|Year : 2010 | Volume
| Issue : 4 | Page : 437-442
Fine needle aspiration cytology of thyroid swellings: How useful and accurate is it?
PK Bagga, NC Mahajan
Department of Pathology, MM Institute of Medical Sciences and Research, Mullana, Ambala, Haryana, India
|Date of Web Publication||4-Dec-2010|
P K Bagga
Department of Pathology, MM Institute of Medical Sciences and Research, Mullana, Ambala, Haryana
Source of Support: None, Conflict of Interest: None
Background: Fine needle aspiration cytology (FNAC) is widely considered as the diagnostic technique of choice in the assessment of thyroid lesions. Aims: The aim of this study is to determine the utility and diagnostic accuracy of FNAC of thyroid lesions performed at our institution and to compare our experience with that of the experts from other regions of the world. Setting and Design: The present study is a five-year retrospective study of FNAC of thyroid lesions performed in the Pathology Department of our institute, during the period January 2004 to December 2008. The FNAC findings were correlated with the histopathological diagnosis, wherever available. Materials And Methods: 0 The records of 252 patients who had undergone FNAC during the study period were retrieved and information about age, sex, FNAC, and Histopathological diagnoses were extracted and the corresponding original slides were reviewed. The cytological results were classified as inadequate, benign, suspicious, and malignant. The histopathology diagnosis was classified as non-neoplastic (benign) and neoplastic (malignant). Results: A total of 252 FNACs of thyroid lesions were done during the study period. The results of the FNA cytological diagnosis showed that four (1.6%) of the patients had FNAs, which were inadequate for cytological assessment, 228 (90.5%) patients had benign lesions, 17 (6.7%) had lesions that were suspicious for malignancy, and three (1.2%) had malignant neoplasms. The correlation of the FNAC findings with the histopathological diagnosis, showed that our FNAC diagnostic accuracy rate was 96.2%, with a sensitivity of 66%, and specificity of 100%. Conclusions: The results of our study are comparable with the current published data and demonstrate that FNA cytology is a sensitive, specific and accurate initial diagnostic test for the preoperative evaluation of patients with thyroid swellings in our setting as well. The clinicians should be encouraged to embrace this procedure in the initial management of such patients.
Keywords: Accuracy, cytology, fine needle aspiration cytology, histopathology, thyroid
|How to cite this article:|
Bagga P K, Mahajan N C. Fine needle aspiration cytology of thyroid swellings: How useful and accurate is it?. Indian J Cancer 2010;47:437-42
| » Introduction|| |
Fine Needle Aspiration Cytology (FNAC) is a well-established, outpatient procedure used in the primary diagnosis of thyroid swellings. Clinicians have available, a variety of tests giving anatomical and functional information about the thyroid gland. FNAC, by giving direct morphological information has supplanted most other tests for preoperative evaluation of thyroid nodules. Practice guidelines set forth by the American Thyroid Association and National Comprehensive Cancer Network, state that FNA should be used as an initial diagnostic test because of its superior diagnostic reliability and cost- effectiveness, before both thyroid scintigraphy and ultrasonography.  As FNAC distinguishes between benign and malignant lesions quite effectively, it is the preoperative screening method of choice worldwide. Its use in recent years has resulted in a significant decrease in the number of surgeries being performed, while increasing the yield of malignant lesions of patients who have undergone surgery. Due to its simplicity, low cost, and absence of major complications, it is the initial investigation in the management of thyroid disease in our teaching hospital. This study is aimed at determining the utility and diagnostic accuracy of FNAC of thyroid lesions performed at our institution and to compare our experience with those of other regions of the world.
| » Materials and Methods|| |
The study aims to determine the cytological pattern of thyroid lesions, in addition to the utility and accuracy of FNAC as an initial diagnostic method in the investigation of thyroid swellings. Two hundred and fifty-two FNAs were performed on patients with diffuse or nodular thyroid enlargement, referred to the Pathology Department of our institute, during the period between January 2004 and December 2008. Thirty-two of these 252 cases underwent surgery, either excision of the nodule or some form of thyroidectomy for a cytologically suspicious / malignant diagnosis, compression symptoms or cosmetic reasons.
The records of the 252 patients who had undergone FNAC during the study period were retrieved and information about the age, sex, FNAC, and histopathological diagnoses were extracted and the corresponding original slides were reviewed.
Fine Needle Aspiration Cytology in all these patients was performed by experienced cytologists. The procedure was performed without local anesthesia with the help of the non-aspiration technique, using 23 - 25 gauze needles. Coagulation screening was not routinely done unless there was a pre-existing risk of bleeding. The procedure was generally well-tolerated with no significant complication. Both air dried and wet fixed smears (fixed in 95% alcohol for about 30 minutes) were made from the aspirated material, stained with May Grunwald Giemsa (MGG) and Hematoxylin and Eosin (H and E) stains, respectively, and examined under a light microscope.
The cytology results were categorized into four groups - inadequate, benign, suspicious, and malignant. The histopathology diagnosis was classified as non-neoplastic (benign) or neoplastic (malignant).
Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FNAC, relative to the final histological diagnoses were analyzed by SPSS software, using the following formulae:
- True positive (TP): Positive result in the FNA for malignancy, and confirmed in the histological study.
- False positive (FP): Positive result in the FNA for malignancy, but not confirmed in the histological study.
- True negative (TN): Negative result in the FNA for malignancy and no carcinoma in the histological study.
- False negative (FN): Negative result in the FNA for malignancy, but with carcinoma in the histological study.
- Sensitivity (S): Proportion of patients with associated carcinoma and a positive result in the FNA for malignancy, S = TP/ (TP + FN)
- Specificity (Sp): Proportion of patients without associated carcinoma and with a negative result in the FNA for malignancy SP = TN (TN + FP).
- Positive predictive value (PPV): Proportion of patients with a positive result and a histological confirmation of PPV = TP (TP + FP)
- Negative Predictive value (NPV): Proportion of patients with negative results, without a carcinoma in the histological study. NPV = TN (TN + FN)
- Diagnostic accuracy (DA): Proportion of patients diagnosed correctly by the diagnostic test, DA = (TP + TN) / (FP + FN + TP + TN)
| » Results|| |
A total of 252 patients underwent FNAC of thyroid swellings in the cytopathology section of the Pathology Department of our institute within the study period. Out of these, 223 were female patients, while 29 were males. Age of the patients ranged from six to seventy-five years. Thirty-two (31 females and 1 male) of these patients subsequently underwent thyroidectomy in our institute, and histopathological examination of the specimens was performed.
The FNA cytology results were compared with the corresponding histological diagnoses. The FNAC results were interpreted as inadequate in four (1.6%), benign in 228 (90.5%), suspicious in 17 (6.7%), and malignant in three (1.2%) [Table 1].
The distribution of benign, suspicious, and malignant cases on cytology was as shown in [Table 2]a, b, and c.
|Table 2: Distribution of benign (a), suspicious (b) and (c) malignant cases on cytology|
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The histopathological findings of 32 cases that underwent surgery were benign in 25 and malignant in six. The malignant cases comprised of papillary carcinoma (50%) [Figure 1] and [Figure 2], follicular carcinoma (33.3%), and medullary carcinoma (16.7%)[Figure 3] and [Figure 4].
|Figure 1: Photomicrograph of papillary carcinoma thyroid: (a) FNAC smears showing sheets and papillary tissue fragments. (MGG, × 200). (b) Histopathology section showing papillary architecture of tumor cells. (H and E, × 100)|
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|Figure 2: Photomicrograph of papillary carcinoma thyroid: (a) FNAC smear showing intra-nuclear cytoplasmic inclusions (black arrow) and nuclear grooves (red arrow) (MGG, Oil immersion) (b) Histopathology section showing intra-nuclear cytoplasmic inclusions (black arrow) and nuclear grooves (red arrow) (H and E, × 400)|
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|Figure 3: Photomicrograph of medullary carcinoma thyroid: FNAC smear showing aggregates and dispersed cells, variable cell pattern - plasmacytoid, small and spindle cells. (H and E, × 200)|
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|Figure 4: Photomicrograph of medullary carcinoma thyroid: (a) Histopathology section showing extracellular, dense, amorphous, pinkish amyloid material. (H and E, × 400). (b) Histopathology section showing amyloid staining red with Congo red stain. (Congo Red, × 400)|
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We identified no false positive cases. There was one false negative case, given as cystic colloid goiter on cytology, which was finally diagnosed as papillary carcinoma on histopathology.
Thyroid FNAC results, grouped malignant (positive results) versus the rest of the diagnoses (negative results) were compared with the results of the final histological study of the excised specimen in order to calculate the values of the test [Table 3]. Unsatisfactory / inadequate aspirates and suspicious lesion groups that gave no definite opinion were excluded from the calculations.
Analysis of the results yielded a sensitivity of 66%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 96%, with a diagnostic accuracy of 96.2%.
| » Discussion|| |
Fine needle aspiration cytology of the thyroid gland has radically changed the management of patients with thyroid disease. FNAC is widely accepted as the most accurate, sensitive, specific, and cost-effective diagnostic procedure in the preoperative assessment of thyroid nodules. The accuracy of the FNAC analysis approaches 95% in the differentiation of the benign nodules from the malignant nodules of the thyroid gland.  FNAC of the thyroid swellings is reported to have a sensitivity range of 65 - 98% and a specificity of 72 - 100%.  In our study, the analysis of the data revealed sensitivity of 66% and specificity of 100%, which translates into a diagnostic accuracy of 96.2%. The results of our study are comparable with the published data from different parts of the world. Kumar et al. in their study on 89 patients with enlarged thyroid gland reported a sensitivity of 77%, specificity of 100%, and diagnostic accuracy of 97.7%.  Similarly, a study conducted by Nggada et al. in a teaching hospital in Nigeria reported a sensitivity of 88.9%, specificity of 96.1%, and diagnostic accuracy of 94.2%.  Our study and the view of other experts suggest that FNAC is more specific than sensitive in detecting thyroid malignancy and therefore its use, as a reliable initial diagnostic test, cannot be overemphasized. It reduces the need for other time-consuming and expensive investigations. Bukhari et al. in their audit of the FNAC procedure of the solitary thyroid nodule, strongly suggest that FNAC should be adapted as an initial investigation of thyroid diseases, in all tertiary hospitals, in developing countries like Pakistan. 
The false negative rate (FNR) is defined as the percentage of patients with benign cytology in whom malignant lesions are later confirmed, after thyroidectomy. The false negative FNAC results may occur because of sampling error or misinterpretation of cytology and are of great concern because they indicate the potential to miss a malignant lesion.  However, it is difficult to calculate the true frequency of false negative results, because only a small percentage of patients with benign cytological findings undergo surgery. Most authorities are of the opinion that the true false negative rate is below 5%, even if all patients with thyroid FNAC have a histopathological examination.  In the present study, false negative FNA has occurred in one out of twenty-five (4%) patients with benign diagnosis. This is consistent with reports in the literature that suggest a false negative rate of 2-7%. ,
The false positive rate (FPR) indicated that a patient with a malignant FNAC result was found on histological examination to have a benign lesion. FPR results were uncommon and it was 0%in our study, which was consistent with other reports that cite FPR results ranging from 0 - 9%. , In the present study, the positive predictive value was 100%, negative predictive value was 96%, with a diagnostic accuracy of 96.2%, which was similar to the experience of others.,
We have categorized cytological results into Inadequate, Benign, Suspicious, and Malignant. This division is very helpful to clinicians in the management of patients, with specific reference to the need of thyroid surgery. As most of the benign conditions can be managed medically, it saves the patient unnecessary surgeries. In our study too, only 32 out of a total of 252 cases underwent surgery for a cytologically suspicious / malignant diagnosis, compression symptoms or cosmetic reasons and a cytopathological correlation was established in these cases.
Fine needle aspiration cytology has certain limitations on account of an inadequate sample and suspicious diagnosis. Intermediate FNAC results and cytodiagnostic errors are unavoidable due to overlapping cytological features, particularly among hyperplastic adenomatoid nodules, follicular neoplasms, and follicular variants of papillary carcinoma.
Among the suspicious group two out of four cases (50%) were diagnosed as malignant on histopathology, in our study. This was mainly due to the limitation of thyroid cytology to distinguish follicular adenoma from follicular carcinoma. The diagnosis required a detailed histopathological examination for vascular and capsular invasion. As the incidence of malignancy in suspicious lesions was high, surgical removal of the nodules should be considered strongly in these cases. Mundasad et al. also concluded in their study that suspicious and intermediate results prove to be an area of uncertainty, often resolved by diagnostic surgical resection. 
Inadequate samples may be because of sclerotic or calcified lesions and more commonly when there are large areas of cystic degeneration or necrosis. FNA of four patients (1.6%) yielded inadequate samples, which again correspond to studies in which inadequate sampling has been reported, from 1 - 5%.  The advent of ultrasound (US)-guided FNA has improved sample acquisition from patients with small thyroid nodules, which are difficult or impossible to detect on physical examination. Borget et al. did an assessment of the cost of FNAC as a diagnostic tool in patients with thyroid nodules and concluded that in future, routine ultrasound guidance and on-site assessment of cytopathological adequacy would help reduce costs. 
It has a high negative value, which is useful to reassure the majority of patients presenting with thyroid enlargement. However, a negative FNA should never exclude malignancy if there is a strong clinical suspicion.
Pitfalls in FNAC of the thyroid as mentioned by Shaha (2000)  are:
Adequacy of specimens (quantitative and qualitative), Accuracy of specimens (nonhomogeneity of needle placement), accuracy of cytopathological interpretation, Cysts (difficulties with degenerative nodules), Follicular lesions (benign vs. malignant), Hurthle cell lesions (benign vs. malignant), and Lymphocytic lesions (Lymphocytic thyroiditis vs. Lymphoma).
The cytopathologists should be aware of the potential diagnostic pitfalls and the interpretational errors that can be reduced further, if the aspirates are obtained from different portions of the nodule, with the use of the ultrasound-guided FNA procedure, with expert cytopathologists to perform and interpret the aspirates, and with the use of immunohistochemical and molecular markers.
| » Conclusion|| |
The results of our study are comparable with the current published data and demonstrate that FNA cytology is a sensitive, specific, and accurate initial diagnostic test for the preoperative evaluation of patients with thyroid swellings in our setting as well. The correlation of cytological and histopathological diagnoses is an important quality assurance method, as it allows cytopathologists to calculate their false positive and false negative results. It is a minimally invasive, safe, easily performed OPD procedure. The clinicians should be encouraged to use FNAC as the initial modality in the evaluation of thyroid lesions.
| » Acknowledgment|| |
The authors wish to thank Dr. Mohit Shahi, Assistant Professor, Department of Pathology, MMIMSR for the technical help.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]
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