Elsevier

European Urology

Volume 46, Issue 2, August 2004, Pages 170-176
European Urology

Review
Non-Invasive Urothelial Neoplasms: According to the Most Recent WHO Classification

https://doi.org/10.1016/j.eururo.2004.03.017Get rights and content

Abstract

The key points of the latest World Health Organization (WHO) classification of non-invasive urothelial tumors are: the description of the categories has been expanded in the current version to improve their recognition; one group (papillary urothelial neoplasm of low malignant potential) with particularly good prognosis does not carry the label of ‘cancer’; it avoids use of ambiguous grading such as grade 1/2 or 2/3 (according to the WHO classification published in 1973, i.e., 1973 WHO classification); the group of non-invasive high grade carcinoma is large enough to contain virtually all those tumors that have biological properties (and a high level of genetic instability) similar to those seen in invasive urothelial carcinoma. This scheme is meant to replace the 1973 WHO classification. Changes in classification have their own inherent problems, tending to lead to confusion, at least for a period of time. From the practical point of view, the use of both the 1973 and the latest WHO classifications is recommended until the latter is sufficiently validated.

Introduction

From the morphological point of view, two basic diagnostic categories are identified on the basis of the pattern of growth of the intraepithelial lesions (flat and papillary), their clinical behavior being also related to the degree of architectural and cytological alteration of the urothelium [1]. Several classifications (including revisions and refinements) have been reported in the literature [2]. The latest World Health Organization classification of non-invasive urothelial tumors [3] is identical to “The World Health Organization/International Society of Urological Pathology Consensus Classification” of 1998 (1998 WHO/ISUP classification). It is adopted in the book Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, i.e., one of the “Blue Books” of the new series of World Health Organization Classification of Tumors. The contents of the book reflect the views of a Working Group made up of uropathologists that convened for an Editorial and Consensus Conference in Lyon, France, December 14–18, 2002.

This review, based on presentations made in recent meetings, gives an overview on the latest WHO classification of non-invasive urothelial tumors. In this contribution it will be referred to as the 2004 WHO classification, based on the publication year (i.e., 2004) of the book. We are aware of the fact that others might refer or have referred to the year 2003 based of the original publication schedule of the book. Others have also used the acronym WHO(2003)/ISUP to indicate both the publication year schedule and the relationship of the current scheme to the 1998 WHO/ISUP classification.

Section snippets

Flat intraepithelial lesions

The 2004 WHO classification of the flat lesions includes urothelial hyperplasia, reactive urothelial atypia, atypia of unknown significance, dysplasia and carcinoma in situ [3] (Table 1). This classification is very similar to that published recently by Lopez-Beltran et al. [4], [5].

Non-invasive papillary urothelial lesions

It distinguishes papilloma, inverted papilloma, papillary urothelial neoplasm of low malignant potential, as well as non-invasive low grade and high grade papillary urothelial carcinoma [8] (Table 1).

Genetics

The genetic studies so far published have used tumors classified according to 1973 WHO scheme and further studies are needed to link available genetic information to the 2004 WHO classification [16]. Current data suggest two genetic subtypes/pathways that correspond to morphologically defined entities [15], [16], [33], [34] (Fig. 1). The genetically stable category includes low grade non-invasive papillary tumors (pTa, G1 and G2). The genetically unstable category contains high grade (including

Translation between 1973 and 2004 WHO systems

Some controversies followed the introduction of the 1998 WHO/ISUP classification of bladder tumors [8], [35], [36], mainly because of lack of validation, reproducibility and translation studies. In particular, no sound translation scheme comparing the 1973 with the 1998 (and 2004) classifications has been put forward. Basically, grade 1 (G1) (WHO 1973 classification) tumors should be subdivided into PUNLMP and low grade carcinomas, whereas most grade 2 (G2) and all grade 3 (G3) cases are

Controversies on the best contemporary classification

The WHO classification introduced in 1999 (WHO 1999 classification) scheme is almost identical to the WHO/ISUP classification, the difference being that the former subdivides the low and high grade spectrum into three grades (grade I, II, and III) [38], [39].

The topic of the best contemporary classification of the papillary neoplasia has been debated in several recent meetings, including the Ancona International Consultation on the Diagnosis of Non-Invasive Urothelial Neoplasms (May 11–12,

Conclusions

  • The consistent use of the 2004 WHO classification of non-invasive urothelial tumors should result in the uniform diagnosis of tumors, stratified according to risk potential, and will facilitate comparative clinical studies, incorporation of molecular data and identification of aggressive, genetically unstable neoplasms.

  • Molecular pathology could have a role in the further refinements of the classification system.

  • Until the 2004 WHO system is fully validated from the clinical and prognostic point

Acknowledgements

This contribution has been supported by the Grant FIS03/0952 (Madrid, Spain) (ALB) and a grant from the Italian Ministry of University and Scientific Research (MIUR 2003) (RM).

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