Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications.

New analyses show that muscle-invasive bladder cancers can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Choi and colleagues introduce the newly identified basal and luminal subtypes of muscle-invasive bladder cancer and explain their implications for the clinical management of this disease.

Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer

Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications

Bladder cancer can be classified histologically as urothelial or non-urothelial. Urothelial cancer has a propensity for divergent differentiation, which has increasingly been recognized in recent years due to heightened awareness and improved immunohistochemistry techniques. Furthermore, the recent World Health Organization classification of urothelial cancers improved clarity on this issue, with its listing of 13 histologic variants of urothelial cancer. The divergent differentiation patterns include, amongst others, squamous, glandular, micropapillary, nested, lymphepithelioma- like, plasmacytoid and sarcomatoid variants of urothelial cancer. Attempts to quantify the amount of divergent differentiation present, such as using the nonconventional differentiation number, have been made recently, which will improve the ability to compare publications from different centres. Genetic-based studies have indicated that the histologic variants of urothelial cancer arise from a common clonal precursor. Mostly, the current evidence suggests that urothelial cancer with divergent differentiation has a worse prognosis when compared with pure urothelial cancer. This article will review the current literature on variant histologies of urothelial cancer, and well as new developments in pure squamous cell carcinoma, small cell carcinoma and adenocarcinoma of the bladder.

/pdf/histologic-variants-of-urothelial-bladder-cancer-and-2e2vzduds8.pdf

Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer

Context Urothelial carcinoma can exhibit a wide range of variant morphologies. Many variants present diagnostic challenges and carry clinical implications that inform prognosis and treatment decisions. Objective To provide an overview of the diagnostic, therapeutic, and prognostic significance of histological variants of urothelial carcinoma. Evidence acquisition A PubMed/MEDLINE-based literature search was conducted using the key terms “urothelial carcinoma”, “variant histology”, “nested”, “micropapillary”, “microcystic”, “sarcomatoid”, “squamous differentiation”, “glandular differentiation”, “clear cell”, “plasmacytoid”, “lymphoepithelioma-like carcinoma”, “squamous cell carcinoma”, “small cell carcinoma”, “adenocarcinoma”, “radiotherapy”, “neoadjuvant chemotherapy”, and “adjuvant chemotherapy”. Evidence synthesis The incidence of variant histology is increasing due to improved recognition. Nonetheless, diagnosis can pose challenges due to sampling limitations and interobserver variability. Although associated with advanced disease at presentation, survival outcomes for most variants do not differ significantly compared with pure urothelial carcinoma of the same stage. Controversy exists regarding optimal management due to the low quality of available evidence. For most cases, radical cystectomy with pelvic lymph node dissection (with neoadjuvant chemotherapy when appropriate) represents the standard of care. Small cell carcinoma and lymphoepithelioma-like carcinoma appear to be particularly chemosensitive. Conclusions Accurate identification of variant histological subtypes is an important part of risk stratification, as these variants exhibit aggressive biological behaviour. Variant histology tumours are associated with advanced disease at presentation, which must be considered when counselling patients regarding survival outcomes. Optimal management remains to be defined but in most cases; neoadjuvant chemotherapy and radical cystectomy with pelvic lymph node dissection remains the mainstay of treatment. Patient summary It is important to recognise histological variants of urothelial carcinoma as they indicate aggressive disease. When compared with patients with pure urothelial carcinoma of the same disease stage, survival does not appear to be significantly worse. In most cases, patients with invasive variant histology should be treated with neoadjuvant chemotherapy and radical cystectomy. Take Home Messages Accurate identification of variant histology is important as it exhibits aggressive biological behaviour and affects treatment. Although associated with advanced disease at presentation, with appropriate treatment, survival outcomes are not significantly different compared with pure urothelial carcinoma of the same stage.

What Is the Significance of Variant Histology in Urothelial Carcinoma

We report the cases of 11 patients who were treated for undifferentiated carcinoma of the urinary bladder with a prominent lymphoid stroma (lymphoepithelioma-like carcinoma [LELC]). The chief complaint of all 11 patients was hematuria. Their ages ranged from 52 to 79 years (mean of 67). All tumors except one invaded the muscle wall and showed the typical syncytial growth pattern of undifferentiated cells with ill-defined cytoplasmic borders, prominent nucleoli, and numerous mitoses. A significant lymphocytic reaction was an essential component of all these tumors. There were three pure LELC tumors without concurrent invasive transitional-cell carcinoma (TCC) or TCC in situ; these cases morphologically simulated large-cell lymphoma. The remainder were mixed TCC and LELC (five predominant and three focal LELC). The tumor cells were immunoreactive for keratin and showed negative results for leukocyte common antigen. The lymphoid population was an admixture of T cells and B cells with a predominance of T cells. Seven patients (four with predominant and three with focal LELC) were treated with various therapeutic methods. Four patients (three with pure and one with predominantly LELC) received only chemotherapy after transurethral resection of the tumor, and follow-up found no evidence of disease for 9-72 months (mean of 38 months). Awareness of an LELC component in a urinary bladder tumor is also important in order to avoid misinterpreting these tumors as malignant lymphoma or severe chronic cystitis. Our data suggest that the pure LELC tumor appears to be morphologically and clinically different from TCC and that it merits recognition as a separate clinicopathologic entity. In addition, there is strong suggestive evidence that it responds to chemotherapy and therefore there is the potential of salvaging bladder function.

Lymphoepithelioma-like carcinoma of the urinary bladder

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Lymphoepithelioma-like carcinoma of the urinary bladder