Fine needle aspiration cytology of thyroid nodules: how accurate is it and what are the causes of discrepant cases?

Fine-needle aspiration cytology (FNAC) is widely accepted as the most accurate, sensitive, specific and cost-effective diagnostic procedure in the assessment of thyroid nodules and helps to select people preoperatively for surgery. The purpose of this study was to evaluate the results of thyroid FNAC in our institution and to determine the reasons for discrepancies between the cytological and histological diagnosis. We evaluated the cytological and histological results of 254 FNACs obtained from 231 patients who underwent subsequent thyroid surgery. All of the material was blindly reviewed for quality control, by one experienced cytopathologist. All FNACs were carried out under ultrasound guidance. The cytological diagnosis was classified as benign, suspicious, malignant or unsatisfactory. The definitive histological study showed benign lesions in 195 of the 231 patients (84%). A benign diagnosis based on FNAC was correct in 105 of the 108 benign cases (97%). FNACs diagnosed as 'suspicious' resulted in a distribution of 49 benign (79%) and 13 malignant (21%) diagnoses. FNAC showed malignancy in 34 cases (13%) and in only one case did the final histology differ from cytology (correlation 97%). The percentage of FNACs that were inadequate for diagnosis was 20%. Review of cytological and histological slides did not lead to any change in the original diagnosis. Our study revealed a cytological-histological discrepancy (2%) in only 4 out of 231 cases over a period of 10 years, due to either a diagnostic or sampling error.     

The role of liquid-based cytology in the investigation of thyroid lesions

Objective:  This study investigates the role of liquid-based cytology by ThinPrep^® technique in the detection of thyroid lesions.
Methods:  In all, 252 specimens from 157 patients for pre-operative evaluation of thyroid nodules, prepared by the ThinPrep^®, were examined. In all cases thyroidectomy followed the initial cytological evaluation. All cytological diagnoses were correlated to the histological ones.
Results:  According to our findings, a sensitivity of 87.80%, a specificity of 99.50%, a positive predictive value of 97.30%, a negative predictive value of 97.56% and an overall accuracy of 97.52% were observed in fine needle aspiration cytology in correlation to the histological diagnosis after thyroidectomy.
Conclusions:  ThinPrep^® technique is a valid method for the pre-operative cytological diagnosis of thyroid nodules, offering the possibility of ancillary techniques, such as immunocytochemical and molecular methods and can, therefore, be potentially complementary to histological evaluation for further investigation of follicular lesions.     

Evaluation of fine needle aspiration (FNA) cytology in the diagnosis of thyroid nodules

FNA cytology of 112 patients with thyroid nodules seen in a 5-year period in a general hospital setting, and the histology obtained from the 53 operated patients, were retrospectively analysed. the inadequacy rate of FNA cytology was 11%, sensitivity was 84% (16/19), specificity was 52% (15/29), positive predictive value was 53% (16/30) and negative predictive value was 83% (15/18). Extrapolating these figures to the whole study group a negative predictive value of 95% is put forward as a more realistic figure. the results and the clinical pitfalls of the use of FNA cytology in diagnosing thyroid nodules are discussed. the authors conclude that FNA cytology is a reliable first diagnostic step in the diagnosis of thyroid nodules, even in a general hospital setting.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

The number of nucleoli in benign and malignant thyroid lesions: a useful diagnostic sign in cytological preparations

The slides of fine needle aspiration cytology specimens from 99 cases of cold thyroid nodules with known histology were reviewed and the number of nucleoli per nucleus counted and correlated with the different histopathological groups. Significant differences were observed between benign and malignant thyroid lesions in the number of nucleoli in the cytological material. Lower values were present in nodular goitres and follicular adenomas compared to carcinomas. In benign lesions the majority of nuclei contained one nucleolus and nuclei with two, three or more nucleoli were less frequent than in follicular, papillary, medullary and anaplastic carcinomas. Only one case of follicular adenoma had cells containing three or more nucleoli compared to more than half the cases of follicular carcinoma.     

Fine needle aspiration cytology of the thyroid: a comparison of 5469 cytological and final histological diagnoses

OBJECTIVE: We evaluated the efficacy of fine needle aspiration cytology (FNAC) of the thyroid in a series of 5469 lesions with histological control and studied the causes of, and the possibility of reducing the limitations of the method. METHODS: FNAC was always performed by a pathologist under the guidance of a clinician, using a 22-gauge needle. Generally two aspirations were carried out, and usually four slides were obtained for each nodule; they were then stained with May-Grünwald-Giemsa and with Papanicolaou. The cytological diagnoses were classified in four groups: inadequate, benign, suspicious and malignant. RESULTS: We obtained a complete sensitivity of 93.4%, a positive predictive value of malignancy of 98.6%, and a specificity of 74.9%. At histological control, the cytological diagnosis of Hurthle cell neoplasm corresponded to a significantly higher incidence of malignant neoplasms than the diagnosis of non-Hurthle cell follicular neoplasm (32.1% versus 15.5%). There were 66 false-negative findings, the main cause of diagnostic error (24 cases) being failure to recognize the follicular variant of papillary carcinoma. The number of inadequate FNACs was low (4.2%). CONCLUSION: Our study confirmed the great efficacy of thyroid FNAC. A cytological diagnosis of Hurthle cell neoplasm should be considered an indicator of high risk. Awareness that failure to recognize the follicular variant of papillary carcinoma was the main problem in the interpretation of thyroid FNAC should lead to a decrease of false-negative diagnoses. The inadequate rate was very low, as it was the pathologist personally who performed the needle aspiration.     

Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thyroid: correlation with histopathology in 260 cases

Objectives:  Fine needle aspiration cytology (FNAC) of the thyroid is a non-invasive, cost-effective screening procedure that is valuable for distinguishing neoplastic lesions from non-neoplastic nodules. The aim of this study was to determine the diagnostic accuracy of FNACs performed at our institution by correlating FNAC results with histopathological diagnoses.
Methods:  Two hundred and seventy-one aspiration cytology specimens followed by thyroidectomy were included in the study, and the results of 260 adequate FNACs were compared with their histological diagnoses.
Results:  The sensitivity and specificity of thyroid FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15 (5.7%) false positives and six (2.3%) false negatives.
Conclusions:  The results showed that follicular cells that exhibit some of the features of papillary carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis, leading to a diagnostic pitfall. In addition, cellularity and overlapping cytological criteria in hyperplasia might lead to a false diagnosis.     

Fine needle aspiration cytology of primary lymphoma of the thyroid: a report of 17 cases.

Between 1980 and 1998, 4272 thyroid surgical specimens with a preoperative fine needle aspirate were sent to our Anatomical Pathology Department. Among these cases there were 17 primary thyroid lymphomas, which constituted 0.3% of all the thyroid lesions and 2.3% of the thyroid malignancies. Seven cases were diffuse large B-cell (DLBC) lymphomas and 10 were MALT lymphomas. Of the DLBC lymphomas six were correctly diagnosed by fine needle aspiration cytology (FNAC) and one was diagnosed as positive for malignancy, and among MALT lymphomas four were diagnosed as lymphoma, four as suspicious for lymphoma, and three as Hashimoto's thyroiditis (HT). Our data indicate that the diagnosis of primary thyroid lymphoma of high grade is easy, and immunocytochemistry (ICC) can confirm suspicious cases. The diagnosis of MALT lymphoma is more difficult; ICC can confirm suspicious cases, and false-negative results seem to be caused by sampling error, because HT usually coexists with MALT lymphoma.     

Diagnostic difficulties in the interpretation of fine needle aspirates of salivary gland lesions: the problem revisited

Diagnostic difficulties in the interpretation of he needle aspirates of salivary gland lesions: the problem revisited
Cases of salivary gland lesions ( n =325), mainly neoplastic but including a small number of non-neoplastic lesions, investigated by fine needle aspiration (FNA) and with histological correlation, are reviewed. The review identified a number of differential diagnostic problems which are discussed in some detail. One false-positive and eight false-negative diagnoses had been made resulting in a 99.5% specificity and a 85.5% sensitivity. If type-specific diagnoses are made only when all defined diagnostic criteria are present and if any uncertainty is clearly conveyed to the clinician, FNA is a safe and accurate tool in the investigation of salivary gland lesions.     

Management of thyroid cytological material,preanalytical procedures and bio‐banking

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on‐site evaluation, sample collection methods (conventional slides, liquid‐based methods, cell blocks) and storage (bio‐banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid‐based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed.     

Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features--multi-layered rosettes, branching monolayered sheets and balls of thick pinkish colloid--were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.     

Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases

S. Kaushal, V. K. Iyer, S. R. Mathur and R. Ray
Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases Background: The cytological features of variants of medullary carcinoma of the thyroid (MCT) are sparsely documented in the literature from case reports. Detailed cytomorphological analysis of MCT variants and features helping to distinguish them from usual MCT are presented here. Materials and methods: A total of 78 aspirates with a diagnosis of MCT over a period of 10 years were re‐evaluated. Cytomorphological details were reviewed and semiquantitatively analysed. Histology slides were reviewed in 36 cases. Results: Most aspirates showed classical features of dispersed polygonal or plasmacytoid cells with areas of spindling. In 54 aspirates, a definite cytological diagnosis of medullary carcinoma was made, which in 87.1% was based on cytomorphology alone and in 12.9% was based on immunocytochemistry for calcitonin. In 30.1% of aspirates from MCT, a guarded report of tumour was given in the absence of calcitonin immunocytochemistry. Of the 78 cases, nuclear grooves were seen in 5.1%, intranuclear cytoplasmic inclusions in 28.2%, cytoplasmic granularity in 23.1% and bizarre cells with abrupt anisocytosis in 85.9%. A follicular arrangement was seen in 14.1% and was more frequent in the follicular type (one case) and mixed follicular and medullary carcinoma (one case). Melanin production was seen in aspirates from two cases. One case of the giant cell type of MCT was seen, in which background cells showed large pleomorphic nuclei and numerous bizarre tumour giant cells, prompting a differential diagnosis with anaplastic carcinoma. One example each of the small cell type, paraganglioma‐like MCT and papillary MCT were seen. Conclusions: MCT has uniform cytological features in the majority of aspirates, including many of the histological variants. Searching for pigment in every aspirate of MCT may be rewarding. The giant cell type of MCT is rare and has to be differentiated from anaplastic carcinoma.     

Thin layer compared to direct smear in thyroid fine needle aspiration

The efficacy of preparing thyroid fine needle aspirations (FNAs) by the thin layer as opposed to the direct smear method has not been evaluated sufficiently in a regional laboratory setting. At the Foothills Hospital (Calgary, Canada), the method of processing thyroid FNAs was changed from direct smear to thin layer in January 1996. The results of 327 patients who had direct smear from 1994 to 1995 were compared to 401 who had thin layer between 1996 and 1997. While there were no significant differences across a broad range of quality indicators, thin layer showed a trend towards a higher proportion of true benign diagnoses (31% vs 24%), a lower proportion of inadequate specimens (41% vs 50%) and, most importantly, a lower false negative rate (3% vs 9%). In conclusion, the changeover to thin layer did not compromise the interpretation of thyroid FNAs.     

Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis

OBJECTIVES: Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto-diagnosis of 30 STT cases. METHODS: Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red-green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining. RESULTS: Among the 30 cases in the present study, unaided cytological diagnoses ranged from 'spindle cell' tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto-diagnosis with FICC, and histopathology results was 83.3% (P < 0.05). CONCLUSION: Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico-cytological correlation is recommended in forming an exact diagnosis in these cases.