2014 -2015

Nephrology
Dr. Lu
Renal Cell Carcinoma
Clinical Presentation
 Renal cell carcinomas account for 90–95% of malignant  The presenting signs and symptoms include:
neoplasms arising from the kidney. o Hematuria - very common
 Notable features include: o Abdominal pain
o Resistance to cytotoxic agents o Flank or abdominal mass.
o Infrequent responses to biologic response o This classic triad occurs in 10–20% of patients.
modifiers such as interleukin (IL) 2 o In the triad, flank pain and hematuria are
o Robust activity to anti-angiogenesis targeted common so sometimes, a differential diagnosis
agents would be renal stones. Then later, meron ka ng
o A variable clinical course for patients with palpable mass
metastatic disease, including anecdotal reports of  Other symptoms are:
spontaneous regression. o Fever
 In patients with RCC, the RBC is normal in size and shape o Weight loss
because the glomeruli is complete laging tandaan bc this o Anemia
is a revalida question   non glomerular bleeding o and a varicocele sa left side
Epidemiology
Classic Triad Frequency
 90-95% of malignancy arising from the kidney 1. Hematuria 40%
 The male to female ratio is 2:1. 2. Flank Pain 40%
 Incidence peaks between the ages of 50 and 70 years, 3. A palpable mass in the 25%
although this malignancy may be diagnosed at any age. flank or abdomen
 Risk Factors: Other signs/symptoms
o the strongest association is with cigarette 1. Weight loss 33%
smoking. 2. Fever 20%
o Acquired cystic disease of the kidney associated 3. Hypertension 20%
with end-stage renal disease 4. Hypercalcemia 5%
o Tuberous sclerosis
5. Night sweats
o Approximately 35% of individuals with Von Hippel
6. Malaise
-Lindau (autosomal dominant) disease develop
clear cell renal cell carcinoma. 7. Varicocele 2% of males
 Most cases are sporadic, although familial forms have been
reported.  Most often, these are detected incidentally when you do
ultrasound. Sometimes the patient goes to the hospital with
Pathology and Genetics a complaint of diarrhea but when ultrasound is done, a solid
mass in the kidney is found. So RCC could be one of the
differentials.
 Renal cell neoplasia represents a heterogeneous group of
tumors with distinct histopathologic, genetic, and clinical  The tumor is most commonly detected as an incidental
features ranging from benign to high-grade malignant finding on a radiograph.
 They are classified on the basis of morphology and histology.  Widespread use of radiologic cross-sectional imaging
procedures (CT, ultrasound, MRI) contributes to earlier
 Categories include:
o Clear cell carcinoma (60% of cases) ito lumabas sa detection, including incidental renal masses detected during
evaluation for other medical conditions.
exam 
 The predominant histology, are found in  The increasing number of incidentally discovered low-stage
>80% of patients who develop tumors has contributed to an improved 5-year survival for
metastases. patients with renal cell carcinoma and increased use of
 Arise from the epithelial cells of the nephron-sparing surgery (partial nephrectomy).
proximal tubules and usually show  A spectrum of paraneoplastic syndromes has been
chromosome 3p deletions. associated with these malignancies, including:
 Usually, it’s a single kidney with a single o Erythrocytosis
mass o Hypercalcemia
o Papillary tumors (5–15%) o Non-metastatic hepatic dysfunction (Stauffer
 tend to be bilateral and multifocal. syndrome)  the cancer in the kidney will try to
o Chromophobic tumors (5–10%) induce the liver to become dysfunctional; if you try
 have a more indolent clinical course to control the problem, the liver dysfunction
o Oncocytomas (benign) (5–10%) disappears.
o Collecting or Bellini duct tumors (<1%) o Acquired dysfibrinogenemia
 Are thought to arise from the collecting  RCC is an internist tumor
ducts within the renal medulla  Erythrocytosis is noted at presentation in only about 3% of
 Are very rare but very aggressive. patients.
 Agents that inhibit proangiogenic growth factor activity  Anemia, a sign of advanced disease, is more common.
show antitumor effects.

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 2014 -2015
Nephrology
Dr. Lu
 The standard evaluation of patients with suspected renal
cell tumors includes:
o a CT scan of the abdomen and pelvis
o chest radiograph  bc of the metastasis
o urine analysis
o urine cytology  you can see malignant cells
 If metastatic disease is suspected from the chest radiograph,
a CT of the chest is warranted.
 MRI is useful in evaluating the inferior vena cava in cases of
suspected tumor involvement or invasion by thrombus.
 Contrast enhanced MRI  greyscale ultrasound image  a
rounder mass extending off from the posterior kidney
 In clinical practice, any solid renal masses should be
considered malignant until proven otherwise; a definitive
diagnosis is required.
 If no metastases are demonstrated, surgery is indicated,
even if the renal vein is invaded.
 The differential diagnosis of a renal mass includes:
o Cysts
o benign neoplasms (adenoma, angiomyolipoma,
oncocytoma)
o inflammatory lesions (pyelonephritis or
abscesses)
o other primary or metastatic cancers.
 Other malignancies that may involve the kidney include:
o transitional cell carcinoma of the renal pelvis
o sarcoma
o lymphoma
o Wilms' tumor
o All of these are less common causes of renal
masses than is renal cell cancer.

Staging and Prognosis

 Staging is based on the American Joint Committee on

Cancer (AJCC) staging system
 Stage I tumors
o are <7 cm in greatest diameter
o confined to the kidney
 Stage II tumors
o are 7 cm
o confined to the kidney
 Stage III tumors
o extend through the renal capsule but are confined
to Gerota's fascia (IIIa)
o or involve a single hilar lymph node (N1)
o Pag may vessel involvement na daw, stage 3 na
 Stage IV disease
o Includes tumors that have invaded adjacent
organs (excluding the adrenal gland)
o or involve multiple lymph nodes or distant
metastases.

 The rate of 5-year survival varies by stage:

o >90% for stage I
o 85% for stage II **when you do renal histopath, they remove the kidney/nephrectomy
o 60% for stage III and you see the clear cell type(most common), yellowish in color.
o 10% for stage IV ** some of the RCC, goes to the atrium, akala mo thrombus un pala
RCC O_O

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Dr. Lu
Treatment: Renal Cell Carcinoma
Localized Tumors
 The standard management for stage I or II tumors and
selected cases of stage III disease is radical nephrectomy.
 Radical Nephrectomy
o involves en bloc removal of Gerota's fascia and its
contents, including the kidney, the ipsilateral
adrenal gland, and adjacent hilar lymph nodes.
 The role of a regional lymphadenectomy is controversial.
 Extension into the renal vein or inferior vena cava (stage III
disease) does not preclude resection even if
cardiopulmonary bypass is required.
 If the tumor is resected, half of these patients have
prolonged survival.
 Nephron-sparing approaches via open or laparoscopic
surgery
o may be appropriate for patients who have only
one kidney, depending on the size and location of
the lesion.
o A nephron-sparing approach can also be used for
patients with bilateral tumors, accompanied by a
radical nephrectomy on the opposite side.
 Partial nephrectomy techniques
o are applied electively to resect small masses for
patients with a normal contralateral kidney.
o Adjuvant therapy following this surgery does not
improve outcome, even in cases with a poor
prognosis.
Advanced Disease
 Surgery has a limited role for patients with metastatic
disease.
 Long-term survival may occur in patients who relapse after
nephrectomy in a solitary site that can be removed.
 One indication for nephrectomy with metastases at initial
presentation is:
o to alleviate pain or hemorrhage of a primary
tumor.
 Cytoreductive nephrectomy before systemic treatment
o improves survival for carefully selected patients
with stage IV tumors.
 Metastatic renal cell carcinoma is highly refractory to
chemotherapy.
 Cytokine therapy with IL-2 or IFN- produces regressions in
10–20% of patients.
 IL-2 produces durable complete remission in a small
proportion of cases.
 In general, cytokine therapy is considered unsatisfactory for
most patients.
 Sorafenib and sunitinib
o inhibits receptor tyrosine kinase signaling through
the VEGF and PDGF receptors.
o Both showed efficacy as second-line treatment
following progression during cytokine treatment,
resulting in approval by regulatory authorities for
the treatment of advanced renal cell carcinoma.
 A randomized phase 3 trial comparing sunitinib to IFN-
showed superior efficacy for sunitinib with an acceptable
safety profile.
o The trial resulted in a change in the standard first-
line treatment from IFN to sunitinib.
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2014 -2015
Nephrology
o Sunitinib is usually given orally at a dose of 50
mg/d for 4 weeks out of 6.
o Diarrhea is the main toxicity.
 Sorafenib is usually given orally at a dose of 400 mg bid.
o In addition to diarrhea, toxicities include rash,
fatigue, and hand-foot syndrome.
 Temsirolimus and everolimus
o inhibitors of the mammalian target of rapamycin
(mTOR)
o show activity in patients with untreated poor-
prognosis tumors and in sunitinib/sorafenib
refractory tumors.
 The prognosis of metastatic renal cell carcinoma is variable.
 Poor prognostic factors short life expectancy 
o No prior nephrectomy
o a KPS (karnofsky performance status) <80; low
performance status/depressed individual
o low hemoglobin
o high corrected calcium
o abnormal lactate dehydrogenase
 Patients with zero risk factor – mean survival of 24 months
 Patients with one or two risk factors – mean survival of 12
months
 Patients with three or more risk factors have a median
survival of 5 months
 These tumors may follow an unpredictable and protracted
clinical course.
 It may be best to document progression before considering
systemic treatment.
Management (Powerpoint)
 Survival rates: 60 – 100% for resected non metastatic
cortical tumors, depends also on the mode of presentation,
tumor histology and size, and pathologic state
 The reason why you do CT scan is to look for metastasis
 20% for stage II, <5% for stage IV
 Prognosis declines for most advance disease
Histologic types (Powerpoint)
 Prognosis of clear cell is less favorable than papillary RCC
 Chromophobic RCC is the most favorable
Varicocele
 Happens only in male (malamang)
 The right kidney is lower than the left
 The extension of this varecocele plexus going back to the
renal vein; ang left side is direct to the renal vein while the
right side is direct to the IVC.
 So when you have a tumor on the left side, this will block the
return of the blood so it goes back to the vessels of the
spermatic cord
 Left varicocele is one of the presentations in RCC because of
the draining
 Varicocele
o +dilated veins of the spermatic cord
o Can be felt and sometimes be seen as a tortuous
mass at the surface of the scrotum
o A varicocele is made up of veins that contain
inadequate valves.