WHO/ISUP Classification of
Papillary Urothelial Tumors: have We Finally Settled for it?
Muhammed
Mubarak
Muhammed Mubarak, Professor, Department of Histopathology, Sindh Institute
of Urology and Transplantation, Karachi-74200, Pakistan
Correspondence to: Muhammed Mubarak, Professor, Department of
Histopathology, Sindh Institute of Urology and Transplantation, Karachi-74200,
Pakistan
Email: drmubaraksiut@yahoo.com
Telephone: +9221
99215752
Fax: +9221 32726165
Received: February 6, 2014
Revised: April 11, 2014
Accepted: April 16, 2014
Published online: June 18, 2014
ABSTRACT
Histological grading of noninvasive papillary urothelial tumors is the most
important prognostic factor short of tumor invasion. Various schemes and
classifications have been proposed since last few decades, all based on
morphological criteria alone. Among these, 1973 WHO classification proved very
successful in clinical practice and dominated for almost three decades. In late
1990s efforts were initiated to reevaluate and reassess the grading schema and
these efforts resulted in the promulgation of WHO and International Society of
Urologic Pathologists (ISUP) classification of noninvasive urothelial neoplasms
in 1998. This classification was further refined and published in the latest
WHO blue book on Pathology and Genetics of Tumours of the Urinary System and
Male Genital Organs as 2004 WHO classification. The later classification has
however not completely replaced the 1973 WHO classification and many centers
are using both the classifications in the pathology report. It is time to
incorporate immunohistochemical, molecular genetic and omics data to further
refine this prognostic classification.
© 2014 ACT. All rights reserved.
Key words: Grading; Histological classification;
Prognosis; Tumors; Urothelial neoplasms
Mubarak M. WHO/ISUP
Classification of Papillary Urothelial Tumors: have We Finally Settled for it? Journal
of Tumor 2014; 2(6): 145-147 Available from: URL: http://www.ghrnet.org/index.php/JT/article/view/730
WHO/ISUP
CLASSIFICATION OF PAPILLARY UROTHELIAL TUMORS: HAVE WE FINALLY
SETTLED FOR IT?
Short of invasion,
histopathological grading remains the most important prognostic factor for the
papillary urothelial neoplasms[1-5]. However, this is also the
feature that has evoked much controversy and confusion with regard to its
appropriate classification. In fact, the history of histological grading
systems of the urothelial neoplasms rivals the lymphoma classification during
the last few decades. The lymphoma classification has finally been rationalized
and standardized by the Revised European-American Lymphoma (REAL)
classification and WHO classifications, but this dream has yet to be fulfilled
for the grading schema for the urothelial neoplasms[6-10].
The first most widely
accepted and used grading schema for noninvasive urothelial neoplasms was the
1973 WHO classification, which dominated the clinical practice for nearly three
decades[11]. Its strong points were its simplicity and the powerful
predictive value. It was well received by all the concerned health care
physicians involved in the diagnosis and care of bladder tumor patients,
particularly the urologists and oncologists[1-5]. Indeed, this
classification is regarded by many as the most successful clinical
classification in use among all the classifications. The main demerits of the
classification were that the histological criteria were not described in
sufficient detail so that interobserver reproducibility was poor and areas of
ambiguity remained at the border zones of grade 1 and 2, and 2 and 3[2,4,5,8,10].
Its potential weaknesses emanating from widespread use coupled with emerging
evidence from newer studies highlighted the need to reevaluate this classification[1-10].
As a result, a number of urologic pathologists, urologists, oncologists and
basic scientists met in 1998 under the auspices of WHO and International
Society of Urologic Pathologists (ISUP) and formulated a newer classification
for flat and papillary noninvasive categories of urothelial neoplasms. This
classification is popularly known as 1998 WHO/ISUP classification[12].
A partially modified version of this classification was adopted by WHO as 1999
WHO classification, which also retained the grading categories of 1973 WHO
classification. But this classification met with very little success right from
the beginning. The 1998 WHO/ISUP classification was however adopted with fine
amendments in the latest Blue Book of WHO as 2004 WHO classification[13].
The later classifications were meant to replace the 1973 WHO classification as
the universal consensus classifications. However, this dream has not yet been
realized completely. Its advantages for urologic pathologists are fairly
straight forward. There are only two grades of carcinoma, low grade and high
grade. This dichotomy is equally advantageous for the management of these
tumors by oncologists. The label of carcinoma is not used for a category of
very low grade urothelial neoplasms with particularly excellent long-term
prognosis (Figure 1). The morphological criteria of diagnostic categories were
described in detail to improve interobserver reproducibility[12]. However,
the 1973 and 2004 WHO classifications are not directly interchangeable[13-20].
Despite the above improvements from the urologic pathologists’ point of view,
there is still no uniformity among the urologists and oncologists in the use of
therapeutic strategies of patients with bladder tumors graded according to 2004
WHO classification. Many centers, like ours, use both the classifications
simultaneously[1-6]. This exercise is meant to educate the treating
physicians about the changes brought about by 2004 WHO classification in
context of the original 1973 WHO classification and may be continued till such
time that the urologists and oncologists completely adopt the new
classification.
But, the most important
question that arises here is that, has 2004 WHO classification attained the
status of gold standard schema amongst the existing grading systems for
histological grading of the noninvasive urothelial neoplasms? The most
pragmatic answer is “No”. The reasons lie in the inherent subjectivity and
interobserver variability of all histopathological assessments. All the
existing classifications of grading urothelial neoplasms including 2004 WHO
classification were developed based on expert opinion and without clinical
evidence base and prior validation[2]. Although not related to
urologic pathology, the Oxford classification of IgA nephropathy has recently
been developed based on true international consensus process and with prior
testing of reproducibility and clinical evidence base[21]. This
classification can serve as a role model for adopting a similar approach for
developing a truly consensus based and reproducible classification in other
areas of pathology[22]. Moreover, the major focus of all existing
classifications has been on morphological criteria only. Perhaps, it is high
time that we focus our research to the discovery and use of immunohistochemical
(IHC), molecular genetic and omics markers to further refine and fine tune the
classification. These markers will also facilitate an objective evaluation of
the biological potential of urothelial neoplasms. A few studies have found that
a small battery of IHC markers can successfully meet this need. Further, large
scale and multicenter studies using novel markers are needed to validate these
findings[23]. For now, it is helpful to use both the 1973 and 2004
WHO classifications simultaneously in order to facilitate the appropriate
management of these neoplasms.
In summary, although 2004
WHO classification of noninvasive urothelial neoplasms represents a significant
improvement over the previous classifications, it has not yet achieved the
coveted gold standard status among the existing classifications. Its use has
not been uniform through out the world and many centers still use both 1973 and
2004 classifications.
CONFLICT
OF INTERESTS
There are no
conflicts of interest with regard to the present study.
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Peer reviewer: Nihal Mohamed, Department
of Urology, Mount Sinai Medical Center, 1 Gustave Levy Place, Box 1272, New
York, NY 10029, the United States.
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