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Characteristics and clinical significance of histological variants of bladder cancer

Key Points

  • The WHO 2016 classification of tumours of the urinary system highlighted the importance of careful morphological description of histological variants in patients with bladder cancer

  • Histological variants are divided in urothelial and nonurothelial subtypes and are present in almost 25% of bladder cancer samples in contemporary series

  • Histological variants present challenges in diagnosis, prognosis, and prediction of outcomes as their biological potential and clinical characteristics are highly variable

  • The percentage of a histological variant in a sample and its association with urothelial carcinoma should be reported by pathologists

  • The presence of variant histology at transurethral resection of the bladder should always be evaluated and the management of bladder cancer should be tailored based on the clinical stage and histological variant present

  • The presence of histological variants in a radical cystectomy specimen is generally associated with adverse pathological features; however, no clear difference in survival outcomes compared with urothelial carcinoma has been reported

Abstract

In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice. Histological variants can generally be divided into urothelial and nonurothelial. Urothelial variants often have similar features that also have specific morphological phenotypes, whereas nonurothelial variants have independent features. Overall, histological variants follow a more aggressive clinical course than conventional urothelial carcinoma, but conclusive data on their effect on survival are currently lacking. The clinical relevance of variant histology can manifest at three different levels: diagnostic, as identification is challenging and misinterpretation is not uncommon; prognostic, for patient risk stratification and outcome estimation; and therapeutic, as particular variants could be responsive to specific treatment strategies. An accurate morphological description of histological variants is necessary for patient consultation and therapy planning. Moreover, the association of variant histology with specific mutation patterns promises to be helpful in discovering targeted therapeutic approaches based on specific molecular pathways.

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Figure 1: Squamous cell carcinoma.
Figure 2: Glandular variant.
Figure 3: Neuroendocrine tumour.
Figure 4: Micropapillary variant.
Figure 5: Gross aspects of a sarcomatoid carcinoma in the bladder.
Figure 6: The plasmacytoid aspects with independent floating cells.
Figure 7: The lymphoepithelioma like variant.
Figure 8: Nested cell carcinoma with dense tumour invasion, occupying the complete lamina propria.
Figure 9: Microcystic urothelial carcinoma with tumour necrosis in the lumina of the microcysts.
Figure 10: Giant cell urothelial carcinoma.
Figure 11: Histological appearance of a lipid rich urothelial carcinoma.
Figure 12: The clear cell variant.
Figure 13: Proposed management of bladder cancer with variant histology.

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M.M., D.D., S.K. Y.I. and E.C. researched data for the article. S.F.S., M.M., D.D'A. and F. S. made substantial contributions to discussions of content. S.F.S., M.M. and D.D'A. wrote the manuscript. M.M., D.D'A., S.K., F.S., E.C. and S.F.S. reviewed and edited the manuscript before submission.

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Moschini, M., D'Andrea, D., Korn, S. et al. Characteristics and clinical significance of histological variants of bladder cancer. Nat Rev Urol 14, 651–668 (2017). https://doi.org/10.1038/nrurol.2017.125

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