RENAL PARENCHYMAL TUMORS

Histological Classification

A. Primitive epithelial renal tumors:

1. benign:
– Adenoma
– Oncocytoma
2. malignant:
-Conventional renal carcinoma (clear cell)
-Papillary renal carcinoma (chromophilic cell)
-Chromophobe renal cell carcinoma
-Bellini duct carcinoma
-Medullary carcinoma
B. Mesenchymal tumors:
1. benign:
-Juxtaglomerular cell tumor
-Medullary fibroma
-Leiomyoma
-Lipoma
-Hemangioma
-Lymphangioma
-Angiomyolipoma
2. malignant (sarcomas)
-Leiomyosarcoma
-Fibrosarcoma
-Liposarcoma
-Osteosarcoma, chondrosarcoma
-Rhabdomyosarcoma
-Angiosarcoma
-Hemangiopericytoma
-Malignant mesenchymoma
C. Renal tumors in hematologic and lymphoid disorders
D. Metastatic tumors.
Benign Renal Parenchymal Tumors
• Because of the impossibility to differentiate
the benign parenchymal tumors using imaging
criteria (ultrasound, computed tomography,
arteriography), all diagnosed parenchymal
tumor masses are treated according to the
principles of the oncologic surgery for renal
carcinomas.
• The most frequent are the renal adenoma and
the renal oncocytoma.
 Renal Adenoma

-the most common benign renal tumor

-well-differentiated, usually asymptomatic
-incidentally found on ultrasound scans,
computed tomography or the
anatomopathological examination of a piece
of nephrectomy performed for another lesion
or pathology.
 Renal Oncocytoma
- unilateral and unifocal,
-The diagnosis of this tumor variety can be
imagistically suggested by renal arteriography:
by a “spoke-wheel” arterial pattern, the absence
of vessels in the capsule of the tumor associated
with a homogenous nephrogram.
-The presence of a star-shaped scar in the
macroscopic examination of the operative
specimen is characteristic for this type of tumor
Malignant Renal Parenchymal Tumors
Epidemiology and Etiology
• renal cancer representing 2-3% of the neoplasiae in adults.
Renal carcinoma constitutes 90% of the renal malignant
tumors.
• Over the past few years, due to the medical imaging
development, there has been an increase in renal tumors
diagnosed in incipient phases, which is correlated to a
decrease in mortality.
• Renal carcinoma is more frequent in men with a 2:1
male/female ratio, with a maximum incidence in the sixth
and seventh decades of life, but with increasing incidence
in young ages.
• The identified risk factors of the development of this
pathology are: smoking, obesity, and arterial hypertension.
 Conventional Renal Carcinoma
(clear cell)
• It represents around 80-90% of the renal tumors.
• Macroscopic aspects. They are circumscribed tumors,
with a pseudocapsule resulted from compressed
parenchyma and fibrous tissue, and with golden yellow
cut surface (in the classical cases) because of the high
lipid content in the cytoplasm of the tumor cells;
• Evolution. Conventional carcinoma is the most virulent
renal cortical carcinoma. Survival is roughly correlated
with the nuclear degree and the tumor status. The
election treatment is the surgical excision.
 Papillary Renal Carcinoma
(chromophilic cell)
• It represents 10-15% of the primitive epithelial renal
tumors.
• Rates by sex M:F = 2-3,9:1
• Macroscopic aspects. In approximately 1/3 of the cases,
they are delimited by a fibrous pseudocapsule (of all the
epithelial renal tumors, papillary carcinoma most often has
a peripheral pseudocapsule) The macro- or microscopic
multifocality is present in more than 45% of the cases.
• Evolution. The prognosis of papillary carcinoma is better
than that of the conventional carcinoma, and less favorable
than that of the chromophobe cell carcinoma.
 Chromophobe Renal Cell Carcinoma
• It represents 4-5% of the epithelial tumors. It is
important to recognize this type of renal carcinoma for
two reasons: a) the chromophobe renal cell carcinoma
has a better prognosis than the conventional
carcinoma; and b) from a morphological point of view,
it is very similar to the oncocytoma, a benign tumor it
can be often mistaken for.
• Macroscopic aspects. The tumor masses are mainly
solid, circumscribed, with sizes of 2 to 23 cm (9 cm on
average), this tumor being the largest epithelial renal
tumor. The tumor tissue is beige or pale – with brown
surface, and it has a vaguely lobular aspect. The radial
central scar is described in almost 15% of the cases
 Bellini Collecting Duct Carcinoma

• less than 1% of the epithelial renal tumors,

• Clinical aspects. Initial symptoms are: hematuria, pain, weight loss, and
palpable mass. More than 40% of these patients show distant metastasis
at the time of diagnosis.
• Macroscopic aspects. This tumor mass is a solitary, solid, weakly
circumscribed mass, usually localized in the renal medulla or in the central
region.
• The tumor tissue is firm, brown and white, with areas of necrosis and
hemorrhage. Most of the lesions extend to the adipose tissue of the renal
sinus and hilum, renal pelvis and suprarenal gland.
• Evolution. Classical cases are characterized by an aggressive evolution,
most of them with exitus in 12-36 months from the diagnosis. Metastases
are frequently developed in: the lymph node system, bones, lung and liver.
 Natural Evolution in Renal Carcinoma

• The local extension of the tumor is relatively slow, with a doubling period
of the tumor mass of 500 days, gradually dislocating and disorganizing the
pyelocalyceal cavities, the renal capsule it gets by, involving the perirenal
adipose tissue and developing a neoplastic mass that attaches the kidney
to the adjacent structures (suprarenal gland, liver, duodenum, pancreas,
colon, diaphragm, psoas muscle, lumbar square, etc).
• The venous extension is the evolutional characteristic specific to renal
carcinoma, with the development of tumor thrombus at the level of the
renal vein and inferior vena cava, which may be extended to the level of
the right atrium.
• Secondary determinations. Approximately 33-35% of the patients with
renal carcinoma present with metastases. They develop in veins, lymph or
both, and they appear irrespective of the size of the tumor and its
evolution stage. The most common metastatic sites are: lungs, bone
system, liver, and extra-regional lymph node system.
 Diagnosis
Signs and Symptoms Determined
by the Tumor
• Hematuria may be microscopic or macroscopic, total, spontaneous, unique or
repeated, associated with renal colic (the consequence of clot eliminations, with
consecutive ureteral obstructions), isolated or related to other signs. This is the
only symptom in approximately half of the patients, and it represents an essential
sign, which requires further diagnosis investigations. Macroscopic hematuria
appears after the penetration of the tumors in the urinary tracts.
• Pain, seen in approximately 40% of the patients, has different characteristics, but
dull and permanent nephralgia triggered by capsule distension and traction of the
renal pedicle is predominant. In case of abundant hematuria with clots, pain is
manifested by renal colic. It is rarely initial and isolated, being usually
accompanied by hematuria and nephromegaly.
• The tumor mass, which has almost the same percentage as pain, according to its
size and location inside the kidney, is precociously palpated when situated in the
lower polar area, and too late when it is hidden by the diaphragmatic volt and the
costal margins. The tumor has clinical signs of hard, irregular retroperitoneal mass,
with lumbar contact and abdominal bloating, presenting anterior loudness when
small and hidden by the intestinal ansae, opacity when abdominalized by volume,
dislocating the intestine, mobile or not with breathing, other times fixed,
according to extension and neoplastic perinephritis.
 Paraneoplastic Syndromes
• Fever is prolonged, permanent, resistant to antibiotics, and without urinary infection or other signs
of infection it is not higher than 38.5 - 390C in plateau.
• Alteration of the general condition with severe weight loss, asthenia, pallor, anemia, anorexia,
signs of deep intoxication etc.
• The hematologic syndrome includes cases with hyperglobulinemia, anemia, and leukemoid
reactions.
• Hepatic affectation. In 1961, Stauffer described a reversible hepatic reaction syndrome associated
with renal parenchymatous carcinoma. The Stauffer syndrome is manifested by non-metastatic
diffuse hepatomegalia, which disappears after the nephrectomy of the kidney with tumor.
• Endocrine forms. Hypercalcemia. The cause of hypercalcemia is the secretion of a parathormon-like
substance in the kidney with tumor. Hypercalcemia leads to intratumoral calcifications and calcium
deposits in the myocardium, brain or periarticular (Sanarelli syndrome). Other endocrine
syndromes that appear along the evolution of renal cancer are: Cushing syndrome, Schwartz-Barter
syndrome, myopathies, IgM paraproteins, protein enteropathy (enteroglucagon), galactorrhea
(prolactin), gynecomastia and decreased libido (gonadotropins), hirsutism, amenorrhea, male
alopecia, etc.
• Cardio-vascular forms are manifested by HTN and heart failure. Systolic high blood pressure (with
normal diastolic pressure), is triggered by the excessive renin secretion by the tumor tissue or by
the normal renal parenchyma ischemiated by tumor compression. In some cases, the tumor
compresses even the trunk of the main renal artery, thus diminishing the renal sanguine flux, as it
also happens in Goldblatt syndrome.
 Physical Examination
• In the initial stages, the physical examination
of the patient brings nothing evocative.
• Palpation of the abdominal tumor and cervical
adenopathies are signs of late diagnosis.
• The detection of irreducible varicocel and
edema of the lower members are signs of
venous extension.
 Laboratory Exams

• Anemia is found in approximately 80% of the

patients suffering from renal carcinoma. Increase
of calcemia or alkaline phosphatase is correlated
to the presence of bone metastases, and it is a
factor of unfavorable prognosis.
• Increase of serum creatinine is present when
there are bilateral renal tumors, if there is
pathology at the level of the kidney without
tumor (lithiasis, pyelonephritis, renal cysts) or if
there is system pathology: high blood pressure,
diabetes.
 Imaging Explorations

• Renal ultrasound (ultrasonography) is usually the first

investigation recommended to a patient suspected of
suffering from renal tumor. It is a non-invasive, non-
radiating, repeatable examination, which is able to make
the difference between liquid and solid tumors, with a
specificity of 98%.
• Doppler ultrasound may certify with great accuracy the
presence of the tumor thrombus in the inferior vena cava
and its extension upstream, including the right cardiac
cavities, situation in which the transesophageal
echocardiography is also compulsory. Ultrasound with
contrast agent is useful when patients are allergic to iodine
substances or gadolinium.
•
 Imaging Explorations

• Computed tomography (CT) is currently the election

method for the detection, characterization and
stadialization of a renal tumor mass.
• The CT abdominal examination brings important
information on the extension of the primary tumor, the
venous extension, the presence of adenopathies, the
functioning and anatomy of the contralateral kidney,
and the liver and suprarenal glands evaluation.
• The cranial CT is used to detect cerebral metastases,
and pulmonary CT is used to highlight secondary
pulmonary determinations.
 Imaging Explorations

Nuclear magnetic resonance (MRI) is a non-radiating method,

with sensibility and specificity similar to CT when detecting
the local and distant tumor extension . It is useful when the
patient is allergic to iodine substances, when the CT
examination is not able to detect the tumor extension, and in
pregnant women not suffering from renal failure
• Renal arteriography and cavography have a limited
part in the diagnosis of renal tumors.

• Radioisotopic investigations – bone scintigraphy –

have an important role in the evaluation of secondary
bone determinations, thus detected 9 to 12 months
before their radiologic expression.

• Chest x-ray is part of the pre-operative investigations

of patients with renal tumors and it helps detecting the
eventual secondary pulmonary determinations.
 Staging I T1 N0 M0
II T2 N0 M0
T3 N0 M0
- Stage I-III: Localized disease
III T1 N1 M0
- Stage IV: Advanced, metastatic T2 N1 M0
disease T4 N0 M0
T4 N1 M0
IV
Any T N2 M0
Any T Any N M1

22
T = primary tumor
TX - primary tumor cannot be evaluated
T0 - there is no evidence of primary tumor
T1 - tumor with maximum diameter  7 cm, limited to the kidney
T1a  4 cm
T1b 4-7 cm
T2 - tumor with maximum diameter  7 cm, limited to the kidney
T2a tumor larger than 7 cm but smaller than 5 cm
T2b tumor larger than 10 cm, limited to the kidney
T3 - tumor extends to the large veins or perinephric adipose tissue,
but it does not invade the suprarenal gland, without going beyond Gerota’s
fascia
T3a - tumor invades the renal vein or the perinephric adipose tissue and/or
the renal sinus, without going beyond Gerota’s fascia
T3b - tumor extension with or without the invasion of the wall in the renal
vein or in vena cava under the diaphragm
T3c - tumor extension with or without the invasion of the wall in vena cava
above the diaphragm or the invasion of the wall of the vena cava
T4 - tumor extends beyond Gerota’s fascia (including continuous
extension in the ipsilateral suprarenal)
N = regional lymph nodes (hilar, para-aortic and
paracaval)
NX - regional lymph nodes cannot be
evaluated
N0 - there are no metastases in the
regional lymph nodes
N1 - metastases in only one regional
lymph node
N2 - metastases in more than one
regional lymph node.
M = distant metastases
MX - distant metastases cannot be
evaluated
M0 - there are no distant metastases
M1 - there are distant metastases
Histopathological G grading:

Gx - the differentiation grade cannot be

evaluated
G1 - well-differentiated tumor
G2 - moderately differentiated tumor
G3 - weakly differentiated / non-
differentiated tumor
 Treatment options

• Surgery
– Rad. Nephrectomy
– Partial nephrectomy( Nephron sparing surgery)
• Minimal invasive methods (thermal ablative therapy)
• Immunotherapy
• Chemotherapy
• Radiotherapy
• Vaccines & cytokines
• Targated agents
• Hormone therapy
 Open

Rad.Neph Lap

Open
Surgical N.S.S Lap
open
modalities
P.C
Minimally Cryoablation

invasive R.F.A open

Lap
approach P.C
LAP

Noninvasive HIFU
ablation
 Renal Carcinoma Treatment
Treatment of Localized Renal Carcinomas (stages
I, II and III)
Radical Nephrectomy
The standard procedure for this goal is radical
nephrectomy, which consists in the primary
ligature of the renal artery and vein, with block
excision of the kidney, the adipose tissue and the
suprarenal gland beyond Gerota’s fascia,
associated with regional lymphodissection from
the level of the diaphragmatic hiatus to the level
of the lower mesenteric artery (Robson, 1969).
The choice of the access path depends on the volume
of the tumor, its topography (upper, lower, mediorenal
pole), the presence or absence of adenopathies,
extension in VCI, conformation, age, and biological
condition of the patient. This type of surgical
intervention is usually performed by transperitoneal
approach, by median subcostal incision extended
pararectally, bilateral subcostal – Chevron) or by
thoracoabdominal approach (thoracophreno-
laparotomy).
 Surgery- Radical nephrectomy
Gold standard treatment for localized RCC with
contralateral normal kidney, adequate surgical margin.

Principles of Surgery- Early ligation of renal artery and

vein , removal of kidney including Gerota’s fascia,
removal of ipsilateral adrenal gland, regional
lymphadenectomy from crus of diaphragm to aortic
bifurcation.

31
Radical nephrectomy
• Robson and colleagues “gold standard”
1969
• Prototype – A then B, Gerota’s intact, ipsi
adrenal, LND (crus to aortic bifurcation)
• Now – no adrenal if: no rad evidence
unless extensive renal involvement,
locally advanced, located upper pole,
immediately adjacent to adrenal
• Surgical approach determined by size,
location of tumor and body habitus
• Transperitoneal
– Subcostal
– thoracoabdominal
• Extraperitoneal
– Flank
• Laparoscopic (trans, retro, hand-assist)
 Rad. Nephrectomy
• ORN was the gold std. for localized RCC
• Surgical approach for R.N is determined by size/location of
tumor & pt related factors.
• Disadvantage of Transperitoneal approach is longer post op.
ileus & intra abd. adhesions.
• R. Nephrectomy consists of early control of vasculature and
removing kidney outside G.F with removal of ipsilat Adr. Gland
• Adrenalectomy should be part of R.N for RCC, as risk of
unexpected microscopic invasion of Adr. has been shown to
be as high as 7.5%.
• Therapeutic value of lymph adenectomy remains
controversial.
 Lap.Rad.Nephrectomy
• L.R.N :- (a) Transperitoneal
(b) R.Peritoneal
becoming std. T/t for localized T1-2 tumors that
are not suitable to NSS.

• Benefits of LRN :- (1) Decreased P.O pain

(2) Shortened hospital stay.
(3) Quick convalescence & improved
cosmesis.
• 5 Yrs disease free rates for Lap R.N & ORN are comparable..
• C/I :- Rad. Neph. shdn’t be done for small < 4 cm size tumor
that is suitable to PN.
Lymphodissection for renal carcinomas may be:
local – removal of the peripedicular tissue.
regional – removal of the lymph adipose
tissue on the adjacent vessel – aorta or
inferior vena cava at the level of the
diaphragmatic hiatus of the lower mesenteric
artery.
extended – removal of the lymph adipose
tissue on the large abdominal vessels from the
diaphragm to the iliac arteries
 Surgical Treatment of Renal
Parenchymatous Carcinomas with
Venous Extension
As we have mentioned earlier, one of the ways of progression of renal cancer is venous; in
approximately 10% of the patients neoplastic thrombosis may be found, that may involve the
inferior vena cava (extension of the renal vein thrombosis), which may get beyond the diaphragm,
extending to the right atrium.
Patients with tumors involving the abdominal inferior vena cava, with the cranial extremity under
the flowing place of the hepatic veins (stage IIIB or T3bN0M0), but without adenopathy and without
metastasis, have a similar prognostic to those in stage II (T2), provided that the tumor is radically
extirpated, including the extraction of the neoplastic thrombus in the vena cava. The thrombus
extraction from the vena cava, as an approach technique, depends on its cranial extension. Usually,
these thrombi are floating and they do not invade the vein wall, which makes their extraction
possible by cavotomy, the lateral resection of the cava being unnecessary.
On the other hand, the adherent thrombus or the one that invades the cava requires, for radical
extraction, the lateral resection of the vena cava or the total resection of a segment of the
abdominal vena cava. For thrombosis involving the supradiaphragmatic or intrapericardial area of
the inferior vena cava or the right atrium, the so-called cavo-cardiac thrombosis, the extraction
requires complex surgical techniques, in mixed urologic-cardiac teams, through bipolar cardiac and
abdominal approach; the surgery requires cardio-pulmonary by-pass with extracorporeal
circulation.
 Conservative surgeries
Enucleoresection of renal tumors has the same oncologic
result as radical surgery for selected cases (T1a).
The indications for conservative surgeries in patients with
parenchymatous renal tumors are:
absolute indications: unique anatomic or functional kidney
relative indications: in patients with benign conditions with
evolutional potential on the controlateral kidney (lithiasis,
pyelonephritis, diabetic nephroangiosclerosis, etc).
elective indications, in patients with normal controlateral
kidney.
 NephronSparingSurgery(NSS)
• OPEN N.S.S- (a) simple enucleation
(b) wedge resection
(c) polar segmentalnephrectomy
(d) transverse resection
(e) Ext.corp.neph.with
auto transplantation
 Laparoscopic Surgery and Minim
Invasive Alternatives
Laparoscopic radical nephrectomy was performed for
the first time in 1990, by Clayman. Laparoscopic radical
nephrectomy is recommended in stage T2, while
laparoscopic partial nephrectomy is recommended in
stage T1, observing the oncologic principles of open
surgery.
Alternatives for the surgical treatment of renal
carcinoma are represented by percutaneous and
minimally-invasive image-guided techniques, such as
ablation by radiofrequency and cryoablation. In the
case of these techniques, the recurrence rates are
higher than in the case of conservative surgery.
 Conclusions
Lap. RN is rapidly replacing the ORN with T1-2
tumor.
ORN is mainly reserved for T3 tumor/tumor of >8 cm
/ tumor with R.V or IVC involv.
NSS will play a major role in small < 4 cm peripheral
tumor.
Open PN is still the std. form of NSS but with refined
tech. Lap PN may be soon coming.
 Systemic Therapy for Renal
Carcinoma in the Metastatic Stage
• Chemotherapy (monotherapy) is not used in the case of metastatic renal
carcinoma.
• Immunotherapy may be used in the treatment of renal carcinoma with
secondary determinations, as follows: Interferon alpha (IFN-alpha) or interleukin-2
(IL2) for selected cases with clear cell histology and good prognostic factors.
• The inhibitor angiogenesis factors (tyrosine kinaze inhibitors) are used in this
type of pathology. At the moment, the approved drugs in USA and the European
Community are:
• Sorafenib (Nexavar®)
• Sunitinib (Sutent®)
• Bevacizumab (Avastin®) combined with IFN-alpha
• Pazopanib (Votrient®)
• Temsirolimus (Torisel®)
• Everolimus (Afinitor®).
• Sunitinib, Bevacizumab combined with IFN alpha, Pazopanib and Temsirolimus are
used as the first line of treatment, and Sorafenib, Everolimus and Axitinib are used
as the second line of treatment.