PATHOLOGY

The addition of a negative 34bE12 stain to a small focus of atypical glands on prostatic core biopsies does not predict a higher incidence of prostatic adenocarcinoma on follow up biopsies
Halushka MK, Kahane H, Epstein JI
The Johns Hopkins Hospital, Baltimore, MD; Dianon Corp., Stratford, CT
Mod Pathol. 2003; 16: 152A

• Background: Atypical glands on prostate needle biopsy with a negative 34bE12 immunostaining, indicating a lack of a basal cell layer, are typically diagnostic criteria of prostate cancer. However, there are certain cases in which a negative 34bE12 immunostaining in a small focus of atypical glands is still not convincing enough to make the diagnosis of cancer. This study is the first report to evaluate the incidence of prostate cancer on follow-up biopsy in individuals with this diagnosis.
• Design: 543 men who had prostate core biopsies diagnosed as a small focus of atypical appearing glands with a negative 34bE12 immunostaining between 1/1/97 and 12/31/00 were selected for study.
• Results: 61% of the 543 individuals had at least one follow up biopsy (n=332). Of these, 43% of repeat biopsies were diagnostic of prostate cancer (n=142). 46 men had at least 2 follow up biopsies, with 48% of these (n=22) being diagnosed as cancer. The percent of carcinomas having Gleason grades 3+2=5, 3+3=6, 3+4=7, 4+3=7 and 4+4=8 were 6%, 86%, 1%, 4% and 3% respectively. The median amount of time to the first follow up biopsy was 79 days, with 52% of follow up biopsies being performed within 90 days.
• Conclusions: A negative 34bE12 immunohistochemical stain in a small focus of atypical glands is not associated with an increased prediction of prostate cancer on follow up biopsy (43%), compared with previously published data for “small focus of atypical glands” alone (approximately 45%). As 48% of men with an initial negative biopsy and multiple follow up biopsies were found to have cancer, more than one repeat biopsy or more extensive sampling on first repeat biopsy may be necessary to maximize the identification of cancer. This is the same as has been shown for men with atypical diagnoses in general, without a negative 34bE12 immunohistochemical stain. Only half of all individuals with a diagnosis of 34bE12 negative focus of atypical glands were rebiopsied within 3 months. Urologists need to be educated as to the significance of an atypical diagnosis and the need for rebiopsy.
  
• Editorial Comment
  The presence of basal cells excludes the diagnosis of adenocarcinoma but their absence does not mean necessarily that the acinus is neoplastic. This article emphasizes the need of morphologic criteria for the diagnosis of adenocarcinoma. The pathologist should not rely on his diagnosis exclusively on the result of immunostaining.
  In cases of “atypical small acinar proliferation” (ASAP), immunostaining is indicated to help making the diagnosis of adenocarcinoma. This study, however, showed that a negative 34bE12 immunohistochemical stain in a small focus of ASAP is not associated with an increased prediction of prostate cancer on follow up biopsy (43%), compared with previously published data (approximately 45%).
  In cases of ASAP the pathologist, besides immunostaining, performs new sections in other levels of the biopsy hoping the lesion appears more extensive. In cases the immunostaining does not show basal cells but the morphologic criteria are still not sufficient for the diagnosis of adenocarcinoma, the diagnosis is ASAP and not adenocarcinoma.

Dr. Athanase Billis
Department of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil