Classifying Histologic Subtypes of Renal Cell Carcinoma

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Classifying Histologic Subtypes of Renal Cell Carcinoma
Classifying Histologic Subtypes of Renal Cell Carcinoma
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With the advent of advanced imaging technology and increased use of new technology, the incidence of renal tumors has risen in the past 30 years. A review of the Surveillance, Epidemiology and End Results (SEER) database has shown that the incidence of renal cell carcinoma (RCC) has increased significantly by as much as 4% in some populations.1

Most of the renal tumors diagnosed as a result of increased imaging are of lower stage, namely T1 tumors with no evidence of metastasis or nodal involvement.2 The disease has shown a lack of stage migration, with overall mortality constant over the past three decades.

This has led urologists to review and rethink their approach to RCC on several points. Has the disease itself changed? Do we need to refine our techniques in treating RCC? How can we improve prognoses?

Histologic typing


To answer the first question, one should look at renal pathology. The evolution of renal pathology has greatly enhanced our understanding of renal tumors. With more tumors for evaluation, histologic typing and grading of renal tumors has become more standardized. In addition to standardizing pathologic subtypes, the increased incidence of renal tumors has led to a better understanding of the histologic subtypes of RCC.

Furthermore, molecular genetics and immunohistochemistry have proved to be invaluable in the subclassification of RCC, allowing clinicians to better predict the natural history of the disease and to make prognoses. We will review the histologic subtypes of RCC, including new subtypes recognized in the 2004 World Health Organization classification of renal tumors. We will describe their appearance, prevalence, prognosis, and association with genetic syndromes, and review new advances in genetics and molecular biology that allow pathologists and urologists to distinguish among subtypes.


While many renal tumors are "incidentalomas," it is important to recognize both the risk factors for and symptoms of RCC. First, as with bladder cancer, smoking is a significant risk factor. Other risk factors include obesity,3 renal failure, and hemodialysis.4 The genetic basis of several subtypes of RCC has been elucidated and will be discussed with each pathologic subtype.


Renal tumors were recognized as distinct entities starting in the early 19th century, though these tumors were poorly characterized and the distinction between benign and malignant tumors was often unclear. Throughout the 1800's, autopsy studies clarified the difference between malignant and benign tumors, whose status was confirmed on histologic evaluation. Through the first half of the 20th century, urologists and pathologists began to understand the distinction between benign and malignant neoplasia as well as histologic, structural, and genetic differences between the different subtypes of malignant tumors.5

RCC pathology prior to 1997 was divided into two categories: clear cell and granular cell carcinoma, with several descriptors associated with each category. In 1986, a European consensus group convened in Mainz, Germany to standardize the classification of renal neoplasms. The group decided that cell cytology and genetics should determine classification, with subcategories defined by histology and tumor architecture. This classification system proved unwieldly and was not used widely outside of Europe.6

In 1997, consensus meetings were held in Rochester, Minn., and Heidelberg, Germany to re-evaluate and standardize the classification of renal tumors. These two consensus meetings defined the more common classifications of RCC in wide use today. Histologic appearance and architecture were used instead of tumor genetics.



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