title: Three-dimensional evaluation of subclinical extension of extramammary Paget disease: visualization of the histological border and its comparison to the clinical border.
abstract: BACKGROUND
  In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown.
  
  
  OBJECTIVE
  To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension.
  
  
  METHODS
  Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well-demarcated lesions. Samples were transparentized and subjected to whole-mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two-photon microscopy. The shape and location of the histological border were compared with those of the clinical border.
  
  
  RESULTS
  In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema.
  
  
  CONCLUSIONS
  In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.|Research Fellow of the Japan Society for the Promotion of Science.
authors.forename: T
authors.identifier: http://orcid.org/0000-0001-8350-1289
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Egawa
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kitoh
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: T
authors.identifier: http://orcid.org/0000-0002-9497-0029
authors.initials: T
authors.lastname: Dainichi
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Tenri Hospital, Tenri, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kore-Eda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kaku
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fujisawa
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyachi
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan.|Singapore Immunology Network (SIgN) and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, Biopolis, 138648, Singapore.|PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000473:pathology*; D046169:Dermoscopy / Q000379:methods; D005260:Female; D006801:Humans; D017496:Hypopigmentation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010145:Paget Disease, Extramammary / Q000473:pathology* / Q000601:surgery; D017785:Photons; D011300:Preoperative Care; D012878:Skin Neoplasms / Q000473:pathology* / Q000601:surgery; D014565:Urogenital Neoplasms / Q000473:pathology*