Chapter 40 – Renal Neoplasia

Chapter 40 Renal Neoplasia Scott E. Delacroix Jr., Christopher G. Wood, and Eric Jonasch Renal Cell Carcinoma, 1508 Chemotherapy, 1525 Other Kidney Tumors, 1528 Epidemiology, 1508 Immunotherapy, 1525 Renal Sarcomas, 1528 Pathology and Cytogenetics, 1509 Nonmyeloablative Allogeneic Wilms’ Tumor, 1528 Molecular Biology and Hereditary Transplantation, 1526 Disorders, 1511 Renal Pelvic Tumors, 1527 Clinical and Laboratory Features, 1513 Clinical Features and Diagnostic Radiologic Diagnosis, 1514 Evaluation, 1527 Staging and Prognosis, 1516 Staging and Grading of Renal Pelvic Surgical Treatment, 1518 Tumors, 1527 Radiation Therapy, 1520 Treatment, 1527 Systemic Therapy, 1520 Renal cell carcinomas arise within the renal cortex and 2% of all cancer deaths. Worldwide, the mortality from renal account for about 80% to 85% of all primary renal neoplasms. cell carcinoma is estimated to exceed 100,000 per year.6 Transitional carcinomas arising from the renal pelvis are the The incidence varies widely from country to country, next most common, accounting for 7% to 8% of primary with the highest rates seen in Northern Europe and North renal neoplasms. Other parenchymal epithelial tumors, such America.7 Although the incidence is reported to be lower as oncocytomas, collecting duct tumors, and renal sarcomas, in individuals living in African countries,7 the incidence is are uncommon but are becoming more frequently recognized equivalent among whites and African Americans living in the pathologically. Nephroblastoma (Wilms’ tumor) is common United States.8 Historically, renal cell carcinoma was twice as in children and accounts for 5% to 6% of all primary renal common in men as in women, but more recent data suggest tumors. that this gap is beginning to narrow. The incidence in Asian Metastatic lesions to the kidney (secondary neoplasms) Americans and Pacific Islanders is half that of their white and occur in 7% to 20% of patients with cancer at autopsy.1-3 African American counterparts.5 Renal cell carcinoma occurs These secondary lesions are very rare in the absence of pro- predominantly in the sixth to eighth decades; it is uncommon gression of the primary neoplasm.4 in patients younger than 40 years of age and rare in children.9-11 This chapter focuses on the epidemiology, pathology, The incidence of renal cell carcinoma has steadily increased genetics, clinical and radiographic presentation, staging meth- over time. Between 1975 and 1995 in the United States the ods, and surgical and systemic management of primary renal incidence rates per 100,000 person-years increased by 2.3%, neoplasms. A brief description of the biology and manage- 3.1%, 3.9%, and 4.3% annually for white men, white women, ment of the less common tumors as well as evaluation of sus- African American men, and African American women, respec- pected metastatic disease is also presented. tively.8 Mortality rates are equivalent for whites (6.2 males and 2.8 females per 100,000 persons) and African Ameri- cans (6.1 and 2.7, respectively), whereas Asian American Renal Cell Carcinoma and Pacific Islanders have the lowest mortality rates (2.4 and 1.2, respectively).5 American Indians and Alaskan Natives Epidemiology have an increased incidence of cancer of the kidney and an alarmingly high mortality rate (9.3 males and 4.3 females per In 2009, it was estimated that renal cell and renal pelvic can- 100,000 persons).5,12 cer would be newly diagnosed in 58,000 people in the United The overall incidence in the United States for all races has States and that almost 13,000 people would die of the disease.5 risen at a rate that is threefold higher than the mortality rate. Renal cell carcinoma represents 3.9% of all U.S. cancers and Since 1950, there has been a 126% increase in the incidence 1508 Chapter 40 Renal Neoplasia 1509 accompanied by a 37% increase in annual mortality.13,14 The in 10% and multifocal in 27.3%, and the histologic subtypes 5-year survival rate of patients with a diagnosis of kidney can- were divided between clear cell renal carcinomas (60%) and cer has improved from 34% for those receiving this diagnosis papillary renal cell carcinomas (40%). These cancers were all in 1954 to 67% for those receiving this diagnosis in 2004.5 staged as T1 disease, and none of the tumors was seen on The proportion of renal cell carcinomas discovered inciden- preoperative imaging. An increased incidence of sarcomatoid tally increased from approximately 10% in the 1970s to 60% features was not seen in this group, possibly because of the in 1998.14 In addition, at one major institution, the percentage benign indications for extirpation. of organ-confined tumors increased from 47% in 1989 to 78% Although most renal cell carcinomas are sporadic, factors in 1998.15 An examination of contemporary data shows that suggesting a hereditary cause include the occurrence of the the mortality rate decreased by approximately 5% between disease in first-degree relatives,30-33 onset before the age of 1990 and 2005.5 There is a continued stage migration, with 40, and bilateral or multifocal disease.34 Several kindreds with stage 1 disease increasing from 43% to 57% between 1993 and familial clear cell carcinoma have been identified that have con- 2004, whereas stage 2 and 3 disease showed a statistically sig- sistent abnormalities on the short arm of chromosome 3.35-38 nificant decline. The incidence of stage 4 disease has remained Other kindreds with papillary tumors have been identified stable over this time same period.16 with different genetic abnormalities,39 which suggests that Numerous environmental and clinical factors have been these tumors represent distinct disease entities. Although the implicated in the etiology of renal cell carcinoma.17 These true prevalence of hereditary renal cell carcinoma is unknown, include tobacco use; occupational exposure to toxic compounds it is estimated that hereditary carcinomas make up 3% to 5% such as cadmium, asbestos, and petroleum by-products; obe- of all renal cell carcinomas.40 A more detailed discussion of sity; acquired polycystic disease of the kidney (typically associ- the molecular biology of renal cell carcinoma is provided in a ated with dialysis); and analgesic abuse nephropathy. Cigarette later section. smoking doubles the likelihood of renal cell carcinoma and contributes to as many as one third of all cases.18-20 The risk of developing kidney cancer in patients with acquired polycystic Pathology and Cytogenetics disease of the kidney has been estimated to be 30 times greater than in the general population.21 In particular, it is estimated Renal cell carcinoma was first reported by Konig in 1826. In that acquired cystic disease develops in 20% to 90% of patients 1883, Grawitz hypothesized on histologic grounds that renal receiving long-term dialysis, depending on the duration of cell carcinomas arose from rests of adrenal tissue within the dialysis,22 and that renal cell carcinoma develops in between kidney.41 Although immunohistologic and ultrastructural anal- 3.8% and 4.2% of these patients.23 Patients with large cysts yses currently point toward the proximal renal tubule as the appear to be an increased risk for malignant transformation. true cell of origin,42 the term hypernephroma continues to be The carcinomas are multiple and bilateral in approximately incorrectly applied to these cancers. one half the cases, a finding that is consistent with the diffuse Renal cell tumors occur with equal frequency in the right nature of the underlying disease.24 The prolonged ingestion and left kidney and are distributed equally throughout the of analgesic combinations, particularly compounds contain- kidney.43 The average diameter is about 7 cm, but tumors have ing phenacetin and aspirin, can lead to chronic renal failure. ranged from less than 2 cm to more than 25 cm in diameter. Such patients are at increased risk of renal pelvic tumors and Previously, renal lesions smaller than 2 to 3 cm were incor- possibly renal cancer, although the latter association remains rectly considered to be benign adenomas. Such distinctions controversial.25-27 Because of its carcinogenic properties, phen- between benign and malignant tumors are no longer made on acetin was removed from the U.S. marketplace by the U.S. the basis of size but rather according to fundamental histo- Food and Drug Administration (FDA) in 1983 and later from logic criteria. Therefore, from a practical standpoint, all solid European markets. renal masses require resection or biopsy for accurate histologic An enhanced risk of renal cell carcinoma has been observed diagnosis. Improved percutaneous biopsy techniques have a in patients with certain inherited disorders, which implicates role in the management of renal masses, but are definitively various genetic abnormalities in its etiology. These disorders less accurate than extirpation in providing pathologic and his- include von Hippel–Lindau syndrome, hereditary papillary tologic information. renal cancer, hereditary leiomyoma renal cancer syndrome, Renal cell carcinomas have historically been classified and Birt-Hogg-Dube syndrome. In addition patients with according to cell type (clear, granular, spindle, or oncocytic) tuberous sclerosis and hereditary polycystic kidney disease, and growth pattern (acinar, papillary, or sarcomatoid).43 This although they do not have a dramatically increased incidence classification has undergone a transformation to more accu- of renal cancer, can have cancers with unique features. rately reflect the morphologic, histochemical, and molecu- Hereditary polycystic kidney disease (autosomal dominant lar features of different types of adenocarcinomas (Table polycystic kidney disease, or ADPKD) has a long-debated 40-1).44-46 Based on research studies, five distinct subtypes association with renal cancer; however, when renal cancer have been identified. These include clear cell (conventional), does occur in patients with this disorder, it typically displays chromophilic (papillary), chromophobic, oncocytic, and col- a number of distinct clinical characteristics.28 The tumors are lecting duct (Bellini duct) tumors.

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