1%) of benign nodules and 47 (25.8%) of malignant nodules showed peripheral vascularity. Difference in the pattern of vascularity between benign and malignant nodules was statistically significant, chi square = 22.4, p < There were neck nodes along with 45 (16.5%) nodules. Five (3.2%) benign nodules had associated significant neck nodes and 40 (35%) of malignant nodules had significant neck nodes. Positive predictive value of TIRADS: Table 4 on page 18 summarizes the TIRADS category of the nodules, cytology diagnosis and surgical histopathology results of patients who underwent surgery. Table 5 on page 19 shows the distribution of benign and malignant nodules in each TIRADS categories with positive predictive value (PPV), positive likelihood ratio and odds ratio. Positive predictive value for malignancy was 6.6%, 32%, 36%, 64%, 59% and 91% for TIRADS 2, 3, 4a, 4b, 4c and 5 categories respectively. Diagnostic performance of TIRADS considering category 4b, 4c and 5 as malignant and category 2, 3 and 4a as benign is as follows: Sensitivity = 60.2%, specificity = 85.1%, PPV = 75.5%, NPV = 73.6% and accuracy = 74.2%. Diagnostic performance of TIRADS considering category 4a, 4b, 4c Page 14 of 29

15 and 5 as malignant and category 2 and 3 as benign is as follows: Sensitivity = 72%, specificity = 68.8%, PPV = 63.9%, NPV = 76.2% and accuracy = 70.2%. Inter-observer agreement for ultrasound features of thyroid nodules and TIRADS: Inter-observer agreement for reproducibility of ultrasound features of thyroid nodules and assigning TIRADS category is given in Table 6 on page 20. In general agreement between observers 1 and 2 who prospectively assessed the thyroid nodules is better than between observers 3 and 1 and observers 3 and 2. Agreement was good between observers for assessment of calcification (k=0.577); fair for composition (k=0.425), shape (k=0.436) and margins (k=0.412) of the thyroid nodules. Agreement was poor for echogenecity (k=0.299) of thyroid nodules. Overall agreement was good between observers (k = 0.569) for assigning TI-RADS category to the thyroid nodules. However, inter-observer agreement for each category of TIRADS was variable (Table 7 on page 21) with good agreement for combined TIRADS category 4c and 5 (k=0.685, p<0.001); poor for TI-RADS category 4a (k=0.201, p<0.001) and 4b (k=0.164, p<0.001) categories and fair for the rest. Images for this section: Page 15 of 29

16 Table 1: Histopathology of 168 nodules treated with surgery. Page 16 of 29

17 Table 2: Performance of FNAC when compared to surgical histopathology in 141 nodules in patients who underwent both FNAC and surgery. Page 17 of 29

18 Table 3: Frequency of ultrasound features of thyroid nodules according to TIRADS descriptors. Page 18 of 29

19 Table 4: Distribution of benign and malignant thyroid nodules in each TIRADS categories with positive predictive value for malignancy (PPV), positive likelihood ratio (LR+), odds ratio and 95% Confidence Interval (CI) Page 19 of 29

20 Table 5: Summary of ultrasound TIRADS category, cytology diagnosis and surgical histopathology for patients who underwent surgery. Note: *Benign nodules: Adenomatous hyperplasia - AH; Cyst with hemorrhage - CH, nodular hyperplasia - NH; Follicular adenoma - FH; Hurtle cell adenoma - HA; Hashimoto thyroiditis - HT **Malignant nodules: papillary carcinoma - PC; follicular variant of papillary carcinoma - FV; poorly differentiated carcinoma - PD; microscopic foci of papillary carcinoma - MPC; medullary carcinoma - MC; Anaplastic carcinoma - AC; lymphoma - LY Number of lesions is next to the hyphen. Page 20 of 29

21 Table 6: Inter-observer agreement between observers for ultrasound findings. Page 21 of 29

22 Table 7: Inter-observer agreement between observers for TIRADS. Page 22 of 29

23 Table 8: Comparison of diagnostic performance of the various ultrasound classification systems for assessing thyroid nodules. Page 23 of 29

24 Conclusion Fitted probablity of thyroid cancer and the risk of malignancy quoted by Kwak JY et al(12) in their study for TI-RADS was like BI-RADS for breast lesions ie. 0% for TIRADS 2; 1.7% for TIRADS 3; 3.3% for TIRADS 4a, 9.2% for TIRADS 4b, % for TIRADS 4c and 87.5% for TIRADS 5.(12) However, the positive predictive value for malignancy found in our study using TI-RADS as described by Kwak JY et al(12) was 6.6%, 32%, 36%, 64%, 59% and 91% for TI-RADS 2, 3, 4a, 4b, 4c and 5 categories respectively. The diagnostic accuracy of TIRADS as described by Kwak JY et al was 70.2%. Accuracy increased to 74.2% when nodules with one suspicious ultrasound feature was considered to be probably benign (TIRADS 3) instead of low risk for malignancy (TIRADS 4a). Most thyroid cancers which were assigned TIRADS 2, 3 (Fig. 8 on page 25) and 4a were follicular variant of papillary carcinoma on histopathology. Table 8 on page 25 shows the diagnostic performance of TIRADS as found in our study when compared to various other ultrasound classification systems available for assessing thyroid nodules. Interobserver agreement for ultrasound descriptors of thyroid nodules were mostly fair to good. Overall, agreement between observers for assigning TIRADS category was good, though there was poor agreement between observers for assigning TIRADS 4a and 4b to the thyroid nodules. Thus, TIRADS as described by Kwak JY et al is a simple and useful method of assessing thyroid nodules and can be used in a teaching hospital. Limitations: 1. Only two of the three observers could prospectively evaluate the thyroid nodules. Third observer retrospectively reviewed the ultrasound images from PACS. 2. There were more number of malignant nodules in our study. This is probably because the study was conducted in a tertiary care institution. 3. Observers had variable experience in interpreting thyroid nodules. Thus the results are more applicable for a tertiary care teaching set up and may not be applicable for highly specialised thyroid units. Page 24 of 29

25 Images for this section: Table 8: Comparison of diagnostic performance of the various ultrasound classification systems for assessing thyroid nodules. Page 25 of 29

26 Fig. 8: TIRADS 3 - probably benign nodules. (a,b) Homogeneous isoechoic, solid, oval thyroid nodules with well defined margins and no calcification which were nodular hyperplasia on histology. (c-e) Isoechoic, solid, oval nodules with heterogeneous echotexture and no calcification. (c and d) were nodular hyperplasia while nodule displayed in panel (e) was a follicular variant of papillary carcinoma. Page 26 of 29

27 Personal information Anuradha Chandramohan, MD,DNB,FRCR Department of Radiology, Christian Medical College, Vellore, India anuradhachandramohan@gmail.com Abhishek Khurana, DMRD Department of Radiology, Christian Medical College, Vellore, India drabhishekkhurana@gmail.com B. Pushpa, DNB Department of Radiology, Christian Medical College, Vellore, India docpushpa@gmail.com A. Deepak, MS, PhD Department of Endocrine Surgery, Christian Medical College, Vellore, India abrahamdt@gmail.com Paul MJ, MS Department of Endocrine Surgery, Christian Medical College, Vellore, India mjpaul@cmcvellore.ac.in References 1. Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population. J Indian Med Assoc Feb;107(2): Brahmbhatt SR, Brahmbhatt RM, Boyages SC. Impact of protein energy malnutrition on thyroid size in an iodine deficient population of Gujarat (India): Is it an aetiological factor for goiter? Eur J Endocrinol Jul;145(1):11-7. Page 27 of 29

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