|Year : 2015 | Volume
| Issue : 3 | Page : 617-622
A correlative study of solitary thyroid nodules using the bethesda system for reporting thyroid cytopathology
P Arul, Suresh Masilamani
Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur, Tamil Nadu, India
|Date of Web Publication||9-Oct-2015|
Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur - 621 113, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Fine needle aspiration cytology (FNAC) is a useful diagnostic modality in the evaluation of solitary thyroid nodules (STN). It can differentiate between benign and malignant lesions in most cases.
Aim: This study was undertaken to determine the utility and diagnostic accuracy of FNAC in the evaluation of STN.
Materials and Methods: In this retrospective study, a total number of 483 thyroid FNACs were retrieved, out of which 209 cases of STN were chosen for this study. The Bethesda system for reporting thyroid cytopathology (TBSRTC) was used for analysis. Their FNACs diagnoses were compared with histopathological diagnoses.
Results: Among 209 FNACs, 88 (42.1%) had non-neoplastic lesions, 6 (2.9%) had atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS), 52 (24.9%) had follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), 33 (15.8%) were suspicious for malignancy and 18 (8.6%) had malignant cytology. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of FNAC in STN cases were 94.4%, 97.6%, 95.8%, 98.1% and 93.2% respectively.
Conclusion: Our study concluded that FNAC reporting using TBSRTC highly correlated with the histopathological diagnosis and our results were comparable with published data. The FNAC diagnosis helps in triaging patients with STN and identifies those who require surgical intervention. It is a simple, convenient, cost effective, sensitive, specific, safe and accurate initial diagnostic method for the preoperative evaluation of STN.
Keywords: Bethesda system, cyto-histological correlation, fine needle aspiration cytology, solitary thyroid nodule
|How to cite this article:|
Arul P, Masilamani S. A correlative study of solitary thyroid nodules using the bethesda system for reporting thyroid cytopathology. J Can Res Ther 2015;11:617-22
|How to cite this URL:|
Arul P, Masilamani S. A correlative study of solitary thyroid nodules using the bethesda system for reporting thyroid cytopathology. J Can Res Ther [serial online] 2015 [cited 2017 Dec 12];11:617-22. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/617/157302
| > Introduction|| |
Solitary thyroid nodule (STN) is defined clinically as the localized enlargement of thyroid with apparently normal rest of the gland.  The epidemiological studies have shown that prevalence of STN in adult population and children ranges from 4-10% and 0.2-1.2% respectively.  The patients with solitary nodules should undergo fine needle aspiration cytology (FNAC) as they have malignant potential, hence evaluation of these nodules is essential.  FNAC is a simple, convenient, rapid, cost effective and safe method. It plays important role in pre-operative screening in the diagnosis of thyroid lesions and valuable tool in the management. , FNAC should be considered the initial diagnostic test compared to other modalities such as scintigraphy and ultrasonography, because of its superior diagnostic reliability and cost effectiveness.  This study was undertaken to determine the utility and diagnostic accuracy of FNAC in the evaluation of STN by comparing the results with histopathological evaluation of excised specimens and also to compare consistency of results with literature.
| > Materials and methods|| |
Cytological slides of 483 patients, who had undergone FNAC from January 2012 to September 2014, were retrieved and evaluated after obtaining approval from the Institutional Ethical Committee. Cytological and histopathological diagnoses were compared among 209 patients who had undergone surgery for STN.
The Bethesda system for reporting thyroid cytopathology (TBSRTC) was used for cytological evaluation.  Cytological diagnoses were categorized into four groups- non-neoplastic, indeterminate, neoplastic group and nondiagnostic. Nodular colloid goiter and thyroiditis were considered as non-neoplastic group, atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) was considered as indeterminate category, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy and malignant cytology were considered as neoplastic group.
Histopathological results of 209 patients were categorized as negative and positive test result. Benign lesions were considered as negative test result and malignant lesions were considered positive test result. On correlation of FNAC diagnoses with histopathological diagnoses, the sensitivity, specificity, accuracy, false positive rate, false negative rate, positive predictive value and negative predictive value of FNAC were calculated. The nondiagnostic results were excluded from the analysis.
Patients with non-neoplastic diagnoses by FNAC, but diagnosed as neoplastic lesions on histopathological examination was considered as false negative and patients with neoplastic diagnoses by FNAC, but diagnosed as non-neoplastic lesions on histopathological examination was considered as false positive. All the statistical analysis was performed using SPSS version 20.
| > Results|| |
The mean age of our study group was 38.22 years, with a range from 16-80 years among 483 patients and majority of cases clustered in third decade. Of these patients, 33 (6.8%) were males and 450 (93.2%) were females with male and female ratio of 1:13. The FNAC results of 483 patients, according to TBSRTC are shown in [Table 1]. In the FNAC, non-neoplastic group consisted of 215 (44.5%), indeterminate group consisted of 14 (2.9%), neoplastic group consisted of 230 (47.6%) and nondiagnostic group consisted of 24 (5%) cases. In the neoplastic group, FN/SFN (21.5%) was more common followed by suspicious for malignancy (15.3%), papillary carcinoma (10.6%) and medullary carcinoma (0.2%).
|Table 1: Distribution of 483 cases of fine needle aspiration cytology diagnoses by Bethesda system for reporting thyroid cytopathology|
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In our study, 209 cases out of 483 patients were STN. Of these, non-neoplastic lesions [Figure 1] was seen in 88 (42.1%), AUS/FLUS was seen in 6 (2.9%), FN/SFN [Figure 2] was seen in 52 (24.9%), suspicious for malignancy was seen in 33 (15.8%), malignant cytology [Figure 3] and [Figure 4] was seen in 18 (8.6%) and nondiagnostic was seen in 12 (5.7%) cases. These 209 cases were operated for STN and results of histopathological diagnoses are shown in [Table 2]. The FNAC results were compared with the corresponding histopathological diagnoses are summarized in [Table 3]. On histopathological examination, nodular colloid goiter (45.9%) [Figure 1] was more common followed by follicular adenoma (25.4%) [Figure 2], papillary carcinoma (24.4%) [Figure 3], follicular carcinoma (3.3%), medullary carcinoma (0.5%) [Figure 4] and thyroiditis (0.5%).
|Figure 1: Nodular colloid goiter. (a) Cytology smear showing thick and thin colloid with few follicular epithelial cells Hematoxylin and Eosin (H and E, ×100). (b) Follow up histopathology showing plenty of colloid filled thyroid follicles (H and E, ×100)|
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|Figure 2: Follicular neoplasm. (a) Cellular cytosmear showing microfollicular pattern with scanty colloid (H and E, ×100). (b) Corresponding histopathology revealing thick intact capsule with microfollicular growth pattern, diagnosed as follicular adenoma (H and E, ×100)|
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|Figure 3: Malignancy of thyroid-Papillary carcinoma. (a) Markedly atypical cellular smear showing intranuclear cytoplasmic inclusion, diagnosed as papillary carcinoma (H and E, ×400). (b) Subsequent histopathology exhibiting papillary architecture with ground glass nuclei (H and E, ×100)|
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|Figure 4: Malignancy of thyroid-Medullary carcinoma. (a) Moderately cellular cytosmear showing discohesive cell clusters with plasmacytoid appearance (H and E, ×100). (b) Follow up histopathology revealing extracellular, amorphous, dense salmon pink amyloid material with tumor cells (H and E, ×100). (c) Histopathology section showing amyloid stained with Congo red stain (Congo red, ×100)|
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|Table 2: Distribution of histopathological diagnoses in solitary thyroid nodules (N=209)|
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|Table 3: Comparison of FNAC and histopathological diagnoses of STN in 209 cases|
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Among the non-neoplastic diagnoses given in FNAC, 5 cases turned out to be follicular adenoma and 1 case of papillary carcinoma on histopathological examination. These cases were considered as false negative. Among the neoplastic diagnoses given in the FNAC, 2 cases (FNAC diagnosis in one case was FN/SFN and other case was suspicious for malignancy) turned out to be nodular colloid goiter on histopathological examination [Figure 5] and [Figure 6]. These cases were considered as false positive. We found 5.6% of false negative rate and 2.4% of false positive rate in our study.
|Figure 5: False positive case-Follicular neoplasm turned out to be nodular colloid goiter. (a) Cellular cytosmear showing repetitive follicles suggestive of follicular neoplasm (H and E, ×100). (b) Subsequent histopathology showing micro and macro follicles in a nodular colloid goiter (H and E, ×100|
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|Figure 6: False positive case-Suspicious for malignancy turned out to be nodular colloid goiter. (a) Suspicious cluster of cells with few nuclear features of papillary carcinoma-Pale chromatin, micronucleoli and nuclear crowding on FNAC (H and E, ×400). (b) Follow-up histopathology section revealing focal nuclear atypia in an otherwise typical nodular colloid goiter (H and E, ×400)|
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The present study showed sensitivity, specificity, accuracy rate, false positive rate, false negative rate, positive predictive value and negative predictive value of FNAC were 94.4%, 97.6%, 95.8%, 2.4%, 5.6%, 98.1% and 93.2% respectively.
| > Discussion|| |
FNAC is widely accepted as the most accurate, sensitive, specific and cost effective diagnostic procedure in the preoperative assessment of thyroid nodules. In 95% of cases it can differentiate benign nodules from malignant nodules of thyroid. ,, It is a first line of investigation and also a preferred diagnostic method for the initial stage of evaluation of thyroid nodules followed by ultrasound examination, thyroid function tests, thyroid scan and antibody levels to select the patients those who require surgical intervention and those who need medical management. ,, FNAC cannot differentiate follicular adenoma from follicular carcinoma, is a major limitation of this procedure. ,
The age range and mean age of the patients in the present study were similar to studies done by Handa et al.,  and Gupta et al.,  and these was lower than Muratli et al., study. The use of FNAC resulted in a decrease in the number of patients who underwent surgical treatment by 25-50%, while increasing the percentage of malignant results in the operated group of patients.  About 5% of patients with solitary nodules show cytological features of malignancy. ,
TBSRTC group has identified six diagnostic categories in which the risk of malignancy increases substantially. The risk of malignancy in nondiagnostic or unsatisfactory, benign, AUS/FLUS, FN/SFN, suspicious for malignancy and malignant cytology were 1-4%, 0-3%, 5-15%, 15-30%, 60-75% and 97-99% respectively. 
In our study the cyto-histological concordance for non-neoplastic group was 82 (93.2%) out of 88 cases which was comparable to study done by Chandanwale et al.  Of the 6 discordant cases, five were diagnosed as follicular adenoma and one as papillary carcinoma. Sometimes it is very difficult to differentiate colloid goiter from follicular neoplasm by cytological evaluation.  In our study discordant results may be due to needle would have aspirated only colloid rich areas of neoplasm.
AUS/FLUS is a heterogenous group of lesions, which do not fulfill the criteria of other categories in TBSRTC and it shows significant nuclear and architectural atypia of follicular cells. The diagnoses of AUS/FLUS, FN/SFN, suspicious for malignancy were categorized as intermediate category in the studies done by Chandanwale et al.,  and Wang et al.  In this study, we interpreted only AUS/FLUS as indeterminate category. We observed AUS/FLUS in 14 (2.9%) cases of among 483 patients and 6 (2.9%) cases out of 209 patients. On histopathological examination, all cases of AUS/FLUS diagnosed as colloid goiter. There was no malignancy observed in AUS/FLUS category in our study. The histopathological examination of FN/SFN and suspicious for malignancy revealed malignancy in 6 (11.5%) and 32 (97%) cases respectively [Table 4].
|Table 4: Histopathologically diagnosed malignancies among different categories of the Bethesda system for reporting thyroid cytopathology in STN|
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In our study, 18 (8.6%) cases were diagnosed as malignant on FNAC out of which 17 (8.1%) were papillary carcinoma and 1 (0.5%) was medullary carcinoma. All 18 cases correlated with the final histopathological examination similar to Gupta et al., study.  We found the cyto-histological concordance for malignancy was 100% which were close to the studies done by Gupta et al., and Basharat et al. ,
The cystic degeneration or necrosis, sclerotic or calcified lesions can lead to nondiagnostic or inadequate aspiration. In our study we found nondiagnostic results in 24 (5%) cases among 483 patients and 12 (5.7%) cases out of 209 patients which was comparable to Kaur et al.  The previously reported studies have shown that nondiagnostic results occur in 2-20%; however it should be limited to no more than 10% of thyroid FNAC. ,, Inadequate sampling can be reduced by ultrasound guidance as it can detect lesion as small as 1mm in diameter. ,
The present study observed false negative rate of 5.6% which was consistent with previously reported in literature ranging from 2-7%. , False negative results can occur due to sampling error or misinterpretation of cytology.  There were six false negative diagnoses in our study, which included five cases of follicular adenoma and one case of papillary carcinoma. All five cases of follicular adenomas were erroneously reported as nodular colloid goiter. The aspirates consisted of variably sized follicles along with moderate amount of colloid. The excision biopsy showed features of mixed macro and micro follicular adenoma, thus accounting for the misinterpretation. One case of papillary carcinoma had been falsely reported as colloid goiter. The aspirate contained only benign follicles and colloid. No suspicious features were noted even on retrospective slide review. The excision specimen showed classical papillary carcinoma features in one focus only. The rest of the thyroid showed benign nodularity. This situation is an example of sampling error which is one of the important issues in thyroid cytology. The sampling error could be minimized by performing multiple aspirates (3-5 passes) and using image (ultrasound) guidance whenever focal lesions are suspected. The patients with benign cytological findings undergoing surgery are very less, hence it is difficult to find out the true frequency of false negative results. 
We found 2.4% of false positive rate in the present study comparable to Basharat et al.  In the present study, there were two cases of false positive diagnoses, one case was FN/SFN and another was suspicious for malignancy turned out to be nodular colloid goiter on subsequent histopathological examination. In the first case of false positive diagnosis, the aspirate consisted predominantly monomorphic microfollicles with minimal colloid only. This made us suspect a diagnosis of follicular neoplasm. Histopathology of that case revealed areas with macrofollicles as well, in addition to micro and normal sized follicles. Colloid was also seen in considerable amount, leading to the diagnosis of nodular colloid goiter. In the other case of false positive diagnosis, there were few suspicious epithelial cell clusters exhibiting few of the nuclear features of papillary carcinoma like nuclear crowding, enlargement, pale chromatin and micronucleoli. However papillary structures or nuclear inclusions were not to be found and hence equivocal diagnosis of suspicious for malignancy was given. In the subsequent histopathology sections, only focal areas of nuclear enlargement were noted. This could be due to endocrine atypia commonly seen in thyroid tissue.
The sensitivity of FNAC in the diagnosis of STN ranges from 65-98% and its specificity ranges from 73-100%. ,,,, In the present study, the sensitivity was 94.4% and the specificity was 97.6%. Differences in the categorization of AUS/FLUS, FN/SFN and suspicious for malignancy diagnoses resulted in wide range of sensitivity and specificity. Some others categorize the follicular lesions as histopathologically benign, while others categorize these lesions as malignant. ,, In the present study, we categorized AUS/FLUS in indeterminate category and FN/SFN, suspicious for malignancy in positive test result. The comparison of sensitivity, specificity, accuracy, positive predictive and negative predictive value of various previous studies with present study is shown in [Table 5].
| > Conclusion|| |
Our study concluded that FNAC reporting using TBSRTC highly correlated with the histopathological diagnosis and our results were comparable with published data. The FNAC diagnosis helps in triaging patients with STN and identifies those who require surgical intervention. It is a simple, convenient, cost effective, sensitive, specific, safe and accurate initial diagnostic method for the preoperative evaluation of STN.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]