FIGURE 57-4

a.Bosniak II-F lesion—short-interval imaging follow-up

b.Bosniak IV—cystic RCC

c.Bosniak II cyst

d.Bosniak III cyst

e.Bosniak I cyst

Answers

1.c. Computed tomography (CT) with and without contrast enhancement.

A dedicated (thin-slice) renal CT scan remains the single most important radiographic image to delineate the nature of a renal mass. In general, any renal mass that enhances with administration of intravenous contrast material on CT scanning should be considered a renal cell carcinoma until proved otherwise.

2.b. Bosniak II cyst. Category II lesions are minimally complicated cysts that are benign but have some radiologic findings that cause concern. Classic hyperdense renal cysts are small (< 3 cm), round, sharply marginated, and do not enhance after administration of contrast material. Hyperdense cysts that are 3 cm or larger are classified as Bosniak II-F lesions.

3.d. Renal metastasis. The traditionally accepted indications for needle aspiration or biopsy of a renal mass are when a renal abscess or infected cyst

is suspected, or when differentiating RCC from metastatic malignancy or renal lymphoma. Fine-needle aspiration or biopsy is now performed with increased frequency for the evaluation of renal masses in other circumstances, particularly for patients in whom a wide variety of treatment options are under consideration.

4.c. Chest radiograph annually for 3 years. Surveillance for recurrent malignancy after radical nephrectomy for RCC can be tailored according to the initial pathologic tumor stage. This patient is low risk (pT1N0M0) and the American Urological Association (AUA) Guidelines recommend an annual chest radiograph for 3 years and only as clinically indicated beyond that time period.

5.b. Tumor size < 5.0 cm. A solitary tumor and a normal contralateral kidney were also required, but criteria for the latter were not well defined.

6.b. Every 6 months for at least 3 years and then annually to year 5.

Surveillance for recurrent malignancy after nephron-sparing surgery for RCC can be tailored according to the initial pathologic tumor stage. This patient is intermediate to high risk and the AUA Guidelines recommend a baseline abdominal scan (CT or MRI) within 3 to 6 months following surgery with continued imaging (ultrasonography, CT, or MRI) every 6 months for at least 3 years and annually thereafter to year 5. Imaging beyond 5 years may be performed at the discretion of the clinician.

7.b. 24-hour urinary protein measurement. Patients who undergo nephronsparing surgery for RCC may be left with a relatively small amount of renal tissue. These patients are at risk for long-term renal functional impairment from hyperfiltration renal injury. Because proteinuria is the initial manifestation of the phenomenon, a 24-hour urinary protein measurement should be obtained yearly in patients with a solitary remnant kidney to screen for hyperfiltration nephropathy.

8.e. Serum creatinine–based estimation of GFR, such as CKD-EPI formula. At present, there are several formulas in clinical use, including the MDRD, Cockcroft-Gault, and CKD-EPI formulas, each of which is an improvement over using serum creatinine alone for identification of patients with or at risk for chronic kidney disease. Serum levels of creatinine are dependent on gender, muscle mass, and other factors and can therefore lead to an underappreciation of kidney disease in certain populations, such as thin, elderly women. Urinary creatinine measurement is impractical and provides only marginally more valuable information than

serum creatinine. Urinary protein measurement can identify patients with early signs of kidney disease (proteinuria) but is not the best screening test. Direct measurement of GFR using iothalamate (or other agents) is costly and not routinely available; it is therefore impractical in most settings.

9.d. A double freeze-thaw cycle. Renal cryosurgery is an ablative nephronsparing treatment option for RCC that can be performed percutaneously under radiographic guidance or laparoscopically under direct vision and ultrasound guidance. The aim of cryosurgery is to ablate the same predetermined volume of tissue that would have been removed had a conventional surgical excision been performed. Established critical prerequisites for successful cryosurgery

include rapid freezing, gradual thawing, and a repetition of the freeze-thaw cycle.

.c. CT and MRI. Both CT and MRI are noninvasive and accurate modalities for demonstrating both the presence and the distal extent of vena caval involvement. Although MRI has been recommended as the test of choice at most centers, several recent studies have demonstrated that multiplanar CT also provides sufficient information for surgical planning, and it has become the preferred diagnostic study at many centers.

.e. Lymph node involvement. In most studies, the presence of lymph node or distant metastases has carried a dismal prognosis that is much more pronounced than the other distractors.

.d. Simultaneous partial nephrectomy and pulmonary lobectomy. The subset of patients with metastatic RCC and a solitary metastasis, estimated at between 1.6% and 3.2% of patients, may benefit from nephrectomy with resection of the metastatic lesion. This patient also needs partial nephrectomy to preclude the need for dialysis.

.e. Observation with follow-up renal imaging in 6 to 12 months. Renal mass biopsy is now performed with increased frequency and should be considered in an elderly patient such as this. For those in whom nonextirpative options are being considered, biopsy can provide important information, such as a definitive nonmalignant diagnosis (as in this example). Given the benign nature of renal oncocytomas, the best answer is observation with follow-up imaging in 6 to 12 months.

.e. Mode of genetic transmission. Approximately 20% of angiomyolipomas are found in patients with the tuberous sclerosis (TS) syndrome, an autosomal dominant disorder characterized by mental retardation, epilepsy, and adenoma sebaceum, a distinctive skin lesion. TS, similar to von Hippel-Lindau, is

transmitted in an autosomal dominant manner.

.a. Selective embolization. Most patients with acute or potentially lifethreatening hemorrhage will require total nephrectomy if exploration is performed, and if the patient has TS, bilateral disease, preexisting renal insufficiency, or other medical or urologic disease that could affect renal function in the future, selective embolization should be considered. In such

circumstances, selective embolization can temporize by controlling hemorrhage and in many cases will prove to be definitive treatment.

.a. They are complex cystic lesions that are typically classified as Bosniak II to III. Cystic nephromas are benign renal neoplasms that occur most commonly in middle-aged women. They appear to be genetically related to mixed epithelial and stromal tumors (MESTs) but generally have a somewhat

different radiographic appearance. Unlike MESTs, which contain a solid stromal component and often appear as solid or Bosniak IV lesions on crosssectional imaging, cystic nephromas are typically characterized as complex cystic lesions without a solid component.

.c. Tobacco use. The most generally accepted environmental risk factor for RCC is tobacco use, although the relative associated risks have been modest, ranging from 1.4 to 2.3 when compared with controls. All forms of tobacco use have been implicated, with risk increasing with cumulative dose or packyears. Other well-established risk factors include obesity and hypertension.

.d. Pheochromocytoma. The familial form of the common clear cell variant of RCC is the von Hippel-Lindau syndrome. Major manifestations include the development of RCC, pheochromocytoma, retinal angiomas, and hemangioblastomas of the brainstem, cerebellum, or spinal cord.

Penetrance for all of these traits is far from complete, and some, such as

pheochromocytomas, tend to be clustered in certain families but not in others.

.c. 41% to 60%. RCC develops in about 50% of patients with von HippelLindau syndrome and is distinctive for early age at onset, often developing in the third, fourth, or fifth decades of life, and for bilateral and multifocal involvement.

.e. RCC. With improved management of the central nervous system manifestations of the disease, RCC has now become the most common cause

of mortality in patients with von Hippel-Lindau syndrome.

.b. Vascular endothelial cell growth factor. Inactivation or mutation of the von Hippel-Lindau gene leads to dysregulated expression of hypoxia

inducible factor-1, an intracellular protein that plays an important role in regulating cellular responses to hypoxia, starvation, and other stresses. This in turn leads to a severalfold upregulation of the expression of vascular endothelial growth factor (VEGF), the primary proangiogenic growth factor in RCC, contributing to the pronounced neovascularity associated with this carcinoma.

.a. The mode of genetic transmission. Studies of families with hereditary papillary renal cell carcinoma (HPRCC) have demonstrated an autosomal dominant mode of transmission, similar to von Hippel-Lindau syndrome. Von Hippel-Lindau syndrome is caused by inactivation or mutation of a tumor

suppressor gene, whereas HPRCC is caused by activation of an oncogene.

.d. Constitutive activation of the receptor for hepatocyte growth factor.

Missense mutations of the met proto-oncogene at 7q31 were found to segregate with the disease, implicating it as the relevant genetic locus. The protein product of this gene is the receptor tyrosine kinase for the hepatocyte growth factor (also known as scatter factor), which plays an important role in regulating the proliferation and differentiation of epithelial and endothelial cells in a wide variety of organs, including the kidney. Most of the mutations in hereditary papillary RCC have been found in the tyrosine kinase domain of met and lead to constitutive activation.

.e. Efflux of large hydrophobic compounds, including many cytotoxic drugs. P-glycoprotein is a 170-kDa transmembrane protein expressed by 80% to 90% of RCCs that acts as an energy-dependent efflux pump for a wide variety of large hydrophobic compounds, including several cytotoxic drugs.

.c. pT3aN1M1. Isolated renal vein involvement is now classified as T3a and nodal classification has been simplified such that all nodal involvement is now classified as N1. Contiguous invasion of the ipsilateral adrenal is now

classified as T4, but metastatic involvement of the contralateral (or ipsilateral) adrenal gland is classified as M1, reflecting a likely hematogenous pattern of dissemination.

.b. Sarcomatoid variants of RCC. Most RCCs are round to ovoid and circumscribed by a pseudocapsule of compressed parenchyma and fibrous tissue rather than a true histologic capsule. Unlike upper tract transitional cell carcinomas, most RCCs are not grossly infiltrative, with the notable exception

of some sarcomatoid variants.

.c. Inactivation of the von Hippel-Lindau tumor suppressor gene. Chromosome 3 alterations and von Hippel-Lindau mutations are

common in conventional RCC, and mutation or inactivation of this gene has been found in over 75% of sporadic cases.

.a. Trisomy of chromosome 7. The cytogenetic abnormalities associated with papillary RCC are characteristic and include trisomy of chromosomes 7 and

17 and loss of the Y chromosome.

.b. 4% to 5%. Chromophobe cell carcinoma is a distinctive histologic subtype of RCC that appears to be derived from the cortical portion of the collecting duct. It represents 4% to 5% of all RCCs.

.e. Metastatic at the time of diagnosis. Renal medullary carcinoma is a rare histologic subtype of RCC that occurs almost exclusively in association with sickle cell trait. It is typically diagnosed in young African Americans, often in the third decade of life. Many cases are both locally advanced and

metastatic at the time of diagnosis. Most patients have not responded to therapy and have succumbed to their disease in a few to several months.

.d. Hypercalcemia. Hypercalcemia has been reported in up to 13% of patients with RCC and can be due to either paraneoplastic phenomena or osteolytic metastatic involvement of the bone. The production of parathyroid hormone–like peptides is the most common paraneoplastic etiology, although tumor-derived 1,25-dihydroxyvitamin D3 and

prostaglandins may contribute in a minority of cases. Medical management includes vigorous hydration followed by diuresis with furosemide and the selective use of bisphosphonates, corticosteroids, and/or calcitonin.

.a. Right radical nephrectomy and regional or extended lymph node dissection. An aggressive surgical approach is still preferred because it will likely prolong survival and represents the only realistic chance for a cure. Lymph nodes in this size range are most likely malignant, and this patient will

likely need to consider adjuvant clinical trials. An extended lymph node dissection includes the interaortocaval nodes and nodes alongside and behind the ipsilateral great vessel from the crus of the diaphragm to the ipsilateral common iliac artery.

.e. A 38-year-old woman with a febrile urinary tract infection and a 3.5-cm solid/cystic, enhancing renal mass. Patients with flank pain, a febrile urinary tract infection, and a renal mass may be considered for percutaneous biopsy or aspiration to establish a diagnosis of renal abscess rather than malignancy.

.d. 46% to 65%. Venous involvement was once thought to be a poor prognostic finding for RCC, but more recent studies suggest that most patients

with tumor thrombi can be salvaged with an aggressive surgical approach. These studies document 45% to 69% 5-year survival rates for patients with venous tumor thrombi as long as the tumor is otherwise confined to the kidney.

.d. Patient age. Although patient age and comorbidity are important predictors of overall survival in patients with RCC and strongly affect the choice of treatment in these patients, they have no effect on the likelihood of dying of cancer-specific causes. Each of the other factors has been incorporated into

one or more RCC prognostic algorithms for cancer-specific outcomes.

.b. The radiographic patterns manifested by renal lymphoma are diverse and can be difficult to differentiate from RCC. Five different radiographic patterns have been described for lymphoma involving the kidney, including a

solitary mass that can be difficult to differentiate from RCC.

.c. Small area measuring less than − 20 Hounsfield units on nonenhanced CT. The presence of even a small focus of fat, as evidenced by a density less than − 20 HU on a nonenhanced CT scan, is diagnostic for AML. The findings described in a, b, and d are all suggestive but not diagnostic for renal AML.

.b. Difficulty differentiating the eosinophilic variants of RCC from renal oncocytoma. The main limitation of renal mass biopsy is difficulty differentiating renal oncocytoma, the most common benign renal mass, from eosinophilic variants of conventional, papillary, and chromophobe RCC on biopsy material. The risk of complications is low in the modern era with the use of smaller gauge needles, and needle tract seeding with RCC appears to be a rare event.

.e. 3.0-cm solid lesion with fat associated with calcification. Tumors with calcification associated with fat are uncommon but are almost always

malignant RCC. In this setting the fat is thought to be a reactive process related to tumor necrosis. Calcification is virtually never seen in association with AML. The lesions described in a–c are Bosniak II renal cysts, with risk of malignancy of < 10%. The lesion described in d is a simple cyst and highly likely to be benign despite its large size.

.d. TFE3 gene fusions. Mutations or translocations resulting in TFE3 gene fusions are common in RCC occurring in the pediatric population. Although these cancers often present with advanced stage, the t(X;17) variant frequently follows an indolent course while t(X;1) cancers can recur with late lymph node metastases.

.a. Hypoxia-inducible factor (HIF) alpha. Inactivation of the VHL protein or loss of its function allows HIF-2 alpha to accumulate, leading to a variety of

downstream events including upregulation of VEGF, erythropoietin, and PEGF. HIF-2 alpha is the primary mediator of these events.

.b. Hypervascularity. Tumors in the von Hippel-Lindau syndrome include adrenal pheochromocytoma, retinal angiomas, cerebellar and brainstem hemangioblastoma, RCC, and others. Most are relatively slow growing and asymptomatic if patients are evaluated and screened in a proactive manner.

The common feature is that almost all are hypervascular.

.e. Incidence of associated tumors in nonrenal organ systems. The incidence of nonrenal tumors is low in the hereditary papillary RCC syndrome in contrast to von Hippel-Lindau syndrome, in which patients commonly

develop tumors in the eyes, spinal cord, cerebellum, adrenal glands, inner ear, epididymis, and pancreas.

.c. Hereditary leiomyomatosis and RCC syndrome. Malignant behavior is particularly common in the hereditary leiomyomatosis and RCC syndrome, and proactive and aggressive surgical management is recommended.

.d. Birt-Hogg-Dubé syndrome. Lung cysts and spontaneous pneumothoraces are well described and relatively common findings in the Birt-Hogg-Dubé syndrome.

.a. Oncocytoma. Both chromophobe RCC and renal oncocytoma are derived from the distal tubules and both are commonly observed in the Birt-Hogg-Dubé syndrome. There are also some overlapping cytogenetic changes, all suggesting a potential relationship between these renal tumors.

.d. Positive staining for Ulex europaeus lectin. Ulex europaeus lectin is expressed by the normal collecting duct, and tumor staining suggests origin from this structure. Most collecting duct carcinomas are centrally located

and exhibit an infiltrative growth pattern and aggressive clinical course, but this is also true for poorly differentiated transitional cell carcinomas (TCCs) of the renal pelvis or centrally located sarcomatoid RCC.

.d. Clear cell and chromophobe. Sarcomatoid differentiation is most commonly found in association with clear cell and chromophobe RCC.

.c. Performance status. Poor performance status (PS) can be used to segregate patients when deciding whether to obtain a bone scan for metastatic RCC. Shvarts and colleagues (2004)* have shown that patients with good performance status (ECOG performance status = 0), no evidence of extraosseous metastases, and no bone pain were extremely low risk for bone

metastasis and did not benefit from bone scanning. They recommended a bone scan for all other patients, and the incidence of bone metastasis in this group was > 15%.

.d. Worse than a pT3a tumor with invasion of the perinephric fat laterally.

Invasion of the perisinus fat medially has been shown to be a poor prognostic sign. Medial invasion places the tumor in proximity to the venous system and likely increases the risk of metastatic dissemination. Ipsilateral adrenal involvement is even worse, and these are now classified as pT4 if due to

direct local extension, or pM1 otherwise, consistent with a hematogenous route of dissemination.

.c. Tumor stage. Although not truly a single factor because it combines tumor size with several other pieces of information obtained from final pathologic

analysis, tumor stage is the most powerful individual predictor of oncologic outcomes. When incorporated into a multi-predictor analysis, such as a nomogram or other multivariable analysis, the predictive ability increases further.

.d. Integrated analysis of prognostic factors. Integrated analysis of a variety of factors such as tumor size, stage, and grade, performance status, and histologic subtype has yielded the most accurate prognostication for RCC. Several studies have documented that nomograms and other algorithms outperform traditional staging systems, clinical opinion, individual risk factors, and chance.

.b. RCC with direct ipsilateral adrenal involvement: pT3a. Several studies have demonstrated that RCC directly invading the adrenal gland is associated with poorer prognosis than RCC with perinephric or renal sinus fat invasion.

Direct ipsilateral adrenal involvement is now grouped with other RCCs that extend beyond Gerota fascia as pathologic stage T4 (pT4). These

patients have a high risk for disease recurrence or progression.

.b. von Hippel-Lindau patient after partial nephrectomy with wedge resection of a single tumor. Local recurrence after partial nephrectomy for von Hippel-Lindau disease is common if patients are followed long-term due to multifocal tumor diathesis. These kidneys have been shown to harbor several hundred incipient tumors, and the risk of local recurrence is thus high during longitudinal follow-up after partial nephrectomy.

.d. Leiomyosarcoma. Leiomyosarcoma is the most common histologic subtype of renal sarcoma, accounting for 50% to 60% of such tumors. The most common type of sarcoma in the retroperitoneum is liposarcoma.

.e. Margin status and grade. Margin status and tumor grade are the primary prognostic factors for sarcoma. Patients with high-grade disease are at risk for systemic metastasis and those with low-grade disease are at risk for local recurrence. Wide local excision with negative margins is essential for minimizing the risk of recurrence for sarcomas because these tumors are derived from the mesenchymal tissues and are typically infiltrative, and

thus do not respect natural barriers.

.b. Carcinoid. All of these tumor types have a relatively poor prognosis except for renal carcinoid, which tends to be associated with good outcomes in most patients.

.b. Clear cell RCC. Targeted molecular therapies, such as tyrosine kinase inhibitors, mostly target VEGF and thus the pathways that are typically

upregulated in clear cell RCC. Most objective responses have been observed in individuals with clear cell RCC. Standard of care for the treatment of metastatic non–clear cell RCC is not well defined at present.

.d. Observation. All randomized postoperative adjuvant trials in patients with resected RCC have failed to demonstrate an improvement in survival or time to progression. Several ongoing clinical trials are evaluating whether targeted molecular therapy will show a benefit, but the results are not available at present. The standard of care continues to be surveillance with periodic radiographic and clinical observations, although enrollment in a clinical trial is highly preferred.

.c. VEGF and mammalian target of rapamycin (mTOR). Several clinical trials indicate that agents targeting VEGF signaling, including sunitinib, sorafenib, and pazopanib, and mTOR pathway signaling, including temsirolimus and everolimus, demonstrate substantial tumor responses or significant improvement in progression-free or overall survival.

.d. Renal function prior to partial nephrectomy. When compared with radical nephrectomy, partial nephrectomy has been associated with better renal functional outcomes. The main determinants of renal function after partial nephrectomy are the quality of the kidney prior to surgery and the quantity of vascularized parenchymal mass that is preserved after excision of the tumor and reconstruction of the kidney. Warm ischemia time, if prolonged, can also contribute to a decline in renal function after partial

nephrectomy.

.d. Increasing chronic kidney disease (CKD) stage has been associated with an increase in morbid cardiovascular events, hospitalization and death on

a longitudinal basis for subjects in the general population. In this setting, CKD is predominantly due to medical causes. CKD due to surgical causes appears to be more stable than that due to medical causes.

.e. 1.5-cm adrenal lesion that is bright on T2-weighted MR imaging.

Several pathologic adrenal lesions can be diagnosed based on their radiographic characteristics without histologic confirmation. Lesions that are bright on T2-weighted MR imaging are suspicious for pheochromocytomas and should be surgically removed. Careful preoperative and intraoperative management are essential for safe management in this circumstance.

Pathology

1.d. Have a partial nephrectomy. Notice the clear cytoplasm due to glycogen characteristic of clear cell carcinoma of the kidney. Because of the patient's young age, a nephron-sparing approach is preferred. Because the tumor is located in the lower pole, is peripheral, and is exophytic, it is ideal for this approach. These tumors are not sensitive to radiation therapy, cryotherapy does not have long-term extended follow-up, and targeted chemotherapy is not appropriate for a surgically curable lesion.

2.e. Be followed closely because the development of metastatic disease is likely. Collecting duct cancers have a high likelihood of being metastatic at diagnosis. None of the other therapies listed are helpful in this disease.

Imaging

1.b. Radical nephrectomy. The images demonstrate a large mass in the lower pole of the right kidney, with tumor extension into the right renal vein, extending to the junction of the right renal vein with the inferior vena cava. The renal vein is enlarged, and tumor vessels are seen within the thrombus in the renal vein. These findings make radical nephrectomy the best option.

2.b. Bosniak IV—cystic RCC. Notice the enhancing nodules within the cyst wall with foci of dystrophic calcification making cystic renal cell carcinoma the most likely diagnosis.

Chapter review

1.A solid mass on CT scan that enhances more than 15 Hounsfield units is suggestive of RCC.

2.Twenty percent of small solid enhancing masses on CT are benign.

3.Hyperdense cysts (Bosniak II) contain old blood and are benign.

4.Clear cell RCCs originate from the proximal tubule; oncocytomas and chromophobe RCCs originate from the distal tubule.

5.There is ample evidence for impaired immune surveillance in RCC.

6.Bilateral involvement in RCC either synchronously or metachronously occurs in 2% to 4% of patients.

7.RCC pathologically is classified as clear cell: 70% to 80%; papillary: 10% to 15%; chromophobe: 3% to 5%; collecting duct: less than 1%; and medullary: rare.

8.Alterations in chromosome 3 are common in clear cell renal carcinoma.

9.Papillary renal cell cancer has a tendency to multifocality.

10.Paraneoplastic syndromes include hypercalcemia, hypertension, polycythemia, and hepatic dysfunction (Stauffer syndrome).

11.Stauffer syndrome is a perineoplastic syndrome associated with RCC that results in elevated liver function tests. If hepatic function does not normalize after nephrectomy, persistent hepatic dysfunction is indicative of persistent disease.

12.Enlarged perirenal lymph nodes noted on CT may be inflammatory, particularly if they are less than 2 cm in diameter. Lymph nodes larger than 2 cm generally contain metastases.

13.Extended lymphadenectomy for renal cell carcinoma has not been shown to be beneficial for the majority of patients over conventional lymphadenectomy, which includes the renal hilar and adjacent paracaval or para-aortic lymph nodes.

14.Fuhrman grading system from 1 to 4 is used to grade the renal tumor and is based on nuclear characteristics.

15.There is an increased incidence of renal cell carcinoma in patients with acquired renal cystic disease.

16.RCC involving the vena cava that infiltrates the wall of the vena cava has an extremely poor prognosis.

17.A patient with a tumor thrombus involving the vena cava associated with metastatic regional nodal disease has a very poor prognosis.

18.A patient with a tumor thrombus involving the vena cava in which the nodes are negative and there is no invasion of the vein wall (except the ostia) has a good prognosis.

19.Ipsilateral adrenalectomy as part of a radical nephrectomy is not

necessary unless there is CT evidence of adrenal involvement, contiguous spread of the tumor to the adrenal, or large upper pole renal masses that are adjacent to the adrenal gland.

20.The risk for developing recurrent malignant disease is greatest in the first 3 years after surgery.

21.In a partial nephrectomy, the amount of renal parenchyma taken with the tumor appears to be immaterial provided the margin itself is negative.

22.RCCs less than 3.5 cm in general grow less than 0.5 cm per year; some may grow up to 1 cm per year.

23.Incomplete excision of a large primary tumor or debulking is rarely indicated as a sole treatment.

24.Sarcomas typically have a pseudocapsule that cannot be relied on for a plane of dissection because tumor will be left behind.

25.Metastatic tumors to the kidney are common, appearing in 12% of patients who die of other cancers; the most common primary lesions are those of the lung, breast, or gastrointestinal tract, melanoma, or hematologic.

26.Positron emission tomography scanning using radiolabeled anticarbonic anhydrase IX is taken up by clear cell renal carcinoma.

27.Major poor prognostic indicators include tumors that extend beyond Gerota fascia, involve contiguous organs, have lymph node involvement, or are metastatic.

28.Patients with von Hippel-Lindau disease should have their tumors treated when they reach 3 cm in size.

29.Patients with a significant reduction in renal mass are at risk for developing long-term renal functional impairment from hyperfiltration renal injury. These patients should have their urinary protein excretion monitored because proteinuria is the initial manifestation of hyperfiltration injury.

30.Established critical prerequisites for successful cryosurgery include rapid freezing, gradual thawing, and a repetition of the freeze-thaw cycle.

31.Approximately 20% of angiomyolipomas are found in patients with the tuberous sclerosis (TS) syndrome, an autosomal dominant disorder characterized by mental retardation, epilepsy, and adenoma sebaceum, a distinctive skin lesion. TS, similar to VHL, is transmitted in an autosomal dominant manner.

32.Cystic nephromas are benign renal neoplasms that occur most commonly

in middle-aged women.

33.The von Hippel–Lindau syndrome's major manifestations include the development of renal cell carcinoma, pheochromocytoma, retinal angiomas, and hemangioblastomas of the brain stem, cerebellum, or spinal cord.

34.Inactivation or mutation of the von Hippel–Lindau gene leads to dysregulated expression of hypoxia inducible factor-1, an intracellular protein that plays an important role in regulating cellular responses to hypoxia, starvation, and other stresses. This in turn leads to a severalfold upregulation of the expression of vascular endothelial growth factor (VEGF).

35.Hereditary papillary renal cell carcinoma has an autosomal dominant mode of transmission.

36.Chromosome 3 alterations and von Hippel–Lindau mutations are common in conventional renal cell carcinoma, and mutation or inactivation of this gene(VHL) has been found in over 75% of sporadic cases.

37.Renal medullary carcinoma is a rare histologic subtype of RCC that occurs almost exclusively in association with sickle cell trait.

38.Most collecting duct carcinomas are centrally located and exhibit an infiltrative growth pattern and aggressive clinical course.

39.Direct ipsilateral adrenal involvement is now grouped with other RCC's that extend beyond Gerota fascia as pathologic stage T4 (pT4).

* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.