By Bahram Robert Oliai, M.D.
In this the third in my series of three reviews on clinicopathologic enigmas in prostate pathology I conclude with a discussion of small foci of adenocarcinoma on prostate biopsy. In this newsletter I present some clinicopathologic issues regarding small foci of prostate cancer, including an alternative therapeutic tact (other than radical prostatectomy and/or radiation).
Small Foci of Prostatic Adenocarcinoma
In cases in which the morphologic and architectural features are characteristic, the diagnosis of prostatic adenocarcinoma can be made on very few acini (FIG 1). Additionally, findings that are absolutely diagnostic of carcinoma, including true perineural invasion (a gland should wholly embrace a nerve for this to be a diagnostic feature), mucinous fibroplasia, and glomerulations can facilitate the diagnosis of cancer in a very limited focus (FIG 2a, 2b, 2c). I define a small focus of cancer as involvement of less than 5% of a core and in these cases I do not assign a percentage involvement, but simply diagnose “small focus of prostatic adenocarcinoma,” followed by the Gleason score. Although the vast majority of these “small focus” cancers are Gleason score 3+3=6, occasionally small foci of higher grade tumors are seen.
In one study of cases with 0.5 mm Gleason 3+3=6 cancer diagnosed on core, approximately 50% of subsequent radical Prostatectomies contained very small foci of cancer (less than 0.1 cc, 2). Given the current era of highly sensitive PSA screening and our ability to diagnose increasingly smaller foci of cancer (thanks in part to our ever expanding armamentarium of immunoperoxidase stains and experience), occasionally subsequent radical prostatectomies will show no identifiable cancer (3). It is essential for both urologists and patients to realize this up front when dealing with
small, focal, tumors. Interestingly this phenomenon of “vanishing tumors” is not unique to the prostate, and I have seen several cases of biopsy proven breast carcinoma, with the subsequent excision showing nothing but biopsy site change. As our diagnostic modalities become more and more sensitive I suspect this will become a slightly more common occurrence.
In patients for whom therapeutic intervention is indicated and desired, one technique gaining popularity is watchful waiting also known as “active surveillance” and “expectant management.” This technique is generally reserved for older patients (as younger patients with small foci of carcinoma may want to consider definitive therapy given their longer life expectancy). The goal here is to
follow older patients with early diagnosed, low grade, small volume cancer without immediate therapy, intervening at the first sign of progression. The criteria for watchful waiting as outlined by Epstein et al. include non-palpable tumor, clinical stage T1c, PSA density of <0.15 ng/ml/cm3, Gleason score of 6 on biopsy, less than 3 cores involved, no more than 50% involvement of any one core, no Gleason score 7 and no Gleason pattern 4 or 5 (4). In their review of watchful waiting, Allaf and Carter followed patients (who underwent initial 12 core biopsies), with PSA and DRE at 6 month intervals with annual biopsy. Once patients progressed (failing the above mentioned criteria), they underwent radical prostatectomy, with the vast majority having curable cancer in the end (1).
In conclusion, I hope you found this series of newsletters useful in managing the diagnosis of HGPIN, atypical acini, and small foci of adenocarcinoma. At ProPath we are always ready to support our clients in their quest for clinical excellence and help their patients find their own unique road to recovery.
1. Allaf ME, Carter HB. Update on watchful waiting for prostate cancer. Current Opinion in Urology 2004; 14: 171-175.
2. Allan RW, Sanderson H, Epstein JI. Correlation of minute (0.5 mm or less) focus of prostate adenocarcinoma on needle biopsy with radical prostatectomy specimen: role of prostate specific antigen density. The Journal of Urology 2003; 170: 370-372.
3. DiGiuseppe JA, Sauvageot J, Epstein JI. Increasing incidence of minimal residual cancer in radical prostatectomy specimens. The American Journal of Surgical Pathology 1997; 21(2): 174-178.
4. Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368-374.
Date of last revision: January 2007.