Answer: Prostate carcinoma

Histology: The tumor consists of nests of cells with marked pleomorphism. The cells have abundant lightly eosinophilic cytoplasm with nuclei in areas showing multinucleation, bizarre shapes, and mitotic figures including atypical mitotic figures. Other areas of the tumor are not quite as pleomorphic where cells are relatively more uniform with smaller nucleoli. No overt glandular differentiation is identified.

Discussion: Based on the morphology, the tumor is most consistent with high grade urothelial carcinoma given the marked pleomorphism. Typical high grade adenocarcinomas of the prostate show relatively uniform nuclei with central prominent nucleoli but relatively very little variation of size and shape from one cell to another. However, in rare cases, adenocarcinoma of the prostate, especially when advanced clinically, may have pleomorphic features identical to urothelial carcinoma. Consequently, in a poorly differentiated tumor involving the bladder/prostate where there is no precursor lesion (i.e. CIS or high grade papillary urothelial carcinoma) one should perform an immunohistochemical battery of stains to differentiate between adenocarcinoma of the prostate versus urothelial carcinoma given the significant treatment implications involved. Whereas advanced urothelial cancer is treated with chemotherapy, advanced prostate cancer would be treated with hormone therapy. The immunohistochemical profile that we perform includes stains for prostate specific antigen (PSA), P501s (prostein) and PSMA (prostate specific membrane antigen) to identify prostatic origin and stains for high molecular weight cytokeratin, p63 and thrombomodulin to label urothelial carcinoma. In the current case, the tumor was positive for PSMA and P501s as well as a stain for prostatic specific acid phosphatase performed at the outside institution. There was focal aberrant expression of high molecular weight cytokeratin with negative results for PSA, p63, and thrombomodulin. The positivity for PSMA and P501s are specific and recognizing that some high grade prostate cancers may aberrantly express high molecular cytokeratin, it is definitive for the diagnosis of adenocarcinoma of the prostate. This case illustrates not only the features of pleomorphic giant cell carcinoma of the prostate (Am J Surg Pathol 2006:30:1254-9), but also shows that some of these tumors may be negative for PSA where it is necessary to do other prostatic stains such as P501s and PSMA. We do not find performing CK7 and CK20 useful in the differential diagnosis of prostate versus urothelial carcinoma as there is overlap between the 2 stains.