Elsevier

European Urology

Volume 70, Issue 1, July 2016, Pages 93-105
European Urology

Platinum Priority – Guidelines
Editorial by Rodolfo Montironi, Liang Cheng, Marina Scarpelli and Antonio Lopez-Beltran on pp. 120–123 of this issue
The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours

https://doi.org/10.1016/j.eururo.2016.02.029Get rights and content

Abstract

The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO “blue book”), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC, succinate dehydrogenase–deficient RCC, tubulocystic RCC, acquired cystic disease–associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non–GCNIS-related tumours in the 2016 WHO classification.

Patient summary

The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours.

Section snippets

The new renal tumour classification

The Vancouver consensus conference of the International Society of Urological Pathology (ISUP) provided the foundation for much of the 2016 World Health Organization (WHO) renal tumour classification [1], [2] (Fig. 1). The revision of the 2004 WHO renal tumour classification was performed after consideration of new knowledge about pathology, epidemiology, and genetics [3], [4], [5].

Important changes from existing renal tumour types

First, the new 2016 WHO classification refers to subtypes that have been named on the basis of predominant cytoplasmic features (eg, clear cell and chromophobe renal cell carcinomas [RCCs]), architectural features (eg, papillary RCC), anatomic location of tumours (eg, collecting duct and renal medullary carcinomas), and correlation with a specific renal disease background (eg, acquired cystic disease–associated RCCs) as well as molecular alterations pathognomonic for RCC subtypes (eg, MiT

New renal tumour entities

Over the past decade, several new tumour entities have emerged; therefore, the WHO working group was entrusted with the responsibility to decide whether enough molecular clinical follow-up data and pathologic data justify the recognition of any new distinct tumour entity within the classification system. The newly recognized epithelial renal tumours in the 2016 WHO classification are HLRCC-associated RCC, SDH-deficient RCC, tubulocystic RCC, acquired cystic RCC, and clear cell papillary RCC.

Emerging or provisional renal tumour entities

The 2013 ISUP Vancouver classification identified a category of emerging or provisional new entities. Some of these emerging entities have been accepted by the WHO, and others were kept as emerging. The WHO classification noted that although these entities appear to be distinct, they are rare tumours that are not yet fully characterized by morphology, immunohistochemistry, and molecular studies. Consequently, further reports are needed to refine their diagnostic criteria and established

Grading of renal tumours

Many grading systems have been proposed for renal cell neoplasia. The Fuhrman system was the most frequently used grading system in RCC but should not be applied for chromophobe RCC [33]. Furthermore, the Fuhrman system has not been validated for most of the new subtypes of renal carcinoma. For these reasons, the four-tiered WHO/ISUP grading system is recommended by the WHO [34]. For grade 1–3 tumours, the system defines tumour grade based on nucleolar prominence. Grade 4 is defined by the

Important future issues in renal tumour pathology

First, the VHL tumour suppressor protein pVHL functions as a tumour suppressor via HIF-dependent regulation in most ccRCC. The chromosome 3p locus, however, contains up to seven potential ccRCC tumour suppressor genes: VHL, PBRM1, BAP1, SETD2, RASSF1A, TU3A, and DLEC1. The elucidation of the effects of different combinations of mutations on the initiation and progression of ccRCC will be an important future area of research [4].

Second, the identification of novel therapeutic agents that are

The new classification of penile tumours

The vast majority of malignant tumours of the penis are squamous cell carcinomas (SCCs) originating in the inner mucosal lining of the glans, coronal sulcus, or foreskin. Most previous classification schemes were exclusively morphology based. The 2016 WHO classification presents a new classification based on clinicopathologic distinctiveness and relation to human papillomavirus (HPV) infection (Fig. 5).

The new classification of testicular tumours

Some important changes have been made in the WHO classification of testicular tumours in 2016 compared with that adopted in 2004 [3]. These revisions were discussed over the course of several months in 2014 through e-mail communications and were finalized in Zurich, Switzerland, in March 2015. The most significant differences between the newly published classification and the prior version concern the germ cell tumours (Fig. 8), but other categories are also affected.

It has been recognized for

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