The first task of the experienced genitourinary pathologist is to distinguish invasive prostate cancer from glandular proliferations that mimic it by virtue of having small or crowded glands. Our Prostate Diagnostic Laboratory (PDL) uses certain immunostains that help establish this diagnosis. Some stain positive in cancer (P504S racemase), while loss of staining for markers of basal cells--the row of cells that encircle benign glands--rules in cancer (cytokeratin 903, cytokeratin 5/6, p63).

The second task of the pathologist is grading the cancer, using the scheme developed by Dr. Donald Gleason in 1966. Cancer grade predicts outcome and is a key datum for choice of therapy on the part of the patient and urologist. The Gleason grade ranges from 1 (lowest) to 5 (highest), although in practice, grades 3 and 4 are by far the most common, particularly in needle biopsies. Prostate cancer can present an array of very different appearances [Gleason 3] [Gleason 4] [Gleason 5], and each bespeaks a certain grade. Thus, the pathologist's adherence to currently accepted grading criteria is essential for standardization of the grade, so the grade is the same no matter what pathologist assigns it. The sum of the most common and second common Gleason grades is called the Gleason score.

A small percentage of men will have no cancer on their biopsies but have a pre-cancerous condition called high-grade prostatic intraepithelial neoplasia [HGPIN]. The 3 glands in this HGPIN lesion stand out because of their darkness and crowded nuclei, but the neoplastic cells are not invasive [HGPIN]. They are confined within gland spaces by a row of basal cells. HGPIN has up to a 35% predictive value for cancer on a repeat biopsy, which slightly exceeds the 25% of men with persistently elevated PSA in whom cancer is found after repeat biopsy. Thus, the finding of HGPIN lesions increases the motivation for a repeat biopsy. Mapping biopsy of the prostate (50- >100 cores) is an excellent way to detect the small areas of invasive cancer that often accompany HGPIN lesions.

In about 3% of cases, pathologists will note a small focus of atypical glands that is not definite for cancer. This is known as atypical small acinar proliferation [ASAP]. When ASAP is detected in the usual 6-10 cores sampled in an initial biopsy, cancer on repeat biopsy is predicted in up to 50% of cases. Mapping biopsy of the prostate is also an excellent approach to detect the often small areas of cancer that prompt an initial diagnosis of ASAP.

Usually, more than one area of the prostate is involved by cancer. Once the 3-D needle core locations of the cancer in the prostate are established, the locations of these cores are matched to a 3-D grid using computer imaging, to determine as precisely as possible the areas and extent of cancer. The mapping often closely approximates the locations of cancer seen in a prostatectomy specimen. [2  pictures to show 1-to-1 correspondence.] The ability to localize the cancer is the great strength of mapping biopsies, allowing targeted focal therapy to be applied to the affected areas. This approach is much the same as "lumpectomy" for breast cancer, in which the portion of the gland not involved by cancer is spared. An array of side effects that commonly follow radical surgery, including impotence and incontinence, are thus avoided.