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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?
  1. Sven Gunia1,
  2. Stefan Koch2,
  3. Matthias May3
  1. 1Department of Pathology, Institute of Pathology at the Johanniter Hospital Stendal, Stendal, Germany
  2. 2Institute of Pathology at the HELIOS Clinic Bad Saarow, Charité-University Medicine Academic Teaching Hospital, Bad Saarow, Germany
  3. 3Department of Urology, St. Elisabeth Clinic Straubing, Straubing, Germany
  1. Correspondence to Sven Gunia, Institute of Pathology at the Johanniter Hospital Stendal, Straße der Demokratie 1, Stendal 39576, Germany; sven-gunia{at}gmx.de

Abstract

Aims 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.

  • Anus
  • Cancer
  • Immunohistochemistry

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