Objective: To date, the impact of digital imaging on routine cytology remains far from perfect. Cellblock (CB) preparations from Pap samples have been shown to be diagnostically valuable. We evaluated the validity of utilizing whole-slide imaging (WSI) prepared from Pap CBs as a screening tool. Study Design: A total of 1,110 CB slides prepared from residual Pap samples were analyzed - 563 normal, 282 atypical squamous cells of undetermined significance (ASCUS), 12 atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion, 188 low-grade squamous intraepithelial lesions (LSIL), 36 high-grade squamous intraepithelial lesions (HSIL), 25 atypical glandular cells of undetermined significance, 1 adenocarcinoma in situ, 2 invasive adenocarcinomas, and 1 squamous cell carcinoma. Virtual slides were obtained using the Aperio system. Test performance characteristics of liquid-based samples and WSI from CB samples were compared. Results: Average sensitivity and specificity of the five WSI reviewers was 58.3 and 85.1% for ASCUS, respectively, 54.1 and 93.9% for LSIL, and 51.8 and 98.8% for HSIL. Overall WSI sensitivity and specificity for detecting lesions was 82.1 and 86.2%, respectively. Agreement (kappa values) between WSI reviewers was 0.56 for ASCUS, 0.69 for LSIL, 0.67 for HSIL, and 0.74 for negative samples. Conclusions: WSI of CB preparations is a feasible method to achieve high-quality specimen preparations. It is as sensitive as liquid-based methods and appears to be highly specific for the detection of LSIL and HSIL.

Keywords:
Whole-slide imaging, Pap test, Cellblock preparations, Atypical squamous cells of undetermined significance, Low-grade squamous intraepithelial lesion, Low-grade squamous intraepithelial lesion
1.
Sasieni P, Cuzick J, Farmery E: Accelerated decline in cervical cancer mortality in England and Wales. Lancet 1995;346:1566-1567.
2.
Gustafsson L, Ponten J, Bergstrom R, Adami HO: International incidence rates of invasive cervical cancer before cytological screening. Int J Cancer 1997;71:159-165.
3.
Peto J, Gilham C, Fletcher O, Matthews FE: The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004;364:249-256.
4.
World Health Organization: Comprehensive Cervical Cancer Control. A Guide to Essential Practice. Geneva, World Health Organization, 2006.
5.
Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
6.
Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F, Ferlay J: Worldwide burden of cervical cancer in 2008. Ann Oncol 2011;22:2675-2686.
7.
Tota JE, Chevarie-Davis M, Richardson LA, Devries M, Franco EL: Epidemiology and burden of HPV infection and related diseases: implications for prevention strategies. Prev Med 2011;53(suppl 1):S12-S21.
8.
Dee FR: Virtual microscopy in pathology education. Hum Pathol 2009;40:1112-1121.
9.
Pantanowitz L, Hornish M, Goulart RA: The impact of digital imaging in the field of cytopathology. Cytojournal 2009;6:6.
10.
Wilbur DC, Madi K, Colvin RB, Duncan LM, Faquin WC, Ferry JA, Frosch MP, Houser SL, Kradin RL, Lauwers GY, Louis DN, Mark EJ, Mino-Kenudson M, Misdraji J, Nielsen GP, Pitman MB, Rosenberg AE, Smith RN, Sohani AR, Stone JR, Tambouret RH, Wu CL, Young RH, Zembowicz A, Klietmann W: Whole-slide imaging digital pathology as a platform for teleconsultation: a pilot study using paired subspecialist correlations. Arch Pathol Lab Med 2009;133:1949-1953.
11.
Hedvat CV: Digital microscopy past, present, and future. Arch Pathol Lab Med 2010;134:1666-1670.
12.
Jara-Lazaro AR, Thamboo TP, Teh M, Tan PH: Digital pathology: exploring its applications in diagnostic surgical practice. Pathol 2010;42:512-518.
13.
Pantanowitz L: Digital images and the future of digital pathology. J Pathol Inform 2010;1:15.
14.
Kalbuss WE, Pantanowitz L, Parwani AV: Digital imaging in cytopathology. Patholog Res Int 2011;2011:264683.
15.
O'Brien MJ, Takahashi M, Brugal G, Christen H, Gahm T, Goodell RM, Karakitsos P, Knesel EA Jr, Kobler T, Kyrkou KA, Labbe S, Long EL, Mango LJ, McGoogan E, Oberholzer M, Reith A, Winkler C: Digital imagery/telecytology: International Academy of Cytology Task Force summary: diagnostic cytology towards the 21st century: an international expert conference and tutorial. Acta Cytol 1998;42:148-164.
16.
Alli PM, Ollayos CW, Thompson LD, Kapadia I, Butler DR, Williams BH, Rosenthal DL, O'leary TJ: Telecytology: intraobserver and interobserver reproducibility in the diagnosis of cervical-vaginal smears. Hum Pathol 2001;32:1318-1322.
17.
Lee ES, Kim IS, Choi JS, Yeom BW, Kim HK, Han JH, Lee MS, Leong AS: Accuracy and reproducibility of telecytology diagnosis of cervical smears: a tool for quality assurance programs. Am J Clin Pathol 2003;199:356-360.
18.
Eichhorn JH, Brauns TA, Gelfand JA, Crothers BA, Wilbur DC: A novel automated screening and interpretation process for cervical cytology using the internet transmission of low-resolution images: a feasibility study. Cancer 2005;105:199-206.
19.
Wright AM, Smith D, Dhurandhar B, Fairley T, Scheiber-Pacht M, Chakraborty S, Gorman BK, Mody D, Coffey DM: Digital slide imaging in cervicovaginal cytology: a pilot study. Arch Pathol Lab Med 2013;137:618-624.
20.
Yeoh GP, Chan KW: Cell block preparation on residual ThinPrep sample. Diagn Cytopathol 1999;21:427-431.
21.
Richard K, Dziura B, Hornish A: Cell block preparation as a diagnostic technique complementary to fluid-based monolayer cervicovaginal specimens. Acta Cytol 1999;43:69-73.
22.
Diaz-Rosario LA, Kabawat SE: Cell block preparation by inverted filter sedimentation is useful in the differential diagnosis of atypical glandular cells of undetermined significance in ThinPrep specimens. Cancer 2000;90:265-272.
23.
Keyhani-Rofagha S, Vesey-Shecket M: Diagnostic value, feasibility, and validity of preparing cell blocks from fluid-based gynecologic cytology specimens. Cancer 2002;96:204-209.
24.
Gupta S, Hadler K, Khan VA, Sodhani P: Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings. Cytopathol 2007;18:309-315.
25.
Fetsch PA, Simir A, Brosky K, Abati A: Comparison of the 3 commonly used cytologic preparations in effusion immunocytochemistry. Diagn Cytopathol 2001;26:61-66.
26.
Afify A, Yu C, Hejazi N, Howell L: The diagnostic utility of cell blocks prepared from residual SurePath Pap material for detection of human papillomavirus. Appl Immunohistochem Mol Morphol 2009;17:108-114.
27.
Amin K, Hernandez-Rios P, Davis M, Fan F, Wilson J, Tawfik O: The potential of telecytology of cell block from Pap smear samples ‘TelePAPology'. Mod Pathol 2010;23(suppl 1):86A.
28.
Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group: Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009;374:301-314.
29.
Cuzick J, Castanon A, Sasieni P: Predicted impact of vaccination against human papillomavirus 16/18 on cancer incidence and cervical abnormalities in women aged 20-29 in the UK. Br J Cancer 2010;102:933-939.
30.
Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER: Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56(RR-2):1-24.
31.
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.
32.
Wagner DG, Russell DK, Benson JM, Schneider AE, Hoda RS, Bonfiglio TA: Cellient™ automated cell block versus traditional cell block preparation: a comparison of morphologic features and immunohistochemical staining. Diagn Cytopathol 2010;39:730-736.
33.
Gorman BK, Kosarac O, Chakraborty S, Schwartz MR, Mody DR: Comparison of breast carcinoma prognostic/predictive biomarkers on cell blocks obtained by various methods: Cellient, formalin and thrombin. Acta Cytologica 2012;56:289-296.
34.
Hecht SA, McCormack M: Comparison of three cell block techniques for detection of low frequency abnormal cells. Pathol Lab Med Int 2013;5:1-7.
35.
Richard K, Dziura B, Hornish A: Cell block preparation as a diagnostic technique complementary to fluid-based monolayer cervicovaginal specimens. Acta Cytol 1999;43:69-73.
36.
Diaz-Rosario LA, Kabawat SE: Cell block preparation by inverted filter sedimentation is useful in the differential diagnosis of atypical glandular cells of undetermined significance in ThinPrep specimens. Cancer 2000;90:265-272.
37.
Keyhani-Rofagha S, Vesey-Shecket M: Diagnostic value, feasibility, and validity of preparing cell blocks from fluid-based gynecologic cytology specimens. Cancer 2002;96:204-209.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.