Minimally invasive diagnostic techniques are increasingly being used to obtain specimens for pathological diagnosis and prediction. Referring to lung cancer, both endobronchial and endoesophageal ultrasound are used worldwide as diagnostic routine methods. Consequently, an increasing number of pathological samples are cytological and fewer are histological. On the other hand, the requirements for specific and sensitive tumor subtyping complemented by predictive analyses are steadily increasing and are an essential basis for evidence-based treatment decisions. In this article we focus on the cell block method as a helpful tool for diagnostic and predictive analyses in lung cancer and point out its advantages and disadvantages in comparison to conventional cytological and biopsy specimens. Furthermore, we retrospectively analyze the diagnostic results of the cell block method in a high-volume center over 5 years. The main advantages of cell blocks are the availability of established and validated protocols, archiving and the opportunity to have serial sections from the same specimens to provide or repeat molecular analyses. Actually, in case of tumor progression, even additional biomarkers can be tested using the original cell block when re-biopsies are not feasible. The cell block method should be considered as a reliable, complimentary approach to conventional cytological or biopsy procedures, which is helpful to fulfill the increasing requirements of high-quality diagnostics and prediction.

Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
Warth A, Muley T, Meister M, Stenzinger A, Thomas M, Schirmacher P, Schnabel PA, Budczies J, Hoffmann H, Weichert W: The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 2012;30:1438-1446.
Warth A, Muley T, Herpel E, Meister M, Herth FJ, Schirmacher P, Weichert W, Hoffmann H, Schnabel PA: Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non-small-cell lung cancer biopsies. Histopathology 2012;61:1017-1025.
Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ: Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693-1703.
Mok TS: Personalized medicine in lung cancer: what we need to know. Nat Rev Clin Oncol 2011;8:661-668.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-957.
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L: Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-246.
V Laffert M, Warth A, Penzel R, Schirmacher P, Jonigk D, Kreipe H, Schildhaus HU, Merkelbach-Bruse S, Buttner R, Reu S, Kerler R, Jung A, Kirchner T, Wolfel C, Petersen I, Rodriguez R, Jochum W, Bartsch H, Fisseler-Eckhoff A, Berg E, Lenze D, Dietel M, Hummel M: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing. Lung Cancer 2013;81:200-206.
Penzel R, Sers C, Chen Y, Lehmann-Muhlenhoff U, Merkelbach-Bruse S, Jung A, Kirchner T, Buttner R, Kreipe HH, Petersen I, Dietel M, Schirmacher P: EGFR mutation detection in NSCLC-assessment of diagnostic application and recommendations of the German Panel for Mutation Testing in NSCLC. Virchows Arc 2011;458:95-98.
Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc Nat Acad Sci 1977;74:5463-5467.
Warth A, Penzel R, Brandt R, Sers C, Fischer JR, Thomas M, Herth FJ, Dietel M, Schirmacher P, Blaker H: Optimized algorithm for sanger sequencing-based EGFR mutation analyses in NSCLC biopsies. Virchows Arc 2012;460:407-414.
Thunnissen E, Kerr KM, Herth FJ, Lantuejoul S, Papotti M, Rintoul RC, Rossi G, Skov BG, Weynand B, Bubendorf L, Katrien G, Johansson L, Lopez-Rios F, Ninane V, Olszewski W, Popper H, Jaume S, Schnabel P, Thiberville L, Laenger F: The challenge of NSCLC diagnosis and predictive analysis on small samples: practical approach of a working group. Lung Cancer 2012;76:1-18.
Pirker R, Herth FJ, Kerr KM, Filipits M, Taron M, Gandara D, Hirsch FR, Grunenwald D, Popper H, Smit E, Dietel M, Marchetti A, Manegold C, Schirmacher P, Thomas M, Rosell R, Cappuzzo F, Stahel R: Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thorac Oncol 2010;5:1706-1713.
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D: International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-285.
Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar JS, Squire J, Thunnissen E, Ladanyi M: Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Mol Diagn 2013;15:415-453.
Rivera MP, Mehta AC, Wahidi MM: Establishing the diagnosis of lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(suppl 5):e142S-e165S.
Gompelmann D, Eberhardt R, Herth FJ: Advanced malignant lung disease: what the specialist can offer. Respiration 2011;82:111-123.
Shure D, Fedullo PF: Transbronchial needle aspiration in the diagnosis of submucosal and peribronchial bronchogenic carcinoma. Chest 1985;88:49-51.
Kacar N, Tuksavul F, Edipoglu O, Ermete S, Guclu SZ: Effectiveness of transbronchial needle aspiration in the diagnosis of exophytic endobronchial lesions and submucosal/peribronchial diseases of the lung. Lung Cancer 2005;50:221-226.
Herth FJ, Krasnik M, Kahn N, Eberhardt R, Ernst A: Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer. Chest 2010;138:790-794.
Zlobec I, Raineri I, Schneider S, Schoenegg R, Grilli B, Herzog M, Savic S, Bubendorf L: Assessment of mean EGFR gene copy number is a highly reproducible method for evaluating FISH in histological and cytological cancer specimens. Lung Cancer 2010;68:192-197.
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P: Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathol 2013;121:500-507.
Thapar M, Mishra RK, Sharma A, Goyal V: Critical analysis of cell block versus smear examination in effusions. J Cytol 2009;26:60-64.
Shivakumarswamy U, Arakeri SU, Karigowdar MH, Yelikar B: Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology. J Cytol 2012;29:11-15.
Bubendorf L, Feicher G, Obermann P, Dalquen P: Zytopathologie: Pathologie, Band 9. Berlin, Springer, 2011.
Weihmann J, Weichert C, Petersen I, Gajda M: Evaluation of a cell block method in cytological diagnostics (in German). Pathologe 2012;33:553-559.
Nathan NA, Narayan E, Smith MM, Horn MJ: Cell block cytology: improved preparation and its efficacy in diagnostic cytology. Am J Clin Pathol 2000;114:599-606.
Mayall F, Chang B, Darlington A: A review of 50 consecutive cytology cell block preparations in a large general hospital. J Clin Pathol 1997;50:985-990.
Gupta S, Halder K, Khan VA, Sodhani P: Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings. Cytopathology 2007;18:309-315.
Nigro K, Tynski Z, Wasman J, Abdul-Karim F, Wang N: Comparison of cell block preparation methods for nongynecologic ThinPrep specimens. Diagn Cytopathol 2007;35:640-643.
Kulkarni MB, Desai SB, Ajit D, Chinoy RF: Utility of the thromboplastin-plasma cell-block technique for fine-needle aspiration and serous effusions. Diagn Cytopathol 2009;37:86-90.
Warth A, Bubendorf L, Gutz S, Morresi-Hauf A, Hummel M, Junker K, Lehmann U, Petersen I, Schnabel PA: Molecular pathological diagnosis in cytopathology of non-small-cell lung cancer: standardization of specimen processing (in German). Pathologe 2013;34:310-317.
Savic S, Bihl MP, Bubendorf L: Non-small cell lung cancer: subtyping and predictive molecular marker investigations in cytology (in German). Pathologe 2012;33:301-307.
Tapia C, Savic S, Bihl M, Rufle A, Zlobec I, Terracciano L, Bubendorf L: [EGFR mutation analysis in non-small-cell lung cancer: Experience from routine diagnostics]. Pathologe 2009;30:384-392.
Savic S, Tapia C, Grilli B, Rufle A, Bihl MP, de Vito Barascud A, Herzog M, Terracciano L, Baty F, Bubendorf L: Comprehensive epidermal growth factor receptor gene analysis from cytological specimens of non-small-cell lung cancers. J Cancer 2008;98:154-160.
Bruno P, Mariotta S, Ricci A, Duranti E, Scozzi D, Noto A, Mancini R, Giarnieri E, Giovagnoli MR: Reliability of direct sequencing of EGFR: comparison between cytological and histological samples from the same patient. Anticancer Res 2011;31:4207-4210.
Rekhtman N, Brandt SM, Sigel CS, Friedlander MA, Riely GJ, Travis WD, Zakowski MF, Moreira AL: Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing. J Thorac Oncol 2011;6:451-458.
Solomon SB, Zakowski MF, Pao W, Thornton RH, Ladanyi M, Kris MG, Rusch VW, Rizvi NA: Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational analysis. Am J Roentgenol 2010;194:266-269.
Chowdhuri SR, Xi L, Pham TH, Hanson J, Rodriguez-Canales J, Berman A, Rajan A, Giaccone G, Emmert-Buck M, Raffeld M, Filie AC: EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection. Mod Pathol 2012;25:548-555.
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