Stanford School of Medicine

Surgical Pathology Criteria

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Prostatic Signet Ring Adenocarcinoma


  • Primary prostatic adenocarcinoma with a prominent population of signet ring cells

Diagnostic Criteria

  • No agreement on percent of signet ring cells required for this diagnosis
    • 5-50% have been described in the literature
  • Nucleus is displaced and indented by clear mucin filled vacuole
    • Vacuole must be positive on mucin stain
    • Mucin-negative vacuolated "signet ring cell-like" adenocarcinoma is more common
      • May be included in many studies
      • These are usually high grade also
      • Gleason pattern 4, with ragged infiltration and poorly formed glands may simulate scattered signet ring cells
    • Cautery in TURP chips may cause stromal cell vacuoles
  • Infiltration pattern may be as single cells up to sheets
  • Gleason pattern 5 by definition
    • May be associated with other patterns, usually 4 or 5
  • Poor response to therapy and poor prognosis
  • PSA, PAP positive
  • Urothelial and non-prostatic origin must be excluded
    • Mucinous urothelial carcinoma
      • HMWCK positive and CK7/20 double positive in most cases
      • PSA and PAP negative (Osunkoya 2007)
        • Some older reports find some positivity
    • GI tract adenocarcinoma must be ruled out
      • PSA and PAP negative
      • CDX2 positive in GI primaries but also reported positive in 30% of signet ring prostate carcinomas (Leite 2008)
      • History, endoscopy and imaging are critical
  • Bibliography (for general references see Prostatic Acinar Adenocarcinoma)
    • Humphrey, P. A. (2012), Histological variants of prostatic carcinoma and their significance. Histopathology, 60: 59–74.
    • Torbenson M, Dhir R, Nangia A, Becich MJ, Kapadia SB. Prostatic carcinoma with signet ring cells: a clinicopathologic and immunohistochemical analysis of 12 cases, with review of the literature. Mod Pathol. 1998 Jun;11(6):552-9.
    • Osunkoya AO, Epstein JI. Primary mucin-producing urothelial-type adenocarcinoma of prostate: report of 15 cases. Am J Surg Pathol. 2007 Sep;31(9):1323-9.
    • Leite KR, Mitteldorf CA, Srougi M, Dall'oglio MF, Antunes AA, Pontes J Jr, Camara-Lopes LH. Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer. Ann Diagn Pathol. 2008 Aug;12(4):260-6.
  • For general diagnostic, grading and staging criteria, see also Prostatic Acinar Adenocarcinoma

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 6/1/12


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