ReviewNon-Invasive Urothelial Neoplasms: According to the Most Recent WHO Classification
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).
References (39)
- et al.
Subvisual changes in chromatin organization state are detected by karyometry in the histologically normal urothelium in patients with synchronous papillary carcinoma
Hum. Pathol.
(2003) - et al.
Frequent genetic alterations in simple urothelial hyperplasias of the bladder in patients with papillary urothelial carcinoma
Am. J. Pathol.
(1999) - et al.
Assessment of basal cell status and proliferative patterns in flat and papillary urothelial lesions: a contribution to the new WHO classification of the urothelial tumors of the urinary bladder
Hum. Pathol.
(2000) - et al.
Diagnosis and grading of bladder cancer and associated lesions
Urol. Clin. North Am.
(1999) - et al.
Evaluation of NMP22 in the detection of transitional cell carcinoma of the bladder
J. Urol.
(1998) - et al.
Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases
Mod. Pathol.
(2003) - et al.
Stage Ta-T1 bladder cancer: the relationship between findings at first follow-up cystoscopy and subsequent recurrence and progression
J. Urol.
(2002) - et al.
Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia
Mod. Pathol.
(2000) - et al.
Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behavior of low-grade papillary urothelial tumors. World/Health Organization/International Society of Urologic Pathology
Mod. Pathol.
(2001) - et al.
Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma
Actas Urol. Esp.
(2001)
Comparison of WHO/ISUP and WHO classification of noninvasive papillary urothelial neoplasms for risk of progression
Urology
Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis
Eur. Urol.
Classification and grading of the non-invasive urothelial neoplasms: recent advances and controversies
J. Clin. Pathol.
The pagetoid variant of bladder urothelial carcinoma in situ A clinico-pathological study of 11 cases
Virchows Arch.
Preneoplastic non-papillary lesions and conditions of the urinary bladder: an update based on the Ancona International Consultation
Virchows Arch.
Genetic and epigenetic alterations in normal bladder epithelium in patients with metachronous bladder cancer
Cancer Res.
The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder
Am. J. Surg. Pathol.
Cytokeratin 20 as an objective marker of urothelial dysplasia
Br. J. Urol.
Cited by (0)
- 1
Co-corresponding author. Fax: +34-957-218229.