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Surgical Pathology Criteria

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Prostatic Small Cell Carcinoma


  • High grade primary prostatic carcinoma composed of histologically undifferentiated cells with neuroendocrine differentiation

Diagnostic Criteria

  • Histologically similar to pulmonary small cell carcinoma
    • Round to spindled cells with scant cytoplasm
    • Hyperchromatic, molded nuclei
      • Nucleoli usually inconspicuous
    • High proliferation rate, frequent necrosis
  • About half have concurrent or prior usual-type adenocarcinoma
    • May be high or low grade
    • Metastases may be mixed or pure small cell
    • May occur as late as 25 years after adenocarcinoma diagnosis
  • Small cell carcinoma is high grade by definition but is not Gleason graded
  • Very poor prognosis
    • Over half present with metastasis
      • Frequently lung or liver, bone is less frequent
    • Serum PSA variable (probably due to concurrent adenocarcinoma)
    • Paraneoplastic syndromes have been reported
  Prostate Small Cell Carcinoma High Grade Usual Prostate Adenocarcinoma Pulmonary and Other Small Cell Carcinoma
CD44 100% neg neg
Synaptophysin, Chromogranin, CD56 90% scatterered cells 90%
TTF1 50% neg 90%
HMW Cytokeratin, P63 35-40% neg neg
PSA, PAP 20% 90-100% neg
  • ERG gene rearrangements appear to be specific for prostate origin in this context
  • Principal differential diagnosis is vs metastasis from another site and high grade adenocarcinoma
    • In addition to the above stains and genetic studies, history 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.
    • Wang W, Epstein JI. Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases. Am J Surg Pathol. 2008 Jan;32(1):65-71.
    • Simon RA, di Sant'Agnese PA, Huang LS, Xu H, Yao JL, Yang Q, Liang S, Liu J, Yu R, Cheng L, Oh WK, Palapattu GS, Wei J, Huang J. CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers. Hum Pathol. 2009 Feb;40(2):252-8.
    • Lotan TL, Gupta NS, Wang W, Toubaji A, Haffner MC, Chaux A, Hicks JL, Meeker AK, Bieberich CJ, De Marzo AM, Epstein JI, Netto GJ. ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol. 2011 Jun;24(6):820-8.
    • Guo CC, Dancer JY, Wang Y, Aparicio A, Navone NM, Troncoso P, Czerniak BA. TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate. Hum Pathol. 2011 Jan;42(1):11-7.
  • 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


Prostatic Carcinomas

Prostatic Benign Lesions/Patterns Simulating Carcinoma

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