Correlation of ultrasonography guided fine needle aspiration cytology of thyroid nodules with histopathology

Materials and Methods: The study was performed in the Department of Pathology, National Academy of Medical Sciences, Bir Hospital over a period of one year. Fine needle aspiration of solid area of thyroid nodule was done in each case with USG guidance. FNAC results were classified according to Bethesda system of reporting. Finally, comparison was done between cytological and histological findings.


INTRODUCTION
The prevalence of thyroid nodules is reported to be 4-7 percent.Of these, one in twenty nine turn out to be malignancy.1Onlyabout 20% of patients undergoing thyroid surgery for suspicion of malignancy after fine needle aspiration cytology actually show malignancy in histopathology.Prior to advent of FNAC, about 50% of the patients with thyroid nodules were operated, with malignancy found in up to 0.55 to 25 percent.Moreover 20-48% of patients with single palpable thyroid nodule are found to have additional nodules when investigated by ultrasonography. 2  Of these, selected patients can be advised for surgery on the basis of FNAC report and rest can be FNAC is simple, minimally invasive, and cost effective.It is considered as the gold standard investigation in diagnosis of thyroid nodules.It provides highly accurate cytological information from which a definitive management plan can be formulated.FNAC has high sensitivity and specificity approaching to 96%.Several studies have reported that USG-FNAC not only reduces the inadequacy rate but also helps to accurately select the patients who actually need surgery; hence, avoiding unnecessary diagnostic thyroidectomies. 3owever, even FNAC has limitations because of low yield of cells and inability to distinguish follicular adenoma from follicular carcinoma.
In this study, fifty patients with thyroid nodules were enrolled.USG-FNAC diagnosis was made and histopathology examination was done following thyroid surgery from ENT-HNS department.Correlation between cytology and histology was done to determine the role of FNAC in thyroid nodules.

MATERIALS AND METHODS
Patients underwent an ultrasound-guided fine-needle aspiration of the thyroid nodules.Prior to conduction of this study, permission was obtained from institutional review committee.Patients of all ages, both male and female who underwent surgery for thyroid swelling with subsequent histopathological study of excised tissue, were included in this study.
Fine needle aspiration of solid area of thyroid nodule was done in each case with USG guidance.Aspiration technique with 23 Gauge needle connecting to a 10-ml syringe was used.Multiple needle passes, usually 3-4 times were made within the lesion at varying angles and depths and with constant negative pressure.Before final withdrawal, the negative pressure was released prior to the needle emerging out from the skin.The cytological material was transferred on to glass slides.The aspirated material was then smeared on 2-4 slides, fixed in 95% ethanol and stained by Papanicoloau stain.The air dried slides were stained with Giemsa stain.The stained slides were seen under light microscope and the FNAC results were classified according to Bethesda system of reporting.The biopsy specimen which was well fixed in 10 % formalin solution, was grossed, processed through automatic tissue processor and stained with H&E stain.Data were collected in Microsoft Excel and were analyzed in SPSS vs. 17.

RESULTS
The age of patients ranged from 16 -70 years.Female to male ratio was 9:1.FNAC diagnosis was made based on Bethesda system of reporting.According to Bethesda system of reporting, nodular hyperplasia, adenomatoid nodule, colloid nodule and colloid goiter were kept under the term 'Benign follicular nodule'.Twenty eight cases (56%) were of follicular nodule, eight cases (16%) were of papillary carcinoma (fig.1), four cases (8%) were of suspicious of follicular neoplasm, three cases (6%) were of suspicious of malignancy, two cases (4%) were of medullary carcinoma (fig.2), two cases (4%) were of follicular lesion of undetermined significance and one case (2%) was of Hashimoto thyroiditis (fig.3).In two cases (4 %) appropriate cytological diagnosis could not be given due to lack of adequate cellular components.These cases were labeled 'inadequate for evaluation'.

DISCUSSION
FNAC is the first line of investigation on thyroid swellings.It provides diagnosis with reasonable accuracy.Management plan can be based on the FNAC diagnosis.If the swelling is diagnosed as benign, patient can be advised for wait and watch policy.But malignant nodules need to be intervened outright with surgery.FNAC has proved to be a great tool to the clinicians as regards decision making in treatment.
FNAC is a reliable test and correct diagnosis can be achieved.But there are some shortcomings as well.Occasionally, only fluid is aspirated and no cells are appreciated in the slide, in which cases a diagnosis cannot be made.Such cases have to be labeled 'inadequate for evaluation'.Repeat test has to be requested in such circumstances.Follicular carcinoma is another arena where FNAC diagnosis falls short.
Since the introduction of USG guided FNAC (USG-FNAC), several studies have reported that USG-FNAC not only reduces the inadequacy rate but also helps to accurately select the patients for surgery. 3Unnecessary thyroidectomies can be avoided with such line of investigation.It does this by selection of the biopsy site.Cystic areas and coarse calcification are also avoided.Its role has been found useful in detecting micro-carcinomas, cystic carcinomas, malignancy associated with benign conditions for example Hashimoto's thyroiditis.Rates of nondiagnostic FNAC results can be reduced with USG-FNAC.However, nondiagnostic samplings still do occur with USG-FNAC too.
The age range and female: male ratio found from this study correlates with similar other studies.[6][7] In the present study, as per Bethesda system of reporting, diagnosis of follicular nodule encompassed colloid nodule, colloid goiter and adenomatoid nodule.Similarly, neoplastic group comprised of diagnosis of suspicious for malignancy, suspicious for follicular neoplasm, papillary carcinoma, medullary carcinoma and follicular lesion of undetermined significance.Two cases could not be diagnosed because of lack of cellular components.In 'Role of fine needle aspiration cytology in diagnosis and management of thyroid lesions' by Uma H, Sukant G, Harsh M, Nitin N , it is elaborated that among 434 cases, twenty two cases were diagnosed as inadequate because of lack of cellularity.Most common lesion was colloid goiter, followed by thyroiditis8.Others were adenomatous goiter and thyroglossal cysts among non-neoplastic lesions.Neoplastic group in FNAC comprised of Hurthle cell neoplasm, papillary carcinoma, medullary carcinoma, anaplastic carcinoma and metastatic carcinoma.
Most of our cases regarding follicular nodule showed moderate cellularity comprising of sheets and clusters of cohesive, evenly spaced, uniform follicular epithelial cells.The background showed abundant colloid and colloid laden macrophages along with red blood cells.Uma H, Sukant G, Harsh M, Nitin N have mentioned the cytologic features of colloid goiter as: follicular epithelial cells, cyst macrophages (59.4%), fire flares (6.34%), lymphocytic infiltrate (2.38%) and Hurthle cell changes (1.58%). 8The smears diagnosed as papillary cell carcinoma showed increased cellularity of tumor cells arranged in monolayered sheets, papillae and clusters.The individual tumor cells were moderate in size, most of them cuboidal in shape with scant cytoplasm and nuclei with "powdery" chromatin.In most of the cases nuclei displayed grooves and pseudo inclusions in few cases.Some of these nuclei exhibited small nucleolus as well.
The thick and irregular nuclear border along with nuclear crowding and overlapping were also noted in the smears.However, psammoma bodies and multinucleated giant cells  were not seen in any of these smears.Papillary carcinoma cases were diagnosed by Uma H, Sukant G, Harsh M, Nitin N based on features of papillary clusters of cells with pale nuclei, intranuclear cytoplasmic invaginations, irregular nuclear outlines, and nuclear grooves. 8Hurthle cell changes were noted in five cases and psammoma bodies were seen in three cases.Ali N, Alaa J H, Rasha K A included following criteria for cytological diagnosis of papillary thyroid carcinoma: hypercellularity, papillary configuration, large hyperchromatic nuclei and opened chromatin. 9Basharat R, Bukhari MH, Saeed S, Hamid T have stressed that slides of papillary thyroid carcinoma showed hypochromasia/pallor, nuclear grooves, intranuclear cytoplasmic inclusions, ovoid nucleus, and micronucleus. 10ere were cases of smears suspicious for follicular neoplasm.The smears showed increased cellularity of follicular epithelial cells arranged in clusters, microfollicles and sheets.Cells were moderately pleomorphic with hyperchromatic nuclei and some even had prominent nucleoli.It also showed scant colloid material in the background.Basharat R, Bukhari MH, Saeed S, Hamid T have described the presence of marked cellularity, discohesion and microfollicles in cases of follicular neoplasm.Marked nuclear atypia, mitosis and necrosis were uncommon in their study. 10Follicular neoplasm was diagnosed by Uma H, Sukant G, Harsh M, Nitin N when smears showed follicular epithelial cells distributed in follicular structures or sheets with a small quantity of colloid.If oxyphilic cells dominated, diagnosis of Hurthle cell neoplasm was made. 8e diagnosis of medullary carcinoma was made in two cases.The aspiration smears showed highly cellular areas of cells arranged predominantly dispersed singly.The individual cells were moderately pleomorphic consisting predominantly of plasmacytoid cells.Amyloid like material was seen.Uma H, Sukant G, Harsh M, Nitin N 8 have discussed that there were three cases of medullary carcinoma, which showed the presence of cuboidal to rounded cells with oval, eccentric, pleomorphic nuclei with abundant cytoplasm.Congo red-positive material was seen in one case.
In the present study, sensitivity and specificity of FNAC (USG-FNAC) were calculated to be 93.33 % and 100 % respectively.Similarly, positive predictive value and negative predictive value were 100 % and 97.05 %, while diagnostic accuracy was 97.91 %.][13] Chandanwale S, Singh N, Kumar H, Pradhan P, Gore C, Rajpal M derived sensitivity, specificity, diagnostic accuracy, PPV and NPV of FNAC as 90 %, 100 %, 87.5 %, 100 % and 90 % respectively.14Meraj FA, Fatemah SR, Perviz FA found sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy to be 89.6 %, 100 %, 100 %, 65 % and 91.25 % respectively.They have emphasized that FNAC is an acceptable and affordable method for diagnosis of thyroid nodules.They have stressed that FNAC and ultrasound studies, significantly reduces unnecessary surgery. 15Prakash JM, Jyothi BL, Hiremath SS, Kishanprasad HL, Nagesh T S, Joshua DJM have concluded that FNAC is a good diagnostic tool for solitary thyroid nodules, while ultrasound guided FNAC would have been better option for increasing accuracy of the diagnosis. 16Gupta M, Gupta S, Gupta BV have emphasized that FNAC diagnosis of malignancy is highly significant and such patients should be subjected to surgery. 17They have also discussed that benign FNAC diagnosis should be viewed with caution as false negative results do occur and these patients should be followed up.Clinical suspicion of malignancy even in the presence of benign FNAC requires surgery.Basharat R, Bukhari MH, Saeed S, Hamid T have concluded that FNAC should be advised for every patient with thyroid nodule for exclusion of malignancy.According to them, as FNAC is a sensitive, specific, an inexpensive, and accurate procedure, it should be adopted as an initial investigation of thyroid diseases in all tertiary hospitals. 10

CONCLUSION
Sensitivity and specificity of USG-FNAC was 93.33 % and 100 %, respectively.The study showed significant correlation between FNAC (USG-guided in this study) and histopathology.Because of high sensitivity and specificity, USG guided FNAC should be adopted as an initial investigation modalities for thyroid disease.