The role of thyroid fine needle aspiration (FNA) cytology in a district general hospital setting

The pilot study was undertaken to evaluate the role of FNA cytology in the clinical management of patients with thyroid swelling, in a District General Hospital (DGH) setting. One hundred and eleven patients were investigated over a period of 3 years, with a total of 142 fine needle aspirations. Statistical analysis showed a sensitivity of 71%, a specificity of 91% and a false negative rate of 2.7%. These results compare very favourably with other institutions. This study therefore shows that thyroid nodule FNA cytology can be performed in a DGH with a high standard of diagnostic accuracy, the results of which play a key role in patient management.     

FNA diagnosis of poorly differentiated thyroid carcinoma. A review of the recent literature

Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell‐derived tumour that was recognised as a distinct entity by the World Health Organisation in 2004. The natural history and pathological features of PDTC are reported to be intermediate between those of well‐differentiated and undifferentiated (anaplastic) thyroid carcinomas. Preoperative identification of PDTC could facilitate better initial patient management in many cases, namely more extensive surgery, without any delay. However, according to some experts, a diagnosis of PDTC can only be rendered on histologic specimens based on criteria recommended in the Turin proposal. Although high‐grade features (namely necrosis and mitoses) can be recognised in FNA material, other cytomorphological features have limited value for the preoperative diagnosis of PDTC and specific features for a definitive diagnosis of PDTC have not yet been clearly defined. Here, we review the current status and future prospects for cytological recognition of PDTC; we emphasise the features that should raise suspicion of this rare condition in FNA cytology and provide an update on molecular features and management of PDTC. Despite proposed histological criteria for the diagnosis of PDTC, its recognition on routine thyroid cytology presents a notable challenge. Current and future advances in molecular testing could contribute to the cytological diagnosis of PDTC.     

Molecular testing of BRAF,RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy

Objective

Liquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations.

Methods

We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen.

Results

Mutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology.

Conclusions

Mutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.

     

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.     

Splenic lesions: FNA findings in 48 cases

OBJECTIVE: To study fine needle aspiration (FNA) cytological findings of splenic lesions and assess the role of FNA in the diagnosis of splenomegaly or splenic tumours. METHODS: This study consisted of 48 cases, 25 males and 23 females. The ages ranged between 3 and 71 years. Most of these cases were aspirated under ultrasonographic guidance and a small number were also aspirated directly by using a 22- to 23-gauge needles. The smears were stained with Wright-Giemsa and Papanicolaou methods. Special stains were used whenever necessary. RESULTS: In this study 14 cases were diagnosed as lymphoma-leukaemia, 7 cases as tuberculosis, 12 cases as kala-azar, 2 cases as hydatid cyst, 3 cases as storage diseases, 3 cases as simple cyst, 2 cases as myeloproliferative disorders, 2 cases as malignant tumours and 3 cases as hamartomas (these were wrongly diagnosed as malignant tumours). CONCLUSION: Splenic aspiration is a safe procedure and is very useful in the diagnosis of parasitic and infectious diseases, especially in endemic countries like Iran.     

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.     

EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology

Y. Aratake, K. Marutsuka, K. Kiyoyama, T. Kuribayashi, T. Miyamoto, K. Yakushiji, S. Ohno, Y. Miyake, T. Sakaguchi, T. K. Kobayashi, A. Okayama, K. Tamura and E. Ohno
EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology Objective: Extracellular matrix metalloproteinase inducer (EMMPRIN) and its induced matrix metalloproteinases (MMPs) play a crucial role in tumour progression, invasion and metastasis. EMMPRIN expression has been demonstrated in several tumours, but its expression profile in thyroid cancer remains unclear. Methods: We evaluated the expression profile of EMMPRIN at various stages of differentiation of thyroid carcinoma, including 20 cases of well‐differentiated papillary carcinoma (WDPC), 15 cases of papillary carcinoma with a poorly differentiated carcinoma component (PC/PDC) and four cases with an undifferentiated carcinoma (UDC) component, using paraffin‐embedded sections for immunohistochemical stains. Also, we used 32 fine needle aspiration cytology and imprint smears from the same cases for immunocytochemical stains. The staining results were evaluated with a scoring system. Results: Immunohistochemical staining showed that EMMPRIN expression was absent or weak in almost all WDPC specimens, whereas it was moderate or strong in PDC and UDC components. In tumours that showed a gradual morphological transformation from WDPC to PDC components, the expression of EMMPRIN was progressively stronger from the areas of WDPC to those of PDC. WDPC, PC/PDC and UDC had expression scores of 4.9, 45.0 and 245.7, respectively. Results of immunocytochemical staining showed almost the same staining profile as those of immunohistochemical staining. The cytological atypia of EMMPRIN‐positive cells was greater than that of negative cells. Conclusion: These results indicated that EMMPRIN expression correlates significantly with the degree of dedifferentiation of thyroid carcinoma. This study demonstrates the feasibility of expression of EMMPRIN using fine needle aspiration samples. Therefore, immunocytochemical analysis of EMMPRIN may be a novel aid to evaluate the differentiation of thyroid 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.     

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.     

Fine needle aspiration cytology of medullary thyroid carcinoma: a review of 18 cases

A series of 18 consecutive medullary thyroid carcinomas (MTC) diagnosed by fine needle aspiration cytology (FNAC) is described. The most important diagnostic cytologic criteria were the dispersed cell pattern, the polygonal appearance of the cells, binucleated cells and the presence of amyloid. Other less common cytologic features are reported and the variable microscopic appearance of MTC is pointed out. The possibility that this cytologic variability of MTC may be by itself an important diagnostic feature is proposed.     

Improved fine needle aspiration (FNA) cytology results with a near patient diagnosis service for breast lesions

This study is a review of the quality of FNA cytology results for breast lesions approximately 18 months before and 10 months after a change from a rapid diagnosis FNA service with consultant pathologist aspirators to a conventional FNA service with clinician aspirators of varied experience. The setting was symptomatic breast clinic in a large hospital in rural New Zealand acting as a tertiary referral centre for a population of 550,000. The results were collected retrospectively and prospectively. The quality of results for pathologist aspirators (total 810) and clinician aspirators (total 403) was compared using the definitions of the NHS Breast Screening Program Guidelines for Cytology Procedures and Reporting in Breast Cancer Screening. There were statistically significant differences in specificity (biopsy cases only) with 73% for pathologists and 49% for clinicians, specificity (full) with 74% and 56%, inadequate rate with 23% and 37%, and complete sensitivity with 76% and 67%. The use of pathologist aspirators allowed the specimens to be reported in a few minutes. Specimens taken by clinicians took at least 30 min to report. The financial aspects of the two approaches are discussed. When compared with clinician aspirators, pathologist aspirators obtained better quality results and these were reported more quickly.     

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.     

分子生物学法分析青少年甲状腺肿物临床病理及特点

探讨青少年甲状腺肿物的临床病理学特点,甲状腺癌的复发、转移和结节性甲状腺肿复发的可能相关因素。按WHO病理分型标准和国际抗癌联盟(UICC)TNM分期标准回顾性分析青少年甲状腺肿物124例及其中部分甲状腺癌和结节性甲状腺肿的随访资料。124例甲状腺肿物患者男女比例约为1 3,甲状腺癌39例(31.5%),其中乳头状癌35例,滤泡癌3例,髓样癌1例;甲状腺腺瘤59例(47.6%),结节性甲状腺肿11例(8.9%),结节性甲状腺肿伴腺瘤7例(5.6%),甲状腺炎5例(4%),甲状舌管囊肿3例(2.4%)。本组资料显示,青少年甲状腺癌以乳头状癌为主,其复发、转移与组织学亚型为弥漫硬化型及甲状腺包膜和其外软组织受侵状态相关。虽然常见淋巴结转移、肺转移以及局部侵犯周围软组织,但患者总体预后较好。结节性甲状腺肿的复发与病变弥漫位于双叶有关,而与患者性别、年龄和是否伴有乳头样及腺瘤样增生关系不密切。     

Cytoplasmic colloid inclusions in thyroid lesions: a cytomorphological study based on fine needle aspiration

INTRODUCTION: Intracytoplasmic lumens (ICL) with or without magenta material and transgressing vessels are features of Hürthle cell neoplasms (HCN). After detection of intracytoplasmic colloid inclusions (CIs) including targetoid (magenta) body-like structures in the Hürthle cells (HC) in a case of Hashimoto's thyroiditis (HT), we reviewed cases of HT, thyroid neoplasms, hyperplastic nodules (HN) and colloid goitres to determine the frequency of these structures. Further, an attempt was made to find out the significance of CIs. METHODS: FNA smears of 120 HT, 101 colloid goitres, 11 HN, and 76 neoplastic goitres were examined. The presence of CIs and empty ICL were noted in epithelial cells in these lesions. An attempt was made to find out the difference between HT with and without CIs in respect of various cytomorphologic features. The groups were compared using the Fisher's exact test of probability. RESULTS: The CIs were present in 36 (30.0%) of HT, 26 (34.2%) of neoplastic goitres, 3 (27.3%) of HN, and 4 (4.0%) colloid goitres. As compared to colloid goitres, CIs were present in a significant higher number of cases in HN (P = 0.0202), neoplastic goitres (P < 0.0001), and HT (P < 0.0001). Among neoplasms the frequency of CIs in HCN (75.0%) was significantly higher than that of papillary thyroid carcinoma (PTC) (33.3%, P = 0.0466), and follicular neoplasm (14.3%, P = 0.0083). The CIs were more frequent in HC in HT and HCN but in follicular cells (FC) in other lesions. The HT cases with CIs differed significantly from those without CIs in respect of HC and their cellularity, cellularity of reactive lymphoid cells, extracellular colloid and empty ICL. CONCLUSION: Care should be taken not to diagnose HT cases with an excessive Hürthle cell component and CIs, and PTC cases with Hürthlization and CIs, as HCN in FNA smears. Based on review of the literature and our findings, it is suggested that the Hürthle cell metaplasia in HT is a survival response of FC and the presence of CIs in Hürthle cell may represent their limited ability to synthesize colloid.     

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.