Cancer grading is a method pathologists use to classify cancer based on the appearance of tumor cells under a microscope. By examining a tissue sample, or biopsy, a pathologist assesses how much the cancer cells differ from normal, healthy cells. This process provides insight into the tumor’s potential behavior and rate of growth.
The WHO/ISUP Grading System Explained
The grading system for bladder cancer has evolved. Pathologists once used a 1973 World Health Organization (WHO) system that classified tumors into Grade 1, 2, and 3. Grade 1 tumors were slow-growing, Grade 3 were fast-growing and abnormal, and Grade 2 was an intermediate category.
This system created ambiguity, so the WHO and the International Society of Urological Pathologists (ISUP) introduced a new system in 2004. This system simplifies classification into low-grade and high-grade urothelial carcinoma. A third category, Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP), was also defined for growths with minimal invasive potential.
Under the modern WHO/ISUP system, what was formerly a Grade 2 tumor is now classified as Low-Grade Urothelial Carcinoma. This change reflects that the clinical behavior of most Grade 2 tumors more closely resembles that of Grade 1 tumors. This updated classification offers a clearer prognosis by separating more unpredictable tumors into the high-grade category.
Cellular Characteristics of a Grade 2 Tumor
When a pathologist examines a low-grade bladder tumor, they observe specific cellular features. The urothelium, the tissue lining the bladder, is normally composed of several layers of orderly cells. In a low-grade tumor, this structure is mostly preserved but with noticeable abnormalities.
The individual cells show some variation in size and shape, and their nuclei may be slightly larger or darker than normal. Despite these changes, the cells maintain a degree of cohesiveness and orient themselves in an organized way. This appearance contrasts with high-grade tumors, where the cellular structure is chaotic and reflects more aggressive potential.
An analogy is to think of the normal bladder lining as a uniform brick wall. A low-grade tumor is like a wall where some bricks are different in size or color but are still laid in a pattern. A high-grade tumor, in contrast, would be a jumbled pile of bricks with no discernible order.
Prognosis and Clinical Behavior
A diagnosis of low-grade urothelial carcinoma carries a specific outlook. The primary concerns are recurrence (the cancer returning) and progression (the cancer becoming more dangerous). Low-grade bladder tumors have a notable tendency to recur but a low risk of progressing to a high-grade cancer.
Recurrence means a new, often low-grade, tumor appears in the bladder after the initial one is removed. This requires ongoing monitoring but does not pose a threat to life. Progression involves the cancer becoming a high-grade tumor that can invade the bladder’s muscle layer, which is a more serious development.
For those diagnosed with a low-grade tumor, the risk of progression to muscle-invasive disease is low, as the clinical behavior is indolent, or slow-moving. The focus of management is centered on controlling local recurrence within the bladder lining.
Common Treatment and Surveillance Protocols
The management of a low-grade bladder tumor begins with its removal. The standard procedure is a Transurethral Resection of Bladder Tumor (TURBT). During a TURBT, a surgeon inserts an instrument through the urethra to cut the tumor from the bladder wall and the removed tissue is sent for grading.
After the tumor is removed, the focus shifts to surveillance due to the high recurrence rate. A regular monitoring schedule is established to detect new growths early. This surveillance is done using cystoscopy, a procedure where a camera is inserted into the bladder for visual inspection.
Monitoring is performed every few months initially and then less frequently if no new tumors appear. This allows for the timely treatment of any recurring tumors, which can be managed with another TURBT. The goal is to manage the condition as a controllable disease and prevent it from advancing.