Answer: High grade adenocarcinoma of the prostate

Histology: The tumor predominantly consists of sheets of cells with large nuclei containing centrally located eosinophilic prominent nucleoli. Despite the poorly differentiated nature of this neoplasm, the tumor cells are relatively uniform one to another without marked pleomorphism. The cytoplasm is lightly eosinophilic. Mitotic figures are present yet not very frequent. Focally, the tumor is arranged in nests of cells and in one focus the tumor shows microacinar formation.

Discussion: A common dilemma in genitourinary pathology is the distinction between poorly differentiated urothelial carcinoma and poorly differentiated adenocarcinoma of the prostate on a transurethral resection from a bladder, bladder neck, or prostatic mass.
Often, clinically the urologist cannot distinguish between these two entities as some high grade adenocarcinomas of the prostate may not have elevated serum PSA levels and tumors may straddle the bladder and prostate such that their site of origin may be unclear.

It is critical to make the distinction between these two entities as the treatment between the two is markedly different. Advanced urothelial carcinomas are treated with chemotherapy whereas advanced adenocarcinomas of the prostate will typically be treated with hormone therapy plus or minus radiation. Although rarely adenocarcinomas of the prostate may show marked pleomorphism equivalent to that seen within urothelial carcinoma, typically poorly differentiated adenocarcinomas of the prostate show more uniform cytology as seen in the current case. In addition the lightly eosinophilic, delicate cytoplasm is typical of adenocarcinoma of the prostate in contrast to urothelial carcinoma which often shows hard eosinophilic cytoplasm as evidence of squamous differentiation.

The finding of microacinar formation also seen in the current case is typical of prostate cancer and not seen in urothelial carcinomas. Although urothelial carcinomas may show glandular differentiation, glandular differentiation typically resembles enteric glands such as seen in adenocarcinomas of the colon rather than the microacinar formation as is seen to a better developed form in cribriform Gleason score 4+4=8 adenocarcinomas of the prostate.

In the current case, stains for PSA were done at an outside institution and were negative. However, upon review, we noted that the control benign prostate tissue stained for PSA showed relatively weak positivity. In order to optimize the staining for PSA one should make sure that the benign prostate glands stain intensely as tumors are often less immunoreactive than benign glands. If the benign prostate control tissue stains weakly then many poorly differentiated adenocarcinomas of the prostate will show false negative staining. We repeated the stain at our own institution and although PSA stains were not diffusely positive areas of the tumor showed definitive strong positivity diagnostic of prostate cancer. Stains were also performed for P501S (Prostein). Antibodies to P501S label a protein that is localized to the golgi complex within both benign and neoplastic prostate tissues but is not present in other normal or malignant tissues. Staining shows granular positivity located to the golgi region.

In our experience, most cases will show similar staining between PSA and P501S yet we have experienced cases such as the current one where P501S staining is much more intense and diffuse as compared to PSA staining on the same case. Consequently, we perform stains for both PSA and P501S when evaluating a poorly differentiated tumor where the differential diagnosis includes adenocarcinoma of the prostate.

Users of the Johns Hopkins Surgical Pathology Web site with a special interest in Genitourinary Pathology should also be aware of a separate web site isuporg.org which is the official site of the International Society of Urological Pathology. On this web site an interesting urological pathology case of the week is presented along with a discussion. To join the ISUP and gain access to this website there is a $40.00 per year membership fee. Some of the most challenging and fascinating urological pathology cases that I see in my consultation service are displayed on the ISUPORG.org web site on a weekly basis.