Renal Masses Series - Part I

Urology Series – Mon. 09th
.May.2016, 07am: part I
&
- Mon. 16th
.May. 2016, 07am: part II
RENAL NEOPLASMS IN ADULTS
Dr. K.J. Mburu
MMed Urology II
Moderators: Dr. Owilla/ Dr. Monda
1

Introduction-Renal Masses
• Renal masses are a biologically heterogeneous group
of tumors ranging from benign masses to cancers that
can be indolent or aggressive.
• The true incidence of renal masses (including
benign lesions) is unknown, but benign lesions comprise
approximately 20 percent of surgically resected tumors.
• Renal masses can be malignant, benign, or
inflammatory as classified by Barbaric (1994)
• They can be classified based on radiographic
appearance (simple cystic, complex cystic, fatty
tumors, and others)
• WHO, 2004, histological classification
2

Benign Renal Masses
• Simple cyst
• Angiomyolipoma
• Oncocytoma
• Renal adenoma
• Metanephric adenoma
• Cystic nephroma
• Mixed epithelial/ stromal tumor
• Reninoma (JG cell tumor)
• Leiomyoma
• Fibroma
• Hemangioma
• Vascular
– Renal artery aneurysm
– Arteriovenous malformation
• Pseudotumor
3

Malignant Renal Masses
• Renal cell carcinoma
– Clear cell
– Papillary
– Chromophobe
– Collecting duct
• Urothelium based
– Transitional cell carcinoma
– Squamous cell carcinoma
– Adenocarcinoma
• Sarcoma
– Leiomyosarcoma
– Liposarcoma
– Angiosarcoma
– Hemangiopericytoma
– Malignant fibrous histiocytoma
– Synovial sarcoma
– Osteogenic sarcoma
– Clear cell sarcoma
– Rhabdomyosarcoma
• Wilms tumor
• Primitive
neuroectodermal
tumor
• Carcinoid
• Lymphoma
• Leukemia Metastasis
• Invasion by
adjacent neoplasm
4

Inflammatory Renal
Masses
• Abscess
• Focal pyelonephritis
• Xanthogranulomatous pyelonephritis
• Infected renal cyst
• Tuberculosis
• Rheumatic granuloma
5

Renal Masses Classified by
Radiographic Appearance
• Simple Cystic
– Cyst
– Multiple cysts
– Peripelvic cysts
– Calyceal diverticulum
– Hydronephrosis
• Complex Cystic
– Cystic nephroma
– Cystic renal cell carcinoma
– Hemorrhagic cyst
– Infected cyst
– Renal abscess
• Fatty Tumors
– Angiomyolipoma
– Lipoma
– Liposarcoma
• All Others
– Renal cell carcinoma
– Sarcomas
– Lymphoma,leukemia
– Metastases
– Oncocytoma
– Renal adenoma
– Metanephric adenoma
– Reninoma (JG cell tumor)
– Leiomyoma
– Fibroma
– Hemangioma
– Carcinoid
– Primitive neuroectodermal tumor
6

WHO,2004, Histological Classification
Of Tumours Of The Kidney
1. Renal cell tumors
2. Metanephric tumors
3. Nephroblastic tumors
4. Mesenchymal tumors
5. Mixed mesenchymal and epithelial tumors
6. Neuroendocrine tumors
7. Haematopoietic and lymphoid tumors
8. Germcell tumors
9. Metastatic tumors 7

Benign Renal Masses
• Are non-cancerous growths of the kidney
that do not metastasize to other sites in
the body
• They are not life-threatening but they can
cause complaints if they exert pressure
effects on adjacent structures.
• As there is universal increase in the use of
radiological imaging, benign renal masses
are being detected more frequently .
9

Renal cysts
• Most common benign renal lesions
– Represents more than 70% of asymptomatic
renal masses
• Can be solitary or multiple, unilateral or
bilateral (terada et al, 2002)
• Sporadic or familial
10

Renal cysts
• Risk factors for development of sporadic
renal cyst; (tarada et al, 2004)
– Increasing age
– Male gender
– Presence of hypertension
– Presence of renal insufficiency
• End stage renal disease - dialysis
11

Bosniak Classification
( Israel & Bosniak,2005; Warren & McFarlane,2005)
• Most useful and widely employed method for
characterizing renal cystic lesions
– and for assessing the likelihood of the presence of
a concomitant malignancy within the cyst
12

Bosniak Class III & IV Lesions
• associated higher risk of malignancy
• Definitive therapy
– surgical excision,
• ablative therapiesof cystic masses have been
reported(Raman et al 2009)
– cryotherapy
– radio frequency ablation
15

Clinical presentation
• Benign cystic lesions of the kidney can grow to
such a large size that they can cause pain or
other symptomatology, including
hypertension (porpigia et all, 2009; zerem et al, 2009)
• Symptoms can also occur as a result of
– hemorrhage within the cyst or
spontaneous/traumatic cyst rapture, (hughes et all, 1995;
rainio et all, 2006; ishikawa et al,2008; vaidyanathan et al, 2008)
– Cyst infection, abscess formation, and/or sepsis
– Erythrocytosis/polycythemia
– Calcification in or around cysts
16

Therapeutic interventions
cho et al,2008;ham et al,2008;baysal&soylu,2009;canguven et al,2008;choi et al,
2009;porpigilia et al,2009
• Aspiration
• Surgical resection
• Cyst decortications
• Sclerotherapy
17

Renal cortical/ Papillary adenoma
• a benign renal neoplasm arising from the renal tubular
epithelium and almost always located within the cortex.
– considered one of the commonest of renal epithelial neoplasms.
(renshaw,2002)
• Epidemiology
– They have been reported in 7% of nephrectomy
specimens and 10-40% of autopsies.
– In autopsy series, the lesions are more common in
older patients (10% of patients <40 years; 40% in
those >70 years).
18

• cytogenetics
– Loss of the Y chromosome, and combined trisomy of
both chromosomes 7 and 17 are early changes in renal
papillary neoplasms.
– small papillary lesions show these changes only, while
PRCC show these, as well as gains of chromosomes
12, 16, and 20.
19

• Incidence of renal adenomas increases
with age and male gender
• these tumors also have been associated
with acquired renal cystic disease that
result in end stage renal failure (leroy et al,2001;denton et
al,2002;snyder et al,2006;ferda et al,2007).
20

• Antemortem pathologic diagnosis of renal
adenoma is much less common
– No reliable histopathological, ultrastructural, or
immunohistochemical criteria
• Renal adenomas have been suggested to be a
premalignant precussor of Papillary RCC (Wang et al;
Brunnelli et al,2003)
– Histologic and genetic abnormalities of renal
adenomas are indistinguishable from papillary RCCs.
21

Clinical presentation,
management and prognosis
• Asymptomatic
• Undetectable radiographically because of
their small size(less than 1 cm)
• Require no further therapy
• Prognosis
– Renal papillary adenomas theoretically have
no metastatic potential.
22

Metanephric adenoma
• Most common benign renal parenchymal tumor
• Reported in 1995 by Davis & Colleagues
– 50 cases of an unusual and novel renal mass lesion
with distinctive histological features and benign
clinical course despite occasional symptomatic
presentation and large tumor size (5-15cm)
– Half the patients presented with flank pain, gross
haematuria, or a palpable mass
– Six patients presented with polycythemia, and
hypercalcemia
23

Metanephric adenoma
• Female predominance (2:1) (jones et al,1995;snyder et al,2006;bastide et
al,2009)
• Incidental presentation most common
• Peak incidence in 5th
-6th
decade (renshaw,2002)
24

Metanephric adenoma
• Polycythemia seen in 10% of patients,
– production of erythropoeitin and other cytokines
by the tumor (yoshioka et al,2007;bastide et al,2009)
• Radiographically, these tumors can have
peripheral or central calcifications and may be
hypovascular on contrast-enhanced CT and
hyperechoic on ultrasonography (bastide et al,2009)
25

Metanephric adenoma
• Ultrasound
–Metanephric
adenoma
appears as an
expansile
hypoechoic or
hyperechoic
mass on
sonography.
26

Metanephric adenoma
• CT
– appear as
heterogeneous,
hypovascular masses
with frequent foci of
hemorrhage and
necrosis.
– Calcification is seen in
20% of cases.
27

Metanephric adenoma
• Positive staining for wilms tumor protein,
WT1,(muir et al,2001;bosco et al,2007)
– mutations or deletions in the WT1 gene on 11p13
– Suggests histogenic relationship with wilms tumor
• Alternative theory for origin of metanephric
adenoma,(Brown & associates,1997),
– Gain of chromosomes 7&17
– Suggests histogenic relationship with pRCC
28

Metanephric adenoma
• Varius histologic stains have been evaluated
to distinguish metanephric adenoma from
other renal neoplasms
– Wilms tumor marker WT1, is frequently expressed
in metanephric adenoma,(muir et al,2001;bosco et al,2007)
– Alpha methylacylcoa racemace is poorly
expressed in metanephric adenoma but highly
expressed in papillary RCC
– S-100 is highly expressed in metanephric
adenoma, weak in wilms tumor, and absent in
papillary RCC.(azabdaftari et al,2008)
29

summary
• Rare
• Lack of highly predictive clinical or
radiographic criteria
• Remains a pathological diagnosis
• Radiologic findings raise the index of suspicion
• percutaneous core biopsy with FNA prove
helpuful
• Observation
• Nephron sparing treatment 30

Angiomyolipoma
• Originally described in 1911 by Fischer, and current
name given by Morgan in 1951
• Accounts for less than 10% of renal tumors
• Consist of thick walled aneurysmal vessels, smooth
muscles and fat (tamboli et al,2000;nelson et al,2002;bissler et al,2004)
• Present in 25-50% of patients with tuberous sclerosis
(lesions in cerebral cortex-epilepsy & mental retardation,
skin abnormalities)
• 2 distinct histologic subtypes
– Classic
– Monotypic epitheliod
31

Angiomyolipoma
• Initially considered to be a harmatoma or
choriostoma
• Recent evidence suggests neoplastic
origin with evidence of a monoclonal,
rather than polyclonal, source (green et al 1996;sepp et
al,1996;katter et al,1999)
• Considered to be of neurocrest
origin,possibly derived from perivascular
epitheliod cells
32

Angiomyolipoma
• Tumor strongly expresses estrogen
receptor-beta and androgen receptor
– Pedominantly found in females, Rarer before
puberty (boorjian et al,2008)
• Sporoadic or associated with TSC
33

Angiomyolipoma
• Typical sporadic presentation is of a
middle aged woman with single
asymptomatic tumor
• Sporadic angiomyolipomas have a slow
growth rate,detected incidentally
• Angiomyolipoma is the most common
neoplasm associated with spontaneous
perirenal hemorrhage,closely followed by
RCC (zhang et al,2003)
34

Angiomyolipoma
• 20-30% of angiomyolipomas are in patients
with TSC
– and ~50% of patients with TSC develop
angiomyolipomas (eble,1998; neumann et al,1998;tamboli et al,200; lendvay et al,2003,
minor et al,2003)
• TSC associated angiomyolipomas typically
present
– at a younger age (mean age 30yrs),
– f:m=2:1,
– with multiple,bilateral, and symptomatic tumors(eble,1998 neumann et al,1998; lendvay et al,2003)
• TSC Classical triad of seizures,adenoma
sebaceum&mental retardation may not be present
(steiner et all,1998) 35

Angiomyolipoma
• Wunderlich syndrome
– Reported in 10% of patients
– Massive spontaneous retroperitoneal
hemorrhage
• Angiomyolipoma followed by RCC
– Most significant complication of renal
angiomyolipoma
– Significant morbidity and potential mortality if
not promptly treated (oesterling et al,1986;steiner et al,1993;eble,1998)
– Pregnancy increases risk of hemorrhage (eble,1998)
36

Angiomyolipoma
• Angiomyolipoma is the only benign renal
tumor that is confidently diagnosed with CT
scan on cross-sectional imaging
– Presence of fat within renal lesion is considered
diagnostic hallmark (jinzaki et al,1997;lemaitre et al,1997; bosniak et al,1998;
simplfendorfer et al,2009)
37

Angiomyolipoma
• Utrasonography
– Well-circumscribed,highly echogenic lesion
with shadowing (siegel et al,1996; lemaitre et al,1997)
• Angiography (ct angiography)
– Aneursysmal dilatation in 50% of
angiomyolipomas
– Size of aneurysms correlate with risk of
rapture (yamakado et al, 2002)
39

Angiomyolipoma
• Radiological ddx
– Retroperitoneal Liposarcoma (very rare) in the
setting of large angiomyolipoma
• On CT, they compress or only extrinsically push
the renal parenchyma (clark &novick,2001;wang et al, 2002)
– Fat containing RCC, may contain
calcifications, usually almost never seen in
angiomyolipomas (henderson et al,1997;lemaitre et al,1997;roy et al,1998)
41

Angiomyolipoma
• Percutaneous biopsy
• Core biopsy
– Eminently accurate in the diagnosis of
angiomyolipoma (lebret et al,2007; silverman et al,2007)
42

Angiomyolipoma-Invariably
benign
• Extrarenal occurrences
– Hilar lymph nodes
– Retroperitoneum
– Liver
– Direct extension into venous system
(Eble 1998;turker koskal et al,2000;gogus et al,2001;nelson and sanda,2002;lin et al,2003;bissler and
kingswood,2004;ackali et al,2006;haritharan et al,2006;blick et al,2008;schade et al,2008)
• Benign clinical course still follows
• Indicates, multicentric origin, rather than malignancy with
metastases
43

Angiomyolipoma
• Pathological ddx
– Many angiomyolipomas exhibit regions of
Cellular atypia
Fibrosarcoma
Leiyomyosarcoma
Liposarcoma
• Positive immunoreactivity for HMB-45,a
monoclonal antibody, is characteristic of
angiomyolipoma
– Differentiate angiomyolipoma from other
sarcomas (eble1998)
44

Epitheliod angiomyolipoma(eble and colleagues,1997)
• Predominant epitheliod component
• Can metastasize
• In patients with/without TSC (Pea et al,1998;l’hostis et
al,1999;martignomi et al,2000;cibas et al,2001; mene et al,2001;nelson and sanda,2002;saito et al,2002;bissler
and kingswood,2004;huang et al,2007;limaiem et al,2008;matsuyuma et al 2008;moudouni et al 2008;zanelli et
al,2008;kato et al,2009)
• This phenotype is characterized by epitheliod
cells that are cytokeratin negative and HMB-45
positive
45

Angiomyolipoma-Optimal
treatment
• Treatment must be individualized
• Management should take into account
– the size of tumor; cut point=4cm (steiner et al,1993;nelson and
sanda,2002)
– presence of symptoms, (pain, bleeding)
– and patients factors.
• Asymptomatic small tumors
– Observed expectantly
– Imaging, 6-12 months, this define growth rate and
clinical siginificance (oesterling et al,1986;De luca et al,1999; martin et al,2008 )
46

Angiomyolipoma
• Intervention
– Large tumors, particularly if patient is symptomatic
– Taking into account
• Patients age
• Comorbidities
• Women of child bearing age
• Access to surveillance or emergency care
– Nephron spearing approach,either by;
• Selective embolization
• Open/laparoscopic/robotic partial nephrectomy-
wedge resection or enucleation even in solitary
kidney (fazeli-matin and novick,1998;boorjian et al,2007; minervin et al,2007)
47

Angiomyolipoma- Selective
embolization
• Preferred modality (nelson and sanda,2002;harabayashi et al,2004)
• Considered as 1st
line, in patients with acute or potentially
life threatening hemorrhage - surgical exporation in this
setting result in total nephrectomy (pappas et al,2006;chang et al,2007)
• Overall complications is 10%,similar to rates of partial
nephrectomy (boorjian et al,2007)
– Hemorrhage
– Abscess formation
– Sterile liquifaction of tumor, which may require;
• Percutaneous drainage
• Surgical intervention
48

Angiomyolipoma-Ablative
therapies
• Include:
– radiofrequency ablation (reduce pain) (prevoo et al,2008)
– and cryoablation (destroy tissue) (bachman et al,2005;bryd et
al,2006; littrup et al,2007; caviezel et al,2008)
• Best for treatment of patients
– with TSC who have multicentric
angiomyolipomas
– Older patients with co-morbidities who require
treatment and are not candidates for
embolization
49

Oncocytoma
• The first case of renal oncocytoma was
reported by Zippel in 1942.
• Renal Oncocytoma (RO) is a benign renal
epithelial neoplasm that accounts for 3%-
7% of kidney tumours (morra and Das 1993)
• Embryologic origin
– Many investigators have suggested that these
tumors originate from intercalated cells of the
collecting system.
50

Oncocytoma
• Etiology
– Renal oncocytomas can present in familial or
sporadic forms.
– Familial RO
• Oncocytomas are the most frequent renal
tumors in patients with Birt-Hogg-Dube
syndrome (BHD) caused by mutations in
the folliculin gene (FLCN).
– The etiology of sporadic RO is not known
51

Oncocytoma
• Genes involved and Proteins
–Mutations in folliculin gene (FLCN,
17p11.2) cause Birt-Hogg-Dube (BHD)
syndrome
• rare inherited genodermatosis
• characterized by
–hair follicle hamartomas,
– kidney tumors,
–and spontaneous pneumothorax. 52

Oncocytoma
• Cytogenetics
– Complete or partial loss of chromosome 1 is the most
common cytogenetic abnormality reported in
approximately 40% of cases (lindgren et al,2004; paner et al,2007).
– Other frequent changes include loss of Y (15%) and
monosomy 14q (15%). (Lindgren et al, 2004; Philips et al, 2001)
– Trisomy 7 has been reported as the most common
chromosomal gain in up to 5% of patients.
– Structural rearrangements involving 11q12-13 have
been reported.
– Approximately 50% of tumors show no chromosomal
abnormalities.
(schwerdtle et al,1997;chao et al,2002; pollascik et al, 2002; lindgren et al, 2004)
53

Oncocytoma pathology
• Renal oncocytomas generally occur and are contained
within a well-deﬁned ﬁbrous capsule
• The tumors are usually solitary and unilateral, although
several bilateral cases and multiple oncocytomas
occurring simultaneously (oncocytomatosis) have been
reported (Tickoo et al, 1999).
• Tan to mahogany brown, homogenous, well
encapsulated
• May achieve large size upto 12cm in diameter
• Metastasis is extremely rare though invasion of the
lymphovascular spaces has been observed.
54

Oncocytoma
• 1/3 of cases,
– hemorrhage,
– extension into perinephric fat,
– cellular atypia,
– prominent nucleoli,and pleomorphism
• may be seen, yet clinical behaviour in this
cases is is within what is expected with a
benign course (amin et al,1997;perez-ordonez et al,1997).
55

Diagnosis of Oncocytoma
• predominantly pathologic because there are
– no reliable distinguishing clinical characteristics.
• Gross hematuria and flank pain occur in <20% of
patients. Males more than Females, peak 70 years
• No characteristic features of the tumors appear on CT,
ultrasound (US), intravenous urography (IVU), or MRI.
• Angiographic features include the “spokewheel”
appearance of tumor arterioles, the “lucent rim sign” of
the capsule, and a homogeneous capillary nephrogram
phase.
– Unfortunately, these findings are not invariable, and
similar findings have been reported in patients with
renal cell carcinoma (RCC). 56

Oncocytoma
• In most cases the treatment options are isolated to
– observation, particularly for the older or sicker patient,
– and surgical resection, particularly for the younger
healthier patient.
• nephron-sparing approach is preferred given the benign
nature of these lesions and the very low probability of
recurrence (Licht, 1995; Romis et al, 2004; Gudbjartsson et al, 2005).
• Thermal ablation, although sometimes reported as a
treatment option,
– commits the patient to long-term radiographic surveillance,
– lower success rates of these procedures
– unknown longterm outcomes,
58

Cystic Nephroma
• Cystic nephroma is a characteristic renal lesion with
bimodal age distribution and benign clinical course (tamboli et
al,2000)
– Diagnostic peak primarily in the first 2-3 years of life
• Predominantly in Males
– 4th
and 5th
decades
• Female prevalence, significant 8:1 (madwell et al,1983; upadhyay
and neely,1989; castillo et al,1991; stamatiou et al,2008; kuzgunbay et al,2009)
• Familial cases have been reported in literature
• Reported cases of sarcomas and clear cell carcinoma
arising from cystic nephroma (bal et al,2005;omar et al,2006; raj et al,2006;ashley
and reinberg,2007)
59

Cystic Nephroma
• Clinical presentation
– Abdominal mass
– pain
– Haematuria
• Majority are Incidental findings (madwell et
al,1983;kuzgunbay et al,2009)
60

Cystic Nephroma
• Radiologically (madwell et al,1983; turbiner et al,2007)
– Solitary
– Centrally located
– Widely variable in size (mean 9 cm)
– Demonstrate culvilinear calcifications
– Herniatiation into the renal collecting system
– Septal enhancement
• NB: radiological differentiation between
cystic nephroma and cystic RCC in adults
and wilms in children is not possible (vujanic et 61

Cystic Nephroma
• Immunohistochemical studies
– Affinity for epithelial component for
cytokerratins
– Stromal components frequently stain positive
for
• CD10,
• calretinin,I
• nhibin,
• estrogen, and progesterone receptor
(turbiner et al,2007; montironi et al,2008)
63

Cystic Nephroma
• Management
– Children, concern for cystic wilms?
• Radical nephrectomy
– Adults,
• Nephron spearing approach with partial
nephrectomy
64

MIXED EPITHELIAL STROMAL
TUMOR (MEST)
• Rare benign adult renal neoplasm
• Made of epithelial and mesenchymal components (adsey et
al,2000)
65

MEST - occurence
• Female predominance (6:1)
• 4th
decade
• Adsay et al,2000, showed that;
– majority of women diagnosed with MEST had
estrogen replacement therapy
– The Only male patient in the largest MEST
series had androgen deprivation therapy for
prostate cancer
66

MEST - presentation
• Similar to those of cystic nephroma
– Abdominal mass
– pain
– Haematuria
• Majority detected incidentally (adsay et al,2000;turbiner et
al,2007;montironi et al,2008)
67

MEST - Radiologic appearance
• CT scan
– Complex cystic renal
mass, indistinguishable
from cystic RCC (adsay
et al,2000)
• MRI
– Involvement of renal
hilum
– Compression of
pelvicalyceal system
– Gross infiltration of
adjacent renal
parenchymal is NOT
seen 68

MEST
• Summary
– A preoperative diagnosis of MEST should be
considered in perimenopausal women
receiving hormone therapy;
– Radiological differentiation from rcc is not
reliable
– surgical intervention, preferably with a
nephron sparing approach should be offered
to appropriately selected patients
69

LEIOMYOMA
• Rare,benign tumors that may arise from smooth muscle
cells anywhere along the genitourinary tract (tamboli et,2000)
• Kidney
– Tumors arise from renal capsule
– Renal pelvis and renal vein sites of origin also
reported (wells et al,1981;steiner et al,1990;o’brien et al,1992;rao et al,2001)
• Majority are Incidental findings during CT-abdomen (romero
et all,2005; derche et al,2008)
• 15 % detectable clinically (romero et al,2005)
70

Leiomyoma
CT SCAN
• Small exophytic renal
mass with/without
enhancement arising
from smooth-muscle-
containing areas of the
kidney including the renal
capsule and renal pelvis.
• Radiological
differentiation from rcc is
not possible (steiner et al,1990;
derchi et al,2008)
71

Leiomyoma
• Gross
– Well encapsulated
– Range from purely cystic to mixed solid/cystic or
solid in appearance
• Histologically
– Reveales intersecting fascicles of smooth muscles
– No evidence of hypercellularity, pleormophism,
mitotic activity or necrosis (steiner et al,1990;
tamboli et,2000)
– Calcification uncommon 72

Leiomyoma
• Immunohistochemical stains
– Confirm smooth muscle nature of the tumor
– Strong diffuse positive staining for smooth muscle
markers desmin and caldesmon (romero et al,2005)
• Management
– Nephron sparing approaches should be
considered for peripherally located small lesions
73

Other benign renal tumors
 Reninoma
– Benign tumor of renal juxtaglomerular cell apparatus
(wong et al,2008)
– Females in 3rd
and 4th
decade are most commonly
affected (martin et al,2001; rubenstein et al,2002; wong et al,2008)
– Clinical presentation, dominated by hypersecretion of
renin (schonfeld et al,1991; rubenstein et al,2002)
• Hypertension
• Hypokalaemia
– Associated symptoms
• Polydipsia
• Polyurea
• Myalgia
• Headache
74

 Reninoma
• The diagnosis is confirmed by Selective renal vein renin
sampling with lateralization
– It has been suggested that renin lateralization ratio (LRR)>1.5
maximizes the specificity of this investigation
• Radiologic appearance
– Small (less than 3cm), solid hypovascular renal mass
• Management
– Surgical excision,sparing remaining renal parencyma.
(dunnick et al,1983; schonfeld et al,1991; tanabe et al,2001)
• Rapid decline of plasma renin levels
• Normalization of blood pressure
• Resolution of associated symptoms
76

 Reninoma
• Histological examination
• Sheets of polygonal to spindle-shaped cells with
indistinct cell borders,abundant eosinophilic
cytoplasm,and minimal atypia (martin et al,2001)
• Immunohistochemistry
• For factor VIII and factor VIII-related antigens is
characteristic
• Confirms deviation from endothelial cell lineage
(sanfilippo et al,1982)
• NB/ only one case of malignant reninoma has been
documented in literature (duan et al,2004)
77

Hemangiomas
• small vascular tumors occurring in the kidney
• Multiple lesions in one kidney occur in approximately 12% of cases
• rarely bilateral.
• source of hematuria in an otherwise well-evaluated patient.
• Risk factors associated with Kidney Hemangioma include:
– Individuals with Sturge-Weber-Krabbe syndrome (encephalotrigeminal
angiomatosis) or von Hippel Lindau (vHL) disease may be at an increased risk of
developing Kidney Hemangiomas
– Hemangiomas of the bowel, liver, bone, or brain may also increase the risk
• The diagnosis may be determined by CT angiography, MR angiography, or
by direct visualization by endoscopy (Ekelund and Gothlin, 1975).
• Treatment methods for Kidney Hemangiomas may include:
– Radiation therapy -Laser-assisted ablation
– Endoscopic surgery - Nephron sparing surgery ? Radical nephrectomy 78

Fibroma
• Fibromas are tumors of the fibrous tissue on, in, or surrounding the
kidney.
• They are rare and are more common in women.
• Their cause is unknown and most do not cause symptoms.
• Usually they grow on the periphery of the kidney and can become
large before becoming clinically obvious.
• While generally benign, these tumors have no special
characteristics to differentiate them from malignant tumors of the
kidney.
• Because of this uncertainty of diagnosis,
– observation
– partial or radical nephrectomy is the standard treatment.
• Good prognosis
82

Renal lipomas
• very uncommon deposits of mature adipose cells without evident
mitosis that arise from the renal capsule or perirenal tissue.
• They are seen primarily in middle-aged females
• owing to the characteristic CT differentiation of fat, are best detected
radiographically on CT scanning.
• Nephrectomy? Partial? radical
83

… end of part I
thankyou.
84

References
1. Campbell Walsh Urology 10th
Edition; 1413-1505
2. Smith and Tanagho’s General Urology 18th
Edition; 330-349
3. AUA guidelines
4. EUA guidelines
5. Pub Med Health
6. http://www.uonbi.ac.ke/ Digital Repository
7. http://www.emedicine.medscape.com
85

MALIGNANT RENAL MASSES
Part II
86

Renal Cell Carcinoma (RCC)
EPIDEMIOLOGY
• Accounts for 2% - 3% of all adult malignant
neoplasms
– 90-95% of neoplasms arising from the kidney.
• 35 patients during the period 1983 to 1997.
– Clinical presentation and management of renal cell
carcinoma, (Oliech JS: East Afr Med J. 1998 Oct;75(10):594-7),
• The tissue of origin for RCC is the proximal renal tubular
epithelium.
• 6th
and 7th
decades of life (pantuck et al,2001wallen et al,2007)
• Male predominanace; 1.5: 1
87

RCC
OCCURRENCE
– sporadic , Majority
– familial (lipworth et al,2006) , 2-3%
– RCC in children is uncommon,
• represent 2.3-6.6% of all renal tumors in
chidren (castellanos et al,1974;chan et al,1983;freedman et al,1996,asanuma et
al,1999;broeker,2000)
• Mean age at presentation in children is 8-9
years
• similar incidence in boys and girls
88

RCC - ETIOLOGY
I. TOBACCO EXPOSURE
– Cigarette smoking is considered a causal risk factor for renal cell cancer by the
International Agency for Research on Cancer (IARC)
– Risk increases with cummulative dose or pack years (kantor,1977;la vecchia et al,1990;
Mclaughlin et al,1995;mclaughlin and lipworth,2000;dhote et al,2004;lindblad,2004;lipwort et al,2006;carrisoza and godley,2009)
– Relative risk is directly related to duration of smoking and begins to fall after
cessation, supporting a cause-and-effect relationship (la vecchia et al,1990; Mclaughin et al1995;
parker et al2003)
– Account for 20-30% of cases of RCC in men and 10-20% in women (mclaughin et
al,1995;mclaughlin et al,1995;mclaughlin and lipworth,2000)
– Cigarette smoking is hypothesized to increase renal cell cancer risk through
chronic tissue hypoxia due to carbon monoxide exposure
– higher level of DNA damage in their peripheral blood lymphocytes induced
by a tobacco-specific N-nitrosamine
89

RCC - ETIOLOGY
II. OBESITY
– major risk factor for RCC
– Excess body weight has been estimated to account for
over 40% of renal cell cancers in the United States
and over 30% in Europe
– Incresed relative risk for each unit of rising body mass
index (chow et al,2000; bergstrom et all,2001;bjorge et al 2004; calle and kaaks, 2004;reeves et al,2007)
– Potential mechanism linking obesity to RCC (kasiske et al,1992;
huang et al,1998; gago-dominguez et al,2002;calle and kaaks,2004)
• Lipid peroxidation leading to DNA adducts
• Increased insulin like growth factor-1 expression,
• increased circulating estrogen levels,
• Increased arterionephrosclerosis and local inflammation
90

RCC - ETIOLOGY
III. HYPERTENSION
– Certain types of renal tumors and cancer treatment
have been shown to cause hypertension.
– there is sufficient evidence to demonstrate that hypertension predisposes to
renal cell cancer development. (tumor-promoting effect for hypertension)
– 3rd
major etiological factor
– Proposed mechanisms (lipworth et al, 2006)
• Hypertension induced renal injury and inflammation
• Metabolic or functional changes in renal tubules that may
increase susceptibility to carcinogens
– chronic renal hypoxia and lipid peroxidation with formation of
reactive oxygen species.
• Users of diuretics and other anti-hypertensive medications also
were associated with an elevated risk of renal cell cancer 91

RCC - ETIOLOGY
IV. OCCUPATION & ENVIRONMENT
• Trichloroethylene exposure
– classified in Group 2A (probable carcinogens)by the IARC (International
Agency for Research on Cancer)
– Widely used as a metal degreaser and chemical additive,
– Relative risks ranging from twofold to sixfold (vamvaka et
al,2000;mandel,2001;moyad,2001;bruning et al,2003,;lipworth et al,2006,lock and reed,2006)
• Asbestos, cadmium, uranium, arsenic, nitrate, and
radon
(colonel,1976;pesch et al,2000moyad,2001;hu et al,2002;dhote et al,2004;lindblad,2004;lipworth et al ,2006;carrizosa and
godley,2009)
– Workers in the metal, chemical, rubber, mining and printing industries
• Low socioeconomic status and Urban
background (kantor,1977;goodman et al,1986;muscat et al,1995;youan et al,1998)
92

RCC - ETIOLOGY
V. DIET AND BEVERAGES
• Diets rich in fruits and vegetables are inversely related to renal
cell cancer
– associations with antioxidant nutrients common in fruits and
vegetables, such as vitamins A, C, and E, and carotenoids, are
mixed.
• Acrylamide, a substance classified by the IARC as Group 2A in
commonly consumed fried and baked foods.
• Alcohol consumption has been inversely associated with renal cell
cancer risk in a dose-response manner in prospective studies,
– with an estimated 28% reduction in risk among those who
drank ≥15 gram/day, equivalent to slightly more than one
alcoholic drink per day 93

RCC -ETIOLOGY
VI. FAMILY HISTORY OF RCC
– Increased RR for individuals with a first-or-second
degree relative (gago-dominguez et al,2001)
VII. IATROGENIC CAUSES
– Thorotrast (used as contrast in the past)
– Radiation therapy (vogelzang and colleagues(1998)
• reported 4 cases of RCC developing in a previously
irradated field
• slightly increased incidence of RCC has been rported in
men who received retroperitoneal irradation for the
treatment of testicula cancer.(wenz,1967;romanenko et al,2000)
94

RCC - ETIOLOGY
VIII. Survivors of childhood WILMS TUMOR also
appear to be at increased risk for RCC,
– possibly related to prior radiation therapy or
chemotherapy (cherullo eat al,2001)
IX. Increased incidence of RCC observed in
patients with ESRD and certain FAMILIAL
SYNDROMES (ishikawa et al,1990;bjornsson et al,1996;neumann and zbar,1997)
X. A history of diabetes mellitus has been linked to renal cell cancer risk in several cohort
studies
XI. Compared to nulliparous women, risk increased 40% to 90% among women who had
given birth and rose with increasing number of births (highest risk among women who
gave multiple births at a relatively young age)
XII. Physical activity has been shown to reduce body weight and blood pressure, improve
insulin sensitivity, and reduce chronic inflammation and oxidative stress, changes that
could contribute to reducing renal cell cancer risk.
95

RCC - TYPES
• Histological subtypes
– Clear cell RCC (ccRCC) – 75%
– Papillary RCC (pRCC) – 15%
• Type basic types
• Type II
• Type III - oncocytic
– Chromophobe (chRCC) - 5%
• Others
– Collecting duct carcinoma
– Renal medullary carcinoma
– Sarcomatoid differentiation
– Unclassified RCC
96

VON HIPPEL-LINDAU DISEASE, VHL
GENE, AND GENETICS OF ccRCC
• The familial form of clear cell RCC is von Hippel-Lindau
disease.
• This is a relatively rare autosomal dominant disorder that
occurs with a frequency of 1 per 36,000 population.
• RCC develops in about 50% of patients with von Hippel-
Lindau disease
– and is distinctive for its early age at onset and for its
bilateral and multifocal involvement (Horton et al, 1976; Go et al, 1984; Green,
1986; Jennings et al, 1988; Lamiell et al, 1989; Maher et al, 1990; Neumann and Zbar, 1997; Vira et al, 2007; Nathanson and
Stephenson, 2009).
– often in the 3rd
, 4th
, or 5th
decade of life
98

Manifestations of the von Hippel-Lindau Syndrome
(Horton et al, 1976; Go et al, 1984; Green, 1986; Jennings et al, 1988; Lamiell et al, 1989; Maher et al, 1990; Neumann and Zbar, 1997; Hansel and
Rini, 2008; Nathanson and Stephenson, 2009).
99

RCC - VHL Gene
• This gene, which is located at chromosome
3p25-26
• its a tumor suppressor gene for both the
sporadic and the familial forms of clear cell
RCC (Gnarra et al, 1994; Linehan et al, 1995; Zbar, 1995; Furge and Teh, 2009;
Nathanson and Stephenson, 2009).
• As with most tumor suppressor genes, both alleles of
the VHL gene must be MUTATED or INACTIVATED
for development of the familial RCC(2-3%).
100

RCC - VHL Gene
• sporadic clear cell RCCs
– harbor mutations or other genetic mechanisms,
such as hypermethylation, that inactivates both
alleles of the VHL gene (Zbar, 1995; Linehan et al, 2003; Nathanson and Stephenson,
2009)
• accounts for 70% to 80% of all RCCs, (Störkel et al, 1997; Eble et al, 2004; Rini et al,
2009).
– exhibit venous tumor extension than any other subtype of RCC (Rabbani et al,
2004).
– worse prognosis compared with papillary or chromophobe RCC (Lau et al,
2002; Cheville et al, 2003; Beck et al, 2004)
101

RCC - VHL Gene
• The function of the VHL protein complex is to target
the hypoxia-inducible factors 1 & 2 (HIF-1 and HIF-2)
– The HIFs are intracellular proteins that play an important
role in regulating cellular responses to hypoxia, starvation,
and other stresses.
• Inactivation or mutation of the VHL gene leads to
dysregulated expression of the HIFs and they begin to
accumulate in the cell. (Maxwell et al, 1999; Yu et al, 2001)
– This, in turn, leads to a severalfold upregulation of the
expression of vascular endothelial growth factor (VEGF), the
primary angiogenic growth factor in RCC, contributing to the
pronounced neovascularity associated with clear cell RCC
(Gnarra et al, 1996; Iliopoulos et al, 1996; Gunningham et al, 2001; Igarashi et al, 2002; Linehan et al, 2003; Sudarshan and
Linehan, 2006; Vira et al, 2007).
102

RCC - VHL protein
• HIFs also upregulate the expression of
–tumor growth factor-α,
–platelet-derived growth factor (PDGF),
–glucose transporter (Glut 1)
–erythropoietin
–carbonic anhydrase IX (CA-IX),(a tumor-
associated antigen with specificity for clear
cell RCC) (Zbar et al, 1999; Wykoff et al, 2000; Turner et al, 2002; Wiesener et al, 2002; Linehan et
al, 2003; Grabmaier et al, 2004; Sudarshan and Linehan, 2006; Vira et al, 2007).
103

.
• The von Hippel-Lindau (VHL)
gene encodes a tumor suppressor
protein (pVHL) that interacts
with a hypoxia-inducible factor
(HIF) that is a "master regulator"
of many genes .
• Mutations in the VHL gene can
therefore alter intracellular
signaling
• When HIF dissociates from pVHL,
it becomes stabilized and induces
expression of hypoxia-induced
target genes, including vascular
endothelial growth factor
(VEGF), which stimulates
angiogenesis; platelet-derived
growth factor (PDGF), which
enhances endothelial
stabilization; and transforming
growth factor-alpha (TGF-
alpha), which stimulates cell
replication
104

Hereditary Papillary RCC and
Genetics of type 1 Papillary RCC
• Papillary RCC,
– In 1995, Zbar and colleagues described familial
syndrome of RCC—hereditary papillary RCC
(HPRCC)
– designated chromophilic RCC in previous classification schemes,
– is the second most common histologic subtype (Störkel et al, 1997; Eble et al, 2004; Pignot et al, 2007;
Gontero et al, 2008).
– It represents 10% to 15% of all RCCs,
– it is more commonly found in patients with end-stage renal failure
and acquired renal cystic disease (Ishikawa and Kovacs, 1993; Störkel et al, 1997).
– characterized by trisomy for chromosomes 7 and
17 and loss of chromosome Y as well as
abnormalities on chromosomes 1, 12, 16, 20, (Störkel et
al, 1997; Oyasu, 1998; Pavlovich et al, 2003). 106

Type 1 Papillary Renal Cell Carcinoma
• Two Basic variants of papillary RCC have been described
(Renshaw et al, 1997; Störkel et al, 1997; Oyasu, 1998; Delahunt et al, 2001; Eble et al, 2004; Yang et al, 2005;Rosner et al,
2009)
– Type 1 papillary RCC,
• the more common form,
• hereditary papillary RCC syndrome, multifocal, bilateral renal
tumors
• mutations of the c-MET proto-oncogene located on chromosome
7 (Schmidt et al, 1997; Pavlovich and Schmidt, 2004).
• Better prognosis (Moch et al, 2000; Lau et al, 2002; Amin et al, 2002; Beck et al, 2004; Zhou,
2009).
– Type 2 papillary RCC
• more aggressive variants
• hereditary leiomyomatosis and RCC syndrome (Delahunt et al, 2001;
Amsellem-Ouazana et al, 2002; Leroy et al, 2002; Renshaw, 2002; Choyke et al, 2003; Gunawan et al, 2003;
Pignot et al, 2007).
• Fumarate hydratase mutation
107

Hereditary Papillary RCC and Genetics
of type 1 Papillary RCC
• HPRCC demonstrate an autosomal dominant
mode of transmission, similar to all of the
familial RCC syndromes
– inciting event is activation of a proto-oncogene,
rather than inactivation of a tumor suppressor
gene (Missense mutations of the c-MET proto-
oncogene at 7q31)
• tumors in HPRCC are tend to be less
aggressive than their sporadic counterparts,
some can metastasize (Schmidt et al, 2004; Vira et al, 2007).
108

Hereditary Papillary RCC and
Genetics of type 1 Papillary RCC
• Unlike von Hippel-Lindau disease, most patients with
HPRCC do not develop tumors in other organ systems (Czene and
Hemminki, 2003; Pfaffenroth and Linehan, 2008; Nathanson and Stephenson, 2009)
• CT is the preferred imaging modality for patients with
HPRCC
– it has the greatest sensitivity for detecting the small,
hypovascular lesions that are common in this syndrome
(Sudarshan and Linehan, 2006; Pfaffenroth and Linehan, 2008; Nathanson and Stephenson, 2009).
109

Type 1 Papillary Renal Cell
Carcinoma
• VHL mutations are rare in papillary RCC,
– confirm distinct genetic pathways to
tumorigenesis (Kenck et al, 1996; Zambrano et al, 1999; Linehan et al, 2003; Rosner et al, 2009).
• Papillary RCC is more likely to be
hypovascular
– owing to the lack of VHL mutations that
regulate VEGF, the primary proangiogenic
molecule in RCC (Blath et al, 1976; Herts et al, 2002; Kim JK et al, 2002).
110

Hereditary Leiomyomatosis and
Type 2 papillary RCC
• described In 2001, Launonen and colleagues;
patients develop
– cutaneous and uterine leiomyomas and
– type 2 papillary RCC
(Choyke et al, 2003; Kiuru and Launonen, 2004; Pavlovich and Schmidt, 2004; Sudarshan and Linehan, 2006; Sudarshan et al,
2007)
• Mean age at diagnosis is in the early 40s (Hansel and Rini, 2008; Nathanson and
Stephenson, 2009).
• Collecting duct RCC, another highly malignant
variant of RCC, has also been observed in this
syndrome
111

Hereditary Leiomyomatosis and
RCC
• Prompt surgical management of the renal
tumors is recommended in this syndrome
– tendency toward invasive and aggressive
behavior (Linehan et al, 2003; Grubb et al, 2005b, 2007; Sudarshan and Linehan, 2006; Vira et al, 2007; Coleman, 2008).
– This is in contrast to other familial syndromes of
RCC, for which management tends to be more
conservative, as discussed later (Grubb et al, 2007; Vira et al, 2007; Pfaffenroth
and Linehan, 2008).
112

Birt-Hogg-Dubé Syndrome
• is named after three Canadian physicians
who first described the cutaneous lesions in
1977(Toro et al, 1999; Linehan et al, 2003; Pavlovich et al, 2003, 2005; Pavlovich and Schmidt, 2004; Adley et al,
2006; Hansel and Rini, 2008).
• patients develop
– cutaneous fibrofolliculomas, (Any of a group of neoplasms formed
by proliferation of the fibrous sheath of the hair follicle)
– lung cysts,
– spontaneous pneumothoraces,
– and a variety of renal tumors primarily derived
from the distal nephron, 113

• renal tumors typically include
– chromophobe RCC,
– oncocytomas,
– and hybrid or transitional tumors that exhibit features of
both of these entities.
– other forms of RCC, including a substantial proportion of
clear cell RCC, have been observed in this syndrome (Pavlovich
et al, 2002; Adley et al, 2006).
• Overall penetrance for renal tumors is 20% to 40%, but
when they occur they are often bilateral and multifocal
(Pavlovich et al, 2002; Linehan et al, 2003; Pavlovich and Schmidt, 2004: Pfaffenroth and Linehan, 2008; Toro et al,
2008)
114

• Average age at renal tumor diagnosis is approximately 50
years (Pavlovich et al, 2005).
• Most renal tumors in Birt-Hogg-Dubé syndrome have limited
biologic aggressiveness, although metastatic behavior and
lethality have been reported (Pavlovich et al, 2005)
115

Chromophobe Renal Cell
Carcinoma
• first described by Theones and colleagues in 1985,
• Chromophobe RCC is seen in the Birt-Hogg-Dubé syndrome,
but most cases are sporadic (Pavlovich et al, 2002).
• derived from the cortical portion of the collecting duct (Störkel et
al, 1997).
• It represents 3% to 5% of all RCCs (Oyasu, 1998; Eble et al, 2004; Klatte et al, 2008).
• Genetic analysis has revealed multiple chromosomal losses,
most frequently the whole chromosomes 2, 10, 13, 17, and 21
(Schwerdtle et al, 1996; Bugert et al, 1997; Iqbal et al, 2000; Polascik et al, 2002).
• increased incidence of TP53 mutations and upregulated
expression of the c-KIT oncogene (type of receptor tyrosine kinase and a type of tumor
marker) has also been reported (Contractor et al, 1997; Yamazaki et al, 2003; Pan et al, 2004; Petit
et al, 2004; Huo et al, 2005).
116

Collecting Duct Carcinoma
• Carcinoma of the collecting ducts of Bellini
• Is a rare subtype of RCC, accounting for less than 1% of
all RCCs (Kennedy et al, 1990; Rumpelt et al, 1991; Carter et al, 1992; Störkel et al, 1997; Srigley and Eble, 1998; Swartz
et al, 2002).
• Many reported cases in younger patients,
– often in the third, fourth, or fifth decades of life (Carter et
al, 1992).
• Most patients are symptomatic at presentation,
– and up to 50% have metastatic disease at the time
of detection (Tokuda et al, 2006).
• Deletions on chromosome 1q and monosomy of
chromosomes 6, 8, 11, 18, 21, and Y have been reported
(Fuzesi et al, 1992; Steiner et al, 1996; Polascik et al, 2002).
• patients with advanced collecting duct RCC have responded to cisplatin- or
gemcitabine-based chemotherapy (Milowsky et al, 2002; Peyromaure et al, 2003; Kobayashi et al,
2008). 117

Renal Medullary Carcinoma
• Subset of RCC that occurs almost exclusively in
association with the sickle cell trait.
• arise from the calyceal epithelium near the renal
papillae but is often highly infiltrative (Davidson et al, 1995; Davis et al,
1995).
• 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 (Davis et al, 1995b; Polascik et al,
2002; Swartz et al, 2002; Zhou, 2009).
– Most patients do not respond to therapy and
succumb to their disease in a few to several
months (Davis et al, 1995b; Herring et al, 1997; Figenshau et al, 1998; Polascik et al, 2002).
118

Sarcomatoid Differentiation
• found in 1% to 5% of RCCs,
– most commonly in association with clear cell RCC or chromophobe
RCC, but variants of most other subtypes of RCC have been described
(Weiss et al, 1995; Störkel et al, 1997; Oyasu, 1998; Delahunt, 1999; dePeralta-Venturina et al, 2001; Kuroda et al, 2003e; Cheville et al, 2004; Zhou, 2009).
• believed that sarcomatoid lesions represent poorly
differentiated regions of other histologic subtypes of
RCC rather than independently derived tumors (DeLong
et al, 1993; Oyasu, 1998; Delahunt, 1999; Eble et al, 2004).
• rare to find a truly pure sarcomatoid renal mass (Delahunt,1999).
• Characterized by infiltrative growth pattern, aggressive local
and metastatic behavior, and poor prognosis (Ro et al, 1987; DeLong et al,
1993; Cangiano et al, 1999; Eble et al, 2004).
• Invasion of adjacent organs is common, and median survival
has been less than 1 year in most series (Ro et al, 1987; Cangiano et al, 1999; Escudier
et al, 2002a; Mian et al, 2002; Nanus et al, 2004; Dall’Oglio et al, 2005; Zhou, 2009).
119

Clinical Presentation - RCC
• Because of the location of the kidney within the
retroperitoneum,
– many renal masses remain asymptomatic and
nonpalpable until they are advanced.
– more than 50% of RCCs are now detected
incidentally (Pantuck et al, 2000).
• Haematuria, abdominal pain, fever of unknown
origin and abdominal mass were the commonest
presenting features.
– Clinical presentation and management of renal cell
carcinoma, (Oliech JS: East Afr Med J. 1998 Oct;75(10):594-
7)
120

…Clinical Presentation - RCC
• Incidental
• Local Tumor Growth
– Hematuria
– Flank pain
• due to hemorrhage and clot
obstruction,
• also occur with locally advanced or
invasive disease
– Abdominal mass
– Perirenal hematoma
• most often AML or RCC.
• Metastases
– Persistent cough
– Bone pain
– Cervical lymphadenopathy
– Constitutional symptoms
– Weightloss/fever/malaise
• Obstruction of the Inferior Vena Cava
– Bilateral lower extremity edema
– Nonreducing or right-sided
varicocele
• Paraneoplastic Syndromes
– Hypercalcemia
– Hypertension
– Polycythemia
– Stauffer’s syndrome
121

Incidence of Systemic Syndromes Associated
with RCC
• Elevated erythrocyte sedimentation rate - 55.6%
• Hypertension - 37.5%
• Anemia - 36.3 %
• Cachexia, weight loss - 34.5 %
• Pyrexia - 17.2 %
• Abnormal liver function - 14.4%
• Hypercalcemia - 4.9 %
• Polycythemia - 3.5 %
• Neuromyopathy - 3.2 %
• Amyloidosis - 2.0%
122

Paraneoplastic syndromes in RCC
• found in 20% of patients with RCC,
• Secondary to Pathological production of:
– 1,25 dihydroxycholecalciferol,
– renin,
– erythropoietin,
– various prostaglandins,
– parathyroid hormone–like peptides,
– lupus-type anticoagulant,
– human chorionic gonadotropin,
– insulin
– various cytokines and inflammatory mediators
(Sufrin et al, 1989; Gold et al, 1996; Ather et al, 2002; Elias, 2005; Altundag et al, 2005; Elias, 2005)
123

Paraneoplastic syndromes in RCC
• Hypercalcemia has been reported in up to
13% of patients with RCC and can be due to
– either paraneoplastic phenomena (Calcitriol)
– or osteolytic metastatic involvement of the bone
(Sufrin et al, 1989; Gold et al, 1996; Magera et al, 2004; Klatte et al, 2007d; Pepper et al, 2007; Schwarzberg and
Michaelson, 2009).
• The production of parathyroid hormone–like peptides is the
most common paraneoplastic etiology, although tumor
derived 1,25-dihydroxycholecalciferol and prostaglandins
may contribute in a minority of cases (Goldberg et al, 1964; Mangin et al, 1988; Sufrin
et al, 1989; Gold et al, 1996; Walther et al, 1997b; Magera et al, 2004; Massfelder et al, 2004; Klatte et al, 2007d; Pepper et
al, 2007).
• patients with RCC who present with hypercalcemia have a compromised
prognosis
124

Paraneoplastic syndromes
• The signs and symptoms of hypercalcemia are nonspecific
– nausea, anorexia, fatigue, and decreased deep tendon
reflexes.
• Medical management includes
– vigorous hydration
– followed by diuresis with furosemide
– selective use of bisphosphonates, corticosteroids, or calcitonin
(Gold et al, 1996; Coleman, 2004; Pepper et al, 2007; Schwarzberg and Michaelson, 2009).
– Indomethacin has also proved useful in a minority of cases
(Gold et al, 1996; Walther et al, 1997).
– nephrectomy and ?metastasectomy, depending on the
clinical circumstances.
– focused radiation therapy for hypercalcemia related to
osteolytic metastases if limited sites of involvement can be
identified (Gold et al, 1996). 125

Paraneoplastic syndromes
(Moein and Dehghani, 2000)
• Hypertension associated with RCC secondary to
i. increased production of renin directly by the tumor;
ii. compression or encasement of the renal artery or its branches,
effectively leading to renal artery stenosis;
iii. or arteriovenous fistula within the tumor (Robertson et al, 1967;
Sufrin et al, 1989).
iv. Less common causes include polycythemia, hypercalcemia, ureteral
obstruction, and increased intracranial pressure associated with
cerebral metastases (Sufrin et al, 1989).
• Polycythemia associated with RCC can be due to
– increased production of erythropoietin, either directly by the tumor
or by the adjacent parenchyma in response to hypoxia induced by
tumor growth (Gross et al, 1994; Wiesener et al, 2007).
126

Stauffer syndrome
• Also referred to as non - metastatic hepatic dysfunction
• reported in 3% to 20% of cases (Stauffer, 1961; Rosenblum, 1987; Giannakos et al, 2005; Moria
et al, 2006; Young et al, 2008).
• Almost all patients with Stauffer syndrome have;
i. an elevated serum alkaline phosphatase level,
ii. 67% have elevated prothrombin time or hypoalbuminemia,
iii. 20% to 30% have elevated serum bilirubin or transaminase levels (Sufrin et al, 1989).
iv. Other common findings include thrombocytopenia and neutropenia, and
v. Elevated serum levels of IL-6 (Blay et al, 1997).
• Typical symptoms include fever and weight loss,
– many patients are found to harbor discrete regions of
hepatic necrosis (Sufrin et al, 1989; Gold et al, 1996).
127

Stauffer syndrome,
• Hepatic function normalizes after nephrectomy in 60%
to 70% of cases.
• Persistence or recurrence of hepatic dysfunction
– indicative of the presence of viable tumor
– represents a poor prognostic finding (Sufrin, 1989).
128

Other paraneoplastic syndromes
• Cushing syndrome,
• hyperglycemia,
• galactorrhea,
• neuromyopathy, amyotrophic lateral sclerosis
• clotting disorders,
• cerebellar ataxia (Ather et al, 2002; Kamra et al, 2002; Hagel et al, 2005; Mohammed et al, 2006;
Ammar et al, 2008).
• Treatment of paraneoplastic syndromes associated with RCC
– surgical excision or
– systemic therapy and,
– except for hypercalcemia, medical therapies have not proved helpful.
129

Laboratory findings
• FHG
– polycythemia
– Anemia occurs in about 30% of RCC patients
– Normochromic Anaemia
• Serum iron and TIBC
– Low (anemia of chronic illness)
• Urinalysis
– Hematuria- gross or microscopic
• ESR
– An elevated erythrocyte sedimentation rate is also commonly seen,
with a reported incidence as high as 75%
• RFTs
• LFTs
– Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 130

Imaging and Radiological findings
• Ultrasonography
– Although ultrasound is very
frequently requested to assess
the renal tract, it is not as
sensitive or specific as CT or MRI.
– The tumour pseudocapsule can
sometimes be visualised with
ultrasound as a hypoechoic halo.
Although this is a relatively
specific sign, it is not
particularly sensitive
– Contrast-enhanced ultrasound
demostrates the lesion to be
heterogenously hypervascular in
the arterial phase with early
wash out in the delayed phase.
131

• CT Scanning
– On non-contrast CT the lesions appear of
soft tissue attenuation. Larger lesions
frequently have areas of necrosis.
Approximately 30% demonstrate some
calcification
– becomes enhanced with the use of
intravenous contrast media.
– CT scanning is also the method of choice in
staging the patient
• visualizing the renal hilum,
perinephric space, renal vein and
vena cava, adrenals, regional
lymphatics, and adjacent organs.
– Evaluation of metastases
– Spiral CT with 3-dimensional
reconstruction has become useful for
evaluating tumors before nephron-
sparing surgery
• delineate the 3-dimensional extent
of the tumor
• outline the vasculature,
• aid the surgeon in preventing
positive surgical margins (Holmes et
al, 1997).
132

Renal Angiography
• markedly diminished utility in the diagnostic
evaluation of RCC
• clinical situations in which angiography may
be useful;
– for example, guiding the operative approach in a
patient with an RCC in a solitary kidney when
attempting to perform a partial nephrectomy
may be indicated
– CT angiography or MR angiography can give
better information with less risk to the patient.
133

Radionuclide Imaging
• Bone metastases
• NB/patients without
bone pain and with a
normal alkaline
phosphatase level have
a very low incidence of
bone metastases (Henriksson
et al, 1992), and thus a
routine bone scan is not
necessary in such 134

 Magnetic Resonance Imaging
• Its primary advantage is in the
evaluation of patients with suspected
vascular extension.
• superior to CT in assessing inferior
vena caval involvement (Kabala et
al, 1991)
• also able to suggest the likely
histology, on the grounds of T2
differences.
– T1: often heterogeneous due to
necrosis, haemorrhage and solid
components
– T2: appearances depend on
histology 6
• clear cell RCC: hyperintense
• papillary RCC: hypointense
– T1 C+ (Gd): often shows prompt
arterial enhancement
135

 Positron Emission Tomography
(PET) and Targeted Imaging
• allows the measurement of
systemically administered
biochemical agents such as 18-
fluoro-2- deoxyglucose (FDG),
which can accumulate in the
kidney.
• useful in monitoring response to
systemic therapy in those with
metastatic disease (Hoh et al,
1998).
• FDG-PET may also be more
accurate than routine CT
scanning in detecting disease
recurrence or progression 136

Fine-needle aspiration in diagnosis of
renal lesions
• Indications
– in patients with clinically apparent metastatic disease who may
be candidates for nonsurgical therapy.
– establishing a diagnosis in patients who are surgical candidates
– differentiating a primary RCC from a renal metastasis in patients
with known primary cancers of nonrenal origin,
– evaluating some radiographically indeterminate lesions
– to confirm the diagnosis of a neoplasm particularly in patients
who may undergo observation or percutaneous ablative therapy
(Shah et al, 2005).
• The accuracy of fine needle aspiration cytology of renal masses is reported to be
slightly lower mainly because of lower sensitivity. Specificity can still be high and
close to 100%.
137

core needle biopsies
• accurately diagnose malignancy in up to 100% of cases >4 cm and
95% of cases <4 cm, (Wunderlich et al, 2005).
– utilized in patients with metastatic disease in order to guide
appropriate targeted systemic therapy (prior to or instead of
cytoreductive nephrectomy),
• since the choice of systemic therapy can be influenced by the specific
RCC histology.
– seeding of the needle tract have been reported but the risk of
seeding is reported to be <0.01% (Volpe et al, 2007).
– The accuracy of needle core biopsies is reported to be >90%
with sensitivity ranging between 70–100% and specificity of
100% (Volpe et al, 2007).
138

Instrumental and Cytologic Examination
• cystoscopy
– Patients presenting with hematuria.
– Blood effluxing from the ureteral orifice identifies
the origin of bleeding from the upper tract.
• endoscopic evaluation
– Most renal pelvis tumors
– bladder, ureters, and renal pelvis
• urine cytologic
– cytologic study of urine with renal pelvis washing is
frequently diagnostic in renal pelvis tumors.
139

TUMOR STAGING
• The ultimate goal of staging
– is select appropriate therapy and obtain prognostic information.
• Appropriate studies for a complete clinical staging evaluation include
– history and physical examination,
– complete blood count,
– serum chemistries (renal and hepatic function),
– urinalysis,
– chest x-ray (chest CT scan for an equivocal exam),
– CT scan of abdomen and pelvis,
– and a radionuclide bone scan (with x-rays of abnormal areas).
• The original staging system by Robson (1963) does not relate directly to
prognosis and hence it is no longer commonly used.
• The tumor- node-metastasis (TNM) system more accurately classiﬁes the
extent of tumor involvement and is currently most often used.
– The TNM classiﬁcation system for RCC has undergone multiple revisions with the most
recent edition being the 2010 version
140

RCC Stage grouping
Stage 1 T1 NO MO
Stage 2 T2 NO MO
Stage 3
T1, T2, T3
T3
N1
N0
MO
MO
Stage 4
T4
ANY T
ANY N
ANY N
MO
M1
142

grading
• Grading has been
based primarily on
nuclear size and shape
and the presence or
absence of prominent
nucleoli. Fuhrman’s
System has been most
generally adopted and
is now recognized as an
independent prognostic
factor for RCC
generally and for clear
cell RCC in particular
(Fuhrman et al, 1982; Pantuck et al, 2001a; Lang et al,
2005; Lohse et al, 2005; Zhou, 2009). 143

Prognostic Factors for RCC
ANATOMIC
• Tumor size
• Venous involvement
• Extension into contiguous
organs
• Adrenal involvement
(direct or metastatic)
• Lymph node metastases
• Distant metastases
• Metastatic burden of
disease
CLINICAL
• Perfomance status
(karnofsky,ECOG,WHO)
• Systemic symptoms
(cachexia,loss of >10% of body
weight)
• Symptomatic vs incidental
presentation
• Anemia
• Hypercalcemia
• Elevated lactate
dehydrogenase
• Elevated erythrocyte
sedimentation rate
• ElevatedC-reactiveprotein
• Thrombocytosis
• Elevated alkaline phosphatase 144

Prognostic Factors for RCC
HISTOLOGIC
• Fuhrman Nuclear grade
• Histologic subtype
• Presence of sarcomatoid
features
• Presence of histologic
necrosis
• Vascular invasion
• Invasion of perinephric
or renal sinus fat
• Collecting system
invasion
• Surgical margin status
MOLECULAR
• Hypoxia inducible factors:
– CA-IX, IGF-1, VEGF, VEGFRs,
CA-XII, CXCR3, CXCR4, HIF
• Costimulatory molecules:
– B7-H1, B7-H3 (tumor
cell/vascular), B7-H4, PD-1
• Cell cycle regulators:
– PTEN, TP53, Bcl2, Cyclin
A, CDKN1B, Skp2
• Adhesion molecules:
– EpCAM, EMA, E-Cad, α-
catenin,Cad-6
• Other factors:
– Ki-67, XIAP, Survivin, EphA2, Smac/DIABLO, PCNA,
Caveolin-1, AR,CD44, AnnexinII,Gelsolin, Vimentin, CA-
125),aberrant DNA methylation, Na+,K+ATPase α1
subunit, vitamin D receptor, retinoidX receptor
145

Management of localized RCC
 T1-2, NO, MO
• Nephron Sparing Surgery (NSS)
– Open, pure laparoscopic, robot-assisted
– Unsuitable in;
• Locally advanced tumor growth
• Partial resection is not feasible due to unfavourable tumor
location
• Significant deterioration in patient health
• Laparoscopic Radical nephrectomy for patients with T2 tumors and
localised masses not treatable by PN
– 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
• Ipsilateral adrenalectomy is not recommended if no clinical evidence of
invasion of the adrenal gland
• LND is not recommended in localized tumor without clinical evidence of
LN invasion 146

• Laparoscopic/robotic radical nephrectomy is being used
increasingly for patients with localized renal tumors.
– This approach results in quicker recovery compared to
open radical nephrectomy
– approach of choice in appropriate patients with <10 cm
tumors and without local extension or a renal vein or
caval thrombus (Gill et al, 2001; Portis et al, 2002).
• Partial nephrectomy (NSS) and wedge resection with an
adequate margin of normal parenchyma
– standard primary surgical therapy for patients with
tumors <4 cm in size, even in the presence of a normal
contralateral kidney.
– Local recurrence of tumor in the same kidney ranges
from 0% to 10%, and it is between 0% and 3% for tumors
<4 cm in size (Hafez et al, 1997; Morgan and Zincke, 1990; Uzzo and Novick, 2001).
147

• Non-surgical management
– Tumors less than 4 cm
– Older and frail patients (more than 75 years)
– Active surveillance (initial monitoring of tumor size by serial abdominal imaging with
delayed intervention reserved for tumors showing clinical progression during follow-up)
• Ablative therapies
– Cryoablation, percutaneous or laparoscopic
– Radiofrequency ablation, laparoscopic or percutaneous
– Other ablative therapies in trial,
• Microwave ablation
• Laser ablation
• High – intensity focussed US ablation
148

• use of cryoablation, high-intensity focused US, and
radiofrequency ablation (Murphy and Gill, 2001).
– for the treatment of small, incidentally discovered renal
lesions
– liquid nitrogen or argon gas, either percutaneously using
MRI guidance or via laparoscopic probes
– in patients with single or multiple small lesions or in
– older individuals with many co morbidities.
– Bleeding, scarring of renal pelvis, and urine leak are
among the commonly reported complications with the
ablative therapies.
149

Management of locally advanced
RCC
• Clinically positive lymph nodes (cN+)
– LND is justified
• Locally advanced unresectable RCC
– Embolization can control symptoms(hematuria,
frank pain)
• RCC with venous thrombus
– Excision of kidney tumor and caval thrombus is
recommended in non-metastatic RCC
• No evidence for the use of adjuvant therapy
VEGF-R or mTOR inhibitors 150

Management of locally advanced
RCC
• Preoperative renal artery embolization (angioinfarction) as
a surgical adjunct to facilitate radical nephrectomy,
– decreases blood loss or facilitates surgery,
– patients with very large tumors in which the renal artery
may be difficult to reach early in the procedure.
– useful to palliate patients with nonresectable tumors and
significant symptoms such as hemorrhage, flank pain, or
paraneoplastic syndromes.
• Radiation therapy has been advocated as a neoadjuvant
(preoperative) or adjuvant method to radical nephrectomy,
– no evidence that postsurgical radiation (adjuvant)
therapy to the renal bed, whether or not residual tumor is
present, contributes to prolonged survival. 151

Management of advanced/metastatic
RCC
Local therapy of advanced/metastatic RCC
1. Cytoreductive nephrectomy – palliative
– Systemic treatments necessary (immunotherapy e.g.
INF-a/ target therapy e.g sunitinib, sorafenib)
– Indications of cytoreductive nephrectomy
– Mrcc patients with good PS
– Large primary tumors
– Low metastatic volume
152

Management of advanced/metastatic
RCC
Local therapy of advanced/metastatic RCC
2. Embolisation of primary tumor
– In patients unfit for surgery, or with non-
resectable disease
– Control symptoms (haematuria or flank pain)
153

Management of advanced/ metastatic
RCC
Local therapy for metastases in mRCC
• Metastasectomy (complete/no/incomplete)
– With exceptionof brain and possibly bone
metastases, metastasectomy remains by default
the most appropriate local treatment for most
sites.
• The decision to resect metastases has to be
taken for each site, and on a case-by-case
basis; performance status, risk profiles, patient
preference and alternative techniques to
achieve local control, must be considered. 154

Management of advanced/ metastatic
RCC
Local therapy for metastases in mRCC
• Radiotherapy to bone and brain metastases
from RCC can induce significant relief from
local symptoms (e.g. pain).
• In individual cases, stereotactic radiotherapy
for bone metastases, and stereotactic
radiosurgery for brain metastases can be
offered for symptom relief.
155

Systemic therapy for
advanced/metastatic RCC
CHEMOTHERAPY
RCC resistant to chemotherapy
• Chemotherapy is moderately effective only if 5-
fluorouracil (5-FU) is combined with
immunotherapeutic agents (INF-a, IL-2)
• In patients with clear-cell mRCC, chemotherapy
is not considered effective.
156

Systemic therapy for advanced/ metastatic RCC
IMMUNOTHERAPY
• INF-a monotherapy and combined bevacizumab
• Conflicting results exist for IFN-a in ccmRCC
• IFN- may only be effective in some patient subgroups,α
including patients with ccRCC, favourable-risk criteria, as
defined by the Memorial Sloan-Kettering Cancer Center
(MSKCC) and lung metastases only
157
RISK FACTORS* CUT-OFF POINT USED
Karnofsky PS < 80
Time from diagnosis to treatment < 12 months
Haemoglobin < Lower limit of laboratory reference range
LDH > 1.5 times the upper limit of laboratory
range
Corrected serum calcium > 10.0 mg/dL (2.4 mmol/L)

Systemic therapy for advanced/ metastatic RCC
• The interferons ,INF alpha
– are natural glycoproteins with antiviral, antiproliferative, and immunomodulatory
properties.
– These agents have a direct antiproliferative effect on renal tumor cells in vitro,
stimulate host mononuclear cells, and enhance expression of major
histocompatibility complex molecules.
• IL-2
– Is a T-cell growth factor and activator of T cells and natural killer (NK) cells.
– IL-2 affects tumor growth by activating lymphoid cells in vivo without affecting
tumor proliferation directly.
– High-dose interleukin-2 (IL-2) can induce durable long-term remission in 10% of
patients with advanced kidney cancer, and must be considered for robust patients
with excellent cardiopulmonary reserve
– The major toxic effect of high-dose IL-2 is a sepsislike syndrome,(progressive
decrease in systemic vascular resistance and an associated decrease in
intravascular volume due to capillary leak). Other toxic effects are fever, chills,
fatigue, infection, and hypotension.
158

Systemic therapy for advanced/ metastatic
RCC
• Use of several antiangiogenic agents and inhibitors of tyrosine kinase and
other cell cycle activators in RCC.
• Bevacizumab
– is a monoclonal antibody that binds and inactivates VEGF A.
– delay disease progression, and improve survival in patients with advanced renal cancer
(Yang et al, 2003).
• Anti-VEGF TKIs (Sorafenib, Sunitinib, and Pazopanib)
– orally bioavailable.
– Sunitinib and pazopanib have signiﬁcant activity in the ﬁrst-line
setting with higher response rates and longer progression-free survival
compared to IFN or placebo (Motzer et al, 2007; Sternberg et al, 2010).
– Sorafenib was shown to have activity in patients who had previously
received cytokine immunotherapy. (Escudier et al, 2009).
– Toxicities
• hypertension, diarrhea, rash, handfoot skin reactions, cardiac
abnormalities, and many others. 159

Systemic therapy for advanced/ metastatic
RCC
• mTOR inhibitors (Temsirolimus, Everolimus )
– Temsirolimus,first line therapy, prolong survival in patients with
advanced renal cancer who present with poor risk or multiple sites of
metastases (Hudes et al, 2007).
– Everolimus prolong progression-free survival as second-line therapy
for patients with metastatic clear-cell RCC (Motzer et al, 2010).
– Toxiicities of mTOR inhibitors
• mouth sores,
• fatigue, pneumonitis,
• hypertriglyceridemia
• among other side effects.
160

FOLLOW-UP AFTER RADICAL NEPHRECTOMY OR
PARTIAL NEPHRECTOMY OR ABLATIVE THERAPIES
FOR RCC
• Surveillance after treatment for RCC allows the urologist to monitor or
identify:
– Postoperative complications
– Renal function
– Local recurrence after PN or ablative treatment
– Recurrence in the contralateral or ipsilateral (after PN) kidney
– Development of metastases
• stage T1 disease
– yearly chest x-rays
– liver and renal function tests.
• Those with stage T2 or T3 disease
– least 3-month or 6-month intervals in the early postoperative period.
– Repeat CT scans of the abdomen, especially in those who have
undergone partial nephrectomy, to rule out local recurrence. 161

FOLLOW-UP AFTER RADICAL NEPHRECTOMY OR
PARTIAL NEPHRECTOMY OR ABLATIVE THERAPIES
FOR RCC
• metastatic disease who are not undergoing therapy
– need continued follow-up to provide appropriate
supportive care.
• Prognosis
– The prognosis of patients is most clearly related to the
stage of disease at presentation.
– stage T1–T2 disease in the 80–100% range,
– stage T3 in the 50–60% range.
– metastatic disease have a poorer prognosis, with only a
16–32% 5-year survival rate.
162

Sarcomas of the Kidney
• Sarcomas represent 1% to 2% of all malignant renal tumors in adults
• peak incidence in the fifth decade of life (Srinivas et al, 1984; Russo, 1991; Spellman et al, 1995;
Frank et al, 2000).
• Renal sarcoma is less common but more lethal than sarcoma of any other
genitourinary site, including the prostate, bladder, and paratesticular
region (Russo, 1991; Russo et al, 1992).
• Differentiation of renal sarcoma from sarcomatoid RCC is often difficult
on the basis of
– clinical presentation,
– radiographic findings, and, in some cases,
– pathologic analysis.
163

• The common signs and symptoms associated with renal sarcoma in adults
– include palpable mass, abdominal or flank pain, and hematuria and are
similar to those seen with large, rapidly growing RCCs (Economou et al, 1987).
– Renal sarcoma should be suspected in any of these circumstances or in any
patient with a very large or rapidly growing renal mass
164

• Abdominal CT typically demonstrates
– a large soft tissue mass involving or derived from the kidney, a
finding that is again similar to that associated with many
sarcomatoid RCCs (Farrow et al, 1968; Shirkhoda and Lewis, 1987; Russo, 1991).
– Specific findings suggestive of sarcoma rather than of RCC include
• apparent origin from the capsule or perisinuous region,
• growth to large size in the absence of lymphadenopathy,
• presence of fat or bone suggestive of liposarcoma or
osteosarcoma, and
• hypovascular pattern on angiography, although one notable
exception is the hemangiopericytoma, which is highly vascular
(Smullens et al, 1982; Shirkhoda and Lewis, 1987).
• MRI can be useful for preoperative planning by defining tissue planes and
proximity to vital structures.
165

• These tumors are derived from mesenchymal
components
– thus free of the natural barriers to dissemination
that confine other tumor types.
• They are typically surrounded by a pseudocapsule
that is readily identifiable
– cannot be relied on for surgical dissection because it is
often infiltrated with cancer cells, which can extend for
some distance into the surrounding tissues
– In many cases this cannot be recognized macroscopically,
– it is often manifested in the form of local recurrences,
which are common after surgical extirpation, even when
a wide excision has been performed.
166

• This is primarily a surgical disease, and wide excision is the goal with
intraoperative monitoring of margin status
– The initial resection is the key event because, for many patients, this is their best chance for
a long-term cure.
– this often mandates radical nephrectomy along with en bloc excision of
adjacent organs (Srinivas et al, 1984; Brescia et al, 2008).
• Chemotherapeutic agents that have demonstrated activity against
metastatic sarcomas
– include doxycycline and ifosfamide, Antman et al, 1993).
• most important prognostic factors for sarcomas are margin status and tumor
grade.
• High-grade sarcomas often metastasize
– Saitoh and colleagues (1982) defined the common sites of metastases of
renal sarcomas: lung first and foremost but also lymph nodes and liver.
• Low-grade sarcomas tend to pursue a more indolent course,
– local recurrences often require repeat resection to prolong survival and
minimize morbidity. 167

• The combination of radiation therapy and
chemotherapy,
– effective in an adjuvant setting for the
management of sarcomas of the extremity,
– not much benefit for renal or retroperitoneal
sarcomas (Russo, 1991).
168

1. Leiomyosarcoma of the Kidney
• is the most common histologic subtype
• accounting for 50% to 60% of such tumors.
• The cell of origin is the smooth muscle cell of the capsule or
other perinephric structures (Moudouni et al, 2001; Deyrup et al, 2004).
• female predominance;
• most patients presented in the fourth through sixth decades
of life.
• Renal leiomyosarcoma, tends to displace rather than invade
the parenchyma, and is characterized by rapid growth rate,
frequent metastasis, and high local and systemic recurrence
rates (Pollack et al, 1987; Deyrup et al, 2004).
169

2. Renal Liposarcoma
• readily distinguished from RCC because of the
– presence of adipose tissue, but it is often confused
with AMLs or with large, benign renal lipomas (Frank
et al, 2000).
– Renal liposarcoma typically develops in the fifth
and sixth decades of life and often grows to
extremely large size (Economou et al, 1987).
– Response to radiation therapy and cisplatin-
based chemotherapy in an adjuvant setting has
been reported (Belldegrun and deKernion 1987)
170

Osteogenic sarcoma of the Kidney
• is a rare but distinctive form of renal sarcoma that
contains calcium and is often rock hard (Micolonghi et al, 1984;
Leventis et al, 1997).
– Extensive calcification in a large, hypovascular
tumor should suggest the diagnosis.
– The appearance on plain films can mimic a
staghorn calculus, but the readily evident mass
effect should suggest xanthogranulomatous
disease or, more rarely, osteogenic sarcoma.
– prognosis is poor; most patients die of disease
progression within a few years after diagnosis
171

Malignant hemangiopericytomas
• present at a mean age of 40years, which is younger
than most other renal sarcomas,
– notable for their extensive vascularity (Argyropoulos et al, 2005;
Chaudhary et al, 2007; Brescia et al, 2008).
– Preoperative angioembolization has been
described and may simplify surgical excision (Smullens et
al, 1982).
172

Other Sarcomas of the Kidney
• Less common histologic subtypes include
– Rhabdomyosarcoma,
– Fibrosarcoma,
– Carcinosarcoma,
– Malignant Fibrous Histiocytoma,
– Synovial Sarcoma,
– Schwannoma,
– Angiosarcoma,
(Raghavaiah et al, 1979; Weiss et al, 1984; Mordkin et al, 1997; Tsuda et al, 1997; Cerilli et al, 1998; Merchant et al, 1998; Chieng et
al, 1999; Koyama et al, 2001; Bella et al, 2002; Chen et al, 2003; Shannon et al, 2005; Khan et al, 2006; Leggio et al, 2006;
Hung et al, 2008; Mirza et al, 2008)
173

Renal Lymphoma and Leukemia
• Renal involvement with hematologic malignant neoplasms, which
include the lymphomas and leukemias, is common
– found at autopsy in approximately 34% of patients dying of progressive lymphoma or
leukemia.
• uncommonly seen in clinical practice
– often silent and generally occur only as a late manifestation of
systemic disease (Richmond et al, 1962; Pollack et al, 1987; McVary, 1991).
• Renal involvement is more common with non-Hodgkin’s lymphoma than
with Hodgkin’s disease, (Richmond et al, 1962; Pollack et al, 1987; Yasunaga et al, 1997; O’Riordan et al,
2001).
• Primary renal lymphoma is rare, given the relative paucity of lymphoid
tissue in the normal renal parenchyma.
• Hematogenous dissemination most common and is thought to occur in
90% of cases;
– direct extension from retroperitoneal lymph nodes accounts for the
remainder.
174

• lymphomas are more common in patients with iatrogenic immune
suppression, acquired immunodeficiency syndrome (AIDS), autoimmune
diseases, or graft-versus-host disease and in patients with a history of
radiation therapy (McVary, 1991).
• Renal lymphoma should be suspected in patients with massive
retroperitoneal lymphadenopathy, splenomegaly, or lymphadenopathy
in other regions of the body or atypical regions within the
retroperitoneum (Jafri et al, 1982; Dimopoulos et al, 1996).
• The CT scan is the radiographic modality of choice for the diagnosis of
renal lymphoma and for monitoring response to therapy (Jafri et al, 1982; Pollack et
al, 1987; Sheeran and Sussman, 1998; Urban and Fishman, 2000).
– Renal lymphoma can present as multiple distinct renal masses;
– as a solitary renal mass, which can be difficult to differentiate from RCC;
– as diffuse renal infiltration;
– or as direct invasion of the kidney from enlarged retroperitoneal nodes (Cohan et al, 1990;
Heiken et al, 1991; Eisenberg et al, 1994; Sheeran and Sussman, 1998; Sheth et al, 2006).
175

• The main landing zones for RCC should be kept in mind
– the interaortocaval region for right RCC
– and para-aortic region for left RCC
– and lymphadenopathy centered outside of these areas should raise
suspicion for lymphoma.
• A hypovascular pattern on angiography is typical for renal
lymphoma (Pollack et al, 1987).
• Any patient with a prior history of lymphoma and a renal
mass should also be evaluated for renal recurrence rather
than for RCC.
176

• Renal involvement related to leukamia
– more common children, paralleling the demographics of the disease
– commonly due to lymphocytic leukemia than the myelogenous forms (Araki, 1982;
Pollack et al, 1987).
– Leukemia typically involves the kidney in a diffusely infiltrative pattern
– often represents a late manifestation of systemic disease.
• Both renal lymphoma and leukemia are commonly silent
– can be associated with hematuria, flank pain, or progressive renal failure.
Fever, weight loss, and fatigue, (B symptoms )(Yasunaga et al, 1997; Zomas et al, 2004).
– Renal failure can be due to extensive replacement of the functioning
parenchyma or bilateral ureteral obstruction associated with enlarged
retroperitoneal lymph nodes (McVary, 1991).
– renal failure in such patients is more often related to medical causes, such as
hypercalcemia or urate nephropathy, that can develop during systemic
treatment of advanced disease.
177

• If lymphoma or leukemic renal involvement is suspected,
– percutaneous biopsy to obtain a pathologic diagnosis;
– and if exploratory surgery is necessary, intraoperative biopsy and
frozen-section analysis should take priority.
• Truong and colleagues (2001) have demonstrated the utility of fine-
needle aspiration in the diagnosis of renal lymphoma
• If lymphoma or leukemia is confirmed,
– the kidney should be spared and complete staging of the neoplasm
should be performed to preclude the need for a secondary procedure
(McVary, 1991).
• Extirpative surgery should be avoided if renal lymphoma and leukemia
are suspected
– treatment of these processes is generally systemic chemotherapy with or without
radiation therapy.
178

• The classic chemotherapy regimen for non-Hodgkin’s lymphoma
– CHOP protocol, which includes cyclophosphamide, doxorubicin,
vincristine, and prednisolone (Colevas et al, 2000).
• Nephrectomy is seldom indicated
– except in patients with severe symptoms, such as uncontrollable
hemorrhage.
– The other notable exception is the extremely rare patient with
primary renal lymphoma in whom a combination of nephrectomy
and systemic chemotherapy may represent optimal therapy (Okuno et al,
1995; Garcia et al, 2007).
• E.g marginal zone B-cell lymphoma (MALT) localized to the
kidney have been described with some apparently cured by
surgery alone (Garcia et al, 2007).
179

Carcinoid tumors
• arise from Primitive stem cells within the kidney or
retained neural crest tissue (Krishnan et al, 1997; Begin et al, 1998).
• This is thus a rare renal malignant neoplasm with
fewer than 60 cases reported in the English
literature (Kawajiri et al, 2004; Mufarrij et al, 2005; Romero et al, 2006; Hansel et al, 2007; Lane et al,
2007b; Canacci et al, 2008).
• A correlation with horseshoe kidneys
• stain positive for markers of neuroendocrine tissue
such as neuron-specific enolase and chromogranin
(Kulke and Mayer, 1999; Lane et al, 2007b).
180

Carcinoid tumors
• Presentation of carcinoid syndrome (Jensen and Doherty, 2001; Romero et al, 2006;
Lane et al, 2007b).
– Median age at diagnosis is 49 years (Romero et al, 2006).
– episodic flushing,
– wheezing,
– and diarrhoea
• diagnosis
– Measurement of urinary or plasma serotonin or its
metabolites can be diagnostic (Kulke and Mayer, 1999).
– renal carcinoids, metastases were found in 46% of patients
at diagnosis (Romero et al, 2006)
– CT findings are nonspecific, and many renal carcinoids are
small and nonaggressive.
181

Carcinoid tumors
• Management
– Surgical excision is the mainstay of treatment (Kawajiri et al, 2004).
– Nephron-sparing surgery is preferred if the diagnosis is suspected
preoperatively.
• prognosis
– Prognosis is good, particularly when associated with a horseshoe
kidney (Krishnan et al, 1997; Begin et al, 1998; Lowrance et al, 2006).
– Significant adverse prognostic factors include (Romero et al, 2006).
• age older than 40 years,
• tumor size greater than 4 cm,
• high mitotic rate,
• purely solid gross morphology,
• metastasis at initial diagnosis,
• and tumor extending through the renal capsule
182

NEUROENDOCRINE TUMORS
• include
– small cell carcinoma and
– large cell neuroendocrine carcinoma
• can occur in the kidney but are even less common than
renal carcinoids (Gonzales-Lois et al, 2001; Majhail et al, 2003; Lane et al, 2007).
• Presentation
– flank pain or hematuria is common (Majhail et al, 2003; Mirza et al, 2007).
– Many small cell carcinomas of the kidney are locally
advanced or metastatic at presentation, and
• Positive staining for neuron-specific enolase,
chromogranin, and synaptophysin is characteristic (Akkaya et al,
2003).
183

Neuroendocrine Tumors
• Preoperative differentiation from RCC is difficult,
although a
– relatively hypovascular pattern may be an indication.
• Multimodal therapy
– with nephrectomy or tumor debulking combined with
platinum-based chemotherapy regimens is advocated
for extrapulmonary small cell carcinoma in general
and may also be useful for the renal manifestation of
this malignant neoplasm (Majhail et al, 2003; Mirza et al, 2007).
• prognosis
– Long-term survivors are described but rare
184

Metastatic Tumors
• most common malignant neoplasms in the kidney,
outnumbering primary renal tumors
– Autopsy studies have shown that 12% of patients dying of
cancer have renal metastases, making the kidney one of
the most common sites for metastatic dissemination (Pollack et
al, 1987).
• The profuse vascularity of the kidney makes it a fertile soil
for the deposition and growth of cancer cells.
– Almost all renal metastases develop through a
hematogenous route of spread;
– only a small minority are caused by direct invasion of
tumors derived from adjacent organs such as the
pancreas, colon, and adrenal gland.
185

Metastatic Tumors
• The most common sources of renal metastases
include lung, breast, and gastrointestinal cancers;
malignant melanoma; and the hematologic
malignant neoplasms (Klinger, 1951; Choyke et al, 1987; Pollack et al, 1987; Aron et al, 2004;
Martino et al, 2004; Sánchez-Ortiz et al, 2004b; Stage et al, 2005).
• renal metastases consists of multiple small nodules
that are often clinically silent,
– can lead to hematuria or flank pain in
exceptional circumstances (Walther et al, 1979; Pollack et al, 1987).
186

Metastatic Tumors
• Renal metastases should be suspected in
– any patient with multiple renal lesions
– widespread systemic metastases
– history of nonrenal primary cancer.
• If there is any uncertainty about the diagnosis,
– a CT- or ultrasound-guided percutaneous renal biopsy usually provides pathologic
confirmation (Gattuso et al, 1999; Sánchez-Ortiz, 2004a).
– CT is the primary diagnostic modality for renal metastases and typically demonstrates
isodense masses that enhance only moderately after administration of intravenous
contrast material (Pollack et al, 1987; Ferrozzi et al, 1997).
• Most patients with renal metastases are managed
– with systemic therapy
– or placed on a palliative care pathway, depending on the clinical circumstances.
– Nephrectomy is almost never required except in extenuating circumstances, such as
uncontrollable renal hemorrhage. 187

References
1. Campbell Walsh Urology 10th
Edition; 1413-1505
2. Smith and Tanagho’s General Urology 18th
Edition; 330-349
3. AUA guidelines
4. EUA guidelines, 2015
5. http://www.uonbi.ac.ke/ Digital Repository
6. http://www.emedicine.medscape.com
7. http://radiopaedia.org/articles/renal-cell-carcinoma
188

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