Objectives: Fine-needle aspiration biopsy is regarded as the most important diagnostic tool for thyroid lesions because of its simplicity, safety, and cost-effectiveness. However, its pivotal role in the correct characterization of the majority of nodules is impaired by the difficulties in discriminating benign from malignant follicular-patterned lesions. Study Design: Liquid-based cytology (LBC) is a semiautomated device that has recently become widely available and has gained popularity as a method of collecting and processing both gynecologic and nongynecologic cytologic specimens. It achieves a diagnostic sensitivity as accurate as conventional preparations, especially for its excellent cell preservation and lack of background which decrease the amount of inadequate diagnoses. Results: In many cases the cytologic features are similar in both methods, but the colloid film and the lymphocytic component are more easily evaluated on direct smears whereas nuclear details and colloid globules are better evaluated in LBC slides. The material stored in the preservative solution could be effectively used for the application of immunocytochemical and molecular techniques. Conclusions: LBC-processed biopsies represent a valid alternative to conventional cytology. The possibility of applying additional techniques enhances the efficacy of the cytologic diagnosis of thyroid lesions.

Keywords:
Thyroid nodules, Fine-needle aspiration cytology, Liquid-based cytology
1.
Fadda G, LiVolsi VA: Histology and aspiration cytology of benign thyroid diseases (in Italian). Rays 1999;24:182–196.
2.
Galera-Davidson H, Gonzalez-Campora R: Thyroid; in Bibbo M, Wilbur D (eds): Comprehensive Cytopathology, ed 3. Philadelphia, Saunders Elsevier, 2008, pp 633–670.
3.
Gharib H, Goellner JR, Johnson DA: Fine-needle aspiration cytology of the thyroid: a 12-year experience with 11,000 biopsies. Clin Lab Med 1993;13:699–709.
4.
Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A: Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules. Thyroid 1998;8:15–21.
5.
Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, Panunzi C, Rinaldi R, Toscano V, Pacella CM: Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab 2002;87:1941–1946.
6.
Redman R, Zalaznick H, Mazzaferri EL, Massoll NA: The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules. Thyroid 2006;16:55–60.
7.
Rossi ED, Fadda G: Thin-layer liquid-based preparation of exfoliative non-gynaecologic and fine-needle aspiration biopsy cytology. Diagn Histopathol 2008;14:563–570.
8.
Duncan LD, Forrest L, Law WM, et al: Evaluation of thyroid needle aspiration cytology: can ThinPrep be used exclusively to appropriately triage patients having a thyroid nodule? Diagn Cytopathol 2011;39:341–348.
9.
Rossi ED, Raffaelli M, Zannoni GF, Pontecorvi A, Mulè A, Callà C, Lombardi CP, Fadda G: Diagnostic efficacy of conventional as compared to liquid-based cytology in thyroid lesions: evaluation of 10,360 fine needle aspiration cytology cases. Acta Cytol 2009;53:659–666.
10.
Lee KR, Papillo JL, St John T, Eyerer GJ: Evaluation of the ThinPrep processor for fine needle aspiration specimens. Acta Cytol 1996;40:895–899.
11.
Biscotti CV, Hollow JA, Toddy SM, Easley KA: Thin prep versus conventional smear cytological preparations in the analysis of thyroid fine-needle aspiration specimens. Am J Clin Pathol 1995;104:150–153.
12.
Poller DN, Ibrahim AK, Cummings MH, Mikel JJ, Boote D, Perry M: Fine-needle aspiration of the thyroid. Cancer 2000;90:239–244.
13.
Linder J: Recent advances in thin-layer cytology. Diagn Cytopathol 1998;18:24–32.
14.
Frost AR, Sidaway MK, Ferfelli M, Tabbara SO, Bronner NA, Brosky KR, Sherman ME: Utility of thin-layer preparations in thyroid fine-needle aspiration. Cancer 1998;84:17–25.
15.
Fadda G, Rossi ED, Raffaelli M, Mulè A, Pontecorvi A, Miraglia A, Lombardi CP, Vecchio FM: Fine-needle aspiration biopsy of thyroid lesions processed by thin-layer cytology: one-year institutional experience with histologic correlation. Thyroid 2006;16:975–981.
16.
Cochand-Priollet B, Prat JJ, Polivka M, Thienpont L, Dahan H, Wassef M, Guillausseau PJ: Thyroid fine needle aspiration: the morphological features on ThinPrep slide preparations – eighty cases with histological control. Cytopathology 2003;14:343–349.
17.
Geers AJ, Bourgain C: Liquid-based FNAC of the thyroid: a 4-year survey with SurePath. Cancer Cytopathol 2011;119:58–67.
18.
Bishop-Pitman M, Abele J, Ali SZ, Duick D, Elsheikh TM, Brooke JR, Powers CN, Randolph G, Renshaw A, Scoutt L: Techniques for thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:407–424.
19.
Saleh HA, Hammoud J, Zakaria R, Khan AZ: Comparison of Thin-Prep and cell block preparation for the evaluation of thyroid epithelial lesions on fine needle aspiration biopsy. Cytojournal 2008;25:3.
20.
Rossi ED, Raffaelli M, Minimo C, Mule A, Lombardi CP, Vecchio FM, Fadda G: Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies. Cancer 2005;105:87–95.
21.
Gharib H: Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract 2004;10:31–39.
22.
Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA, Moore FD, Kim BW, Nosé V, Marqusee E, Larsen PR, Alexander EK: Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer 2007;111:508–516.
23.
Haider AS, Rakha EA, Dunkley C, Zaitoun AM: The impact of using defined criteria for adequacy of fine needle aspiration cytology of the thyroid in routine practice. Diagn Cytopathol 2011;39:81–86.
24.
Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Bishop-Pitman M, Abati A: The National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference: a summation. Cytojournal 2008;5:6.
25.
Chow LS, Gharib H, Goellner JR, Van Heerden JA: Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Thyroid 2001;11:1147–1151.
26.
Guidelines of the Papanicolaou Society of Cytopathology for the examination of fine-needle aspiration specimens from thyroid nodules: the Papanicolaou Society of Cytopathology Task Force on Standards of Practice. Diagn Cytopathol 1996;15:84–89.
27.
Rossi ED, Morassi F, Santeusanio G, Zannoni GF, Fadda G: Thyroid fine-needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results. Cytopathology 2010;21:97– 102.
28.
Bellantone R, Lombardi CP, Raffaelli M, Traini E, De Crea C, Rossi ED, Fadda G: Management of cystic or predominantly cystic thyroid nodules: the role of ultrasound-guided fine-needle aspiration biopsy. Thyroid 2004;14:37–43.
29.
Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, Vielh P, DeMay RM, Sidawy MK, Frable WL: Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008;36:425–437.
30.
Hasteh F, Pang Y, Pu R, Michael CW: Do we need more than one ThinPrep to obtain adequate cellularity in fine needle aspiration? Diagn Cytopathol 2007;35:740–743.
31.
British Thyroid Association: Guidelines for the Management of Thyroid Cancer, ed 2. London, Royal College of Physicians of London, 2007.
32.
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Shlumberger M, Sherman SI, Steward DL, Tuttle RM: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1–48.
33.
Busseniers AE, Oertel YC: ‘Cellular adenomatoid nodules’ of the thyroid: review of 219 fine-needle aspirates. Diagn Cytopathol 1993;9:351–354.
34.
Tulecke MA, Wang HH: ThinPrep for cytologic evaluation of follicular thyroid lesions: correlation with histologic findings. Diagn Cytopathol 2003;30:7–13.
35.
Yang J, Schnadig V, Logrono R, Wassermann PG: Fine-needle aspiration of thyroid nodules: a study of 4,703 patients with histologic and clinical correlations. Cancer 2007;111:306–315.
36.
MacDonald L, Yazdi HM: Fine needle aspiration biopsy of Hashimoto’s thyroiditis: sources of diagnostic error. Acta Cytol 1999;43:400–406.
37.
Kumar N, Ray C, Jain S: Aspiration cytology of Hashimoto’s thyroiditis in an endemic area. Cytopathology 2002;13:31–39.
38.
Das DK: Marginal vacuoles (fire-flare appearance) in fine needle aspiration smears of thyroid lesions: does it represent diffusing out of thyroid hormones at the base of follicular cells? Diagn Cytopathol 2006;34:277–283.
39.
Anderson SR, Mandel S, LiVolsi VA, Gupta PK, Baloch ZW: Can cytomorphology differentiate between benign nodules and tumors arising in Graves’ disease? Diagn Cytopathol 2004;31:64–67.
40.
Fadda G, Basolo F, Bondi A, Nardi F, Basolo F, Bussolati G: Cytological classification of thyroid nodules: Proposal of the SIAPEC-IAP Italian Consensus Working Group. Pathologica 2010;102:405–408.
41.
Bronner MP, LiVolsi VA: Oxyphilic (Askenazy/Hürthle cell) tumors of the thyroid: microscopic features predict biologic behavior. Surg Pathol 1988;1:137–150.
42.
Carcangiu ML, Bianchi S, Savino D, Voynick IM, Rosai J: Follicular Hürthle cell tumors of the thyroid gland. Cancer 1991;68:1944–1953.
43.
Mete O, Asa SL: Oncocytes, oxyphils, Hürthle, and Askanazy cells: morphologic and molecular features of oncocytic thyroid nodules. Endocr Pathol 2010;21:16–24.
44.
Pu RT, Yang J, Wassermann PG, Bhuiya T, Griffith KA, Michael CW: Does Hürthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol 2006;34:330–334.
45.
Giorgadze TA, Rossi ED, Fadda G, Gupta PK, LiVolsi VA, Baloch ZW, et al: Does the fine-needle aspiration diagnosis of ‘Hürthle cell neoplasm/follicular neoplasm with oncocytic features’ denote increased risk of malignancy? Diagn Cytopathol 2004;31:307–312.
46.
Nguyen GK, Husain M, Akin MR: Cytodiagnosis of benign and malignant Hürthle cell lesions of the thyroid by fine-needle aspiration biopsy. Diagn Cytopathol 1999;20:261–265.
47.
Renshaw AA: Hürthle cell carcinoma is a better gold standard than Hürthle cell neoplasm for thyroid fine-needle aspirates: defining more consistent and specific cytologic criteria. Cancer 2002;96;261–266.
48.
Elliott DD, Pitman MB, Bloom L, Faquin WC: Fine-needle aspiration biopsy of Hürthle cell lesions of the thyroid gland: a cytomorphologic study of 139 cases with statistical analysis. Cancer 2006;108:102–109.
49.
Montone KT, Baloch ZW, LiVolsi VA: The thyroid Hürthle (oncocytic) cells and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008;8:1241–1250.
50.
Sanchez N, Sevaggi SM: Utility of cell block in the diagnosis of thyroid aspirates. Diagn Cytopathol 2006;34:89–92.
51.
Ravetto C, Colombo L, Dottorini ME: Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients. Cancer 2000;90:357–363.
52.
Lu L, Gu F, Dai WX: Clinical and pathological features of Riedel’s thyroiditis. Chin Med Sci J 2010;25:129–134.
53.
Malle D, Valeri RM, Pazaitou-Panajiotou K, Kiziridou A, Vainas I, Destouni C: Use of thin-layer technique in thyroid fine needle aspiration. Acta Cytol 2006;50:23–27.
54.
Cavaliere A, Colella R, Puxeddu E: Fine needle aspiration cytology of thyroid nodules: convetional vs. thin layer cytology. J Endocrinol Invest 2008;31:303–308.
55.
Rossi ED, Raffaelli M, Mulè A, Zannoni GF, Pontecorvi A, Santeusanio G, Minimo C, Fadda G: Relevance of immunocytochemistry on thin-layer cytology in thyroid lesions suspicious for medullary carcinoma: a case-control study. Appl Immunohistochem Mol Morphol 2008;16:548–553.
56.
Papi G, Corsello SM, Cioni K, Corrado S, Scaltriti L: Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: a multicenter study. J Endocrinol Invest 2006;29:427–437.
57.
Colasacco C, Mount S, Leiman G: Documentation of immunocytochemistry controls in the cytopathologic literature: a meta-analysis of 100 journal articles. Diagn Cytopathol 2011;39:245–250.
58.
Pazaitou-Panayiotou K, Mygdakos N, Boglou K, et al: The immunocytochemistry is a valuable tool in the diagnosis of papillary thyroid cancer in FNAs using liquid-based cytology. J Oncol 2010;2010:963926.
59.
Leung SW, Bedard YC: Immunocytochemical staining on ThinPrep processed smears. Mod Pathol 1996;9:304–306.
60.
Dabbs D, Abendroth CS, Grenko RT, Wang X, Radcliffe GE: Immunocytochemistry on the thin prep processor. Diagn Cytopathol 1997;17:388–392.
61.
Grubbs EC, Rich TA, Li G: Recent advances in thyroid cancer. Curr Probl Surg 2008;45:156–250.
62.
Schmitt FC, Longatto-Filho A, Valent A: Molecular techniques in cytopathology practice. J Clin Pathol 2008;61:258–267.
63.
Xing M: BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 2007; 28:742–762.
64.
Zhang Y, Fraser JL, Wang HH: Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep preparations. Diagn Cytopathol 2001;24:378–383.
65.
Nikiforov YE, Steward DL, Robinson-Smith TM: Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009;94:2092–2098.
66.
Nikiforova MN, Nikiforov Y: Molecular diagnostics and predictors in thyroid cancer. Thyroid 2009;19:1351–1361.
67.
Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R, Sobrinho-Simoes M: BRAF mutations and RET/PTC rearrangements are alternative events in the ethiopathogenesis of PTC. Oncogene 2003;22:4578–4580.
68.
Cheung CC, Carydis B, Ezzat S: Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer. J Clin Endocrinol Metab 2001;86:2187–2190.
69.
Musholt TJ, Fottner C, Weber MM: Detection of papillary carcinoma by analysis of BRAF and RET/PTC1 mutations in fine-needle aspiration biopsies of thyroid nodules. World J Surg 2010;2:2595–2603.
70.
Eszlinger M, Paschke R: Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol 2010;322:29–37.
71.
Park SY, Park YJ, Lee YJ, et al: Analysis of differential BRAF(V600E) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci. Cancer 2006;107:1831–1838.
72.
Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R, Sobrinho-Simoes M: BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Arch 2004;444:572–576.
73.
Ohori NP, Nikiforova MN, Schoedel KE: Contribution of molecular testing to thyroid fine-needle aspiration cytology of ‘follicular lesion of undetermined significance/atypia of undetermined significance’. Cancer Cytopathol 2010;118:17–23.
74.
Moses W, Weng J, Sansano I: Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg 2010;34:2589–2594.
75.
Saleh HA, Hammoud J, Zakaria R, Khan AZ: Comparison of Thin-Prep and cell block preparation for the evaluation of thyroid epithelial lesions on fine needle aspiration biopsy. Cytojournal 2008;25:3.
76.
Fadda G, Rossi ED, Martini M, Lombardi CP, Zannoni GF, Vellone VG, Ferrara AM, Pontecorvi A, Rindi G: BRAF mutation (V600E) in papillary carcinoma identified on LBC processed thyroid aspiration biopsies. Mod Pathol 2011;24:89A.
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