Renal cell carcinomas have several peculiar clinical characteristics that create especially difficult and challenging diagnostic problems. The signs and symptoms vary, but the most frequent presenting manifestation is hematuria, occurring in more than 50% of cases. Macroscopic hematuria tends to be intermittent and fleeting, superimposed on a steady microscopic hematuria. Less commonly, the tumor may declare itself simply by virtue of its size, when it has grown large enough to produce flank pain and a palpable mass. Because of the widespread use of imaging studies for unrelated conditions, even smaller tumors are detected. Extrarenal effects are fever and polycythemia, which, because they are nonspecific, may be misinterpreted for some time before their association with the renal tumor is appreciated. Polycythemia affects 5% to 10% of affected individuals and results from production of erythropoietin by the cancer cells. Uncommonly, these tumors produce other hormone-like substances, resulting in hypercalcemia, hypertension, Cushing syndrome, or feminization or masculinization. These, as noted in Chapter 6, are paraneoplastic syndromes. In some patients, the primary tumor remains silent and is discovered only after metastases produce symptoms. The common locations for metastases are the lungs and the bones. It must be apparent that renal cell carcinoma manifests in many ways, some quite devious, but the triad of painless hematuria, a palpable abdominal mass, and dull flank pain is characteristic.
Renalcellcarcinomasaccountfor2%to3%ofallcancersinadultsandareclassifiedintothreemaintypes:
Clear cell carcinomas arethemostcommonandareassociatedwithhomozygouslossorinactivationoftheVHLtumorsuppressorprotein;tumorsfrequentlyinvadetherenalvein.
Papillary renal cell carcinomas frequentlyareassociatedwithincreasedexpressionandactivatingmutationsoftheMET oncogene;theytendtobebilateralandmultipleandshowvariablepapillaformation.
Chromophobe renal cell carcinomas arelesscommon;neoplasticcellsarenotasclearasintheotherrenalcellcarcinomas.
Although Wilms tumor is rare in adults, it is the third most common solid (non-hematologic) cancer in children younger than 10 years of age. These neoplasms contain a variety of cell and tissue components, all derived from mesoderm. Wilms tumor, like retinoblastoma, may arise sporadically or be familial, with the susceptibility to tumorigenesis inherited as an autosomal dominant trait. This neoplasm is discussed in greater detail in Chapter 7 along with other tumors of childhood.
Bu F, Maga T, Meyer NC, et al: Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome, J Am Soc Nephrol 25:55, 2014. [An in-depth review of molecular abnormalities in hemolytic uremic syndrome.] http://ebooksmedicine.net
Cornec-Le Gall E, Audrézet MP, Le Meur Y: Genetics and pathogenesis of autosomal dominant polycystic kidney disease: 20 years on, Hum Mutat 35:1393, 2014. [A review of the discovery of the major genes leading to polycystic kidney disease, along with their phenotypic manifestations.]
Cramer MT, Guay-Woodford LM: Cystic kidney disease: a primer, Adv Chronic Kidney Dis 22:297, 2015. [An excellent review on the pathophysiology of renal cystic diseases, with emphasis on the role of ciliary dysfunction in tubular epithelial cells.]
Crumley SM, Divatia M, Truong L, et al: Renal cell carcinoma: Evolving and emerging subtypes, World J Clin Cases 1:262, 2013. [An upto-date review of emerging subtypes of renal cell carcinoma.]