INTRODUCTION
Disorders of thyroid gland are very common endocrine disorders worldwide with India no exception and they are being increasingly diagnosed with greater awareness. Iodine-deficiency disorders are endemic in some parts of India and are considered as national health issue.[1–4] Fine needle aspiration cytology (FNAC) of thyroid swelling is a rapid and easy diagnostic procedure. It is used to prevent any unnecessary surgery in thyroid nodules. Investigations such as ultrasonography, thyroid function test (TFT), serological investigations, and thyroid scan are not as effective a tool as FNAC. The nonaspiration technique is better suited for than the aspiration technique.[5–11]
A standardized approach is needed for reporting of FNAC smears of thyroid to make it easier for clinicians for the therapeutic management.[12,13] However, the technique has its own shortcomings due to inter- and intraobserver variability and lack of uniformity in reporting systems used which vary from country to country, laboratory to laboratory, and even in individuals working in the same laboratories.[14]
Over the years, various reporting systems such as conventional system, UK/RC Path system, and “The Bethesda System of Reporting Thyroid Cytology” (TBSRTC) have been used to help create a standard reporting format.[15] In spite of exhaustive and extensive work, there is still an ongoing dispute as to which classification system is the best for the management of the patient with thyroid lesions. The aim of this study is to access the utility of three cytology reporting systems in cytological evaluation of thyroid swellings.
MATERIALS AND METHODS
The present study was a prospective cohort study done over the period of 2 years from 2018 to 2020 and included 50 patients with thyroid swelling.
Inclusion criteria
Patients with thyroid enlargement, irrespective of age and sex and clinical diagnosis.
Exclusion criteria
Patients with already diagnosed thyroid lesions on cytology or on histology and undergoing treatment. The Institutional Ethical Committee clearance was taken for the study with reference to letter DPU/R and R (M)/19/(30)/2019 dated 8/1/2019. A detailed clinical history, clinical findings, and radiological and TFTs were noted.
Cytology smears were stained with Leishman’s stain and hematoxylin and eosin stain. Only adequate smears were included in the study. Only smears containing five to six groups of follicular cells and each group containing at least 10 thyroid follicular cells were taken as adequate smears. Cases in which colloid or blood-tinged material was obtained, adequacy criteria was not followed.
FNAC smears were studied in detail and were looked for the presence or absence of colloid, morphology of thyroid follicular cells, inflammatory cells, giant cells, macrofollicles or microfollicles, papillae, Hurthle cells, Psammoma bodies, etc. Smears of each case were reported and categorized as per the three reporting systems. Cases in which surgical specimens were received for histopathological examination and tissue sections were formalin fixed and paraffin processed. 3–5 microns sections were cut and stained with hematoxylin and eosin. Histopathology diagnosis was correlated with cytology diagnosis wherever possible.
RESULTS
Out of 50 cases, 94% (n = 47) were female and 6% (n = 3) were male. Maximum patients (n = 27) were in the age group of 20–40 years, 21 patients were between 41 and 80 years, and only two patients were below 20 years of age. Maximum cases in our study were in euthyroid state. Table 1 shows detailed distribution of diagnosis of 50 thyroid lesions on FNAC as per the conventional reporting system. Out of 50 cases, maximum (n = 38) were benign lesions (Category I) and nodular goiter was the most common (n = 20) lesion. Table 2 shows detailed distribution of diagnosis of thyroid lesion based on TBSRTC. Table 3 shows distribution of 50 thyroid lesions on FNA as per the UK/RC Path system. Out of the 50 cases, maximum cases were seen in Thy2 category (n = 33), followed by Thy3 category (n = 8). Table 4 shows comparison of the conventional, TBSRTC, and UK/RC Path reporting systems of 50 thyroid FNAC lesions. Comparison showed equivocal cases in the benign category.
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Table 1: Fine needle aspiration diagnosis of 50 thyroid lesions as per the conventional reporting system
Table 2: Fine needle aspiration C diagnosis of 50 thyroid lesions as per The Bethesda System of Reporting Thyroid Cytology
Table 3: Distribution and frequency of 50 thyroid lesions on fine needle aspiration as per the UK/royal college path system
Table 4: Comparison of conventional, The Bethesda System of Reporting Thyroid Cytology and UK/royal college path reporting system
Out of the 50 cases in which fine needle aspiration (FNA) was done, surgical specimens of 16 cases came for histopathological examination. Out of 16 cases, thyroid was removed in 13 cases for relieving pressure symptoms, in two cases for colloid cyst and in one case for neoplastic lesion. Cytology diagnosis of nodular colloid goiter and colloid cyst was confirmed by histopathological examination in 13 and 2 cases, respectively. In one case, cytology diagnosis of follicular neoplasm turned out to be follicular carcinoma of thyroid.
DISCUSSION
Majority of the patients in our study were females with a male: female ratio of 1:15. Similar observations were made by many studies.[16–20] In contrast, studies by Chang SH et al.[17] and Singh SK et al.[21] found that the ratio was significantly lower at 1:3. In the present study, the mean age was 38.82, which was in concordance with studies done by Shanmuga PS et al.[18] and Singh SK et al.[21] The ages of the patients ranged from 14 to 86 years. Maximum patients (n = 27) in our study were in the age group of 20–40. Similar observations were made by Singh SK et al.[21] Shanmuga PS et al.,[18] and Azad S et al.,[19] while Gupta V et al.[20] found majority of the patients in the 20–29 years’ age group. Variations in sex and age is possibly due to different geographical area and the type of lesions in particular geographical area.
Clinically, multiple nodules in thyroid (n = 20) were the most common cause of thyroid enlargement in our study. Similar observations were made in many studies.[16,17,19,20] As per the conventional reporting system, no case was included in Category I (nondiagnostic) because only smears with adequate cellularity were included in our study. The benign category (Category II) had 38 (76%) cases with multinodular goiter (n = 20) being the most common lesion followed by Hashimoto’s thyroiditis (n = 13) and colloid cyst (n = 5). The results were in concordance with various studies.[20–22] The intermediate category (Category III) included those cases in which FNA smears were not clearly benign, but were also not diagnostic of neoplastic lesions (n = 4). The Azad S et al.[19] reported 5.8% of the cases, Mamatha M et al.[22] reported 8.3% of cases, and Gupta V et al.[20] reported 4.3% of cases in their studies. Their findings were similar to those seen in our study.
The Category IV (FN/FN-HCT type) lesions were 12% (n = 6) and included follicular neoplasm (FN) and FN Hurthle cell type. Mamatha M et al.[22] showed 15% cases in this category, while in contrast, Gupta V et al.[20] reported only 3.3% and Azad S et al.[19] reported 2% of lesions.
Category V (Malignant) Included two (4%) cases in our study out of which the one case was of papillary thyroid carcinoma (PTC) and the other case was anaplastic carcinoma. Gupta V et al.[20] showed similar frequency in their study. In contrast, Azad S et al.[19] and Mamatha M et al.[22] reported slightly higher percentage of 7.8% and 6.6%, respectively.
The same cytology smears were categorized as per the TBSRTC into six categories. Category I (nondiagnostic) cases were not in our study. The 76% (n = 38) of smears were categorized as benign (Category II). The cytology smears of nodular goiter showed hyperplastic follicular cells in sheets or in loose clusters, thick and thin colloid on the background with scattered macrophages [Figure 1a and insight]. The presence of numerous lymphocytes and Hurthle cells in cytology smears suggested diagnosis of Hashimoto’s thyroiditis [Figure 1b and c]. Aspiration of colloid material and presence of abundant colloid on the background with cyst macrophages suggested diagnosis of colloid cyst [Figure 1d]. Similar observations were made by many authors who reported incidence between 77.6% and 94.2% in Category II.[19,23–28]
Figure 1: (a) Colloid goiter (Leishman’s stain, ×400), (b) Hashimoto’s thyroiditis (Leishman’s stain, ×100), (c) Hashimoto’s thyroiditis (Leishman’s stain, ×400), (d) Colloid cyst (Leishman’s stain, ×400)
Category III (atypia of undetermined significance/follicular lesion of undetermined significance - 8%) in TBSRTC included 4 cases, and smears in these cases showed follicular cells with architectural and cytological atypia, but not to the extent to call it as follicular neoplasm(FN)/Suspicious of follicular neoplasm (SFN) or suspicious of follicular malignancy (SFM) or as malignancy. The two cases of HT showed cytological features of HT with few atypical cells with enlarged nuclei, slightly pale chromatin, increased N/C ratio. The nuclear contour in a few of the cells was irregular. One case was diagnosed as follicular lesion, in which cytology smears showed cellular and nuclear atypia with moderate cellularity and few microfollicles [Figure 2a]. Occasionally, at places, scanty colloid was also seen. In the study by Gupta V et al.[20] and Shanmuga PS et al.,[18] 2% and 1.94% of the cases were included in this category. A slightly higher percentage was seen in the studies conducted by Mehra P et al.[23] and Yassa L et al.[25] at 4.9% and 4%, respectively.
Figure 2: (a) Follicular lesion of undetermined significance (Leishman’s stain, ×400), (b) Follicular neoplasm (Leishman’s stain, ×100), (c) Follicular neoplasm (Leishman’s stain, ×400)
Category IV (follicular neoplasm [FN]/SFN) included 4 (8%) cases, of which two were reported follicular neoplasm and the remaining two were follicular neoplasm Hurthle cell type. Cytology smears in follicular neoplasm were markedly cellular and follicular cells were arranged in sheets, showing nuclear crowding and overlapping and many microfollicles. The follicular cells were relatively uniform, with scant to moderate cytoplasm. Nuclei were round, slightly hyperchromatic with inconspicuous nucleoli. There was no colloid [Figure 2b and c].
In the two cases of FN Hurthle cell type, smears showed highly cellular smears, with no colloid in the background. The aspirate consisted of sheets and syncytial cluster of Hurthle cells which show abundant eosinophilic granular cytoplasm, with a slightly enlarged often eccentrically located nuclei and a prominent central nucleolus [Figure 3a and b]. Studies conducted by Gupta V et al.,[20] Azad S et al.,[19] and Mehra P et al.[23] showed 3%, 3.9%, and 2.2% cases in this category, respectively. The percentage is being slightly lower when compared to our study. Variation can be attributed to different geographical areas. Only one patient underwent surgical excision and specimen was received for histopathological examination and it was diagnosed as follicular carcinoma of thyroid.
Figure 3: (a) Follicular neoplasm hurthle cell type (Leishman’s stain, ×100), (b) Follicular neoplasm hurthle cell type (Leishman’s stain, ×400), (c) Suspicious of malignancy (Leishman’s stain, ×400)
In Category V, suspicious of malignancy (SM) was reported in 2 (4%) lesions. FNA smears in these cases showed sheets of follicular cells arranged in tight clusters and overlapping each other [Figure 3c]. Occasional thyroid follicular cells showed features of intranuclear pseudoinclusions and nuclear grooves. Psammoma bodies and papillae were not seen. Features pointing outright toward papillary carcinoma were not seen therefore not warranting the case to be classified under Category VI (malignancy). Studies by Mehra P et al.[23] showed 3.6% of cases in Category V, which was close to the 4% seen in our study. Studies by Azad S et al.,[19] Gupta V et al.,[20] and Joe VY et al.[26] showed 2%, 1%, and 2.3% of the cases in Category V, respectively. Another study by Yassa L et al.[25] showed 9% of the cases being classified under SM.
Category VI (malignancy - 4%): This category included 2 cases in our study. One case was diagnosed as PTC and the other as anaplastic carcinoma of the thyroid. Gupta V et al.,[20] Azad S et al.,[19] Yassa L et al.,[25] and Jo VY et al.[26] reported 5%–7% cases in their studies. While Mehra P et al.[23] showed a lower percentage of cases(2.2%) in Category VI. Possible reason can be geographical variation in occurrence of lesions. Cytology smears of PTC showed cellular smears with thyroid follicular cells arranged in a papillary configuration. Many cells showed intranuclear pseudoinclusion, nuclear grooves, and enlarged crowded nuclei. The nuclear contour was irregular and the nuclei were pale with powdery chromatin. Chewing gum colloid was also seen in places [Figure 4a and b]. While smears of anaplastic thyroid carcinoma showed scattered and clusters of bizarre large pleomorphic cells with large nuclei and prominent nucleoli [Figure 4c and d].
Figure 4: (a) Papillary thyroid carcinoma (Leishman’s stain, ×100), (b) Nuclear groove and intranuclear pseudo inclusions (insight) (Leishman’s stain, ×400), (c) Anaplastic thyroid carcinoma (Leishman’s stain, ×100), (d) Large pleomorphic cells in anaplastic carcinoma (Leishman’s stain, ×400)
The UK/RC path system of reporting thyroid cytology was published first in 2009 and then later updated in 2016. It includes five categories that are designated with a prefix “Thy” (Thy1-Thy5). Thy1 category i.e., nondiagnostic, no cases were included in our study because only smears with adequate material were included in our study. Thy2 category, i.e., nonneoplastic, was split into two subcategories, Thy2 and Thy2c (the c stands for “cystic lesions”). Thy2 category includes specific diagnosis such as nodular goiter and Hashimoto’s thyroiditis and Thy2c category included colloid cyst. The equivalent Bethesda category for this group is Category II. In the present study, Thy2 included 66% (n = 33) of lesions and Thy2c included 10% (n = 5).
Thy3 category, i.e., possible neoplasm, is split into Thy3a and Thy3f, where a stands for “atypia” and f stands for “FN/FN Hurthle cell type.” In the present study, the Thy3 category includes eight cases, of which Thy3a and Thy3f categories include 4 cases each (8% each). The equivalent Bethesda category to the Thy3a category is Category III and Thy3f category is Category IV. In the study carried out by Gupta V et al.,[20] the Thy3a category included 2% of the cases and the Thy3f category included 3% of the cases, which was slightly lower in comparison to our study.
Thy4 category (suspicious for malignancy) in the current study included only 2 cases (4%). The equivalent Bethesda category to Thy4 is Category V. While the study by Gupta V et al.[20] found 1% of the cases in Thy4 category. Thy5 category, i.e., malignant, included 2 (4%) cases which were of PTC and anaplastic thyroid carcinoma each.
There were no cases included in Category I of all the reporting systems. In all the three systems, the benign lesions were 38 in numbers. viz. Category II of TBSRTC, UK/RC path System (Thy2) and conventional reporting system (intermediate category) and Category III of TBSRTC has four cases, while the Thy3 category of the UK/RC Path system had eight cases (4 each in Thy3a and 3f). FN/SFN category in the conventional system included six cases, while the TBSRT included only four cases and the UK/RC (Thy3) path system included 8 cases. TBSRTC had an additional category called SFM which included two cases, which in the conventional system were included in the FN/SFN group and in the UK/RC Path system they were included in Thy4 category (SFM). The malignant category of all three reporting systems two cases.
CONCLUSION
In the vast majority of the cases, it showed that TBSRTC and UK/RC Path systems lead to better diagnostic yield, high sensitivity, and timely treatment of patients. TBSRTC has diagnostic accuracy of almost 98%. The categories in TSBRCT have been described in a format that is easy to read and interpret which helped in improving patient prognosis and management that ultimately helps avoid unnecessary surgery.
One of the most challenging categories in both the above systems was the Category III in or Thy3a which are heterogeneous category. The smears in these categories include features which do not permit them to be classified as either benign or malignant. Such cases are put under the atypical category. Redefinement of “atypical” or “suspicious” category by ancillary techniques should be done, and that the criteria in this category should not discourage clinicians from adopting the UK/ RC Path or the Bethesda system. Detection of lesions Which are suspicious or malignant, indicate definitive surgery. Therefore, adapting either the UK/RC path system or the Bethesda system helps in providing a clearer view and understanding of diagnosis of thyroid lesions. It is more helpful to the clinicians as it suggests a management plan.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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