Survival among Patients with Variant Histologies of Bladder Cancer

Mahsa Khayat Khoei^*
*Correspondence: Mahsa Khayat Khoei, Department of Cardiology, University of Medicine and Dentistry of New Jersey, New Jersey, USA, Email:

Introduction

Patients with divergent differentiation of the urothelium had significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy before cystectomy, while those with nonpure urothelial carcinoma histology with variant histology had nearly equivalent response rates and survival benefits with neoadjuvant chemotherapy as those with pure urothelial carcinoma.In about 25% of cases, urothelial carcinoma develops into various histological subtypes. Every histological variety presents a distinct diagnostic and therapeutic challenge due to its distinct characteristics, which include metastatic potential, expression of immunotherapy targets, and susceptibility to radiation or chemotherapy. However, due to the rarity of each individual variety, there is a chance that the pathological diagnosis may be overlooked and the clinical care would be inadequate. It is crucial to ensure awareness among pathologists and widespread acquaintance with the subtleties of variations among urologists. Additionally, different histologies might serve as a transitional stage between bladder cancer's traditional clinicopathological staging and developing molecular categorization [1].

Description

Patients with localised illness and variable histology BC are typically treated surgically. Radical cystectomy (RC) with pelvic lymph node dissection should be performed for invasive cancers. However, there is still a lack of information on the management of non-urothelial BCs, which has resulted in suggestions and low-level evidence. Clinical trials typically do not emphasise mixed histology, making it impossible to extract specific data or advice that could be applied as clinical recommendations. Routine pre- or postoperative chemotherapy (CTX) or radiotherapy (RTX) are currently not advised because there is a dearth of data because pure non-urothelial cancers are typically not included in phase III trials.Less than 2% of bladder cancers in North America and Europe are primary adenocarcinomas, which are uncommon. Adenocarcinomas come in a variety of forms, including glandular, colloid, papillary, signet-ring, and clear cell. Adenocarcinomas can also be divided into urachal and non-urachal types, with urachal adenocarcinomas accounting for 10% of all primary bladder adenocarcinomas [2].

It has long been known that bladder urothelial cancer has a predisposition to develop along distinct histologic trajectories. About 25% of bladder tumours have different histologies, which can present specific diagnostic and therapeutic difficulties that are essential to the best management of bladder cancer generally. Even if any one variety can be seen as being very uncommon, they collectively account for a sizable portion of patients. Therefore, it is crucial for the practising urologist to be familiar with the changing subtleties of these various entities. Variant histology also serves as a link between the traditional clinicopathologic categorization of bladder cancer and the developing molecular classification of bladder cancer in an era of molecularly targeted therapy [3].

Due to the prevalence of variable histology in bladder cancer, it is crucial for the pathologist to keep these variants in mind at all times when analysing the histologic sections of a bladder tumour. The first difficulty is being aware of the various variants, especially for a pathologist who is not particularly interested in genitourinary pathology and is therefore more prone to overlook a variant. Even experienced genitourinary pathologists commonly produce conflicting reports because of the substantial interobserver variability in the assessment of histologic variations. Additionally, despite efforts to provide uniform criteria, there is still a great deal of subjectivity involved in the determination of histologic variations. The fact that most variations are present in just a percentage of any given tumour and that there is sometimes a discrepancy create additional obstacles for the pathologist.

Since micropapillary carcinoma has received the greatest attention among the variant histologies in recent years, many pathologists may be more familiar with it than other variants. Tight clusters of high-grade tumour cells without a fibrovascular core and around by retraction gaps are the hallmark of micropapillary bladder cancer. It is difficult to diagnose micropapillary carcinoma due to the intricacies of borderline situations, and there is no agreement on stringent criteria for doing so.

The histologic appearance of sarcomatoid bladder cancer resembles an intermediate form between a genuine epithelial carcinoma and a sarcoma. It exhibits high-grade spindle cell morphology while expressing recognisable epithelial markers. Since the epithelial-to-mesenchymal transition is a putative pathogenic mechanism of sarcomatoid differentiation, sarcomatoid urothelial cancer displays mesenchymal markers such ZEB1 and TWIST1. On the range between urothelial carcinoma and true sarcoma, carcinosarcoma is a distinct disease. It is an amalgam of genuine sarcomatous components and urothelial cancer. True sarcoma must be recognised from sarcomatoid cancer and carcinosarcoma. Neuroendocrine tumours can develop in a variety of organs, but they are particularly common in the gastrointestinal system, where they arise from cells that look like nerves and have secretory granules like endocrine cells. Neuroendocrine tumours can be small cell or large cell, and they can be well differentiated (like paraganglioma) or poorly differentiated.

The management of BC with varied histology is complicated; in particular, the diagnosis and selection of an appropriate medication are tough because there is a dearth of comprehensive data on these scenarios. The majority of therapeutic suggestions are based on extrapolating data from pure urothelial BC and retrospective case reports. Particularly, it is unknown how sensitive variant histology BC is to multimodal therapy, including CTX, radiation, and intravesical drugs. Additionally, variable histology BC frequently manifests at an advanced stage of the illness, further complicating therapy choices given the short window of time. Early radical surgery is strongly advised for the majority of non-metastatic non-UC bladder tumours in a scenario of confined disease, and in some variants (SCBC), even in conjunction with multimodal therapies [4,5].

Conclusion

The prognosis is poor for patients with muscle invasive bladder cancer (MIBC) with variable histology. The association between neoadjuvant chemotherapy and pathological downstaging or better overall survival (OS) for patients with variable histology is unknown. Our goal was to determine whether receiving neoadjuvant treatment, pathological downstaging, and OS were related in patients with MIBC with variable histology.Beyond histologic variances, two developments might influence how bladder cancer is categorised. First, molecular classification might shed light on the biological variations that the aberrant histomorphology reflects. It is also possible to classify diseases more precisely using molecular patterns. The discovery of a neuroendocrine-like subtype of bladder cancer is the most notable instance of the convergence of histology and molecular characterisation, building on the RNA-based molecular categorization of urothelial carcinoma. With a neuroendocrine gene expression and a very bad prognosis consistent with genuine neuroendocrine bladder cancer.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

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