Carcinoma Renal

INTRODUCTION
• Malignant neoplasms involving the kidney may be primary or
secondary tumors. Secondary renal neoplasms are usually
clinically insignificant and discovered at postmortem examination.
• Renal cell carcinomas (RCCs), which originate within the renal
cortex, constitute 80 to 85 percent of primary renal neoplasms.
Transitional cell carcinomas of the renal pelvis are the next most
common (approximately 8 percent). Other parenchymal epithelial
tumors, such as oncocytomas, collecting duct tumors, and renal
sarcomas, are rare. Nephroblastoma or Wilms tumor is common
in children (5 to 6 percent of all primary renal tumors).
EPIDEMIOLOGY
• Incidence — Globally, the incidence of renal cell carcinoma
(RCC) varies widely from region to region, with the highest
rates observed in the Czech Republic and North America. In
the United States, there are approximately 80,000 new cases
and almost 14,000 deaths from RCC each year. Worldwide,
there are over 400,000 new cases of RCC and over 170,000
deaths annually due to kidney cancer.
• Mexico ???

PubMed Epidemiology and risk factors for kidney cancer. Chow WH, Dong LM, Devesa SS. Nat Rev Urol.
2020;7(5):245. 
Sex and age
• RCC is approximately twofold more common in males
compared with females [3]. RCC occurs predominantly in the
sixth to eighth decade of life with median age at diagnosis
around 64 years of age; it is unusual in patients under 40
years of age and rare in children
Mortality
•  — The five-year survival rate of patients with kidney cancer
has doubled over the last 60 years,
• The incidence of RCC has risen more than threefold higher
than the mortality rate [3].
• This improved survival and case-fatality rate is mostly due to
earlier detection of these tumors at smaller sizes (ie, <4 cm)
and curative surgical treatment
ESTABLISHED RISK FACTORS
• Smoking — Cigarette smoking is associated with an
increased risk of developing renal cell carcinoma (RCC).

• Obesity — Excessive body weight is a risk factor for RCC in

both males and females [21,22]. This was shown in a
prospective analysis of over 300,000 participants in the
National Institutes of Health and American Association for
Retired Persons (NIH-AARP) Diet and Health Study [22]. The
relative risk (RR) of RCC increased progressively with
baseline body mass index (BMI).
• Acquired cystic disease of the kidney and chronic kidney
disease — The risk of developing RCC has been estimated to
be up to 30 times greater in dialysis patients with acquired
polycystic disease of the kidney than in the general
population 

• Occupational exposure — Occupational exposure to toxic

compounds, such as cadmium, asbestos, and petroleum
byproducts, has been associated with an increased risk of
RCC
• Analgesics — The prolonged ingestion of analgesic
combinations, particularly compounds containing
phenacetin (of which acetaminophen is a major metabolite)
and aspirin, can lead to chronic renal failure. Such patients
are at increased risk for renal pelvic and urothelial tumors.
• Genetic factors — The risk of a second, metachronous RCC
is increased in patients who have been treated for one renal
cancer. This increased risk is most pronounced with younger
age at the first RCC, suggesting that early onset renal cancer
has a genetic component
• Cytotoxic chemotherapy — The use of cytotoxic
chemotherapy in childhood for malignancies, autoimmune
disorders, or bone marrow transplant conditioning has been
associated with the subsequent development of
translocation RCC 
• Chronic hepatitis C infection — An epidemiologic study of
over 67,000 patients found that chronic infection with
hepatitis C virus was associated with a significantly
increased risk of RCC after correcting for age, ethnicity, sex,
and the presence of chronic kidney disease 
• Sickle cell disease — Patients with sickle cell trait and (to a
lesser extent) sickle cell disease are at risk for renal
medullary carcinoma.

• Kidney stones — A history of kidney stones may be

associated with both RCC and transitional cell carcinoma of
the upper urinary tract.
OTHER FACTORS THAT MODIFY RISK
• Diabetes mellitus
• Alcohol
• Other factors — Additional clinical factors that may
increase the risk of developing RCC include dietary factors
such as the intake of nitrite from processed meat sources
subtypes of RCC
• Several distinct subtypes of RCC have been identified,
including the following:
• ●Clear cell (75 to 85 percent of tumors)
• ●Papillary (10 to 15 percent)
• ●Chromophobe (5 to 10 percent)
• ●Oncocytic (3 to 7 percent)
• ●Collecting duct (very rare)
• ●Molecularly defined renal cell carcinomas (rare) –
 CLINICAL MANIFESTATIONS
• Patients with RCC can present with a range of symptoms;
unfortunately, many patients are asymptomatic until the
disease is advanced. At presentation, approximately 25
percent of individuals either have distant metastases or
advanced locoregional disease [1].

Garnick MB. Primary neoplasms of the kidney. In: Therapy in Nephrology and Hypertension: A Companion to Brenner
and Rector's the Kidney, Brady HR, Wilcox CS (Eds), WB Saunders, Philadelphia 1998. no abstract available
 • Patients with localized disease can present with a wide array
of symptoms and/or laboratory abnormalities, or they may
be diagnosed incidentally.
• the most common presenting symptoms were hematuria,
abdominal mass, pain, and weight loss [2]

Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases.AUSkinner DG, Colvin
RB, Vermillion CD, Pfister RC, Leadbetter WF SOCancer. 1971;28(5):1165. 
Symptoms and signs 
• — For patients not diagnosed incidentally, symptoms and
signs are generally related to invasion of adjacent structures
or distant metastases.
 • Hematuria is observed only with tumor invasion of the
collecting system. In an early series, hematuria was
observed in almost 40 percent of patients [5]. When severe,
the bleeding can cause clots and "colicky" discomfort. Clot
formation does not occur with glomerular bleeding; thus,
the presence of clots is a significant finding in patients with
otherwise unexplained hematuria.

Manifestations of renal cell carcinoma. Gibbons RP, Monte JE, Correa RJ Jr, Mason JT Urology. 1976;8(3):201. 
 • An abdominal or flank mass, which is associated with lower pole
tumors, is more commonly palpated in the thin adult. The mass is
generally firm, homogeneous, nontender, and moves with respiration.
• ●Scrotal varicoceles, the majority of which are left sided, are observed
in as many as 11 percent of males with RCC [6]. Varicoceles typically
fail to empty when the patient is recumbent. This finding should
always arouse suspicion for a kidney tumor that has obstructed the
gonadal vein where it enters the renal vein.
• ●Inferior vena cava involvement can produce a variety of clinical
manifestations, including lower extremity edema, ascites, hepatic
dysfunction (possibly related to a Budd-Chiari syndrome), and
pulmonary emboli.
PubMed Medical aspects of renal carcinoma. PINALS RS, KRANE SM  ,Postgrad Med J. 1962;38:507. 
• Among patients with disseminated disease, signs or
symptoms may be due to metastatic tumor; the most
common sites of involvement include the lungs, lymph
nodes, bone, liver, and brain. In this setting, the diagnosis is
often made by biopsy of an accessible metastasis in the
setting of a renal mass on abdominal computed
tomography 
 Paraneoplastic symptoms
•  Patients with RCC can present with or subsequently develop
systemic symptoms or paraneoplastic syndromes [7-9]. In
some instances, these may be due to ectopic production of
various hormones (eg, erythropoietin, parathyroid
hormone-related protein [PTHrP], gonadotropins, human
chorionic somatomammotropin, an adrenocorticotropic
hormone [ACTH]-like substance, renin, glucagon, insulin)

PubMedTIParaneoplastic manifestations of renal cell carcinoma.AUGold PJ, Fefer A, Thompson JA SOSemin Urol
Oncol. 1996;14(4):216. 
 Anemia
•  — Anemia, which can precede the diagnosis of RCC by
several months, has been reported in around 60 percent of
patients with advanced disease [6,9-11]. The anemia is often
disproportionately severe, can be either normocytic or
microcytic, and is frequently associated with iron studies
typical of those observed with the anemia of chronic
disease.

PubMed Systemic effects of hypernephroma. Cherukuri SV,

Johenning PW, Ram MD. Urology. 1977;10(2):93. 
Hepatic dysfunction 
• — Hepatic dysfunction is an uncommon occurrence in
patients with RCC, which is called Stauffer syndrome when it
occurs in the absence of liver metastases 
• When hepatic dysfunction is present, it frequently is
associated with fever, weight loss, fatigue, and a poor
prognosis [15]. The dysfunction may result from tumor
production of cytokines, such as granulocyte-macrophage
colony-stimulating factor (GM-CSF) and possibly interleukin
6 (IL-6) 
PubMedTINon-metastatic hepatic dysfunction associated with renal carcinoma.AUBoxer RJ, Waisman J,
Lieber MM, Mampaso FM, Skinner DG SOJ Urol. 1978;119(4):468. 
• The classic triad of RCC (flank pain, hematuria, and a
palpable abdominal renal mass) occurs in at most 9 percent
of patients; when present, it strongly suggests locally
advanced disease [2,4].

DeKernion JB. Real numbers. In: Campbell's Urology, Walsh PC, Gittes RF, Perlmutter AD (Eds), WB Saunders,
Philadelphia 1986. p.1294. 
• Fever ever, which occurs in up to 20 percent of patients, is
usually intermittent and is frequently accompanied by night
sweats, anorexia, weight loss, and fatigue
• Hypercalcemia Hypercalcemia occurs in up to 15 percent of
patients with advanced RCC and can result from a number of
different mechanisms:
Lytic bone metastases.
Cachexia
Erythrocytosis — Erythrocytosis occurs in 1 to 5 percent of
patients with advanced RCC 
• Secondary (AA) amyloidosis — Secondary (AA) amyloidosis is found in
up to 5 percent of patients [31,32]. This finding reflects a chronic
inflammatory response as the amyloid fibrils are composed of
fragments of the acute phase reactant serum amyloid A protein.
• Thrombocytosis — Thrombocytosis is rare in patients with RCC, but its
presence is associated with a poor prognosis [33,34]. The underlying
mechanism is not firmly established but could be related to IL-6
production by the tumor.
• Polymyalgia rheumatica — A syndrome resembling polymyalgia
rheumatica has been reported with RCC [35]. In contrast to idiopathic
disease, the symptoms do not respond to prednisone but are often
corrected by nephrectomy.
DIAGNOSTIC EVALUATION
• Patients with unexplained hematuria or other symptoms,
signs, or findings suggestive of possible RCC must undergo
imaging evaluation for the presence of a renal mass. In
addition, incidental diagnosis of RCC is becoming more
common due to the frequent use of abdominal computed
tomography (CT) and/or ultrasonography for evaluation of
an unrelated problem.
CT or ultrasonography 
• — The usual first test is
abdominal computed
tomography (CT) (image 1) or,
occasionally, abdominal
ultrasound.

• Although ultrasonography is less

sensitive than CT in detecting a
renal mass, it is useful to
distinguish a simple benign cyst
from a more complex cyst or a
solid tumor.
• Summarized briefly, there are
three major criteria that allow a
simple cyst to be differentiated
from a tumor or abscess on
ultrasonography

• Ver diapo siguiemte

• The cyst is round and sharply demarcated with smooth walls
• There are no echoes within the cyst ("anechoic")
• There is a strong posterior wall echo, indicating good transmission through a
cyst

If all of these criteria are fulfilled, no further evaluation is necessary since the
likelihood of a malignancy is extremely small. If the criteria for a simple cyst by
ultrasonography are not satisfied, the patient should undergo CT before and
after injection of iodinated contrast. On CT, a simple cyst has a smooth
appearance without a clearly delineated wall, has no enhancement with
intravascular contrast, and is the density of water. CT urography allows imaging
of both the renal parenchyma and the collecting system.
• By comparison, thickened
irregular walls or septa (
image 2) and
enhancement after
contrast injection are
suggestive of malignancy
MRI
•  — Magnetic resonance imaging
(MRI) may be useful when
ultrasonography and/or CT are
inconclusive or if iodinated
contrast cannot be administered
because of allergy or poor renal
function
TISSUE DIAGNOSIS
• For patients with localized disease, nephrectomy or partial
nephrectomy is used in most cases to obtain tissue for
diagnosis of RCC. For patients presenting with metastatic
disease who plan to omit or defer cytoreductive
nephrectomy, establishing diagnosis via a biopsy of a
metastasis is preferred. After the presumptive diagnosis has
been made based upon imaging studies, the patient must
be evaluated for the extent of local involvement and the
presence of metastatic disease prior to surgery.
STAGING STUDIES
• Abdominal CT — The extent of local and regional involvement is
determined primarily by abdominal computed tomography (CT), which is
extremely accurate in staging RCC. In a retrospective study of 100 RCCs, for
example, preoperative CTs were compared with the findings obtained at
surgery [38]. The following results were obtained:
• ●For the detection of renal vein invasion, CT was 78 percent sensitive and
96 percent specific.
• ●For the detection of metastatic adenopathy, CT was 83 percent sensitive
and 88 percent specific.
• ●For the detection of perinephric invasion, CT was only 46 percent
sensitive but was 98 percent specific.
• ●For the detection of adjacent organ invasion, CT was 100 percent specific.
Other imaging studies 
• — Other imaging studies that may be useful for assessing for distant metastases include bone scan,
CT of the chest, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT:
• ●Bone scan – Bone scan is indicated only in patients with bone pain and/or an elevated serum
alkaline phosphatase. In one series, for example, less than 5 percent of such patients had occult
bone metastases [41]. Bone scan can be falsely negative since bone metastases are frequently
osteolytic rather than osteoblastic.
• ●Chest CT or radiograph – CT of the chest is useful to evaluate for evidence of pulmonary or
mediastinal lymph node metastases. Alternatively, patients with a small renal mass may be offered
a chest radiograph. (See 
"Diagnostic approach, differential diagnosis, and management of a small renal mass", section on 'D
efinition'
.)
• ●MRI – MRI scanning with gadolinium is superior to CT for evaluation of the inferior vena cava and
right atrium when tumor involvement is suspected [42].
• ●PET/CT – PET scanning has high sensitivity and specificity for the primary lesion. Although PET/CT
may be more sensitive than radionuclide scanning for the detection of bone metastases, it is
expensive and has limited use for routine staging [43-45].
TNM STAGING SYSTEM
• The eighth (2017) Tumor, Node, Metastasis (TNM) staging system is
used for staging all histologic variants of RCC. This system is supported
by both the American Joint Committee on Cancer (AJCC) and the
International Union for Cancer Control (UICC) [49]. These TNM criteria
use the anatomic extent of disease to define prognostic stage gro
• The TNM system is shown in the table (table 2). In this system, tumors
limited to the kidney are classified as T1 or T2 based upon size. T3
tumors extend into the renal vein or perinephric tissues but not beyond
the Gerota fascia, while T4 tumors extend beyond the Gerota fascia,
including direct extension into the ipsilateral adrenal gland. Nodal and
distant metastases are simply classified as absent or present.ups. 
Isolated renal mass 
• — For patients with
isolated solid renal
masses, resection with
either a partial or
complete nephrectomy
is preferred over
biopsy because it
provides the diagnosis,
pathologic tumor (T)
and nodal (N) staging
• definitive treatment. Preoperative needle biopsies
are usually not used for resectable renal lesions
because of their low specificity [46] and concerns
about tumor seeding of the peritoneum.
• Although solid renal masses less than 3 cm were
once thought to represent benign adenomas,
distinctions based upon size are no longer used,
since even small tumors frequently represent
carcinomas that will grow over time [47]. Most solid
renal masses require a histologic diagnosis; in
patients with significant comorbidities, "watchful
waiting" might be appropriate. 
Metastatic disease 
• — When metastatic disease is suspected at initial
presentation, pathologic confirmation is required prior to
starting therapy. Biopsy of a metastatic site is often easier
and more informative than biopsy of the primary tumor.
• In patients with a previously diagnosed nonrenal
malignancy, metastatic disease is more likely than a new
primary RCC. If the renal mass is nonenhancing and there is
clinical evidence of progression of the nonrenal malignancy,
biopsy confirmation may be unnecessary
Overview of the treatment of renal
cell carcinoma
• GENERAL APPROACHThe initial approach to a patient with
presumed RCC needs to consider the extent of disease, as
well as the patient's age and comorbidity
RCC can be classified as:

• ●Localized disease – This includes stage I, II, and III

• ●Advanced disease – This includes tumor invading beyond

Gerota's fascia or extending into the ipsilateral adrenal
gland (T4) and metastatic disease (M1). Either of these
findings constitutes stage IV RCC.
LOCALIZED RENAL CELL CARCINOMA
• When patients with RCC present with localized disease,
definitive therapy can often be curative.

• Definitive treatment — Surgery is curative in the majority

of patients with RCC who do not have metastases. Surgery is
therefore the preferred treatment for patients with stages I,
II, and III disease.
• Multiple primary renal cell carcinomas — Bilateral RCCs
are more common among patients with inherited conditions
(eg, von Hippel-Lindau disease, tuberous sclerosis, papillary
RCC) and occasionally are seen in those with sporadic
tumors. In these situations, surgery is recomended.