title: Classification of follicular lymphoma: the effect of computer aid on pathologists grading.
abstract: BACKGROUND
  Follicular lymphoma (FL) is one of the most common lymphoid malignancies in the western world. FL cases are stratified into three histological grades based on the average centroblast count per high power field (HPF). The centroblast count is performed manually by the pathologist using an optical microscope and hematoxylin and eosin (H&E) stained tissue section. Although this is the current clinical practice, it suffers from high inter- and intra-observer variability and is vulnerable to sampling bias.
  
  
  METHODS
  In this paper, we present a system, called Follicular Lymphoma Grading System (FLAGS), to assist the pathologist in grading FL cases. We also assess the effect of FLAGS on accuracy of expert and inexperienced readers. FLAGS automatically identifies possible HPFs for examination by analyzing H&E and CD20 stains, before classifying them into low or high risk categories. The pathologist is first asked to review the slides according to the current routine clinical practice, before being presented with FLAGS classification via color-coded map. The accuracy of the readers with and without FLAGS assistance is measured.
  
  
  RESULTS
  FLAGS was used by four experts (board-certified hematopathologists) and seven pathology residents on 20 FL slides. Access to FLAGS improved overall reader accuracy with the biggest improvement seen among residents. An average AUC value of 0.75 was observed which generally indicates "acceptable" diagnostic performance.
  
  
  CONCLUSIONS
  The results of this study show that FLAGS can be useful in increasing the pathologists' accuracy in grading the tissue. To the best of our knowledge, this study measure, for the first time, the effect of computerized image analysis on pathologists' grading of follicular lymphoma. When fully developed, such systems have the potential to reduce sampling bias by examining an increased proportion of HPFs within follicle regions, as well as to reduce inter- and intra-reader variability.
authors.affiliation: Faculty of Engineering, Multimedia University, 63100, Cyberjaya, Selangor, Malaysia.
authors.forename: Mohammad Faizal Ahmad
authors.initials: MF
authors.lastname: Fauzi
authors.affiliation: Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pennell
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Berkman
authors.initials: B
authors.lastname: Sahiner
authors.affiliation: Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Weijie
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Arwa
authors.initials: A
authors.lastname: Shana'ah
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hemminger
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gru
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Habibe
authors.initials: H
authors.lastname: Kurt
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Losos
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Joehlin-Price
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Kavran
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Nowacki
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Sharmeen
authors.initials: S
authors.lastname: Mansor
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lozanski
authors.affiliation: Department of Biomedical Informatics, The Ohio State University, 250 Lincoln Tower, 1800 Cannon Drive, Columbus, OH, 43210, USA. metin.gurcan@osumc.edu.
authors.forename: Metin N
authors.initials: MN
authors.lastname: Gurcan
mesh_terms: D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008224:Lymphoma, Follicular / Q000145:classification* / Q000473:pathology; D060787:Neoplasm Grading / Q000379:methods*