New Histologic Classification and Revised Staging System for Renal Cell Carcinoma
October 1, 2000 5 minutes read
New Histologic Classification and Revised Staging System for Renal Cell Carcinoma
ABSTRACT & COMMENTARY
Synopsis: In 1997, the TNM Staging System for renal cell carcinoma was modified and a revised histologic classification, consistent with the current genetic understanding of the disease, was recommended. In this review of 588 renal cell carcinomas in patients who underwent radical nephrectomy between 1970 and 1994, more than 80% were classified as clear cell carcinomas, 11% as papillary, 5% as chromophobe, and 1% as collecting duct renal cell carcinomas. The 1997 pathologic tumor staging was strongly correlated with patient survival; histologic grade, presence of necrosis, and sarcomatoid differentiation provided independent prognostic information for patients with clear cell carcinoma. The dismal overall prognosis associated with sarcoma-type differentiation was confirmed. Two types of papillary carcinoma were identified, one of which was associated with extremely good prognosis. A separate recent series of 643 patients also confirmed the relevance of the revised TNM staging criteria and suggested that tumor grade and histologic classification may be more important than previously recognized.
Source: Moch H, et al. Cancer 2000;89:604-614.
As a result of international efforts toward a uniform categorization of renal cell carcinoma (RCC), modifications to the TNM classification and a new histologic classification of renal cortical epithelial neoplasms appeared in 1997.1 Pathologic stage has most consistently been shown to influence the outcome of patients with RCC. In the 1997 revision of the TNM classification, pT1 was changed to include tumors up to 7 cm in size from the previous 2.5 cm. Since few tumors are detected as less than 2.5 cm, few tumors were ever included in the older pT1 classification. Previously, tumors that extended into the renal vein or inferior vena cava were classified as T3b tumors. Reflecting the surgical difficulties in removing caval tumors that extend above the diaphragm,2 these tumors have now been reclassified as T3c.
The new histologic classification system is consistent with the genetic changes that have been identified in renal cancer subtypes. Conventional renal cell carcinoma is now the term used for the most common carcinoma of the renal tubular epithelium and accounts for more than 80% of the cases reviewed. This classification includes tumors that were formally referred to as clear cell carcinomas and also includes those tumors that are morphologically similar but have eosinophilic cytoplasm. These tumors are characterized by a loss of genetic material in 3p; sarcomatoid change occurs in approximately 5%. Papillary renal carcinoma accounted for 11% of the cases reviewed and is not associated with abnormalities of 3p. Instead, these tumors are characterized by trisomies in chromosomes 3q, 7, 12, 16, 17, and 20 and a loss of the Y chromosome. These tumors have a papillary architecture that predominates in most and is present at least focally in almost all. Chromophobe renal carcinoma accounted for 5% of this series and typically stains blue with Hale’s colloidal iron stain. In routine sections, there appears to be a halo around the nucleus due to condensation of cytoplasm near the cell membranes. The cells vary widely in size and a solid architecture is the most common pattern. Chromophobe renal cell carcinomas are typically characterized by monosomy of multiple chromosomes and hypodiploidy. Collecting duct carcinomas accounted for 1% of the cases reviewed and can be a difficult diagnostic problem. The best accepted morphology is one of irregular channels lined by highly atypical epithelium that sometimes has a hobnail appearance. A variant, medullary carcinoma of the kidney, is believed to arise from the collecting ducts of the renal medulla and is associated with sickle cell trait. Because collecting duct tumors are rare and the published cases are morphologically heterogeneous, no consistent pattern of genetic abnormalities has been established.
In this series, approximately one-half of the clear cell carcinomas presented as pT½, whereas approximately 70% of papillary and chromophobe tumors were organ confined. Approximately one-third of the papillary tumors were low grade compared to 12% of clear cell tumors. While the pT was strongly correlated with patient survival (P < 0.0001), histologic subtype did not have independent prognostic significance when stage and histologic grade were also considered. Basophilic (Type I) papillary carcinomas had a much better prognosis than eosinophilic (Type II). Of 18 patients with basophilic papillary carcinoma, there were no tumor-related deaths. Sarcomatoid differentiation is no longer considered a separate histological classification but rather simply represents a very high-grade tumor that may occur with any renal cell carcinoma. The dismal prognosis associated with a sarcomatoid differentiation was confirmed in this review and was particularly poor when more than 50% of the tumor cells were sarcomatoid.
COMMENT BY MICHAEL J. HAWKINS, MD
The staging and histologic classification systems for renal cell carcinoma have been modified in recent years to reflect advances in surgical technique and improved understanding of genetic changes. The prognosis for patients with primary tumors less than 7 cm in this series was better but not statistically significantly different (P = 0.08) than for patients with pT2 primaries. Because of increased surgical risks associated with removal of clots above the diaphragm, an additional subclassification pT3c has been created. The new histologic grading system is simpler and better reflects the genetic abnormalities that are known to be associated with various forms of renal cell carcinoma. In a separate report from UCLA,3 the overall TNM stage and tumor grade were the most important prognostic indicators (P < 0.001). Eastern Cooperative Oncology Group classification was a less significant predictor (P = 0.031) and overall tumor stage was not shown to have an independent effect on patient survival (P = 0.138). High-grade lesions in this series portended a poor prognosis even in the face of early stage disease. For example, the five-year cancer-specific survival rate for patients with T1 lesions was 91% for grade I, 83% for grade II, 60% for grade III, but 0% for grade IV.
The heterogeneity of renal cell carcinoma is well recognized. Attempts to prospectively identify the 15-20% of patients who will respond to immunotherapy-based regimens have been unsuccessful. While not generally felt to be of benefit in most patients with renal cell carcinoma, some poorly differentiated or sarcomatoid variants may respond to chemotherapy. In addition, many patients are best observed without therapy until clear evidence of progression develops. It is possible that with progressively more sophisticated classification systems and increasing focus on genetic abnormalities, it may be possible to better tailor treatment regimens for renal cell carcinoma. For the immediate future, therapeutic clinical trials in renal cell carcinoma should be analyzed by histologic classification to identify possible differences in responsiveness.
References
1. Storkel S, et al. Cancer 1997;80:987-989.
2. Staehler G, et al. J Urol 2000;163:1671-7165.
3. Tsui K, et al. J Urol 2000;163:1090-1095.
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