The performance of digital microscopy for primary diagnosis in human pathology: a systematic review

  • Anna Luíza Damaceno Araújo
  • Lady Paola Aristizábal Arboleda
  • Natalia Rangel Palmier
  • Jéssica Montenegro Fonsêca
  • Mariana de Pauli Paglioni
  • Wagner Gomes-Silva
  • Ana Carolina Prado Ribeiro
  • Thaís Bianca Brandão
  • Luciana Estevam Simonato
  • Paul M. Speight
  • Felipe Paiva Fonseca
  • Marcio Ajudarte Lopes
  • Oslei Paes de Almeida
  • Pablo Agustin Vargas
  • Cristhian Camilo Madrid Troconis
  • Alan Roger Santos-SilvaEmail author
Review and Perspectives


Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the performance of WSI devices by evaluating intraobserver agreement reported in previously published studies as the best evidence to elucidate whether DM is reliable for primary diagnostic purposes. In addition, this review delineates the reasons for the occurrence of discordant diagnoses. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 13 articles were included. The total sample of 2145 had a majority of 695 (32.4%) cases from dermatopathology, followed by 200 (9.3%) cases from gastrointestinal pathology. Intraobserver agreements showed an excellent concordance, with values ranging from 87% to 98.3% (κ coefficient range 0.8–0.98). Ten studies (77%) reported a total of 128 disagreements. The remaining three studies (23%) did not report the exact number and nature of disagreements. Borderline/challenging cases were the most frequently reported reason for disagreements (53.8%). Six authors reported limitations of the equipment and/or limited image resolution as reasons for the discordant diagnoses. Within these articles, the reported pitfalls were as follows: difficulties in the identification of eosinophilic granular bodies in brain biopsies; eosinophils and nucleated red blood cells; and mitotic figures, nuclear details, and chromatin patterns in neuropathology specimens. The lack of image clarity was reported to be associated with difficulties in the identification of microorganisms (e.g., Candida albicans, Helicobacter pylori, and Giardia lamblia). However, authors stated that the intraobserver variances do not derive from technical limitations of WSI. A lack of clinical information was reported by four authors as a source for disagreements. Two studies (15.4%) reported poor quality of the biopsies, specifically small size of the biopsy material or inadequate routine laboratory processes as reasons for disagreements. One author (7.7%) indicated the lack of immunohistochemistry and special stains as a source for discordance. Furthermore, nine studies (69.2%) did not consider the performance of the digital method—limitations of the equipment, insufficient magnification/limited image resolution—as reasons for disagreements. To summarize the pitfalls of digital pathology practice and better address the root cause of the diagnostic discordance, we suggest a Categorization for Digital Pathology Discrepancies to be used in further validations studies. Among 99 discordances, only 37 (37.3%) had preferred diagnosis rendered by means of WSI. The risk of bias and applicability concerns were judged with the QUADAS-2. Two studies (15.4%) presented an unclear risk of bias in the sample selection domain and 2 (15.4%) presented a high risk of bias in the index test domain. Regarding applicability, all studies included were classified as a low concern in all domains. The included studies were optimally designed to validate WSI for general clinical use, providing evidence with confidence. In general, this systematic review showed a high concordance between diagnoses achieved by using WSI and conventional light microscope (CLM), summarizes difficulties related to specific findings of certain areas of pathology—including dermatopathology, pediatric pathology, neuropathology, and gastrointestinal pathology—and demonstrated that WSI can be used to render primary diagnoses in several subspecialties of human pathology.


Whole slide imaging Intraobserver agreement Systematic review 


Authors’ contributions

All authors had substantial contributions to the conception, draft and design of this work, (Anna Luíza Damaceno Araújo, Natália Rangel Palmier, Cristhian Camilo Troconis, Paul M. Speight, Oslei Paes de Almeida, Marcio Ajudarte Lopes and Alan Roger Santos-Silva), as well as participation of the acquisition (Lady Paola Aristizábal Arboleda, Natália Rangel Palmier, Jéssica Montenegro Fonsêca, Mariana de Pauli Paglioni, Ana Carolina Prado Ribeiro, Pablo Agustin Vargas, Luciana Estevam Simonato and Wagner Gomes-Silva), analysis (Anna Luíza Damaceno Araújo, Felipe Paiva Fonseca and Lady Paola Aristizábal Arboleda), and interpretation (Anna Luíza Damaceno Araújo, Cristhian Camilo Troconis, Thaís Bianca Brandão and Alan Roger Santos-Silva) of data for the work. The final version of this work was reviewed and approved for publication by all parts included. Authors Anna Luíza Damaceno Araújo and Alan Roger Santos-Silva takes full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript.

Funding information

Financial support was received from the Coordination for the Improvement of Higher Education Personnel (CAPES/PROEX, Brazil), the National Council for Scientific and Technological Development (CNPq, Brazil) and the grants from São Paulo Research Foundation (FAPESP, Brazil) process number: 2009/53839-2.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical responsibilities of author section

All authors had substantial contributions to the conception, draft and design of this work, as well as participation of the acquisition, analysis and interpretation of data for the work. The final version of this work was approved for publication by all parts included. If there is a need, all authors agreed to be accountable for any aspects of the work and we ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors also state that the material is original, has not been published elsewhere, and is being submitted only to the Virchows Archiv.

Supplementary material

428_2018_2519_MOESM1_ESM.doc (98 kb)
Supplementary Table 1 (DOC 98 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Anna Luíza Damaceno Araújo
    • 1
  • Lady Paola Aristizábal Arboleda
    • 1
  • Natalia Rangel Palmier
    • 1
  • Jéssica Montenegro Fonsêca
    • 1
  • Mariana de Pauli Paglioni
    • 1
  • Wagner Gomes-Silva
    • 1
    • 2
    • 3
  • Ana Carolina Prado Ribeiro
    • 1
    • 2
    • 4
  • Thaís Bianca Brandão
    • 2
  • Luciana Estevam Simonato
    • 4
  • Paul M. Speight
    • 5
  • Felipe Paiva Fonseca
    • 1
    • 6
  • Marcio Ajudarte Lopes
    • 1
  • Oslei Paes de Almeida
    • 1
  • Pablo Agustin Vargas
    • 1
  • Cristhian Camilo Madrid Troconis
    • 7
  • Alan Roger Santos-Silva
    • 1
    Email author
  1. 1.Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba Dental SchoolUniversity of Campinas (UNICAMP)São PauloBrazil
  2. 2.Dental Oncology Service, Instituto do Câncer do Estado de São PauloFaculdade de Medicina da Universidade de São Paulo (FMSUP)São PauloBrazil
  3. 3.Medical School of Nove de Julho UniversitySão PauloBrazil
  4. 4.Faculdade de Odontologia, FernandópolisUniversidade BrasilSão PauloBrazil
  5. 5.Unit of Oral and Maxillofacial Pathology, School of Clinical DentistryUniversity of SheffieldSheffieldUK
  6. 6.Clinic, Pathology and Odontological Surgery Department, Minas Gerais Dental SchoolFederal University of Minas Gerais (UFMG)Belo HorizonteBrazil
  7. 7.Dentistry Program, Health of Science FacultyCorporación Universitaria Rafael Nuñez (CURN)Cartagena de ÍndiasColombia

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