Small cell carcinoma

As the spindle morphology, reminiscent of the histologic features of neuroendocrine carcinomas are commonly found in patients with high grade TCC, especially as it evolves over time. At present, there is no exact consensus on diagnostic criteria for declaring a "small cell" or a subset of "neuroendocrine". Some authorities put more emphasis on the histomorphology and others in the expression of neuroendocrine markers. In the MD Anderson Cancer Center, has been our understanding that the morphology is more predictive of clinical outcome of a particular pattern of immunohistochemical markers, and so still prefer the term "small cell carcinoma" and do not require immunohistochemistry "confirmation" to apply the term. As can be deduced from clinical observation, LOH studies of the coexistence of small and TCC cells suggest descent from a common precursor, as has been shown that sarcomatoid carcinoma. In part because of the lack of well defined diagnostic criteria, incidence of small cell carcinoma is very difficult to estimate. To record the MD Anderson (which obviously reflects the referral bias), we find small cell carcinoma has an incidence of 3% (115 of 3833). Other researchers have suggested 0.5 to 0.7%.

One occasionally encounters patients with small cell carcinoma found in the prostate and it is unclear whether this is interpreted as prostate or urothelial origin. In general, there is no urothelial dysplasia in the prostatic urethra (in favor of a urothelial origin), or signs of dysplasia in the prostatic acini (in favor of a prostatic origin.)Indeed, the distinction hardly matters, as the cornerstone of therapy for either primary site is the early exposure to systemic chemotherapy (eg, etoposide and cisplatin) followed by local concentration (which would be radical surgery in our center).

As is well established for other sites, small cell carcinoma of the urothelium is an aggressive cancer characterized by early development of micrometastases, a high incidence of liver disease, and significantly, for the brain as a "sanctuary" site metastasis. The rapid growth within the bladder is also typical. Indeed, it is not uncommon for patients with large tumors that had been "completely excised" only 2 to 3 weeks earlier. This may be the basis of the relatively poor results (detailed below) with the surgical treatment of this variant.

Once a small cell component has been identified, it is important to free up a little rehearsal studios. Even for patients with minimal invasion into the bladder, the possibility of metastasis is important, and therefore all patients should have a computed tomography (CT) scan of abdomen and pelvis in search of lymph node and liver. It is also very important to maintain surveillance for the development of brain metastases at any point in the clinical course of the disease. As more effective systemic therapy is available, the issue of prophylactic cranial irradiation (as is done for some patients with small cell carcinoma of the lung) will probably have to be studied. We have recently seen two patients treated with neoadjuvant chemotherapy and surgery who later succumbed to brain metastases without any evidence of other sites of involvement. It has long been recognized that cystectomy, in this context is associated with a cure rate much lower than obtained with conventional TCC. , existing clinic has been the rule, with a maximum of 76% of patients with small cell tumors metastatic to cystectomy.

In a recent study by MD Anderson Cancer Center in experience found that pathological stage was higher than expected in 56% of patients treated with initial cystectomy. Furthermore, 20% of patients in whom cystectomy is planned initial found that surgically unresectable during surgery, despite an average of 24 days from diagnosis to surgery. In light of this experience, many institutions have reported the addition of multimodal systemic therapy approaches with radiation and / or surgery. In a review of the literature since 1995, Abbas said that the best disease-free survival was observed when cystectomy was followed by adjuvant chemotherapy with a median survival of 21.1 months.

Of the 19 patients studied by Grignon, 12 four of the five survivors were treated with adjuvant chemotherapy after cystectomy. The University of Southern California-Norris Cancer Center reported an improvement in overall survival and relapse free for patients receiving multimodal therapy, most of whom received adjuvant chemotherapy.

However, the median survival in these patients was only 13 months with a 5-year survival of 10%. Initial chemotherapy (ie, neoadjuvant systemic therapy) has also been investigated, and with more promising results. Walther reported that five of the seven patients were alive and free of the disease in more than 36 months after combined modality treatment, and indeed, the five who were alive were treated with preoperative chemotherapy. A retrospective analysis of our own experience10 in 46 patients, who were the two candidates for surgery and had potentially resectable disease, found a statistically improved survival of patients treated with preoperative chemotherapy. Patients treated with initial cystectomy had median cancer-specific survival (CSS) of 23 months, and 36% CSS at 5 years (see Figure 2). By contrast, for those treated with preoperative chemotherapy median CSS has not been reached, and 5 years was 78% of CSS. There were only four cancer-related deaths among 21 patients treated with initial chemotherapy, and none in the subset, a lower stage "for pT2N0M0 or less. It is interesting note that 7 of 25 patients treated with initial cystectomy received adjuvant chemotherapy, however, survival was no better than those treated with cystectomy alone. Given these results, the view that all patients with small cell component should be treated first (and promptly), with three or four cycles of chemotherapy incorporating etoposide and cisplatin. After chemotherapy, we favor surgical consolidation. This is based on observations that most of these patients have generalized dysplasia often show glandular elements after chemotherapy. Therefore, we can infer that a significant fraction of patients do not have a good long-term control in the bladder through the radio-therapy. Limited data from case series suggest that this radiation is indeed the case.

Unfortunately, given the rapid progression and metastatic potential of bladder cancer early small cells, many patients have surgically unresectable or metastatic disease at presentation. The most common sites are lymph nodes, liver, bone, lung and brain. With chemotherapy, the median survival ranges from 7.5 months to 15 months. There are few long-term survivors, but about 20% are alive at 3 years, which is more than 2 years longer than untreated natural history of disease. Despite the disappointing outcome in the long term, small cell urothelial tumors are highly sensitive to systemic chemotherapy, and most patients experience marked objective response is associated with rewarding (albeit temporary) palliation of symptoms

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".

Rare cancers of the bladder

Found rare tumors that arise in the bladder fall naturally into two groups: rare histologies and tumor urothelial origin nonurothelial. Our discussion follows these lines, and took the unusual urothelial cancer in the first place, since these are by far the most common and clinically important. Most of what is called transitional cell carcinoma, about 80%, in fact, low histological grade and reflects mainly hyperplastic process. This process typically results in the papillary architecture of the mass thickness of cell proliferation, but not invasive. These injuries, known as "Ta", tend to recur and may progress to dysplasia and invasion in 15 to 20% of patients. However, for the most part, these tumors are more similar to polyps’ true carcinomas. An averlapping but definite pattern can be recognized in the remaining 20% of cases. In this group, high histological grade dysplasia and invasion are hallmarks.

These "non-papillary" cancers are the cause of most mortality, and show a significant range of histomorphology. In the end, they are so different from transitional cell carcinoma (TCC) that called for an alternative taxonomy. Although very rare as "pure" variant, the fact remains that about one third of non-papillary bladder cancers exhibit at least focal areas of unusual histologies discussed below. Therefore, in practice, there is considerable uncertainty about which of the cases showing lesser degrees of histological variant is considered really outside the normal spectrum of TCC, and should be classified as distinct entities.