title: Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma.
abstract: OBJECTIVE
  Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) is associated with a favourable prognosis and microsatellite instability-high (MSI-H) status. However, there is a lack of consensus on optimal criteria for CLR assessment. The aim of this study was to comparatively validate traditional and novel assessment criteria for CLR.
  
  
  METHODS
  CLR status in 212 MSI-H CRCs was assessed independently by two pathologists using three different criteria: (1) traditional semiquantitative criteria (Graham-Appelman criteria), (2) the largest lymphoid aggregate (LA) size-based criteria (Ueno criteria) and (3) LA density-based criteria (Väyrynen-Mäkinen criteria).
  
  
  RESULTS
  Among the three criteria, the Väyrynen-Mäkinen criteria-based CLR assessment showed the best interobserver agreement (κ value, 0.71; intraclass correlation coefficient, 0.76). Pathologically, intense CLR (grade 2) by Graham-Appelman criteria, active CLR (largest LA size ≥1 mm) by Ueno criteria and high-density CLR (≥0.38 LAs/mm) by Väyrynen-Mäkinen criteria significantly correlated with an early cancer stage (stage I/II). In Kaplan-Meier analysis, both CLR statuses determined by Ueno criteria and Väyrynen-Mäkinen criteria were associated with significant differences in disease-free survival in MSI-H CRC patients (p=0.005 and p=0.001, respectively). In multivariable analysis, both active CLR and high-density CLR proved to be independent favourable prognostic factors in MSI-H CRC (HR, 0.47; 95% CI 0.24 to 0.9 for active CLR and HR, 0.5; 95% CI 0.28 to 0.89 for high-density CLR).
  
  
  CONCLUSIONS
  Our study confirms that the two recently suggested criteria (Ueno criteria and Väyrynen-Mäkinen criteria) for CLR assessment are fairly reproducible methods and can serve as superior prognosticators in CRC.
authors.affiliation: Department of Pathology, SMG-SNU Boramae Medical Centre, Seoul, Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Ju
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ye-Young
authors.initials: YY
authors.lastname: Rhee
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D003424:Crohn Disease / Q000473:pathology*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D012189:Retrospective Studies
keywords: COLORECTAL CANCER; GUT PATHOLOGY; HISTOPATHOLOGY; TUMOUR IMMUNITY