Iczkowski, Kenneth A.

Abstract Context. —Minimal volume prostatic adenocarcinoma (defined as involving less than 5% of biopsy tissue) is diagnosed increasingly today because of successful cancer screening. We previously described the diagnostic category called atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy, present in about 2.5% of routine prostatic needle biopsy specimens. Objective. —To establish the criteria enabling a distinction between ASAP and cancer. Design. —We prospectively evaluated clinical and histologic findings from all 319 patients consecutively diagnosed as having ASAP or minimal cancer by prostatic needle biopsy in a consultation service. Seventeen histopathologic features were assessed. Results. —Fifty-six patients (18%) had ASAP, and 100 (31%) had minimal cancer; the remaining 163 (51%) had benign diagnoses, high-grade prostatic intraepithelial neoplasia, or larger amounts of cancer. The mean age of patients with ASAP did not differ from that of patients with minimal cancer (64.2 years vs 63.3 years; P = .65). In 10 of 17 histopathologic findings, ASAP differed significantly from minimal cancer. Among architectural findings, ASAP foci averaged 0.4 vs 0.8 mm ( P < .0001) and comprised a mean of 11 vs 17 acini ( P < .0001). Infiltrative growth occurred in 75% of ASAP foci and 100% of minimal cancers ( P < .0001). Among cytologic findings, ASAP was significantly less likely than cancer to have mitotic figures (0% vs 10%, respectively; P < .01) or prominent nucleoli in at least 10% of cells (55% vs 100%, respectively; P < .0001) and showed more frequent nuclear hyperchromasia (44% vs 9%, respectively; P < .0001) and less nuclear enlargement ( P = .0002). Luminal blue mucin secretions were less common in ASAP than cancer (6% vs 33%, respectively; P < .0001), but eosinophilic granular secretions and crystalloids were about equally frequent. Concomitant high-grade prostatic intraepithelial neoplasia was present in 23% of ASAP cases and 57% of cancers ( P < .0001). Moderate-to-severe atrophy confounded 59% of cases with ASAP and 35% of cancers ( P = .003); both ASAP foci and cancer were associated with inflammation in about a quarter of cases. In each case with ASAP, we stratified our level of suspicion among 3 categories (favor benign, uncertain, and favor carcinoma). As suspicion increased so did the mean nuclear enlargement and percentage of cases with infiltrative growth and nuclear hyperchromasia (all P < .05). Conclusions. —These criteria, which differ significantly between ASAP and minimal volume cancer, can help to separate patients for whom a second biopsy is recommended from candidates for prostatectomy or other therapy.

AimsDespite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading.Methods and resultsThe International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62–0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two‐thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non‐members are able to access a limited number of cases.ConclusionsIt is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified.