International Journal of Surgical Pathology

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The Use of the Bethesda Terminology in Thyroid Fine-Needle Aspiration Results in a Lower Rate of Surgery for Nonmalignant Nodules: A Report From a Reference Center in Turkey Yasemin Ozluk, Esmehan Pehlivan, Mine G. Gulluoglu, Arzu Poyanli, Artur Salmaslioglu, Nese Colak, Yersu Kapran and Dilek Yilmazbayhan INT J SURG PATHOL published online 26 July 2011 DOI: 10.1177/1066896911415667 The online version of this article can be found at: http://ijs.sagepub.com/content/early/2011/07/08/1066896911415667

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415667 et alInternational Journal of Surgical Pathology

IJSXXX10.1177/1066896911415667Ozluk

The Use of the Bethesda Terminology in Thyroid Fine-Needle Aspiration Results in a Lower Rate of Surgery for Nonmalignant Nodules: A Report From a Reference Center in Turkey

International Journal of Surgical Pathology XX(X) 1–11 © The Author(s) 2011 Reprints and permission: http://www. sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896911415667 http://ijs.sagepub.com

Yasemin Ozluk, MD1, Esmehan Pehlivan, MD1, Mine G. Gulluoglu, MD1, Arzu Poyanli, MD1, Artur Salmaslioglu, MD1, Nese Colak, MD1, Yersu Kapran, MD1, and Dilek Yilmazbayhan, MD1,

Abstract The Bethesda system (BS) for reporting thyroid fine-needle aspiration (FNA), which classifies nodules as nondiagnostic (ND), benign (B), atypia/follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm (SFN/ FN), suspicious for malignancy (SFM), or malignant (M), uses clinically valuable management guidelines. The authors employed a similar in-house classification system (IS) for thyroid FNAs, using the categories of ND, B, suspicious follicular cells (SFC), follicular lesion/neoplasm (FL/FN), SFM, and M. The authors compared IS and BS, and assessed the utility of BS in clinical practice. A total of 581 nodules with cytological/histological follow-up were examined and indeterminate lesions by BS were reclassified. The sensitivity and specificity for malignancy using IS were similar to that of BS (77% vs 99%). However, when SFN/FN and SFM were both considered positive, the results for IS and BS were as follows: sensitivity, 85% versus 85%; specificity, 87% versus 94%; and diagnostic accuracy, 86% versus 90%, respectively. Discrepancies between cytological and histological data were evident in 35 cases among all categories of BS except AUS/FLUS. The rate of surgery for nonmalignant nodules was lesser (20% vs 9%) by BS. Among 34 AUS/FLUS cases with follow-up data, hypocellularity was the case in 11 (46%) nonneoplastic and 10 (100%) neoplastic nodules. The use of BS results in a lower rate of surgery for nonmalignant nodules even though patients with borderline cytopathologic features are still encountered. AUS/FLUS category can be separated into subgroups according to the factors causing difficulties in the interpretation. There is a need of accumulation of AUS/FLUS cases to do further evaluations and studies. Keywords thyroid, fine-needle aspiration, cytopathology, Bethesda system, reporting

Introduction Thyroid fine-needle aspiration (FNA) is a well-established procedure used in diagnosis of thyroid nodules. FNA allows classification of nodules as benign or malignant, and patients with malignant nodules are scheduled for surgery.1,2 Various organizations have provided diagnostic guidelines for reporting of thyroid FNA results, but communication difficulties between pathologists and clinicians continue to exist.3-5 For example, Redman et al6 reported that pathologists use various diagnostic categories and that clinicians differ in their perceptions of pathology reports. Thus, there is a need for a classification system that considers

communication and collaboration between pathologists and clinicians; the method must employ evidence-based clinical management. At the National Cancer Institute (NCI) Thyroid FNA State-of-the-Science Conference (October 2007), various aspects of thyroid FNA were discussed by 6 committees.7 Committee IV was responsible for diagnostic terminology 1

Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Corresponding Author: Yasemin Ozluk, Istanbul Tip Fakultesi, Temel Tip Bilimleri Binasi, Patoloji AD, 34390 Capa-Fatih, Istanbul, Turkey Email: [email protected]


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International Journal of Surgical Pathology XX(X)

and for establishing the morphological criteria of thyroid FNA.8 The proposed 6-tier system for classification of thyroid FNA included the following diagnostic categories: nondiagnostic (ND), benign (B), atypia of undetermined significance or a follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm/ follicular neoplasm (SFN/FN; including Hurthle cell lesions), suspicious for malignancy (SFM), and malignant. The criteria and explanatory notes for each category were subsequently published in an atlas.9 The most problematic lesions in thyroid cytopathology are those with focal cellular atypia, a high degree of cellularity, scant colloid, and a predominance of microfollicles.10-13 The similarity of morphologic features between benign and malignant follicular lesions causes discrepancies among cytological and histological data when follicular patterned lesions are examined. The Bethesda reporting system classifies thyroid follicular lesions showing microfollicle predominance and lack of colloid into the suspicious for follicular neoplasm category. This system allows patients showing focal atypia to undergo repeat aspiration opposed to surgery. However, patients with repeated AUS/FLUS diagnoses will usually go for surgery given that the rate of malignancy approaches 20%.9 Our institution used a similar 6-tier system before adopting the 2007 proposal of the NCI, although there were some differences in both terminology and diagnostic criteria (described in the Materials and Methods section). In the present study, we compare our in-house reporting system with the new Bethesda classification. Our specific questions were as follows:

Medicine, Istanbul University, between January 2004 and December 2007. A total of 581 nodules from 515 patients, who had received either histologic or cytologic follow-up, were included. In patients with multiple nodules, data on each aspirated nodule were included. Patient age, gender, nodule size, and nodule location (lobe or isthmus of the thyroid) were recorded when possible. In patients who had experienced multiple aspirations of the same nodule, the FNA with higher diagnostic category and histological follow-up data were considered. On-site evaluation is routinely performed on most thyroid aspiration samples taken at our institution. FNA was performed by an endocrinologist or radiologist under ultrasound guidance using a 25-gauge needle. One to two slides for each nodule were stained with hematoxylin–eosin for the evaluation of specimen adequacy. All other slides were subjected to Papanicolau staining after 95% (v/v) alcohol fixation and Romanowsky staining after air drying. The needle was washed with 50% (v/v) alcohol prior to cell block preparation. In our department, a classification scheme similar to that developed by the NCI Thyroid Fine-Needle Aspiration Stateof-the-Science Conference (Bethesda) was in use for thyroid FNA specimens until the 2007 Bethesda classification was promulgated. Our categories were as follows: 1, nondiagnostic; 2, benign cytology; 3, suspicious follicular cells; 4, follicular lesion or neoplasia; 5, suspicious for malignancy; and 6, malignant. All patients were classified by the Bethesda system, and definite diagnoses were used whenever possible in the present report. Our detailed criteria were as follows:

1. Does the new classification offer any advantages (compared to our existing system) in reporting thyroid FNA results and facilitating clinical management in routine practice? 2. Do the new detailed diagnostic morphologic criteria resolve problems with the classification of indeterminate lesions? 3. Is the new classification better than our in-house system when used to triage patients with thyroid nodules?

1. Nondiagnostic (ND): The adequacy criteria used were 6 to 10 clusters of well-preserved follicular cells with 10 to 20 cells per group, on 2 different slides.14 Patients who did not fulfill these criteria, and who did not show cytologic atypia, were classified as nondiagnostic. 2. Benign cytology (B): Nodules categorized as benign had abundant colloid, mixed follicular and Hurthle cells in mostly macrofollicular patterns, and no cytologic or architectural atypia. Aspirations with accompanying abundant lymphocytic infiltration, a finding compatible with diagnosis of chronic lymphocytic thyroiditis (CLT), were included in this category. 3. Suspicious follicular cells (SFC): This category was used for patients showing focal cellular atypia with chromatin clearing and/or crowding, and/or nuclear overlapping, that were not sufficient for a diagnosis of papillary thyroid carcinoma (PTC). Those showing cellular groups with macrofollicular patterns, enlarged nuclei, prominent nucleoli, vesicular chromatin with/without nuclear irregularities,

We reviewed all thyroid FNAs with histological followup that were diagnosed in our department between 2004 and 2007. We also performed a detailed analysis of instances where cytology and histology results were discordant, to identify possible sources of error in classification.

Materials and Methods Our data were acquired from a retrospective computerized search of data on all thyroid FNA patients (n = 3444) interpreted at the Department of Pathology, Istanbul Faculty of


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Ozluk et al. atypical spindle cells with a suspicion of a cystic cavity, and reactive changes, were included in this category. Colloid was described as scant, compact, or dark-stained. Patients with low cellular material with mild cellular atypia, or a moderate-to-high cellular material, with 3-dimensional grouping and/ or microfollicles, were included in this category. 4. Follicular lesion or neoplasia (FL/FN): Patients showing cellular material with crowding and overlapping without or with scant colloid, including those with Hurthle cell differentiation, were placed in this category. Patients with more microfollicular than macrofollicular cells, and with the presence of remarkable discohesive cells, were also included. 5. Suspicious for malignancy (SFM): This category included patients showing evidence of malignancy but lacking in some features of any specific type of malignant thyroid tumor, usually PTC. Some patients showing a predominant monotonous microfollicular pattern were included in this category, with suspicion of a follicular carcinoma. 6. Malignant: Patients showing typical features of any type of thyroid malignancy were placed in this grouping. The diagnoses included PTC, follicular thyroid cancer (FC), medullary thyroid cancer (MC), and other thyroid cancers. Discrepancies in the classification of indeterminate follicular lesions are evident in the literature, and we therefore reevaluated patients placed in categories 3 (SFC), 4 (FL/ FN), and 5 (SFM), and reclassified these patients according to the Bethesda method, which features well-defined cytologic criteria for each category within a 6-tiered system.8 The reevaluation of the slides was made by 2 experienced cytopathologists (DY, YO) who were blind to histologic data and previous cytologic category. Discordant cases were discussed and a mutual decision was made for each discordant case. The Bethesda categories are nondiagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm/follicular neoplasm (SFN/FN), suspicious for malignancy (SFM), and malignant. Cytologic or histologic follow-up was used as the gold standard for evaluation of cytologic diagnosis. Rates of malignancy (positive predictive values [PPVs]) were calculated for each diagnostic category, as were sensitivity and specificity. Data on patients showing discrepancies between cytologic and histologic diagnoses were reanalyzed to determine the possible reasons for error. All findings were entered into a computerized database. χ2 analysis and Student’s t test were performed, as appropriate, to identify significant differences between diagnostic and clinical findings.

Table 1. Demographic Data on 581 Nodules From 515 Patients n (%) Age in years (n = 503) Gender (n = 515) Female Male Nodule diameter (mm) (n = 410) Localization (n = 424) Right lobe Left lobe Isthmus Follow-up (n = 581) Histology Cytology

Mean ± SD

Median

50.4 ± 13.2

52 18

421 (82) 94 (18) 20.8 ± 13

218 (51) 179 (42) 27 (7) 442 (76) 139a (24)

a

Reaspirations from 122 nodules.

Results Demographic Data We examined 581 nodules from 515 patients, all of whom had cytological or histological follow-up (Table 1). Among the 581 nodules, histological follow-up data were available for 442. The other 139 biopsies, featuring reaspirations from 122 nodules, were examined by cytological follow-up only. In all, 94 patients (18%) were male and 421 (82%) were female. Nodule diameters were calculated from ultrasound data in the pathology reports. The mean nodule diameter was 20.8 ± 13.03 mm (median = 18 mm; range = 3.5-90 mm; n = 410). Of all nodules, 218 (51%) were in the right lobe, 179 (42%) in the left lobe, and 27 (7%) in the isthmus.

Cytologic Diagnoses According to the In-House and Bethesda Reporting Systems The overall distribution of cytologic diagnoses using our in-house system was as follows: 67 (11.5%) nondiagnostic, 284 (48.9%) benign, 57 (9.8%) SFC, 55 (9.4%) FL/FN, 38 (6.5%) SFM, and 80 (13.8%) malignant. We reclassified patients with follicular patterned lesions, and who were in the suspicious categories (SFC, FL/FN, and SFM), using the Bethesda system. Of the 57 diagnoses of SFC, Bethesda diagnosis classified 20 as benign, 25 as AUS/FLUS, 2 as SFN, and 10 as SFM (Figure 1). For the 55 diagnoses of FL/FN, the Bethesda system classified 13 as benign, 6 as AUS/FLUS, 33 as SFN/FN, and 3 as SFM. For the 38 diagnoses of SFM, the Bethesda method classified 2 as benign, 3 as AUS/FLUS, 2 as SFN/FN, 30 as SFM, and 1 as malignant. Thus, the overall distribution of cytologic diagnoses based on the Bethesda classification was as follows: 36 (8.1%) nondiagnostic, 223 (50.5%) benign, 25 (5.7%) AUS/FLUS, 35 (7.9%) SFN, 42 (9.5%)


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International Journal of Surgical Pathology XX(X) was diagnosed as SFM based on data from 2 aspirations before surgery.

Patients With Only Cytological Follow-Up

Figure 1. Changes in diagnoses of patients with follicular patterned or suspicious lesions made using our in-house reporting system when the Bethesda criteria were employed (n = 150)

Abbreviations: SFC, suspicious follicular cells; FL/FN, follicular lesion/ follicular neoplasm; AUS/FLUS, atypia/follicular lesion of undetermined significance; SFN/FN, suspicious for follicular neoplasm/follicular neoplasm; SFM, suspicious for malignancy.

SFM, and 81 (18.3%) malignant (Table 2). Two cytomorphologic examples of cases that displayed changes in diagnostic category for two reporting systems are shown in Figure 2.

Histologic Follow-Up Among the 442 thyroidectomy samples, 253 (57%) were benign and 177 (40%) malignant. However, in 12 patients (3%), histology indicated that the tumor could not be considered either benign or malignant, so the diagnosis was follicular thyroid tumor of uncertain malignant potential (TT-UMP). Of the 253 benign lesions, 72 (29%) were follicular adenoma/adenomatoid nodules, 105 (42%) hyperplastic nodules, 11 (4%) chronic lymphocytic thyroiditis (CLT), 64 (25%) goiter and CLT, and 1 paraganglioma. Of the 177 malignant tumors, 144 (83%) were papillary carcinoma (PTC), 6 (3%) follicular carcinoma (FC), 7 (4%) differentiated thyroid carcinoma not otherwise specified (DTCNOS), 7 (4%) medullary carcinoma (MC), 2 (1%) poorly differentiated carcinoma (PDC), 2 (1%) undifferentiated (anaplastic) thyroid carcinoma (ATC), 5 (3%) metastases, and 1 (1%) lymphoma. A total of 10 patients underwent at least one repeat aspiration before thyroidectomy. Four of these patients had benign lesions, as shown by all aspiration data and also after thyroidectomy. Cytology classified 5 lesions as higher class and histological follow-up indicated the presence of neoplasms, 4 of which were malignant. One malignant lesion

Among the 122 nodules that were followed-up by cytology only, 29 were originally classified as nondiagnostic, 80 B, 9 SFC, 2 FL/FN, and 2 SFM. Reclassification revealed 1 B and 9 AUS/AFLUS out of 13 initially suspicious lesions (including SFC, FL/FN, and SFM). Among the 29 nondiagnostic aspirations, 4 (14%) were diagnosed as nondiagnostic, 22 (76%) as benign, 1 (3%) as AUS/AFLUS, and 2 (7%) as SFN/FN in the follow-up aspiration. A total of 80 nodules that appeared benign on examination of initial aspirations were also benign on follow-up aspiration. Nine AUS/FLUS nodules were benign on repeat aspiration. Benign diagnoses on repeat aspiration were seen for 4 patients, 2 of whom had initially been diagnosed with SFN/FN and 2 with SFM.

Correlation Between Cytological and Histological Data Table 2 shows the distribution of histological follow-up diagnoses according to the Bethesda system for the 442 thyroidectomy patients. The malignancy rates of nodules in various Bethesda categories were as follows: 25% for nodules nondiagnostic, 10% for benign, 36% for AUS/FLUS, 66% for SFN/FN, 81% for SFM, and 95% for malignant (Table 2). In the AUS/FLUS category, when data on patients with only cytologic follow-up were added, the final PPV was 27%. Table 3 compares the 2 diagnostic schemes in terms of malignancy prediction for patients with follicular patterned lesions, and nodules in suspicious categories, based on histological follow-up data (n = 137). When cytologic diagnostic categories were employed, including the “follicular lesions,” “SFM,” and “malignant” categories of our in-house and Bethesda reporting systems, benign histologic diagnoses were evident in 34 (20%) and 15 patients (9%), respectively (Figure 3). This indicates that the use of the Bethesda system would lead to lesser number of patients who underwent surgery for nonmalignant nodules than would our in-house system. Sensitivity and specificity analyses were performed in 2 ways. First, we included only patients in the benign and malignant categories, as shown by both cytology and histology, and thus did not include those with TT-UMP. In this analysis, the sensitivity of both classification systems was 77% and the specificity 99%. Second, we included FL/FN and SFM patients as positive in both classification systems, and also considered TT-UMP to be histologically positive. In this analysis, the in-house and Bethesda sensitivities were 85% versus 85%; the specificities 87% versus 94%; the PPVs 78% versus 89%; the negative predictive values (NPVs) 91% versus 92%; and the diagnostic accuracies 86% versus 90% (Table 4).


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Ozluk et al. Table 2. Classification of the 442 Patients for Whom Histological Follow-Up Data Were Available, Based on the Bethesda Reporting System

Nondiagnostic Benign AUS/FLUS SFN/FN SFM Malignant

Total n (% of all cases)

Benign n (% of each cytologic category)

Malignant n (% of each cytologic category)

36 (8) 223 (51) 25 (6) 35 (8) 42 (9) 81 (18)

25 (69) 198 (89) 15 (60) 6 (17) 7 (17) 2 (2)

9 (25) 22 (10) 9 (36) 23 (66) 34 (81) 77 (95)

Unknowna n (% of each cytologic category) 2 (6) 3 (1) 1 (4) 6 (17) 1 (2) 2 (3)

Abbreviations: AUS/FLUS, atypia/follicular lesion of undetermined significance; SFN/FN suspicious for follicular neoplasm; SFM, suspicious for malignancy. a Unknown lesions are nodules diagnosed as follicular thyroid tumors of uncertain malignant potential (TT-UMP).

Figure 2. (A and B) This thyroid fine-needle aspiration (FNA) was interpreted as suspicious follicular cells due to hypercelluarity, the presence of cellular enlargement, and mild irregular nuclear contours by the in-house reporting system. However, reevaluation by the Bethesda reporting system resulted in a benign diagnosis. (C and D) The interpretation of this FNA specimen revealed a diagnosis of a follicular lesion/neoplasm by the in-house system. There were loosely cohesive microfollicles formed by enlarged follicular cells. Because of a lack of microfollicle predominance, cellular crowding, and overlapping, criteria that were overinterpreted in initial reading, this case was called as benign by the Bethesda system. Histologic follow-up of both cases displayed a hyperplastic nodule in thyroidectomy (Papanicolau stain 400×)


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Table 3. Distribution of Follicular Patterned and Suspicious Lesions in Patients for Whom Histological Follow-Up Data Were Available (n = 137), Based on Cytologic Diagnoses Using the In-House and Bethesda Reporting Systems Cytologic Diagnosis In-House Reporting System SFC (n = 48) FL/FN (n = 53) SFM

Histologic Diagnosis; n (%) Bethesda Reporting System

Total

Benign

Malignant

Benign AUS/FLUS SFN SFM Total Benign AUS/FLUS SFN SFM Total Benign AUS/FLUS SFN SFM Malignant Total

19 (40) 17 (35) 2 (4) 10 (21) 48 (100) 13 (25) 6 (11) 31 (59) 3 (5) 53 (100) 2 (6) 2 (5) 2 (5) 29 (81) 1 (3) 36 (100)

18 (95) 8 (47) 1 (50) 2 (20) 29 (60) 13 (100) 5 (83) 5 (16) 0 (0) 23 (44) 2 (100) 2 (100) 0 (0) 5 (17) 0 (0) 9 (25)

0 (0) 8 (47) 1 (50) 7 (70) 16 (34) 0 (0) 1 (17) 21 (68) 3 (100) 25 (47) 0 (0) 0 (0) 1 (50) 24 (83) 1 (100) 26 (72)

Unknowna 1 (5) 1 (6) 0 (0) 1 (10) 3 (6) 0 (0) 0 (0) 5 (16) 0 (0) 5 (9) 0 (0) 0 (0) 1 (50) 0 (0) 0 (0) 1 (3)

Abbreviations: SFC, suspicious follicular cells; FL/FN, follicular lesion/neoplasm; AUS/FLUS, atypia/follicular lesion of undetermined significance; SFN/ FN, suspicious for a follicular neoplasm/follicular neoplasm; SFM, suspicious for malignancy. a Unknown lesions are nodules diagnosed as follicular thyroid tumors of uncertain malignant potential (TT-UMP).

Table 4. Comparison of In-House and Bethesda Reporting System Diagnoses in the Identification of Thyroid FNAs as Neoplasmsa

Sensitivity (%) Specificity (%) PPV (%) NPV (%) Diagnostic accuracy (%)

Figure 3. Malignancy rates in the suspicious and malignant cytologic categories diagnosed using both the in-house and Bethesda reporting systems. Note the decrease in the proportion of surgeries for nonmalignant nodules when the Bethesda reporting system is employed (20% vs 9%).

Abbreviations: FL/FN, follicular lesion/follicular neoplasm; SFN/FN, suspicious for follicular neoplasm/follicular neoplasm; SFM, suspicious for malignancy.

Evaluation of Discrepancies Of the 35 nodules for which cytologic findings and histological follow-up data showed discrepancies, 22 were cytologically benign but histologically malignant, 16 of which were

In-House Reporting System

Bethesda Reporting System

85 87 78 91 86

85 94 89 92 90

Abbreviations: FNA, fine-needle aspiration; PPV, positive predictive value; NPV, negative predictive value. a The analysis included patients with follicular patterned lesions and suspicious for malignancy as showing positive cytologic diagnoses, similar to that of the malignant category, for both reporting systems; histologic diagnoses of follicular thyroid tumor of uncertain malignant potential (TT-UMP) were also included as neoplasms. Instances of atypia of undetermined significance/follicular lesion of undetermined significance were not included.

identified as PTC, 2 as FC, 1 as DTCNOS, 2 as MC, and 1 as PDC in a papillary carcinoma background (Figure 4A). An additional three instances of benign cytology were diagnosed as TT-UMP on histological follow-up. A review of these data indicated that material was inadequate in 8 instances,


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Ozluk et al.

Figure 4. Distribution of the histologic diagnoses of patients showing discrepant features, according to the Bethesda terminology

Abbreviations: PTC, papillary thyroid carcinoma; FC, follicular carcinoma; DTCNOS, differentiated thyroid carcinoma not otherwise specified; MC, medullary carcinoma; PDC, poorly differentiated carcinoma; FVPC, follicular variant of papillary carcinoma; DSVPC, diffuse sclerosing variant papillary carcinoma; CVPC, classic variant papillary carcinoma; HN, hyperplastic nodule; FA, follicular adenoma; CLT, chronic lymphocytic thyroiditis.

very focal cellular atypia was evident in 7, technical artifacts were apparent in 2, and interpretation errors were evident in 5 instances. Overall, 24 cases (15 with histologic, 9 with cytologic follow-up) out of 34 in AUS/FLUS category were detected to be benign and among 10 cases all with histologic followup 9 were malignant and 1 was TT-UMP. Hypocellularity was the case in 46% (11/24) of nonneoplastic and 100% (10/10) of neoplastic nodules. The remaining benign nodules displayed excessive blood and/or technical artifacts and/or mild cytologic atypia in a very few cells. Six nodules in the SFN/FN group were classified as benign based on data obtained after thyroidectomy; 3 had CLT in the thyroid tissue and 3 showed the dominant nodules of multinodular goiter (Figure 4B). The cytological findings that resulted in SFN/FN diagnoses in these instances were high cellularity; predominance of a microfollicular pattern; and the presence of scant, dark, thick colloid. We also found that Hurthle cell differentiation sometimes accompanied CLT. Seven nodules in the SFM category were benign, based on data obtained after thyroidectomy; 3 were hyperplastic;

1 was a CLT; and 3 were FA (Figure 4C). A review of the microscopy data from these post-thyroidectomy samples indicated that some nodules featured hyalinization, calcification, and intracystic papillary hyperplasia. Two nodules in the malignant category had benign lesions on follow-up. The reactive changes in the nodules were the same as seen in the instances of discrepancy within the SFN category.

Patient Age, Nodule Size, and Malignancy Analysis of the relationship between patient age and malignancy indicated that malignancy rates were greater in patients younger than 40 years (P < .001; Table 5). The mean ages of patients with benign and malignant nodules were 52.4 ± 11 and 47.9 ± 15 years, respectively (P < .001). The mean diameter of benign and malignant nodules was 23.3 ± 13.2 and 18.9 ± 13 mm, respectively (P > .05). There was no significant difference in diameter between the diagnostic categories of the Bethesda system, and no significant difference in malignancy rate was evident between men and women (57% and 60%, respectively; P > .05).


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Table 5. Age and Nodule Size in Benign and Malignant Lesions n Age (years)a ≤40; n (%) >40; n (%) Age (mean ± SD) Nodule size in mm (mean ± SD)

81 (100) 339 (100) 420 299

Benign 29 (36) 223 (66) 52.4 ± 11 23.3 ± 13.2

Malignant

P

52 (64) 116 (34) 47.9 ± 15 18.9 ± 13