Bladder Cancer

Diagnosis and Clinical Management

Seth P. Lerner, Mark P. Schoenberg, Cora N. Sternberg

• Publisher: Wiley-Blackwell
• Year: 2015
• ISBN:
  9781118674857
• Edition: 1
• Topic: Medicine
• Subtopic: Urology

B ladder Cancer: Diagnosis and Clinical Management is a 100% clinically-focused guide to bladder cancer, providing practical, modern and evidence-based guidance to the latest in diagnosis and management of the condition. It differs from other books in its complete clinical focus as opposed to a heavy analysis of pathogenesis or basic science. As a result, practicing urologists and oncologists in the clinical setting will find it an essential resource to consult.

In addition to the latest in diagnostic tools and imaging methods, core focus is on the management of each form of cancer at its various stages with up to date genomic data and targeted therapies. Both drug therapies and the range of surgical options are covered, ensuring that this is the perfect tool for clinicians to consult when considering which type of management program is appropriate for each individual patient. A key addition is the final section dedicated to optimizing health care delivery, featuring chapters on highly topical issues such as quality of life, patient advocacy and surgical education.

Full color throughout, and packed with excellent images, each chapter contains concise and didactic practical tips and tricks to enrich the reading experience, in addition to management algorithms and the very latest guidelines from the ASCO, AUA, ESMO and EAU concerning clinical management of bladder cancer.

PART I
Diagnosis and treatment of non-muscle-invasive bladder cancer

CHAPTER 1
Pathology

Hikmat Al-Ahmadie¹ and Donna E. Hansel²

¹ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

² Division of Anatomic Pathology, University of California, San Diego, La Jolla, CA, USA

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KEY POINTS

• Bladder cancer is a heterogeneous disease that encompasses superficial lesions of papillary or flat phenotype as well as invasive disease.
• Superficial bladder cancer may include lesions with different morphology and biology such as low-grade and high-grade papillary urothelial carcinoma, flat urothelial carcinoma (in situ) and invasive urothelial carcinoma into the lamina propria.
• Multiple grading systems for bladder cancer exist but the most commonly used grading scheme is adopted by the World Health Organization (WHO/International Society of Urological Pathology (ISUP)) and divides papillary carcinomas into low-grade and high-grade instead of the three-tier system of Grades 1, 2, and 3; the Who system also introduced a papillary lesion with very low risk of progression in PUNLMP (papillary urothelial neoplasm of low malignant potential).
• Divergent differentiation is a common phenomenon in bladder cancer, most commonly present in the forms of squamous and glandular phenotypes.
• The vast majority of bladder cancer is of the urothelial type but many subtypes or variants also exist within the spectrum of urothelial neoplasia, some of which may be clinically relevant.

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Histopathological evaluation of bladder lesions represents one of the more challenging areas of pathology. In part, this reflects both the plasticity of the urothelium and the variety of processes that can affect the bladder. The frequent lack of objective ancillary markers to confirm or exclude a diagnosis contributes to the additional complexity in the analysis of bladder biopsies or resections. In this chapter we will outline common lesions that affect the bladder and highlight various challenges in their diagnosis.

Benign urothelium

Normal urothelium ranges from four to seven cell layers in thickness and contains a basal cell layer, intermediate urothelial cell layers, and a superficial umbrella cell layer (Figure 1.1). The overall thickness may be increased in the context of inflammation and reparative changes or may be diminished during a number of benign processes that induce denudation or expansion of the bladder. Normal urothelium is characterized by uniform nuclear size, nuclei oriented towards the luminal surface, nuclear grooves, and regular spacing between cells. Under normal conditions, cell layers of urothelium are relatively easy to identify. However, in instances where the morphology is disrupted or extensive inflammation is present, immunohistochemical stains may be helpful. Specifically, in normal urothelium, cytokeratin 20 stains the umbrella cell layer and p53 variably labels the basal and intermediate cell layers; [1, 2]. In contrast to the normal urothelium, neoplastic processes may show full-thickness cytokeratin 20 expression, intense nuclear p53 expression in the majority of cells, and loss of CD44, although these findings are often variable and may not be especially helpful in individual cases [3–5].

Figure 1.1 a) Normal urothelium. b) Reactive urothelium. c) Reactive urothelial atypia occurring after radiation.

Reactive urothelium

Although the description of normal urothelium appears relatively straightforward, physiologic variations can induce a spectrum of morphologic changes. Delineating reactive changes from early neoplastic processes in the bladder is a major challenge in pathology. The most common conditions that incite reactive changes include inflammation and prior chemotherapy or radiation therapy [6, 7]. In the former case, marked acute and chronic inflammation can increase the cellularity of the urothelium and thus decrease the organization of the background urothelial cells. Reactive changes, such as nuclear enlargement and the presence of pinpoint nucleoli may be identified (see Figure 1.1). The presence of inflammatory cells, however, does not per se render a benign diagnosis; a small percentage of urothelial carcinoma in situ cases may be associated with concurrent inflammation. In these instances, immunohistochemical stains may help with the final diagnosis. A second form of reactive change is associated with a prior history of radiation therapy, which itself is a risk factor for the development of bladder cancer [8]. Reactive changes associated with radiation include enlarged, hyperchromatic nuclei that appear more degenerative in nature. On occasion, reactive squamous metaplasia may also be present (see Figure 1.1). The underlying lamina propria in these cases may show fibrosis, inflammation, hyalinization of the blood vessels, extravasated red blood cells, fibrin thrombi in small vessels and occasional stromal cell atypia. When reactive changes are partially obscured by intense inflammation or when secondary processes are present, a diagnosis of “atypia of uncertain significance, favor reactive” may be rendered, which suggests the process is benign, although not all cells can be either definitely seen or characterized.

Urothelial hyperplasia

In urothelial hyperplasia, abnormal thickening of the urothelium is often evident at low magnification and often extends beyond ten cell layers [9, 10]. Despite the greater number of cells, the urothelium appears otherwise normal to slightly increased in cellularity with retained po...

Table of contents

• Cover
• Title page
• Table of Contents
• List of contributors
• Preface
• Acknowledgments
• PART I: Diagnosis and treatment of non-muscle-invasive bladder cancer
• PART II: T2-4
• PART III: Primary bladder-sparing therapy
• PART IV: Urinary tract reconstruction
• PART V: Treatment of regionally advanced and metastatic bladder cancer
• PART VI: Genomics and the current status of urothelial cancer
• PART VII: Optimizing healthcare delivery
• Index
• End User License Agreement