Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract

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Abstract
BACKGROUND Although many articles have been published regarding neuroendocrine tumors (NET) and neuroendocrine carcinomas of both low- and high-grade malignancy (NEC) of the genitourinary tract, the histologic diagnosis and therapeutic strategies for treating these entities remains difficult. In the current study the author discusses the significant differences between NET and NEC of the urinary bladder and the prostate, including therapeutic consequences. METHODS Four hundred eighty neoplasms of the urinary bladder and prostate with a small cell pattern were analyzed not only on slides stained with hematoxylin and eosin but also by means of immunohistochemical stains demonstrating a neuroendocrine origin. The avidin-biotin complex method was used with the following markers: MIB-1, chromogranin A (Chr A), synaptophysin (SNP), cytokeratin (CK) 34βE12, CK20, androgen receptor (AR), and prostate specific antigen (PSA). RESULTS Twenty tumors of the urinary bladder and 26 of the prostate demonstrated a diffuse neuroendocrine pattern. Only two patients were found to have a low-grade NEC of the prostate with a low proliferative index but strong expression of neuroendocrine markers. All other patients with small cell neuroendocrine carcinomas of the bladder and prostate demonstrated extremely high proliferation activity (>80%) and expressed Chr A and SNP. CK34βE12, 20, PSA, and AR were not found to be expressed. The mean survival time was 6.9 months. Fourteen of 20 patients with NEC of the urinary bladder died of the disease and 19 of 24 patients with prostatic NEC died. The therapy for urinary bladder NEC was repeated transurethral resection and antiandrogen therapy was given for NEC of the prostate. Only one patient was treated with chemotherapy, which to the author's knowledge currently is the only treatment for NECs of the genitourinary tract. CONCLUSIONS Undifferentiated carcinomas of the urinary bladder and prostate should be analyzed not only by means of hematoxylin and eosin but also by immunohistochemical staining for Chr A and SNP to demonstrate a neuroendocrine origin. Because the prognosis of small cell NECs is very poor, pathologists should indicate in their final report the peculiarities of small cell NECs of the prostate and the urinary bladder with special emphasis on different therapeutic strategies. Cancer 2002;95:1415–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10840