Soft tissue tumors of the urinary bladder, part I: myofibroblastic proliferations, benign neoplasms, and tumors of uncertain malignant potential

Most bladder tumors arise from the urothelium. However, there are several uncommon but significant bladder lesions that must be differentiated from urothelial carcinomas. These include both benign and malignant spindle cell lesions. The first half of this 2-part review will describe benign myofibroblastic proliferations including inflammatory myofibroblastic tumor and postoperative spindle cell nodule; benign neoplasms including leiomyoma, hemangioma, neurofibroma, and schwannoma; and tumors of uncertain malignant potential including paraganglioma, granular cell tumor, and perivascular epithelioid cell tumor. Common clinical presentations, morphological characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. This review also describes current theories as to the pathogenesis of inflammatory myofibroblastic tumor and postoperative spindle cell nodule and details the current molecular markers identifying several of these lesions

Unique clinicopathologic and molecular characteristics of urinary bladder tumors in children and young adults.

In children and young adults, urothelial carcinoma and other epithelial neoplasms of the urinary bladder are rare. When these tumors do occur, they appear to exhibit unique clinicopathologic features, with preferentially low-grade morphology and decreased likelihood of recurrence and progression, although some debate exists regarding their biologic behavior. In contrast, a subset of soft tissue tumors is more commonly seen in pediatric patients, with rhabdomyosarcoma being the most common malignancy in this location. Likewise, inflammatory myofibroblastic tumor may be a source of differential diagnostic complexity. In the setting of previous bladder augmentation, patients appear to have a distinctive disposition to develop epithelial neoplasms later in life. Data regarding the molecular characteristics and clinical behavior of pediatric bladder tumors are, with the exception of rhabdomyosarcoma, less well understood than those of adult/elderly patients. In this article, we review the distinguishing features of urinary bladder neoplasms in pediatric and young adult patients, with special emphasis on unique clinicopathologic features, molecular-genetic abnormalities, and syndromic associations of urothelial neoplasms in this patient population

Natural history of urothelial inverted papilloma

BACKGROUND: Inverted urothelial papilloma is an uncommon urothelial neoplasm. Although it is traditionally regarded as a benign tumor, conflicting data on multiplicity, recurrence rate, and association with urothelial carcinoma have left uncertainties concerning its biologic behavior. METHODS: The authors analyzed the clinicopathological characteristics of 75 cases of inverted papilloma in the urinary tract without prior or concurrent urothelial carcinoma to determine its biologic behavior and prognosis, and to correlate these findings with surveillance strategies. RESULTS: These patients ranged in age from 26 to 85 years (mean, 60 years). Of the 46 patients for whom tobacco use history was available, 28 gave a history of smoking. Inverted papillomas were located in the urinary bladder (67 cases), prostatic urethra (4 cases), and ureter (4 cases). The majority of vesical tumors arose from the trigone or near the bladder neck. Common presenting complaints included hematuria, dysuria, and irritative voiding symptoms. In 1 case of vesical inverted papilloma, there was a recurrence. All other patients were free of tumor recurrence or progression during a mean follow-up of 68 months (range, 2-240 months). CONCLUSIONS: Both the extremely low incidence of tumor recurrence (1%) and strikingly favorable prognosis suggest that inverted urothelial papilloma, when diagnosed according to strictly defined criteria, is a benign urothelial neoplasm not related to urothelial carcinoma. Therefore, complete transurethral resection of inverted papilloma is adequate surgical therapy, and surveillance protocols as rigorous as those employed in the management of urothelial carcinoma seem unnecessary

Laser Capture Microdissection in the Genomic and Proteomic Era: Targeting the Genetic Basis of Cancer

The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy

Soft tissue tumors of the urinary bladder Part II: malignant neoplasms

Most bladder tumors arise from the urothelium. However, there are several uncommon but significant malignant bladder lesions that must be differentiated from urothelial carcinomas and from benign lesions of the bladder. The second half of this two-part review will describe rare nonurothelial malignant tumors of the urinary bladder including leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, malignant fibrous histiocytoma (undifferentiated sarcoma), primitive neuroectodermal tumor, malignant peripheral nerve sheath tumor, hemangiopericytoma, and alveolar soft-parts sarcoma. Common clinical presentations, morphologic characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. Because the distinction between malignant and benign lesions has significant therapeutic and prognostic implications, key factors for differentiating them are presented

Urothelial lesions with inverted growth patterns: histogenesis, molecular genetic findings, differential diagnosis and clinical management

Inverted lesions of the urinary bladder comprise a spectrum of changes ranging from von Brunn's nests to inverted urothelial carcinoma. Differentiating these lesions is important because their proper clinical management and their expected clinical outcomes are distinctly different. In this article, we review the spectrum of inverted urothelial lesions of the bladder, including current morphological criteria, key differential diagnosis, molecular genetic findings and histogenesis. We have refined the diagnostic criteria for various bladder lesions with inverted growth patterns. A number of well-recognized urothelial lesions with inverted morphology occur in the urinary bladder. Some are so common that they are considered normal variants of urothelium, whereas others are rare. It is important for the surgical pathologist to recognize these lesions and their overlapping morphological features, because in some cases establishing an accurate diagnosis is challenging. In this article, we review the spectrum of inverted urothelial lesions of the bladder. Emphasis is placed on differential diagnosis, molecular genetic findings, morphology and histogenesis

The S100 proteins for screening and prognostic grading of bladder cancer

The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer managemen