PATHOLOGY

Gleason grading of prostatic adenocarcinoma with glomeruloid features on needle biopsy
Lotan TL, Epstein JI
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
Hum Pathol. 2009; 5: [Epub ahead of print]

• Glomerulations in prostatic adenocarcinoma are characterized by dilated glands containing intraluminal cribriform structures with a single point of attachment, resembling a renal glomerulus. On prostate biopsy, glomerulations are exclusively associated with carcinoma and not associated with benign mimickers. However, the Gleason grading of carcinoma with glomerulations on needle biopsy remains controversial. We prospectively collected 45 prostate needle biopsies containing carcinoma with glomeruloid features from our consult files for a 9-month period and examined the association between glomerulations and the presence of concurrent high-grade carcinoma. Glomerulations were overwhelmingly associated with high-grade cancer on the same core, composed of either Gleason pattern 4 (n = 36, 80% of cases) or Gleason pattern 5 (n = 2, 4% of cases). Only a minority of glomerulations were surrounded exclusively by pattern 3 cancer (n = 7, 16% of cases) on the same core. Most of the cases with surrounding pattern 4 cancer were scored as 3 + 4 = 7 (n = 24, 66%), whereas a smaller fraction were scored as 4 + 3 = 7 (n = 9, 26%), and only a minority were 4 + 4 = 8 (n = 3, 9%). In most cases, glomeruloid change was present on the same core as the highest Gleason score carcinoma of the case. None of the pattern 3 cases and only a minority of the pattern 4 cancers had higher Gleason score carcinoma on additional cores (n = 5, 14%). Glomeruloid structures are a rare but diagnostic feature of prostatic carcinoma on needle biopsy. Our data indicate that glomerulations are overwhelmingly associated with concurrent Gleason pattern 4 or higher-grade carcinoma. In several cases, transition could be seen among small glomerulations, large glomeruloid structures, and cribriform pattern 4 cancer. These data suggest that glomerulations represent an early stage of cribriform pattern 4 cancer and, until follow-up data are available, are best graded as Gleason pattern 4.
  
  
• Editorial Comment
  The grading of prostatic adenocarcinoma with glomeruloid structures is controversial (1-3). Some urological pathologists do not assign a grade to this pattern and just grade the surrounding tumor. Other experts in the field feel that all glomeruloid structures should be assigned a Gleason pattern 4.
  The glomeruloid feature in adenocarcinoma of the prostate refers to an architectural pattern of growth that mimics the renal glomerulus (1,3,4). Glomeruloid structures have been described in Wilm’s tumor (5) probably representing differentiation of neoplastic cells toward a primitive form of renal glomerulus and are sometimes present in gliomas (6). In a rare case of adenoma (hamartoma) of bladder in siblings, spaces, often cystic, lined with neoplastic epithelial cells with hyperchromatic nuclei were crowded at one of the poles which strikingly resembled primitive glomeruli (7).
  This distinctive pattern of prostate cancer was first described in 1995 by Epstein in his book Prostate biopsy interpretation and called the lesion glomerulations (8). In 1998, Pacelli et al. (1) published a series of prostatic adenocarcinoma with glomeruloid features in biopsies and radical prostatectomies. The frequency of adenocarcinoma with glomeruloid features in 100 needle prostatic biopsies was 3% in Pacelli’s series.
  Glomeruloid structures appear to be a specific but uncommon finding in prostate cancer. They are not seen in benign prostatic tissue, nodular hyperplasia, basal cell hyperplasia, atypical adenomatous hyperplasia, or prostatic intraepithelial neoplasia (3,4).
  In Lotan and Epstein’s study glomeruloid structures were associated to Gleason pattern 4 or 5 in more than 80% of the cases. In only 16% of the cases were associated exclusively to Gleason pattern 3. The authors suggest that glomerulations represent an early stage of cribriform pattern 4 cancer and, until follow-up data are available, are best graded as Gleason pattern 4.
  In a similar study based on 264 needle biopsies, we found 28/264 (10.6%) biopsies showing glomeruloid structures; 9/28 (32.14%) biopsies the glomeruloid structures were surrounded by Gleason low-grade tumor and in 19/28 (67.85%) biopsies surrounded by Gleason high-grade tumor (9). All patients in our study were submitted to radical prostatectomy. Comparing the findings for several clinicopathologic variables between patients with and without glomeruloid structures, no statistical significance was found and at 5 years, the PSA progression-free survival rates were 57% and 52% for patients without and with glomeruloid structures (log-rank, p = 0.26). Glomeruloid structures were associated more frequently with Gleason high-grade surrounding tumor, however, the presence of this architectural pattern was not associated to any other adverse clinicopathologic findings. It seems in our study that glomeruloid feature per se should not interfere in the grading of a tumor.

References
1. Pacelli A, Lopez-Beltran A, Egan AJ, Bostwick DG: Prostatic adenocarcinoma with glomeruloid features. Hum Pathol. 1998; 29: 543-6.
2. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005; 29: 1228-42.
3. Epstein JI, Netto GJ: Biopsy Iterpretation of the Prostate, 4th ed., Philadelphia, Lippincott Williams & Wilkins. 2008.
4. Baisden BL, Kahane H, Epstein JI: Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. Am J Surg Pathol. 1999; 23: 918-24.
5. Murphy WM, Beckwith JB, Farrow GM: Tumors of the Kidney, Bladder, and Related Urinary Structures. In: Atlas of Tumor Pathology, 3rd series, fascicle 11. Washington DC, Armed Forces Institute of Pathology. 1994.
6. Haddad SF, Moore SA, Schelper RL, Goeken JA: Vascular smooth muscle hyperplasia underlies the formation of glomeruloid vascular structures of glioblastoma multiforme. J Neuropathol Exp Neurol. 1992; 51: 488-92.
7. Billis A, Lima AC, Queiroz LS, Cia EM, Oliveira ER, Pinto W Jr: Adenoma of bladder in siblings with renal dysplasia. Urology. 1980; 16: 299-302.
8. Epstein JI. Evaluation in Needle Biopsy Specimens. In: Prostate Biopsy Interpretation, 2nd ed., Philadelphia, Lippincott Raven. 1995, pp. 95-6.
9. Quintal MM, Billis A, Meirelles L, Freitas LL, Duarte AG, Silva CA, Bisson MA, Magna LA: Glomeruloid structures on needle prostatic biopsies: should they be assigned a grade or rather just grade the surrounding tumor? Mod Pathol. 2009; Abstract [in press].

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br