title: Criteria for biopsy diagnosis of minimal volume prostatic adenocarcinoma: analytic comparison with nondiagnostic but suspicious atypical small acinar proliferation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. iczkowskik@readinghospital.org
authors.forename: K A
authors.initials: KA
authors.lastname: Iczkowski
authors.forename: D G
authors.initials: DG
authors.lastname: Bostwick
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D002455:Cell Division; D002467:Cell Nucleus / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019048:Prostatic Intraepithelial Neoplasia / Q000175:diagnosis; D011471:Prostatic Neoplasms / Q000175:diagnosis*