Fine Needle Aspiration Cytology of Solitary Thyroid Nodule with Histopathology Correlation

Background: Solitary thyroid nodule (STN) is a localized thyroid enlargement with apparently normal rest of the gland clinically. Preoperative Fine Needle Aspiration Cytology (FNAC) aids in distinguishing benign and malignant nodules and planning the treatment. Based on the cytology findings, patients can be followed in cases of benign diagnosis and thereby decreasing the rate of unnecessary surgery. However the accuracy of FNAC is found to be varied in different studies. The aim of the study was to study the cytological findings in STN and to correlate the FNAC and histopathology results. Methods: A retrospective study including FNAC of 107 patients presenting with solitary thyroid nodule from January 2015 to June 2017 was done at Department of Pathology. Cytology and histopathology correlation was available in 40 cases. Results: Solitary thyroid nodules involved females more commonly than males with a ratio of 10.8:1. Malignancy was present in 12.5% of cases and papillary carcinoma was the commonest malignancy. For malignancies, FNAC showed sensitivity of 40%, specificity of 97.1%, Positive predictive value of 66.6%, Negative predictive value 91.9% and Efficacy of 90%. Conclusion: FNAC of solitary thyroid nodules has high specificity and efficacy. Low sensitivity of FNAC in STN necessitates caution and patient follow up in cases with cytological benign diagnosis.


Introduction
Solitary thyroid nodule (STN) is a localized thyroid enlargement with apparently normal rest of the gland clinically. The prevalence of thyroid nodules is 3-7% by palpation, 20-76% on basis of ultrasound and upto 50% at autopsy. Prevalence also depends on the regional iodine deficiency. It is up to 50% of adults in iodine deficient areas. It occurs more commonly in women than men. Malignancy is encountered more frequently in solitary nodules than multinodular goiters, with reported higher incidence in childhood STN than in adults. Malignancy occurs in approximately 5% of all the thyroid nodules. [1][2][3][4][5][6] FNAC is a rapid, cost effective and reliable diagnostic tool for detecting malignancy in STN. Preoperative FNA plays a pivotal role in distinguishing benign and malignant nodules and treatment plan. Unnecessary extensive surgery and its related adverse effects, such as hypothyroidism, hypocalcemia and recurrent laryngeal nerve injury could be avoided. [2] Radionucleotide scanning is the imaging technique useful in preoperative diagnosis of thyroid nodules, though unaffordable in many institutes. Ultrasound guided FNAC can be used for better sampling, especially in cystic and small lesions. The objective was to study FNAC findings in solitary thyroid nodules and correlate with histopathology.

Materials and Methods
A cross sectional study was done at Department of Pathology after obtaining approval from Institutional ethical committee. A retrospective analysis of cases and slide archives in the Department was done including cases from January 2015 to June 2017. Patients presenting with solitary thyroid nodule were included, irrespective of the thyroid profile status. Patients with diffuse thyroid enlargement and multiple nodules were excluded. FNAC was done using 23 guage needle and 5 ml syringe under aseptic precautions. Non aspiration technique or aspiration by minimal negative pressure was followed in majority of cases. Smears fixed in ethanol and stained with Haematoxylin and Eosin stain (H&E), Papanicolaou stain and air dried smears stained with Giemsa stain were analysed.
Histopathological examination of hemithyroidectomy, subtotal or total thyroidectomy cases with preoperative cytology diagnosis were included in the study. Histopathology and cytology results were correlated and analysed. Sensitivity, specificity, efficacy, positive and negative predictive values for neoplasms and malignancies were calculated. 9 male and 98 female patients. Age group of patients ranged from 18 to 75 years. Adequacy criterion of atleast 6 clusters, with 10-15 cells per cluster, was followed. Of the 107 cases, 2 FNACs had inadequate material and no opinion was possible. FNA results were as shown in Table1. Colloid goiter (28.9%) (Fig 1.a,b), Colloid goiter with secondary changes(6.5%), Nodular colloid goiter with cystic change(21.5%), Nodular colloid goiter with adenomatous hyperplasia(14.7%), Hashimotos thyroiditis (3.7%).Follicular neoplasm constituted 8.4% of total cases (Fig 3). Papillary carcinoma (Fig.2), medullary carcinoma ( Fig.1-c) and anaplastic carcinoma accounted for 3.7%, 1.9% and 0.9% respectively. The most common neoplasm was Follicular neoplasm. The commonest malignancy was papillary carcinoma.
Papillary Carcinoma Thyroid (PCT) -Tall cell variant showed Cells whose height were at least three times their width constituting 50% or more of papillary ca cells. Lesion was highly papilliferous with Invasion to skeletal muscle, showing PCT nuclear features .Nucleus located basally, with abundant oxyphilic cytoplasm and focal Sub nuclear clearing . (Fig.d,e,f) Minimally invasive follicular carcinoma showed microscopic , single capsular invasion. (Fig.3-e,f) Results of cytology and histopathology with correlation were as shown in Table 2. In 30 cases, same diagnoses were given in both. Distribution of cases in non neoplastic and neoplastic category with correlation revealed 7 False negatives and 2 False positives for neoplasms, 1 false positive and 3 False negatives for malignancy (Table 3). 32 cases were diagnosed as non neoplastic lesions on cytology. On histopathologic evaluation of these cases,25nodular colloid goitre, 5 follicular adenoma, 2 papillary carcinoma were reported.8 cases were diagnosed as neoplastic lesions by FNAC (4 follicular neoplasm, 1 hurthle cell neoplasm, 2 papillary carcinoma, and 1 medullary carcinoma). Among these, 2 non neoplastic lesions, 3 benign neoplastic lesions and3 malignancies were reported on histopathology. As per these results, 1 False positive and 3 false negatives for malignancy, 2 False positives and 7 False negatives for thyroid neoplasms were noted.        [2,[8][9][10][11][12][13] Statistics showed 7 false negatives and 2 false positives for neoplasms, 1 false positive and 3 false negatives for malignancy. These are of concern. False positives usually are seen with Atypical or Follicular adenoma and colloid nodules. Paucicellularity, degenerative changes simulating malignancy are the other causes. [8,14,15] 1 follicular adenoma was misdiagnosed as medullary carcinoma on FNAC.
2 papillary carcinoma cases were misdiagnosed as non neoplastic on cytology(1 nodular colloid goiter and 1 nodular colloid goitre with adenomatous hyperplasia on FNA). Histopathology of one of these cases showed papillary carcinoma and nodular colloid goiter in adjacent thyroid. The papillae and pseudo papillae can be seen in Papillary carcinoma, Grave's disease and hyperplastic nodule. Characteristic nuclear features such as nuclear grooves in more than 20% of follicular cells and presence of more than three intranuclear inclusions in the enlarged nuclei on single aspirate is pathognomonic of papillary thyroid carcinoma. Nuclear features and high cellularity are valuable in diagnosis of papillary carcinoma. But in cases with cystic change in papillary carcinoma, low cellularity and degenerative changes could be the causes for false negative result. Ultrasound guided FNA would help to reduce such false negatives by sampling the small foci of malignancy and avoiding nonmalignant parts of the lesion. Though only 10-15% of the cysts are neoplastic, FNA from solid area would reduce the misinterpretation and false negativity in cystic neoplasms. [16,17,18] For  [6,8,[19][20][21][22][23][24][25][26] Akerman et al have quoted that the reasons for low sensitivity could be that tumor being missed at aspiration, misinterpretation of cytologic findings, cellular atypia, indeterminate diagnosis. [27] The difficulty in cytological diagnosis in certain cases is attributed to overlap of cytological patterns between neoplastic and non-neoplastic lesions. The differentiation between adenomatous nodule and follicular neoplasm is difficult. Increased nuclear size and pleomorphism, cellularity, the presence of microfollicles, scant and thick background colloid increase the likelihood of accurately detecting neoplasms. Haemorrhagic aspirate with microfollicles is seen in follicular neoplasms because of high microvessel density in the nodule. [1,28] Although many studies suggest features to differentiate the two, the diagnostic dilemma in interpretation of adenomatous hyperplasia and follicular neoplasm continues to concern.
Conclusion FNAC of solitary thyroid nodules has high specificity and efficacy.It is one of the rapid, reliable, cost effective procedures for the diagnosis of thyroid malignancy and effective management. In view of false negative results, in cases with high clinical suspicion of malignancy, a non neoplastic diagnosis on FNAC should be viewed with caution and advised periodic follow up.