title: Histopathological diagnosis of graft-versus-host disease of the skin: an interobserver comparison.
abstract: BACKGROUND
  Histopathology is an important tool in diagnosing cutaneous graft-versus-host disease (GvHD). Minimum diagnostic criteria for active chronic GvHD have recently been defined. However, they are not specific and their interpretation is dependent on observer judgement.
  
  
  OBJECTIVE
  
  
  
  OBJECTIVE
  i) to explore interobserver variability in the interpretation of histopathological changes in GvHD, and ii) to analyse the impact of detailed clinical data on histopathological diagnosis of GvHD.
  
  
  METHODS
  Histopathological slides from 15 skin biopsies of GvHD and from dermatoses with histopathologically similar appearance were sent in two phases to four dermatopathologists experienced in cutaneous GvHD in France, Germany, Italy and Switzerland (first round of 'blind' review followed by a second round with complete clinical information provided).
  
  
  RESULTS
  Interface dermatitis, especially vacuolar alteration, was the most inconsistently evaluated, particularly in cases with minor alterations. Interestingly, for vacuolar alteration and apoptotic keratinocytes, interobserver variability was lower in the adnexal epithelia than in the interfollicular epidermis. Complete clinical information resulted in increased diagnostic confidence and greater concordance on the final diagnosis, rising from 53% (first round, k = 0.345, fair agreement) to 80% (second round, k = 0.529, moderate agreement). The percentage of correct diagnoses increased from 33.3% to 80%.
  
  
  CONCLUSIONS
  For the diagnosis of GvHD, histopathological analysis is of importance, but, for correct diagnosis, the correlation of pathological findings with clinical results is crucial. In cases of minor alteration, histopathologists should focus on the interpretation of vacuolar changes and apoptotic keratinocytes, possibly on the adnexal epithelia.
authors.affiliation: Department of Dermatology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ziemer
authors.forename: P
authors.initials: P
authors.lastname: Haeusermann
authors.forename: A
authors.initials: A
authors.lastname: Janin
authors.forename: D
authors.initials: D
authors.lastname: Massi
authors.forename: M
authors.initials: M
authors.lastname: Ziepert
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.forename: U
authors.initials: U
authors.lastname: Hillen
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001706:Biopsy; D003937:Diagnosis, Differential; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D010338:Pathology, Clinical / Q000379:methods; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000175:diagnosis* / Q000473:pathology*; D014617:Vacuoles / Q000473:pathology