Micropapillary BLADDER CANCER

The histomorphologic spectrum of many epithelial cancers is now recognized to include a subset of cells characterized by groups of nesting high in lacunar spaces that have a "micropapillary" architecture. This pattern was first reported in 1982 by The Henderickson et al. described an aggressive variant of endometrial adenocarcinoma. In this context, an infiltrating pattern, biologically aggressive expansion behavior remarkably reminiscent of ovarian serous papillary carcinoma was evident. Subsequently, a micropapillary variant has been recognized in cancers arising from breast, bladder, thyroid, lung and pancreas, and has therefore come to be seen as a general feature of epithelial cancer. It seems likely that this phenotype arises from a fundamental aspect of epithelial carcinogenesis, and the finding of a "genetic signature" recognizable that cuts across these different sites would not be surprising. Researchers at the MD Anderson Cancer Center were the first to report a subset of bladder cancers showing a micropapillary histomorphology, the publication of the first series of 18 patients in 1994.

As discussed in the context of sarcomatoid and small cell morphology is typical of a micropapillary component seen in a context that includes more typical of CBT. From this first series of patients, micropapillary variant was observed to have a more aggressive clinical course and a particular tendency for prominent lymphovascular invasion. Subsequently published a series of cases in Sweden, Harvard, Australia, Wayne State University, and the City of Mexico, along with many individual case reports. These reports established that micropapillary bladder cancer has a characteristic morphology that can be identified reliably. Moreover, the trend first reported to the clinical subclassification, aggressive behavior, and the relatively poor response to standard systemic chemotherapy has been fully confirmed. Ultrastructural studies in the context of micropapillary breast cancer suggested secretory granules along the basement membrane, ie, loss of normal cell polarity which is the secretory activity in the basal surface, not only on the surface apical.

This concept of "inside out" morphology has been reinforced by the demonstration that the gene product mucinous glycoprotein MUC1 is abnormally located at the basal surface micropapillary cancers, including bladder origin. Although not yet formally established, it seems likely that a mechanical connection is made between this type of abnormal phenotype, early submucosal infiltration and early access to the lymphatic vessels that characterize the clinical course of these cancers. In our experience, the unusual finding of a bladder cancer is the stage pT1N1 almost always associated with micropapillary histology. micropapillary bladder cancer has been reported to occur infrequently. In the series of cases of Sweden, on the basis of a population-based registry, the incidence of bladder cancer was 0.7%. That report-biased Mexico City put the incidence of 38/630 (6%). In a similar registry biased at the MD Anderson Cancer Center, we found 162 cases for an incidence of 4.2%. Of course, these reports come from genetic and environmental contexts very different, and it is very possible that the incidence of different geographic region. The clinical management of micropapillary bladder cancer should take into account the very real possibility that clinically understaged and can grow quickly. Therefore, we call for "early" cystectomy for any tumor that invades the lamina propria, and certainly calls for any patient with disease cT1 or higher after a trial of intravesical therapy will be guided to cystectomy without delay. For patients with locally advanced disease, the prognosis is worse than for patients with TCC conventional systems. In the MD Anderson Cancer Center experience, patients with cT4a cT3b or treated with a combination of systemic chemotherapy and surgery (in any order), had a lower overall cure rate compared with patients with conventional systems TCC. In the metastatic setting, both the response rate and overall survival of patients with micropapillary cancer are below our historical expectations. Despite the aggressive implementation of combination chemotherapy, patients with micropapillary cancer still have a relatively poor outcome. This has been methotrexate / vinblastine / doxorubicin / cisplatin (MVAC), with ifosfamide-based combinations, and gemcitabine / cisplatin. It is important to recognize, however, that
although the overall results are lower than those obtained for patients with conventional TCC, many patients do well, and therefore continue to offer conventional therapy for patients in this subgroup

Sarcomatoid Carcinoma

The clinical course of advanced urothelial cancer is generally characterized by a more aggressive biological behavior over time. This is typically accompanied by phenotypic evolution patterns is readily recognized to reflect the more aggressive biological behavior. In this context, recognition of areas with spindled histomorphology is fairly common. When this pattern becomes dominant, cancers are often described as sarcomatoid carcinomas. These cases have long recognized, and many series of cases and fixes are available.

There remain several reports of sporadic cases each year. Almost always, recognizable as Highgrade nonspindled TCC areas are also present, suggesting that this pattern of results of evolution from a common ancestor. Indeed, by immunohistochemistry, the spindle areas are generally positive for keratin, epithelial membrane antigen and vimentin. (When the epithelial markers are lost in a significant fraction of tumor cells, the term carcinosarcoma is adequate, but the literature makes no systematic distinction between these two terms.) Clonality analysis based on loss of heterozygosity (LOH) of microsatellite markers5, 6 provides strong evidence that despite the various components can and should evolve independently once they diverge, they do, in fact, derive from a common precursor.

While it is clear that we can define a subset of sarcomatoid appearance, which is more important to know what such an important biological morphology portends. Although there appear to be particular risk factors or clinically distinctive features at initial presentation, a recurrent theme in the clinical experience with sarcomatoid urothelial cancer is having an aggressive natural history and poor outcome in relation to the classics of TCC . This is confirmed by the registration of MD Anderson in both locally advanced and metastatic settings. In view of this, we believe that the presence of a sarcomatoid component in bladder cancer minimally invasive otherwise be a strong indicator of early cystectomy. We know of no data to recommend a specific therapeutic approach of systemic therapy. Although we have investigated more intensive chemotherapy in this subgroup, who have no sense that this is justified by better results and does not endorse this approach in the absence of a clinical trial. It is very important to realize that not everything that appears spindle is dangerous.

In particular, the post-resection of sarcomatous nodules and inflammatory pseudotumor should not be confused with aggressive cancers that have some resemblance. In addition to the clinical context, it is reported that the presence of necrosis at the interface of muscle and nuclear atypia are the most useful features that distinguish true sarcomas or sarcomatoid carcinomas of these benign conditions. Although extremely rare, true sarcomas without an epithelial component occur in the bladder, and listed in the section of "sarcoma".