The growth of digital methods in pathology is accelerating. Digital images can be used for a variety of applications in cytology, including rapid interpretations, primary diagnosis and second opinions, continuing education and proficiency testing. All of these functions can be performed using small static digital images, real-time dynamic digital microscopy, or whole-slide images. This review will discuss the general principles of digital pathology, its methods and applications to cytologic specimens. As cytologic specimens have unique features compared to histopathology specimens, the key differences will be discussed. Technical and administrative issues in digital pathology applications and the outlook for the future of the field will be presented.

1.
Yamashiro K, Taira K, Matsubayashi S, Azuma M, Okuyama D, Nakajima M, Takeda H, Suzuki H, Kawamura N, Wakao F, Yagi Y: Comparison between a traditional single still image and a multiframe video image along the z-axis of the same microscopic field of interest in cytology: which does contribute to telecytology? Diagn Cytopathol 2009;37:727–731.
2.
Weinstein RS, Descour MR, Liang C, Barker G, Scott KM, Richter L, Krupinski EA, Bhattacharyya AK, Davis JR, Graham AR, Rennels M, Russum WC, Goodall JF, Zhou P, Olszak AG, Williams BH, Wyant JC, Bartels PH: An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study. Hum Pathol 2004;35:1303–1414.
3.
Evered A, Dudding N: Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology. Cytopathology 2010 May 17. DOI: 10.1111/ j.1365-2303.2010.00758.x.
4.
Dee FR, Donnelly A, Radio S, Leaven T, Zaleski MS, Kreiter C: Utility of 2-D and 3-D virtual microscopy in cervical cytology education and testing. Acta Cytol 2007;51:523–529.
5.
Weinstein RS, Descour MR, Liang C, Bhattacharyya AK, Graham AR, Davis JR, Scott KM, Richter L, Krupinski EA, Szymus J, Kayser K, Dunn BE: Telepathology overview: from concept to implementation. Hum Pathol 2001;32:1283–1299.
6.
Weinstein RS, Graham AR, Richter LC, Barker GP, Krupinski EA, Lopez AM, Erps KA, Bhattacharyya AK, Yagi Y, Gilbertson JR: Overview of telepathology, virtual microscopy, and whole slide imaging: prospects for the future. Hum Pathol 2009;40:1057–1069.
7.
Williams S, Henricks WH, Becich MJ, Toscano M, Carter AB: Telepathology for patient care: what am I getting myself into? Adv Anat Pathol 2010;17:130–149.
8.
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.
9.
Singh N, Akbar N, Sowter C, Lea KG, Wells CA: Telepathology in a routine clinical environment: implementation and accuracy of diagnosis by robotic microscopy in a one-stop breast clinic. J Pathol 2002;196:351–355.
10.
Kim B, Chhieng D, Jhala N, et al: Dynamic telecytopathology has equivalent efficacy with on site rapid cytology diagnosis for pancreatic carcinoma. Cancer Cytopathol 2006;108:357.
11.
Delta Mea V, Cataldi P, Pertoldi B, Beltrami CA: Dynamic robotic telepathology: a preliminary evaluation on frozen sections, histology and cytology. J Telemed Telecare 1999;5(suppl 1):S55–S56.
12.
Kerr SE, Bellizzi AM, Stelow EB, Frierson HF Jr, Policarpio-Nicolas ML: Initial assessment of fine-needle aspiration specimens by telepathology: validation for use in pathology resident-faculty consultations. Am J Clin Pathol 2008;130:409–413.
13.
Alsharif M, Carlo-Demovich J, Massey C, Madory JE, Lewin D, Medina AM, Recavarren R, Houser PM, Yang J: Telecytopathology for immediate evaluation of fine-needle aspiration specimens. Cancer Cytopathol 2010;118:119–126.
14.
Heimann A, Maini G, Hwang S, Shroyer KR, Singh M: Use of telecytology for the immediate assessment of CT guided and endoscopic FNA cytology: diagnostic accuracy, advantages, and pitfalls. Diagn Cytopathol 2010 Dec 3 [Epub ahead of print].
15.
Kaplan KJ: Telecytopathology for immediate evaluation of fine-needle aspiration specimens. Cancer Cytopathol 2010;118:115–118.
16.
Weinstein RS: Telepathology comes of age in Norway. Hum Pathol 1991;22:511–513.
17.
Raab SS, Zaleski MS, Thomas PA, Niemann TH, Isacson C, Jensen CS: Telecytology: diagnostic accuracy in cervical-vaginal smears. Am J Clin Pathol 1996;105:599–603.
18.
Ziol M, Vacher-Lavenu MC, Heudes D, Ferrand J, Mayelo V, Molinie V, Slama S, Marsan C: Expert consultation for cervical carcinoma smears. Reliability of selected-field videomicroscopy. Anal Quant Cytol Histol 1999;21:35–41.
19.
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.
20.
Allen EA, Ollayos CW, Tellado MV, Butler DR, Buckner SB, Williams BH, O’Leary TJ: Characteristics of a telecytology consultation service. Hum Pathol 2001;32:1323–1326.
21.
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;119:356–360.
22.
Wilbur DC, Prey MU, Miller WM, Pawlick GF, Colgan TJ: The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice. Acta Cytol 1998;42:214–220.
23.
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.
24.
Dziura B, Quinn S, Richard K: Performance of an imaging system vs. manual screening in the detection of squamous intraepithelial lesions of the uterine cervix. Acta Cytol 2006;50:309–311.
25.
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.
26.
Eichhorn JH, Buckner L, Buckner SB, Beech DP, Harris KA, McClure DJ, Crothers BA, Wilbur DC: Internet-based gynecologic telecytology with remote automated image selection: results of a first-phase developmental trial. Am J Clin Pathol 2008;129:686–696.
27.
Galvez J, Howell L, Costa MJ, Davis R: Diagnostic concordance of telecytology and conventional cytology for evaluating breast aspirates. Acta Cytol 1998;42:663–667.
28.
Della Mea V, Puglisi F, Bonzanini M, Forti S, Amoroso V, Visentin R, Dalla Palma P, Beltrami CA: Fine-needle aspiration cytology of the breast: a preliminary report on telepathology through Internet multimedia electronic mail. Mod Pathol 1997;10:636–641.
29.
Briscoe D, Adair CF, Thompson LD, Tellado MV, Buckner SB, Rosenthal DL, O’Leary TJ: Telecytologic diagnosis of breast fine needle aspiration biopsies. Intraobserver concordance. Acta Cytol 2000;44:175–180.
30.
Ayatollahi H, Khoei A, Mohammadian N, Sadeghian MH, Azari JB, Ghaemi MR, Khoob MK: Telemedicine in diagnostic pleural cytology: a feasibility study between universities in Iran and the USA. J Telemed Telecare 2007;13:363–368.
31.
Marchevsky AM, Nelson V, Martin SE, Greaves TS, Raza AS, Zeineh J, Cobb CJ: Telecytology of fine-needle aspiration biopsies of the pancreas: a study of well-differentiated adenocarcinoma and chronic pancreatitis with atypical epithelial repair changes. Diagn Cytopathol 2003;28:147–152.
32.
Jialdasani R, Desai S, Gupta M, Kothari A, Deshpande R, Shet T, Ramadwar M, Kane S, Chinoy R: An analysis of 46 static telecytology cases over a period of two years. J Telemed Telecare 2006;12:311–314.
33.
Yamashiro K, Kawamura N, Matsubayashi S, Dota K, Suzuki H, Mizushima H, Wakao F, Azumi N: Telecytology in Hokkaido Island, Japan: results of primary telecytodiagnosis of routine cases. Cytopathology 2004;15:221–227.
34.
Georgoulakis J, Archondakis S, Panayiotides I, Anninos D, Skagias L, Stamataki M, Peros G, Karakitsos P: Study on the reproducibility of thyroid lesions telecytology diagnoses based upon digitized images. Diagn Cytopathol 2010 Aug 20 [Epub ahead of print].
35.
Archondakis S, Georgoulakis J, Stamataki M, Anninos D, Skagias L, Panayiotides I, Peros G, Karakitsos P: Telecytology: a tool for quality assessment and improvement in the evaluation of thyroid fine-needle aspiration specimens. Telemed J E Health 2009;15:713–717.
36.
Maiolino P, Restucci B, Papparella S, De Vico G: Evaluation of static telepathology in veterinary diagnostic cytology. Vet Clin Pathol 2006;35:303–306.
37.
Kayser K, Kayser G, Becker HD, Herth F: Telediagnosis of transbronchial fine needle aspirations – a feasibility study. Anal Cell Pathol 2000;21:207–212.
38.
Pinco J, Goulart RA, Otis CN, Garb J, Pantanowitz L: Impact of digital image manipulation in cytology. Arch Pathol Lab Med 2009;133:57–61.
39.
Hitchcock CL Hitchcock LE: Three years of experience with routine use of telepathology in assessment of excisional and aspirate biopsies of breast lesions. Croat Med J 2005;46:449–457.
40.
Rojo MG, Garcia GB, Mateos CP, Garcia JG, Vicente MC: Critical comparison of 31 commercially available digital slide systems in pathology. Int J Surg Pathol 2006;14:285–305.
41.
Wilbur DC, Black-Schaffer WS, Luff RD, Abraham KP, Kemper C, Molina JT, Tench WD: The Becton Dickinson FocalPoint GS Imaging System: clinical trials demonstrate significantly improved sensitivity for the detection of important cervical lesions. Am J Clin Pathol 2009;132:767–775.
42.
Fallon MA, Wilbur DC, Prasad M: Ovarian frozen section diagnosis: use of whole-slide imaging shows excellent correlation between virtual slide and original interpretations in a large series of cases. Arch Pathol Lab Med;134:1020–1023.
43.
Li X, Liu J, Xu H, Gong E, McNutt MA, Li F, Anderson VM, Gu J: A feasibility study of virtual slides in surgical pathology in China. Hum Pathol 2007;38:1842–1848.
44.
Furness P: A randomized controlled trial of the diagnostic accuracy of internet-based telepathology compared with conventional microscopy. Histopathology 2007;50:266–273.
45.
Rojo MG, Gallardo AJ, Gonzalez L, Peces C, Murillo C, Gonzalez J, Sacristan J: Reading virtual slide using web viewers: results of subjective experience with three different solutions. Diagn Pathol 2008;3(suppl 1):S23.
46.
Fine JL, Grzybicki DM, Silowash R, Ho J, Gilbertson JR, Anthony L, Wilson R, Parwani AV, Bastacky SI, Epstein JI, Jukic DM: Evaluation of whole slide image immunohistochemistry interpretation in challenging prostate needle biopsies. Hum Pathol 2008;39:564–572.
47.
Slodkowska J, Chyczewski L, Wojciechowski M: Virtual slides: application in pulmonary pathology consultations. Folia Histochem Cytobiol 2008;46:121–124.
48.
Ho J, Parwani AV, Jukic DM, Yagi Y, Anthony L, Gilbertson JR: Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies. Hum Pathol 2006;37:322–331.
49.
Gilbertson JR, Ho J, Anthony L, Jukic DM, Yagi Y, Parwani AV: Primary histologic diagnosis using automated whole slide imaging: a validation study. BMC Clin Pathol 2006;6:4.
50.
Molnar B, Berczi L, Diczhazy C, Tagscherer A, Varga SV, Szende B, Tulassay Z: Digital slide and virtual microscopy based routine and telepathology evaluation of routine gastrointestinal biopsy specimens. J Clin Pathol 2003;56:433–438.
51.
Demichelis F, Barbareschi M, Dalla Palma P, Forti S: The virtual case: a new method to completely digitize cytological and histological slides. Virchows Arch 2002;441:159–164.
52.
Grabe N, Lahrmann B, Pommerencke T, von Knebel Doeberitz M, Reuschenbach M, Wentzensen N: A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides. Cell Oncol 2010;32:109–119.
53.
Pantanowitz L, Hornish M, Goulart RA: The impact of digital imaging in the field of cytopathology. Cytojournal 2009;6:6.
54.
Mulford DK: Telepathology education: Reaching out to cytopathology programs throughout the country. ASC Bull 2006;43:25–30.
55.
Stewart J, 3rd, Bevans-Wilkins K, Bhattacharya A, Ye C, Miyazaki K, Kurtycz DF: Virtual microscopy: an educator’s tool for the enhancement of cytotechnology students’ locator skills. Diagn Cytopathol 2008;36:363–368.
56.
Neel JA, Grindem CB, Bristol DG: Introduction and evaluation of virtual microscopy in teaching veterinary cytopathology. J Vet Med Educ 2007;34:437–444.
57.
Glatz K, Willi N, Glatz D, Barascud A, Grilli B, Herzog M, Dalquen P, Feichter G, Gasser TC, Sulser T, Bubendorf L: An international telecytologic quiz on urinary cytology reveals educational deficits and absence of a commonly used classification system. Am J Clin Pathol 2006;126:294–301.
58.
Taylor RN, Gagnon M, Lange J, Lee T, Draut R, Kujawski E: CytoView. A prototype computer image-based Papanicolaou smear proficiency test. Acta Cytol 1999;43:1045–1051.
59.
Gagnon M, Inhorn S, Hancock J, Keller B, Carpenter D, Merlin T, Hearn T, Thompson P, Whalen R: Comparison of cytology proficiency testing: glass slides vs. virtual slides. Acta Cytol 2004;48:788–794.
60.
Marchevsky AM, Khurana R, Thomas P, Scharre K, Farias P, Bose S: The use of virtual microscopy for proficiency testing in gynecologic cytopathology: a feasibility study using ScanScope. Arch Pathol Lab Med 2006;130:349–355.
61.
Stewart J 3rd, Miyazaki K, Bevans-Wilkins K, Ye C, Kurtycz DF, Selvaggi SM: Virtual microscopy for cytology proficiency testing: are we there yet? Cancer 2007;111:203–209.
62.
Tsuchihashi Y, Okada Y, Ogushi Y, Mazaki T, Tsutsumi Y, Sawai T: The current status of medicolegal issues surrounding telepathology and telecytology in Japan. J Telemed Telecare 2000;6(suppl 1):S143–S145.
63.
Leung ST, Kaplan KJ: Medicolegal aspects of telepathology. Hum Pathol 2009;40:1137–1142.
64.
Kayser K, Radziszowski D, Bzdyl P, Sommer R, Kayser G: Towards an automated virtual slide screening: theoretical considerations and practical experiences of automated tissue-based virtual diagnosis to be implemented in the Internet. Diagn Pathol 2006;1:10.
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