title: Is CDX2 immunostaining useful for delineating anorectal from penile/vulvar squamous cancer in the setting of squamous cell carcinoma with clinically unknown primary site presenting with histologically confirmed inguinal lymph node metastasis?
abstract: OBJECTIVE
  Penile, vulvar and anal squamous cell carcinomas (SCCs) share histomorphological overlap and are prone to lymphatic dissemination into inguinal nodes. Anal SCCs might derive from the anorectal zone (ARZ), anal transitional zone, squamous zone or from perianal skin. These anatomically distinct zones differ in terms of their embryological development. We sought to investigate the role of caudal-related homeobox 2 (CDX2), a homeobox gene implicated in the development and anterior/posterior pattern specification from duodenum to rectum including the ARZ, in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with histologically confirmed inguinal lymph node metastasis.
  
  
  METHODS
  By immunohistochemistry (IHC) employing a panel of antibodies directed against CK5/6, CK7, CK20, p63, p16, CEA and CDX2, we compared 89 penile, 11 vulvar and eight anal SCCs with respect to their staining profiles. Moreover, anal SCCs were subjected to in situ hybridisation (ISH) for high-risk human papillomavirus (HPV) subtypes.
  
  
  RESULTS
  By IHC, CDX2 expression was observed in 2/8 anal SCCs (25%) while being absent from all penile and vulvar SCCs examined. High-risk HPV subtypes were detected by ISH in all anal SCCs examined, which were uniformly p16-positive by IHC.
  
  
  CONCLUSIONS
  CDX2 might be valuable in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with inguinal lymph node metastasis. However, despite its favourable specificity, the diagnostic benefit achieved by this observation is limited by the low sensitivity.
authors.affiliation: Department of Pathology, Institute of Pathology at the Johanniter Hospital Stendal, Stendal, Germany. sven-gunia@gmx.de
authors.forename: Sven
authors.initials: S
authors.lastname: Gunia
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.forename: Matthias
authors.initials: M
authors.lastname: May
mesh_terms: D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000556:secondary / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis*; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D010412:Penile Neoplasms / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014846:Vulvar Neoplasms / Q000737:chemistry* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004279:DNA, Viral; D018398:Homeodomain Proteins