This document summarizes renal cell carcinoma (RCC), the most common type of kidney cancer. Key points include: - RCC originates in the renal cortex and arises mostly from the upper pole of the kidney. - Common subtypes include clear cell, papillary, and chromophobe carcinomas. - Risk factors include male sex, older age, smoking, obesity, and genetic conditions like von Hippel-Lindau syndrome. - Symptoms may include hematuria, flank pain, and palpable flank mass. Imaging like CT and MRI are used to diagnose and stage disease. - Treatment depends on stage but typically involves surgical removal (radical or partial nephrectomy

1. RENAL CELL CARCINOMA
Dr. Arkaprovo Roy (MS)
ASSISTANT PROFESSOR, SURGERY
MALDA MEDICAL COLLEGE
WEST BENGAL
INDIA

2. • Originates within the renal cortex.
• Arises mostly from the upper pole.
• Responsible for 80% to 85% of all primary renal
tumours.
• Transitional cell carcinomas of the renal pelvis
are the next most common (∼8%) renal
neoplasms.
• Nephroblastoma or Wilms' tumor is common in
children (5%-6% of all primary renal tumors).

3. Classification of renal tumour
Benign
Cyst
Leiomyoma
Lipoma
Hemangioma
Angiomyolipoma
Adenoma
Juxtraglomerular cell tumour
Malignant
• RCC
• Transitional Cell Ca
• Oncocytoma
• Sarcoma
• Lymphoma
• Metastasis(Lung, Breast,
GIT,Prostate, Pancreas,
Melanoma)

4. Aetiology
• Males are affected twice as commonly as
females
• Peak incidence of sporadic RCC is 6th to 8th
decade.

5. Studies have shown associations with
Environmental
• urban dwelling
• low socio-economic status
• tobacco chewing
• smoking cigarettes, pipe, or cigars
• renal failure and dialysis (30-fold risk)
• obesity
• hypertension
• asbestos exposure
• the analgesic phenacitin
• thorium dioxide

6. Nutrition
• Asian migrants to Western countries are at
increased risk of RCC;
• Vitamins A, C, E, and fruit/vegetable
consumption are protective.

7. Anatomical risk factors include
Polycystic kidneys Horseshoe kidneys

8. Numerous conditions predispose to renal cell
cancer, including
• von Hippel-Lindau syndrome (cerebellar
hemangioblastomas, retinal angiomatosis, and
bilateral renal cell carcinoma),
• tuberous sclerosis, and
• acquired renal cystic disease developing in
patients with end-stage renal disease

9. Genetic
von Hippel Lindau (VHL) syndrome
• 50% of individuals with this autosomal dominant
syndrome,
• characterized by phaeochromocytoma, renal and
pancreatic cysts, and cerebellar haemangioblastoma,
• develop RCC, often bilateral and multifocal.
• Patients typically present in 3rd, 4th, or 5th decades.
• VHL syndrome occurs due to loss of both copies of a
tumour suppressor gene at chromosome 3p.

10. • Inactivation of the VHL gene leads to effects on
gene transcription, including dysregulation of
hypoxia inducible factor 1 (HIF-1), an intracellular
protein that plays an important role in the cellular
response to hypoxia and starvation.
• This results in upregulation of vascular
endothelial growth factor (VEGF), the most
prominent angiogenic factor in RCC, explaining
why some RCCs are highly vascular.

11. • A papillary variant of RCC also has an
autosomal dominant familial component,
• characterized by trisomy 7 and 17,
• with activation of the c-MET proto-oncogene.
• c-MET encodes the receptor tyrosone kinase
for hepatocyte growth factor, which regulates
epithelial proliferation and differentiation in a
wide variety of organs, including the normal
kidney.

12. Histologically, RCC is most often
• A Mixed Adenocarcinoma Containing Clear
Cells,
• Granular Cells, And,
• Occasionally, Sarcomatoid-appearing Cells.
The classifications of the subtypes of RCC are
based on morphology and cytogenetic
characteristics.

13. • Most RCCs are classified into 1 of the following
Histologic Subtypes:
• Conventional Clear Cell,
• Papillary (Chromophilic),
• Chromophobe,
• Collecting Duct,
• Neuroendocrine, And
• Unclassified.

14. Benign renal tumors are
• Papillary Adenoma,
• Renal Oncocytoma, And
• Metanephric Adenoma.

15.  Clear cells are rounded or
polygonal with abundant
cytoplasm, which contains
cholesterol, triglycerides,
glycogen, and lipids.
 The cells present in the
papillary (chromophilic)
typecontain less glycogen
and lipids, and electron
microscopy reveals that the
granular cytoplasm contains
many mitochondria and
cytosomes.
• Chromophobe-type
carcinomas contain large
polygonal cells with distinct
cell borders and reticulated
cytoplasm, which can stain
diffusely withHale’s colloidal
iron .

16.  Oncocytic RCC or
oncocytomas tend to
have cytoplasm packed
with mitochondria, giving
it a granular appearance.
o Collecting duct tumors
tend to have irregular
borders and a basophilic
cytoplasm with extensive
anaplasia
o likely to invade blood
vessels and cause
infarction of tissue.
 Sarcomatoid cells are
spindle-shaped and form
sheets or bundles.
 This later cell type rarely
occurs as a pure form and
is most commonly a small
component of either the
clear cellor papillary cell
type (or both).

17. Clinical Findings
Symptoms and Signs
• Painless gross or microscopic hematuria throughout the urinary
stream ("total hematuria") occurs in 60% of patients.
• The degree of hematuria is not necessarily related to the size or
stage of the tumor.
• A triad of hematuria, flank pain, and a palpable flank mass
suggests renal cell carcinoma, fewer than 10% of patients will be
present.
• Both pain and a palpable mass are late events occurring only with
tumors that are very large or invade surrounding structures or
when hemorrhage into the tumor has occurred.
• Symptoms due to metastases may be the initial complaint (eg, bone
pain, respiratory distress).

18.  Paraneoplastic syndromes are
common in renal cell carcinoma
and are often what suggests the
diagnosis.
These syndromes include
• hypercalcemia,
• erythrocytosis,
• hypertension, fever of unknown
origin,
• anemia, and
• hepatopathy (Stauffer's
syndrome).
 Renal cell carcinoma has a
predilection for producing
occlusive tumor thrombi in the
renal vein and the inferior vena
cava (particularly from the right),
manifested by signs of lower
extremity edema and acute
scrotal varicocele when occluding
the left renal vein.
 This phenomenon of inferior vena
cava thrombus occurs in
approximately 5% to 10% of
patients.
 Occasionally, the tumor
thrombus reaches up through the
inferior vena cava to the right
atrium.

19. RCC is known to produce a multitude of other
biologically active products that result in clinically
significant syndromes, including
• adrenocorticotropic hormone (Cushing’s syndrome),
• enteroglucagon (protein enteropathy),
• prolactin (galactorrhea),
• insulin (hypoglycemia), and
• gonadotropins (gynecomastia and decreased libido; or
hirsutism, amenorrhea, and male pattern balding).

20. Laboratory Findings
• Microscopic urinalysis reveals hematuria in most
patients.
• The erythrocyte sedimentation rate may be elevated
but is nonspecific.
• Elevation of the hematocrit and levels of serum
calcium, alkaline phosphatase, and aminotransferases
occur in less than 10% of patients. These findings
nearly always resolve with curative nephrectomy and
thus are not usually signs of metastases.
• Anemia unrelated to blood loss occurs in 20% to 40%
of patients, particularly those with advanced disease.

21. Imaging Studies
• The diagnosis of renal cell carcinoma is often
made by CT (and, less frequently, by
intravenous urography) performed as an initial
step in the workup of hematuria, an enigmatic
metastatic lesion, or suspicious laboratory
findings.
• Ultrasonography and CT scan often reveal
incidental renal masses, which now account
for 50% of the initial diagnoses of renal cancer
in patients without manifestations of renal
disease.

22. • Plain abdominal x-rays may reveal a calcified renal mass,
but only 20% of renal masses contain demonstrable
calcification. (Twenty percent of masses with peripheral
calcification are malignant; over 80% with central
calcification are malignant.)
• The initial technique for workup of hematuria is currently
CT urography; intravenous urography alone defines only
75% of renal mass lesions.
• Differentiation of the most common renal mass (ie, a
simple benign cyst) can be made by the finding of a
radiolucent center with a thin wall and a sharp interface
between the mass and the renal cortex (the typical "beak
sign" of a cortical cyst).

23. • Ultrasonography: Further definition of all
renal masses seen on intravenous urography is
required. Occasionally, some masses detected
on CT require further characterization by
ultrasound. Abdominal ultrasonography can
define the mass as a benign simple cyst or a
solid mass in 90% to 95% of cases. Abdominal
ultrasound can also identify a vena caval
tumor thrombus and its cephalad extent in
the cava.

24. • Isotope Scanning: Occasionally, a renal mass is
suspected on intravenous urography but is
equivocal or not seen on ultrasound. In these
cases, a renal cortical isotope scanning agent
such as technetium-99m DMSA is helpful.
Isotope scans of a renal tumor or cyst show an
area of decreased uptake, whereas an area of
increased uptake indicates a renal
"pseudotumor" or a hypertrophied column of
Bertin.

25. • CT Scan: CT scan is the diagnostic procedure of choice
when a solid renal mass is noted on ultrasound. CT
scan accurately delineates renal cell carcinoma in over
95% of cases. Over 80% of tumors are enhanced by
iodinated contrast medium, reflecting their high
vascularity.
CT scan is also helpful in local staging and can reveal
tumor penetration of perinephric fat; enlargement of
local hilar lymph nodes, indicating metastases; or
tumor thrombi in the renal vein or inferior vena cava.
CT angiography can delineate the renal vasculature,
which is helpful in surgical planning for partial
nephrectomies.
• .

26. • MRI: MRI is not more accurate than CT and is
much more expensive.
• It is, however, the most accurate noninvasive
means of detecting renal vein or vena caval
thrombi.
• MRI has become one of the primary techniques
for staging solid renal masses.
• Magnetic resonance angiography (MRA) has
become particularly useful for mapping the blood
supply and the relationship to adjacent structures
in candidates for partial nephrectomy

27. Other Diagnostic or Staging Techniques:
• Isotopic bone scanning is useful in patients with bone pain,
elevated alkaline phosphatase, or known metastases.
• Chest x-ray is sufficient if negative, but if equivocal, then CT
scan of the chest can be used to detect metastases.
• There are currently no tumor markers specific for renal cell
carcinoma.
• Occasionally, aspiration cytology of the mass can be useful
in an enigmatic case.
• The diagnosis is most often made by noninvasive means,
and needle aspiration is required only in indeterminate
cases (< 10%).

28. • Differential Diagnosis: A variety of lesions in the
retroperitoneum and kidney other than renal cysts may
simulate renal cancer.
• These include lesions due to
• hydronephrosis,
• adult polycystic kidney disease,
• tuberculosis,
• xanthogranulomatous pyelonephritis,
• metastatic cancer from another primary cancer,
• angiomyolipoma or other benign renal tumors, or adrenal
cancer and
• retroperitoneal lipomas, sarcomas, or abscesses.

29. • In general, the radiographic, MRI, or
ultrasonographic techniques described previously
should make the differentiation.
• Hematuria may be caused by renal, ureteral, or
bladder calculi; renal pelvis, ureteral, or bladder
tumors; or many other benign conditions usually
delineated by the studies described.
• Cystoscopy is obligatory in hematuric patients
with a normal CT scan or intravenous urogram to
rule out disease of the bladder and to determine
the source of the hematuria.

31. TREATMENT
Localized disease—
• Surgical removal of the early-stage lesion
remains the only potentially curative therapy
available for RCC patients.
• Appropriate therapy depends almost entirely on
the stage of tumor at presentation and therefore
requires a thorough staging evaluation.
• The prognoses of patients with stages T1-T3a
disease are similar following radical nephrectomy.

32. • Radical nephrectomy is the
primary treatment for
localized RCC. Its goal is to
achieve the removal of tumor
and to take a wide margin of
normal tissue.
• Radical nephrectomy entails
en bloc removal of the kidney
and its enveloping fascia
(Gerota’s) including the
ipsilateral adrenal, proximal
one-half of the ureter, and
lymph nodes up to the area of
transection of the renal
vessels.

33. • Preoperative renal artery embolization (angioinfarction)
has been used in the past as a surgical adjunct to facilitate
radical nephrectomy,
• There is no conclusive evidence that preoperative
embolization actually decreases blood loss or facilitates
surgery,
• Its use should be limited to patients with very large tumors
in which the renal artery may be difficult to reach early in
the procedure.
• Additionally, this technique may be useful to palliate
patients with nonresectable tumors and significant
symptoms such as hemorrhage, flank pain, or
paraneoplastic syndromes.

34. • RCC may invade renal vascular spaces and produce tumor thrombi
extending into renal veins, inferior vena cava, hepatic veins, and,
occasionally, the right atrium.
• Between 5% and 10% of patients presenting with RCC have some
degree of vena caval involvement
• Patients presenting with involvement of the renal vein and vena
cava below the hepatic veins (T3bN0M0) but without evidence of
regional or distant metastases have a prognosis similar to patients
with stage T2 disease when treated by radical excision.
• The surgical approach to the removal of caval thrombi depends
entirely on the level of cephalad extension.
• In general, these thrombi do not invade the wall of the cava and
therefore can be removed without resection of the caval wall.
• For tumor thrombi that have reached the level of the right atrium,
the use of cardiopulmonary bypass is typically required.

35. • Laparoscopic radical nephrectomy and partial
nephrectomy can also be accomplished successfully
and safely.
• Laparoscopic radical nephrectomy is being used
increasingly for patients with localized renal tumors.
• This approach results in quicker recovery with efficacy
comparable to that of open radical nephrectomy and is
now the approach of choice in appropriate patients
with <10 cm tumors and without local extension or a
renal vein or caval thrombus.

36. • For small exophytic lesions that do not
extensively involve the major vessels or
urinary collecting system, a partial
nephrectomy (also referred to as "nephron
sparing surgery") can be performed.
• Radiation therapy is an important method in
the palliation of patients with metastatic RCC.

37. Biologic response modifiers
• RCC "elicits an immune response, which
occasionally results in dramatic spontaneous
remissions.
• " This has encouraged a strategy of using
immunomodulating therapies, such as cancer
vaccines and interleukin-2 (IL-2), to reproduce
this response.

38. • Studies using partially purified human
leukocyte interferon in renal cancer were first
reported in 1983, with subsequent studies
using human lymphoblastoid interferon.
• More recently, recombinant interferon-alpha
(r-IFN-α) is used. Various doses and schedules
of r-IFN-α have demonstrated reproducible
overall response rates of 10–15% in advanced
renal cancer.

39. • Interleukin-2 (IL-2), a T-cell growth factor, was
first identified in 1976.
• Recombinant IL-2 is the only agent approved
by the US Food and Drug Administration for
patients with advanced renal carcinoma.
• Controversy persists regarding the optimal
dose and schedule for IL-2 administration,

40. • Randomized trials comparing IFN-α, IL-2, and
IL-2 plus INF-α have demonstrated higher
objective response rates to the combination
therapy, with no difference in survival and
significantly higher toxicity associated with the
combination.

41. Newer biologic agents
• Another strategy is to restore the function of the VHL gene, which is to
destroy proteins that promote inappropriate vascularization.
• Oral agents such as Bevacizumab and Sunitinib can specifically inhibit
receptors for VEGF and PDGF thereby halting tumor angiogenesis and
tumor progression.
• Bevacizumab, an antibody to VEGF, has significantly prolonged time to
progression.
• Bevacizumab is a monoclonal antibody that binds and inactivates VEGF A.
It has shown the ability to yield partial responses, delay disease
progression, and improve survival in patients with advanced renal cancer.
• Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitorand
sorafenib — a protein kinase inhibitor both interfere with tumor growth
by inhibiting angiogenesis as well as tumor cell proliferation.

42. • Temsirolimus (CCI-779) is an inhibitor of mTOR kinase
(mammalian target of rapamycin) that was shown to
prolong overall survival vs. interferon-α in patients with
previously untreated metastatic renal cell carcinoma with
three or more poor prognostic features.
• Renal Cell Carcinoma Afinitor (everolimus) is an oral once-
daily inhibitor of mTOR indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) after
failure of treatment with sunitinib or sorafenib.
• Treatment with tyrosine kinase inhibitors
including nexavar, pazopanib, and rapamycin have shown
promise in improving the prognosis for advanced RCC.

43. • Chemotherapy:Most of
the currently available
cytostatics are ineffective
for the treatment of RCC.
• Vaccine: Cancer
vaccines, such
as TroVax, have shown
promising results.

44. Follow up
• There is no universal agreement on the
frequency or studies required in the follow-up
care of patients with RCC.
• A stage-specific follow-up schedule is
recommended for patients who have
undergone radical or partial nephrectomy.
• Patients with stage T1 disease need less
stringent follow-up, with yearly chest x-rays
and liver and renal function tests.

45. • Those with stage T2 or T3 disease require more
frequent follow-up of at least 3-month or 6-
month intervals in the early postoperative period.
• Repeat CT scans of the abdomen should also be
obtained, especially in those who have
undergone partial nephrectomy, to rule out local
recurrence.
• Patients with metastatic disease who are not
undergoing therapy need continued follow-up to
provide appropriate supportive care.