Renal cancer Most renal cancers are renal cell carcinoma, which is the seventh most common tumor type in the developed world. The highest incidence is in Belarus, Czech Republic, Slovakia, and the Baltic countries (Estonia, Latvia, and Lithuania). Renal cell carcinoma is almost exclusively cancer of adults and it is two to three times more common in men than in women. Risk factors include smoking, obesity, occupational exposure to industrial chemicals (e.g. trichloroethylene, asbestos, cadmium), and overuse of acetaminophen, a popular painkiller. Up to 4% of renal carcinomas occur in inherited cancer syndromes such as von Hippel-Lindau syndrome, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis, and renal cell carcinoma, Birt-Hogg-Dubé syndrome, and Tuberous sclerosis.
Most of the renal cancers are found accidentally using imaging methods. They can present with hematuria, flank pain, palpable mass, or with a variety of symptoms caused by hormone production by tumor (erythropoietin, parathyroid-related hormone peptide, or adrenocorticotropic hormone). Several cases present initially as metastatic carcinoma of unknown primary.
Renal cell carcinoma is derived from the epithelium of renal tubules and consists of a large family of carcinoma types classified by their morphological and genetic features. Tumors can arise anywhere in the renal cortex and are typically surrounded by a fibrous pseudocapsule. The most common types of renal cell carcinoma are clear cell renal cell carcinoma(70–90%), papillary renal cell carcinoma (10–15%), and chromophobe renal cell carcinoma (3–5%). Other types are encountered less frequently.
Clear cell renal cell carcinomas typically have cells with abundant clear cytoplasm surrounded by a network of capillaries of uniform small caliber. The clarity of the cytoplasm is due to the ample content of lipids and glycogen. Small and large cysts, hemorrhage, and areas of necrosis are common findings. Papillary renal cell carcinomas have a predominantly papillary or tubulopapillary growth pattern and are further classified into type 1 or type 2, based on their differing cytological features. Chromophobe renal cell carcinomas are characterized by large cells with prominent cell membranes, pale cytoplasm, and crinkled ‘raisinoid’ nuclei with perinuclear halos. All renal cell carcinomas can exhibit sarcomatoid features. The four-tiered grading system based on nuclear and nucleolar features of tumor cells is applied only in clear cell renal cell carcinoma.
Benign tumors in the kidney also exist as adenomas, which are smaller tumors (less than 0.5 cm in diameter) compared to renal cell carcinomas, and oncocytomas which are characterized by tumor cells exhibiting large, intensely eosinophilic and finely granular cytoplasm and rounded nuclei.
The most common type of renal cancer in childhood is nephroblastoma (Wilms tumor). It is one of the most common cancer types in childhood, excluding hematological malignancies. It is most often found in children up to 5 years old, and is uncommon in older children and adults. Microscopically, nephroblastoma is composed of various proportions of histological components called blastemal, epithelial, and stromal component. The proportion and the degree of maturation of these components determines the risk group (low, intermediate, and high risk), and therapy, together with tumor stage.
Diagnosis of renal cell cancer is often based on morphological features, while histochemical staining and immunohistochemistry have value in tumors with unclear morphology. Clear cell renal cell carcinoma shows the expression of vimentin and carbonic anhydrase 9 (CAIX). Chromophobe carcinoma is positive on Hale’s colloidal iron staining and immunohistochemistry with antibodies against KIT and cytokeratin 7 (KRT7). Papillary renal cell carcinoma is positive for vimentin, cytokeratin 7 (KRT7), and alpha-methylacyl-CoA racemase (AMACR). Molecular investigations have a role in the diagnosis of rare cancer types, such as rearrangements of TFE3 and TFEB genes in MiT family translocation renal cell carcinomas. Mutations in succinate dehydrogenase genes can be shown in rare inherited type called succinate dehydrogenase-deficient renal cell carcinoma but immunohistochemical staining for SDHA and SDHB could be used as surrogate.
The main therapy of renal cancer is surgery with removal of part or whole kidney. Most of the types occurring in adulthood are resistant to radio- and chemotherapy (unlike many childhood cancers). The clinical course or renal cancer is unpredictable and recurrence ten years or more after the initial resection of a primary tumor is not uncommon. Chromophobe renal cell carcinoma is one of the least aggressive variants. Presence of sarcomatoid features in renal carcinomas and higher grades in clear cell renal carcinoma bear poor prognosis. The extent of spread of the primary tumor is the dominant factor that determines prognosis. Renal cell carcinomas frequently invade the renal venous system and metastasize via the hematogenic route. Metastases in regional lymph nodes without hematogenic spread to distant organs are uncommon. A 5-year relative survival rate for renal cancer is 93% for localized disease and only 13% for advanced cancer with distant spread.