The Importance of Being Grade 3: WHO 1999 Versus WHO 2004 Pathologic Grading

The most important event to predict for patients with non– muscle-invasive (NMI) bladder cancer is progression to muscle-invasive growth. European Organization for Research and Treatment of Cancer (EORTC) risk tables have been used and validated as a prognostic tool for both cancer recurrence and progression. The tables include tumor grade according to the World Health Organization (WHO) 1973 system, tumor stage, and presence/absence of carcinoma in situ (CIS), complemented by three clinical parameters: prior recurrence rate, tumor diameter, and number of tumors. In the European Association of Urology (EAU) guidelines for NMI bladder cancer from2011, gradingwith both the threetiered WHO 1973 and the two-tiered 2004 systems are recommended [1]. The argument in favor of WHO 2004 has been less interobserver variability. However, the threetieredWHO 1999 has more precise criteria for grading than WHO 1973, reduces the interobserver variability, and is used in 30% of pathology laboratories in Europe, in addition to theWHO2004 system [2]. TheWHO1999 andWHO2004 systems are completely congruent and WHO 1999 is easily translated to WHO 2004; grade 2 and grade 3 tumors in WHO 1999 constitute high-grade carcinoma in the WHO 2004 system [3]. As opposed to the WHO 2004 system, WHO1999 can also be used for EORTC risk tables. Themajor difference between the WHO 1999 and WHO 2004 grading systems is that WHO 1999 defines a more distinct highgrade (G3) group of tumors. In this article, we give