Journal of Cytology
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 25  |  Issue : 1  |  Page : 6-9
Cytodiagnosis of thyroid lesions-usefulness and pitfalls: A study of 288 cases

1 Medical College, Kolkatta, India
2 Dr. B.C. Roy Memorial Hospital for Children, Kolkatta, India
3 Bankura Sammilani Medical College, Bankura, West Bengal, India

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Background: Fine needle aspiration cytology (FNAC) of the thyroid gland has been widely and successfully utilized for diagnosis.
Aim: Our aim was to demonstrate the effectiveness of this cheap and simple procedure for the diagnosis of different thyroid lesions, particularly, differentiation of malignant and nonmalignant lesions. In addition, we sought to highlight probable causes of error and possible remedies in the cases showing lack of correlation between cytological and histological diagnoses.
Materials and Methods: A total of 288 cases of thyroid swellings were aspirated in our two-year study period. Cases were divided into four groups, namely, aspiration inadequate where diagnosis was not offered; a nonneoplastic group which included different goiters and thyroiditis; an indeterminate group which included cases showing features of follicular or Hurthle cell neoplasms, and a malignant group that included nonfollicular malignant tumors of the thyroid. Cases showing cytohistologic disparity were reevaluated.
Results: Almost 14% of the cases could not be reported because of inadequate aspiration, however, an overall cytohistological correlation was achieved in 82.66% of all cases. Sensitivity and specificity for the diagnosis of malignancy were 92.7 and 98.2%, respectively. There were four false negative malignant cases with one false positive case and 13 cases failed to show any cytohistological correlation.
Conclusions: FNAC is the single most important test for preoperative assessment of thyroid pathology if attention is paid to the clinical features and collection of samples from proper sites.

Keywords: FNAC; pitfalls; thyroid lesions.

How to cite this article:
Guhamallick M, Sengupta S, Bhattacharya N K, Basu N, Roy S, Ghosh A K, Chowdhury M. Cytodiagnosis of thyroid lesions-usefulness and pitfalls: A study of 288 cases. J Cytol 2008;25:6-9

How to cite this URL:
Guhamallick M, Sengupta S, Bhattacharya N K, Basu N, Roy S, Ghosh A K, Chowdhury M. Cytodiagnosis of thyroid lesions-usefulness and pitfalls: A study of 288 cases. J Cytol [serial online] 2008 [cited 2022 Sep 29];25:6-9. Available from:

   Introduction Top

Fine needle aspiration cytology (FNAC) of the thyroid gland is now a well-established, first-line diagnostic test for the evaluation of diffuse thyroid lesions as well as of thyroid nodules with the main purpose of confirming benign lesions and thereby, reducing unnecessary surgery. [1] Although there is a large body of world literature claiming the accuracy and usefulness of thyroid cytology, there is also evidence showing possible limitations and pitfalls of this procedure. [2],[3]

Different imaging techniques are now used for preoperative diagnosis of thyroid nodules like radionuclide scanning, high-resolution ultrasonogrphy etc. However, FNAC is still regarded as the single most accurate and cost-effective procedure, particularly if ultrasound is used as a guide for better sample collection, [4] especially for cystic lesions. [5] Aspirations were done without any guidance in this study. Aspiration cytology of thyroid lesions and wherever possible, the histology samples was extensively examined by us to evaluate the role of FNAC for the diagnosis of thyroid lesions. We scrutinized the cases showing any discrepancy in cytohistological findings with the aim of establishing possible causes of the errors.

   Materials and Methods Top

This study was done in the Department of Pathology, Bankura Sammilani Medical College, Bankura, West Bengal, and Medical College, Kolkata, West Bengal for a period of two years from August 2004 to July2006. Thyroid swellings were aspirated using 23/24 gauge disposable needles fitted with 10/20 ml disposable syringes using standard procedures. [6] All the slides were stained with Leishman-Giemsa, hematoxylin and eosin, and Papanicolaou stains following recommended steps. [7]

Diagnosis of cytological smears was done according to standard criteria defined by various authors. [1],[2],[8] All the available resected samples were routinely processed, stained with hematoxylin and eosin. Cases with cytohistological disparity were selected. Case history and cytological smears of these cases were reevaluated for the detection of possible causes of failure.

   Results Top

A total of 288 cases of thyroid swellings were aspirated during the study period and only in 249 cases were samples found to be adequate for reporting. Even after repeated aspiration at different sittings, 39 cases (13.5%) could not be reported because of inadequate samples. Among the reportable cases, female cases far outnumbered males in the ratio of 2.3:1. Most of the cases reported were in the age group of 41-60 years.

The majority of the cases reported cytologically were nonneoplastic (197), followed by indeterminate (27) and malignant lesions (25). Follicular neoplasms (follicular adenoma, atypical adenoma, and follicular carcinoma) and Hurthle cell neoplasms (Hurthle cell adenoma and carcinoma) cannot be classified as benign or malignant lesions by cytology. [1] Hence, in our study, these tumors were classified under the indeterminate group, as recommended by other authors. [5] All malignant lesions without any overt follicular architecture, were included in the malignant group. The nonneoplastic group included simple colloid goiter, nodular colloid goiter, hyperplasia of thyroid, and different cases of thyroiditis.

Surgical samples were available in 32 of the 197 cases diagnosed as nonneoplastic lesions by cytology. In 25 (78.1%) cases, histological findings were consistent with the cytology results. Three turned out to be benign neoplasms and the remaining four cases showed malignant histology [Table - 1].

Of the 27 indeterminate cases, histopathological studies were possible in 20 cases [Table - 1]. Among these, nine cases were follicular adenomas, two were Hurthle cell adenomas, five follicular carcinomas, two showed features of nodular goiter, one showed features of Hashimoto's thyroiditis, and the remaining one was histologically diagnosed as a follicular variant of papillary thyroid carcinoma (FVPTC). Cytohistologic correlation and predictability of malignancy in this group were not considered due to its cytologically indeterminate nature.

Excised samples were available for histopathological study in 23 out of 25 cases found to be malignant by cytology and the histological findings were consistent in 21 cases (91.3%). Of the other two cases, one case was diagnosed as a nodular colloid goiter (nonneoplastic) and another as a follicular carcinoma [Table - 1].

Overall, cytohistological correlation in all categories excluding the indeterminate group, was 83.6%.

Four false negative cases were identified in the nonmalignant group, which were missed by cytological examination. Among malignant cases, only one case was found to be false positive by cytology. Sensitivity and specificity of cytodiagnosis for detection of malignancy in our series were 92.7 and 98.2%, respectively [Table - 1].

   Discussion Top

An adequate cytological smear of the thyroid should contain five to six groups of well-preserved follicular cells, with each group containing ten or more cells. [6] Almost 14% of the cases in our study group could not be reported because of inadequate sampling. Comparable experiences have been reported by others. [7] The abundance of female cases in our series was also consistent with other reports. [1]

The number of false positive cases (1.8%) in our series was comparable with that reported by another study. [8] The specificity in our series for cancer detection along with overall cytohistologic correlation rates were also quite comparable with those reported by similar studies. [5],[9]

Most of the earlier studies reported higher numbers of false negative cases in their series; [8],[10] we had similar results. This high rate of failure to diagnose cancer could be attributed to the failure of aspiration from precise locations. In our series, there were 13 cases (5.22%) with cytohistological discrepancy. These have been divided into eight groups to discuss the possible sources of error and methods to rectify these problems [Table - 2].

In Group I, cytological features from all three cases showed abundant colloid with moderate numbers of follicular cells arranged in sheets and occasional macrophages, favoring the diagnosis of a nodular colloid goiter. Histology of these cases showed the presence of microscopic foci of a papillary carcinoma. The cause of detection/diagnosis failure was possibly the presence of small minute foci of a papillary thyroid carcinoma that were missed during aspiration. Similar cases have been encountered by others. [1],[5]

The cytological smear of the patient in Group II showed clumps of Hurthle cells with a focal presence of lymphocytes suggesting a diagnosis of Hashimoto's thyroiditis. Histological features were consistent with those of Hurthle cell carcinoma. Importance was probably not given to the absence of follicular cells, dyscohesiveness of Hurthle cell clumps, prominent anaplasia, nucleoli of Hurthle cells, and only the focal presence of lymphocytes. Similar mistakes have been reported earlier. [1],[5] If aspirates consist of more than 75% Hurthle cells, the possibility of a Hurthle cell neoplasm should be considered, in the absence of which, nonneoplastic lesions are suspected. [11]

In Group III, the smears showed moderate cellularity with small clumps of thyroid follicular cells arranged in poorly cohesive groups with few colloid drops suggesting the diagnosis of nodular colloid goiter. Histological features though were consistent with those of a follicular adenoma. Cytological differentiation between follicular neoplasms and nodular goiters is often very difficult. [1],[3] Aspirations in these cases were probably done over colloid-rich macrofollicular areas of the neoplasm. [1] As possible remedial measures, cytological features like increased cellularity with nuclear crowding and overlapping, repetitive uniform cell patterns, syncytial clusters, microfollicular structures, scanty, or no colloid may be helpful in distinguishing follicular neoplasms from nodular goiters, although none of them is conclusive. [12]

Cytological smears of the two cases of Group IV showed clusters of follicular cells arranged in clumps with scanty colloid with the diagnosis of a follicular neoplasm of the thyroid. The histology though, showed features of a nodular colloid goiter. Aspiration was probably done from the hypercellular areas of colloid nodules which led to over diagnosis. As already discussed, cytological distinction between these two conditions is often difficult. A possible remedy is multiple aspirations from different parts of the swelling that could demonstrate hypocellular, polymorphic, and colloid-rich areas. Demonstration of monolayered sheets of epithelial cells representing macrofollicles and degenerative changes would suggest the possibility of nonneoplastic lesions. [13]

In Group V, the smears showed small and large clumps of Hurthle cells with scanty colloid pointing to a diagnosis of a Hurthle cell neoplasm. The histological features were consistent with those of Hashimoto's thyroiditis. Failure to demonstrate lymphocytes and to appreciate the nonneoplastic nature of Hurthle cells were the causes behind failure in these cases. Others have also reported similar problems. [5] Multiple aspirations from various parts of the lesion could be helpful to get a correct cytological diagnosis. Cytological features favoring a diagnosis of thyroiditis over neoplasm in a Hurthle cell-rich smear include the absence of poorly organized cell clusters having nuclear pleomorphism, particularly, anisonucleosis of Hurthle cells in thyroiditis. [14],[15]

In Group VI, a case of a follicular variant of papillary carcinoma (FVPTC) was wrongly interpreted as a follicular neoplasm. The smears had shown numerous follicular cells arranged in clusters, often with syncytial cell aggregation. There was prominent nuclear crowding and overlapping without any colloid. The presence of follicular structure led to misinterpretation, as has been encountered by others. [16] A possible remedial measure could be to repeat aspirations from different parts which could unravel the typical nuclear features of a papillary carcinoma. Recent studies now stress that even focal presence of papillary nuclear features in a follicular pattern should be dealt with caution. On review of cytological smears with prominent follicular patterns, a group of authors reported that papillary nuclear features in more than 20 cells would have a greater risk of occurrence of papillary carcinoma, [17] although these findings may also lead to over interpretation. [5]

The cytological smears of cases in Group VII were moderately cellular showing numerous macrophages, thick colloid, cohesive clumps, and sheets of follicular cells arranged in vague papillary patterns with nuclear overlapping and crowding. Few cells contained moderate amount of blue cytoplasm and round nucleus with pale open chromatin. Intranuclear inclusions were demonstrated in few cells. Cytological features were suggestive of papillary thyroid carcinoma (PTC). The histology showed features consistent with those of a nodular colloid goiter. Misinterpretation of partly degenerated nonneoplastic follicular cells as cells of PTC, too much stress on papillary architecture and intranuclear inclusions were probably the causes of error in these cases. Multiple samples collected from different parts of the lesion could help in proper diagnosis. For cytodiagnosis of PTC, the three most important features suggested are intranuclear cytoplasmic inclusions, dense metaplastic cytoplasm of cells, and papillary structures with distinct anatomical border and without adherent blood vessels. [18] These features can lead to a decrease in the wrong diagnosis of PTC.

In Group VIII, cytologic smears of the subject showed abundant thyroid follicular cells arranged in small clusters and monolayered sheets with nuclear crowding and overlapping. Few cells showed abundant blue cytoplasm with monomorphic round nucleus having pale, powdery chromatin, and prominent nuclear grooves. Cytological features were suggestive of FVPTC. Histology showed the features of follicular carcinoma. Detailed clinical examination and multiple aspirations from different sites would be the possible remedial measures. [5] Some workers reported that syncytial arrangement of cell clusters and presence of globular colloid along with typical nuclear features were essential prerequisites for diagnosing a predominantly follicular smear as FVPTC. [19]

   Conclusion Top

FNAC is a cheap and quick procedure which is also highly sensitive and specific in categorization of thyroid lesions. We have discussed the pitfalls encountered by us and possible inexpensive remedies for them in this report.

   References Top

1.Orell SR. In : Orell SR, Sterrett GF, Walters MN, Whitakar D, editors. Manual and atlas of fine needle aspiration cytology. 4th ed. New Delhi: Churchill-Livingstone; 2005. p. 125-64.  Back to cited text no. 1    
2.Hamburger JI, Husain M, Nishiyama R, Nunez C, Solomon D. Increasing the accuracy of fine needle biopsy for thyroid nodules. Arch Pathol Lab Med 1989;113:1035-41.  Back to cited text no. 2  [PUBMED]  
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5.Jogai S, Al Jassar A, Temmim L, Dey P, Adesina AO, Amanguno HG. Fine needle aspiration cytology of the thyroid: a cytohistologic study with evaluation of discordant cases. Acta Cytol 2005;49:483-8.  Back to cited text no. 5    
6.Smit TJ, Safali H, Foster EA, Reinhold RB. Accuracy and cost-effectiveness of fine needle aspiration biopsy. Am J Surg 1985;149:540-5.  Back to cited text no. 6    
7.Hall TL, Layfield LJ, Philippe A, Rosenthal DL. Sources of diagnostic error in fine needle aspiration of thyroid. Cancer 1989;63:718-25.  Back to cited text no. 7  [PUBMED]  
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9.Bakhos R, Selvaggi SM, De JS, Gordon DL, Pitale SU, Hermann M, et al. Fine needle aspiration of the thyroid: rate and causes of cytohistologic discordance. Diagn Cytopathol 2000;23:233-7.  Back to cited text no. 9    
10.Al-Hureibi KA, Al-Hureibi AA, Abdulmughni YA, Aulagi SM, Salman MS, Al-Zooba EM. The diagnostic value of fine needle aspiration cytology in thyroid swellings in a university hospital, Yemen. Saudi Med J 2003;24:499-503.  Back to cited text no. 10    
11.Asa AL. My approach to oncocytic tumours of the thyroid. J Clin Pathol 2004;57:225-32.  Back to cited text no. 11    
12.Atkinson B, Ernest CS, Livolsi V. Cytologic diagnosis of follicular tumours of the thyroid. Diagn Cytopathol 1986;2:1-5.  Back to cited text no. 12    
13.Suen KC. How does one separate cellular follicular lesions of the thyroid by fine needle aspiration biopsy? Diagn Cytopathol 1988;4:78-81.  Back to cited text no. 13  [PUBMED]  
14.Kini SR, Millen JM, Hamburger JL. Cytopathology of Hurthle lesions of the thyroid gland by fine needle aspiration. Acta Cytol 1981;25:647-52.  Back to cited text no. 14    
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16.Yang GCH, Liebeskind D, Messina AV. Should cytopathologists stop reporting follicular neoplasms on fine needle aspiration of the thyroid? Diagnosis and histologic follow up of 147 cases. Cancer Cytopathol 2003;114: 681-3.  Back to cited text no. 16    
17.Renshaw AA. Focal features of papillary carcinoma of the thyroid in fine needle aspiration material are strongly associated with papillary carcinoma at resection. Am J Clin Pathol 2002;118:208-10.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Miller TR, Bottles K, Holly EA. A step-wise logistic regression analysis of papillary carcinoma of the thyroid. Acta Cytol 1986;30:285-93.  Back to cited text no. 18    
19.Powari M, Dey P, Saikia UN. Fine needle aspiration cytology of follicular variant of papillary carcinoma of thyroid. Cytopathology 2003;14:212-5.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]

Correspondence Address:
N K Bhattacharya
Flat 4-A, Shanti Apartment, 7/3, Motijheel Avenue, Kolkatta - 700 074
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.40650

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