title: RANKL expression is a useful marker for differentiation of pagetoid squamous cell carcinoma in situ from extramammary Paget disease.
abstract: BACKGROUND
  Pagetoid squamous cell carcinoma in situ (SCCIS) is a histopathologic variant of SCCIS composed of cells that display an abundant, pale-staining cytoplasm in a pagetoid distribution within the epidermis. As pagetoid SCCIS is sometimes difficult to differentiate from extramammary Paget disease (EMPD) histopathologically, specific markers for pagetoid SCCIS or EMPD are needed by dermatopathologists.
  
  
  METHODS
  In this report, we employed immunohistochemical staining for receptor of activated nuclear factor kappa ligand (RANKL) and programmed death-ligand 1 (PD-L1) in six cases each of pagetoid SCCIS and EMPD.
  
  
  RESULTS
  The Paget cells strongly expressed RANKL in EMPD, whereas the atypical keratinocytes did not express RANKL in any of the six cases of pagetoid SCCIS. In all cases of pagetoid SCCIS, atypical keratinocytes expressed PD-L1. In EMPD, Paget cells expressed PD-L1 in half of the cases at a lower level of expression than was seen in the surrounding keratinocytes.
  
  
  CONCLUSIONS
  This study suggested that RANKL, but not PD-L1, could be a marker to differentiate between pagetoid SCCIS and EMPD.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kambayashi
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kakizaki
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Furudate
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000175:diagnosis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000175:diagnosis*; D053245:RANK Ligand / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: PD-L1; RANKL; extramammary Paget disease; pagetoid squamous cell carcinoma in situ