Carcinoma in situ (CIS)
Carcinoma in situ, or CIS, is the presence of cancerous-appearing cells, proliferating in an abnormally high number, but are confined to the transitional epithelium. That is, they have not invaded into deeper tissue layers such as muscle, or even the fibrous layers separating the epithelium from the muscle. CIS represents a rather confusing stage in the development of bladder cancer. As described previously(see What Is Cancer?), cancer occurs when a tumor has the potential to invade into a different tissue layer. However, in the case of CIS, the cancerous condition has not yet penetrated beyond its normal position in the body. In general CIS tends to be a far more malignant process with greater metastatic potential than some large low grade tumors that have begun to invade through the bladder wall.
CIS is often invisible to the naked eye, although it can quite frequently be identified as a red, velvety area along the surface of the normally, pink, translucent bladder wall. It is most often diagnosed after the urologist takes random biopsies of the bladder mucosa?a procedure that may have been prompted by the discovery of cancerous cells in the urine. A diagnosis of CIS-even if detected in one area of the bladder-is considered diffuse. That is, it is assumed that the entire bladder mucosa is affected and not just the area of biopsy. This is in contradistinction to the diagnosis of a solitary bladder tumor where only the area observed is presumably involved. It is this difference that has prompted investigators to question whether CIS and the solitary tumor represent 2 completely different abnormal processes that have taken place within cells.
Invasive Transitional Cell Carcinoma (TCC)
Between the transitional cell layer and the muscle fibers is a layer of connective tissue and cells known as the lamina propria. The lamina propria is a landmark that is useful to help determine the aggressiveness of transitional cell tumors. As abnormal cells continue to multiply, more mutations in their genetic machinery tend to occur. Ordinarily, these mutations might be repaired, but that ability is limited in these cells. Eventually, genetic changes and further growth results in the cells' ability to destroy and penetrate the underlying lamina propria. This is the beginning of an invasive transitional cell tumor.
Superficial vs. Invsive TCC
An important distinction is the difference between "superficial" TCC and "muscle-invasive" TCC. Essentially, any tumor that has not invaded the muscle layer is considered superficial. Once the muscle layer has been breached, however, the diagnosis is muscle-invasive TCC. This distinction is critical because it predicts the natural history of these tumors. Superficial TCCa tends to recur multiply, but the recurrences are almost always superficial tumors that respond well to local resection. Only 15% of superficial tumors will transform or recur as high grade, invasive lesions. On the hand, recurrent CIS lesions or high grade/invasive tumors are much more difficult to control, and are more likely to result in metastatic spread.
Metastatic Transitional Cell Carcinoma (TCC)
In addition to acquiring the ability to penetrate a barrier such as the lamina propria, cancer cells can eventually penetrate lymph channels(lymphatics) or blood vessels. At this point it is possible for those cancer cells to travel to other organs throughout the body, where they can be deposited and subsequently grow as metastatic sites of tumor. The most common sites that develop metastases are the local lymph nodes in the pelvis, liver, lung, bone, and adrenal glands. Indeed, any organ can be involved once cells have acquired this ability.
Non-Transitional Cell Carcinomas
Several other tumors can develop within the bladder, though in the United States they are rare compared to TCC. The second most common type in the U.S.-though in some countries such as Egypt, the most common-is squamous cell carcinoma (SCC). Long-term irritation of the bladder by infectious agents or foreign bodies can cause the transitional epithelium to change into a different cell type known as squamous or "flat" cells. In Egypt the most common infectious agent that provides constant irritation of the bladder leading to squamous cell carcinoma is a parasitic infection known as bilharziasis. In the U.S. the offending agent is more often chronic urinary infections, indwelling catheters or stones. It should emphasized that the change to squamous cells(a process known as "metaplasia") does not denote the development of cancer, although the risk of subsequent degeneration in squamous cell carcinoma is significantly increased.
Any of the various different cell types within the bladder can theoretically develop into cancers-muscle cells(rhabdomyosarcoma), gland cells(adenocarcinoma), nerve cells(neural cell tumors), and even immune-type cells(lymphomas). Tumors arising from adjacent organs can also invade into the bladder and appear as "bladder tumor" (e.g. cervical carcinoma or colon cancers). However, the behavior of these other tumors(and their treatment) is dependent on their site of origin.