Prostatic Small Cell Carcinoma

Definition

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

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