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Renal tumors
1. Tumors of the kidney
Moderator: Dr. Sharad Seth (Professor and Head)
Department of Surgery
By Dr. Shruti Devendra JR1 Surgery
Date: 2 June 2020
RMCH, BLY
2.
3. Benign renal tumors
1. Majority of the renal masses are benign renal tumors
2. Majority are found incidentally or on autopsy
3. Majority are confused with RCC on radiology and at times with histology
with different variants of RCC
4. Generally more common in females (except, papillary adenoma and
onycocytoma)
5. Can be confirmed by immunohistochemistry if biopsy done before
surgery
6. Sporadic are mostly benign, solitary, unilateral, hereditary are multifocal,
at times malignant
7. Management by watchful waiting, nephron sparing surgery, or ablation
5. Sporadic renal cyst
Renal cyst are the most common benign renal lesions.
70% of all the asymptomatic renal masses.
Regarding the risk factors for the development of cysts,
increasing age, male gender, presence of hypertension,
and presence of renal insufficiency were all associated
with the development of sporadic renal cysts
6. Renal cystic lesions can be imaged through ultrasonography, CT, and
MRI.
The Bosniak classification for renal cystic lesions, is widely employed
method for characterizing renal cystic lesions and for assessing the
likelihood of the presence of a concomitant malignancy within the cyst
7.
8.
9. Polycystin 1 and 2 proteins complex to form a critical ion channel in the
kidney, the loss of which leads to intracellular calcium dysregulation
Defects in primary cilia—nonmotile organelles present on the surface of
renal tubular epithelial cells
PKHD1 (polycystic kidney and hepatic disease 1) gene, were found to
be the cause of ARPKD
10. Papillary adenoma
• The incidence increases with age (40% of patients over 70 years of age in
autopsy studies)
• Male sex, and
• Associated with acquired renal cystic disease
• Found on autopsy 7 to 23%
• To be considered papillary adenomas, these lesions should histologically
be 5 mm or smaller
11. Well circumscribed; characterized by
uniform basophilic or eosinophilic cells
Benign-appearing nuclear and cellular
features; and
Arranged in papillary, tubular, or
tubulopapillary architecture
12. There are no reliable histopathologic, ultrastructural, or
immunohistochemical criteria to distinguish benign from malignant
lesions of the kidney
These lesions may be linked to the development of papillary RCC and
represent as a premalignant precursor. Papillary adenoma associated
with papillary RCC are multiple
13.
14. Renal adenoma
Renal adenoma is defined as a tumor with nuclear grade I and a
diameter of at least 1 cm
Tumors larger than 3 cm were associated with metastases.
All solid renal epithelium-derived masses are potentially malignant and
therefore should undergo treatment
15. ANGIOMYOLIPOMA
Less than 10% of renal tumors
On autopsy series and ultrasound-screened populations showing incidences of
0.3% and 0.13%
younger age (mean age 30 years)
female-to-male predominance (2 : 1)
Derived from perivascular epithelioid cells referred to as PEComas
(perivascular epithelioid cell tumors)
16. Strongly expresses estrogen receptor β, progesterone receptor, and
androgen receptor; is predominantly found in females
Rare before puberty, suggesting a potential hormonal influence
17. • TSC1 on chromosome 9q (encoding for hamartin protein) – 10%
• TSC2 on chromosome 16p (encoding for tuberin protein) -68%
• No mutation -22%
• Sporadic presentation: seen in middle-aged woman with a single
asymptomatic tumor
Approximately 50% of patients with TSC develop angiomyolipomas
Tuberous sclerosis complex (TSC)
18.
19. Benign neoplasm; in its classic form it consists of thick-walled poorly
organized blood vessels, smooth muscle, and varying levels of mature
adipose tissue
Most common renal neoplasm associated with spontaneous perirenal
hemorrhage, closely followed by RCC
20. The Wunderlich syndrome, or massive retroperitoneal hemorrhage, the
most significant complication was reported in up to 10% of patients and
could be associated with significant morbidity and potential mortality if
not promptly treated
Pregnancy appears to increase the risk of hemorrhage from
angiomyolipoma
21. A, Computed tomography scan
demonstrating large bilateral renal
angiomyolipomas in a patient with
tuberous sclerosis.
B, Typical microscopic appearance of
angiomyolipoma with admixture of mature
adipose tissue, smooth muscle, and thick
walled blood vessels.
22. Renal angiogram shows increased vascularity
and aneurysmal dilation characteristic of
angiomyolipoma.
23. Because of non-specific nature of this tumor it is often treated as
presumed RCC
In case of high suspicion core biopsy should be done
Immunohistochemistery with HMB-45 (human melanoma black 45
monoclonal antibody is characteristic of angiomyolipoma
24. Once diagnosis is confirmed. Tumor size is the cutoff for management
<4 cm tumors are less than 20% times symptomatic (slow growth and less
risk of hemorrhage)
Whereas >4 cm are more than 82% times symptomatic with 9% presenting
with haemorrhagic shock
25. Multifocal angiomyolipoma or asso. With TS have higher growth rate
(20% per year)
In contrast for solitary, sporadic tumore growth rate is 5% per year
27. Sacrolimus : mTOR pathway inhibitor, (-) IL2 – (-) T and B cell
activation. When used as a neoadjuvant the tumor volume shrinkage is
shown to be of about 38% to 95%
28. Renal cell carcinoma
2% to 3% of all adult malignant neoplasms, is the most lethal of the
common urologic cancers
5 years survival rate of 71%
Male-to-female predominance of 3 : 2
Seen between 50 and 70 years of age
29. The majority of cases are sporadic
Only 2% to 3% are proven to be familial
Incidence rates are 10% to 20% higher and 5-year survival rates 5%
lower in African-Americans
30. RCC in childhood is uncommon, only 2.3% to 6.6% of all renal tumors
in children
If present in children it is usually high grade, locally advanced and
symptomatic
31. RCC - Etiology
Tobacco exposure carries relative risk of 1.4 to 2.5 (20-30% cases of
RCC in men and 10-20% cases in women)
Obesity with relative risk of 1.07 for each additional unit BMI
• increased insulin-like growth factor-1 expression
• increased circulating estrogen levels
• increased arteriolar nephrosclerosis and local inflammation
Hypertension third major etiologic factor for RCC. Due to renal injury
and functional changes
32. Family history of RCC in 1st and 2nd degree relatives with relative risk of
2.9
Regular NSAIDs use with relative risk of 1.51
Retroperitoneal radiation therapy for wilm’s or testicular tumor
End-stage renal disease and familial syndromes such as tuberous
sclerosis
33. Other factors which have conflicting data are
• Western diet (high in fat and protein)
• Increased dairy products
• Coffee or tea
• People working in metal, rubber or painting industries
• Urban background or low socioeconomic status
34. Familial renal cell carcinoma
1. von Hippel-Lindau Disease
• Autosomal dominant
• RCC develops in about 50%
• Major manifestations include the development of RCC,
pheochromocytoma, retinal angiomas, and hemangioblastomas of the
brainstem, cerebellum, or spinal cord
35. VHL tumor suppressor gene:
• Translocations involving chromosome 3 (3p25-26) leads to loss of
tumor suppressor action
• Related to both sporadic and familial forms of clear cell RCC
36.
37.
38. VHL protein mediates
degradation of hypoxia-
induced factor 2 alpha
(HIF 2alpha) leading to
its degradation
In VHL gene mutation
HIF 2 alpha accumulates
in the cell
HIF is a stress response
protein to hypoxia and
starvation
On accumulation it
stimulates VEGH, PDGF,
GLUT 1
39.
40. Other genes related to clear cell RCC
Include PBRM1, BAP1, and SETD2, are all involved in chromatin
remodeling and histone methylation
41. 2. Familial Papillary Renal Cell Carcinoma
Second most common subtype after VHL
Type 1 papillary RCC: HPRCC (hereditary papillary RCC)
Type 2 papillary RCC: Familial syndrome
42. Missense mutations of the c-MET proto-oncogene at 7q31 is the most
important mutation related to HPRCC and also found in sporadic
papillary RCC in 13 % cases
The protein product of this gene is the receptor tyrosine kinase for
hepatocyte growth factor, also known as scatter factor, and its activation
leads to cellular proliferation and other potential tumorigenic effects
43. Type 2 papillary RCC: Familial syndrome in which patients commonly
develop cutaneous and uterine leiomyomas
Fumarate hydratase gene on chromosone 1q42-44
Fumarate hydratase is an essential enzyme in the Krebs cycle of
oxidative metabolism.
44. Inactivation of mitochondrial oxidative metabolism prevents creating
ATP from glucose cell senses anaerobic or hypoxic environment
increased expression of growth factors promote tumorigenesis.
45.
46. 3. Succinate Dehydrogenase Renal Cell Carcinoma
• Multiple genes encoding subunits of the Krebs cycle enzyme
succinate dehydrogenase are at increased risk for RCC
• SDH-RCC typically present with early onset and aggressive disease
• Wide surgical excision of these tumors when suspected is
recommended
50. RCCs were traditionally thought to arise primarily from the proximal
convoluted tubules, and this is probably true for the clear cell and
papillary variants.
However, we now know that other histologic subtypes of RCC, such as
chromophobe RCC and collecting duct carcinoma, are derived from the
more distal components of the nephron
51. RCC - Pathology
Most RCC are
Ovoid, circumscribed with pseudocapsule due parenchymal
compression and fibrous tissue
Not grossly infiltrative except collecting duct cancer
Average size is 4-8 cm but can fill entire abdomen
52. RCC consists of yellow, tan or brown tumor interspersed with fibrous,
necrotic or hemorrhagic area
Cystic degeneration in 10-25% cases
Calcification: stippled or plaque like 10-20% cases
Venous system involved in 10% cases (most commonly IVC can extend
to right atrium)
53. Frank invasion and perforation of the renal capsule, renal sinus, or
collecting system are found in approximately 20% of cases
Most sporadic RCCs are unilateral and unifocal
Bilateral seen with familial RCC such as VHL disease
Multicentricity associated with papillary histology and familial RCC
54. All RCCs are, by definition, adenocarcinomas
Common type arises from PCT cell lining
Aggressive subtypes collecting duct and renal medullary carcinoma
56. A, Clear cell renal cell carcinoma (RCC)
with typical golden yellow color.
B, Low power view of typical microscopic
appearance of a low-grade clear cell RCC
demonstrating a delicate vascular network
interspersed within homogeneous nests of
cells with clear cytoplasm.
58. A, Papillary renal cell carcinoma (RCC) often presents
with multiple small, mildly enhancing renal tumors as
demonstrated on this computed tomography image. B,
Microscopic appearance of type 1 papillary RCC
demonstrating basophilic cells with scant cytoplasm and
low-grade nuclei. C, In contrast, type 2 papillary RCC
consists of eosinophilic cells with abundant granular
cytoplasm and high-grade nuclei.
60. A, Chromophobe renal cell
carcinoma (RCC) typically
appears as a wellcircumscribed,
homogeneous, tan tumor.
B, Chromophobe RCC with
admixture of classic
(chromophobic) and
eosinophilic cells.
Characteristic features include
distinct cytoplasmic borders,
perinuclear “halos,” and nuclear
“raisins.” The classic variant is
notable for its “plant cell”
appearance.
C, Chromophobe RCC stains
positive for Hale colloidal iron
and demonstrates multiple
microvesicles on analysis by
electron microscopy.
61. Sarcomatoid Differentiation (unclassified RCC): association with clear cell RCC or chromophobe RCC, but variants of
most other subtypes of RCC. Extremely poor prognosis
62. Clinical presentation
Because of the sequestered location of the kidney within the
retroperitoneum, many renal masses remain asymptomatic and
nonpalpable until they are locally advanced
More than 60% of RCCs are now detected incidentally
Classic triad of flank pain, gross hematuria, and palpable abdominal
mass is now rarely found (refer to it as the “too late triad.”)
63.
64. Constitutional symptoms such as weight loss, fever, and night sweats
Physical examination findings such as palpable cervical
lymphadenopathy
Symptoms directly related to metastatic disease, such as bone pain or
persistent cough
65. More than 50% of patients present with perirenal hematoma of unclear
etiology have an occult renal tumor
Paraneoplastic syndrome seen in 10-20% cases
Hypercalcemia (13%) –
• parathyroid hormone–like peptides is the most common
• tumor-derived 1,25-dihydroxycholecalciferol and prostaglandins
(minor cause)
Zoledronic acid, 4 mg intravenously every 4 weeks
66. Hypertension –
• Renin production from tumor
• Renal artery – encasement by tumor, stenosis
• A-V fistula
Polycythemia –
• Production of erythropoietin from tumor
• Hypoxia induced by growth of tumor
67. Nonmetastatic hepatic dysfunction (Stauffer syndrome) 3% to 20%
• elevated serum alkaline phosphatase level
• 67% have elevated prothrombin time
• hypoalbuminemia,
• 20% to 30% have elevated serum bilirubin or transaminase levels.
On biopsy hepatitis associated with a prominent lymphocytic
infiltrate and elevated IL-6
71. CT and MRI for staging
radiographic staging of RCC can be accomplished in most cases with a
high-quality abdominal CT scan and a routine chest radiograph, with
selective use of MRI
Overall, the accuracy of CT or MRI for detection of involvement of the
perinephric fat is low, reflecting the extracapsular spread often occurs
microscopically
72.
73.
74.
75.
76. Hilar or retroperitoneal lymph nodes (2 cm or more in diameter) on CT
almost always harbor malignant change
The sensitivities of CT for detection of
• renal venous tumor thrombus 78% and
• IVC involvement 96%,
Venous enlargement, abrupt change in the caliber of the vein, and
filling defects
78. Metastatic evaluation in routine
• Chest radiograph,
• Systematic review of the abdominal and pelvic CT or MRI,
• And liver function tests
Bone scan reserved for patients with elevated serum alkaline
phosphatase, bone pain, or poor performance status
Chest CT scan for patients with pulmonary symptoms or an
abnormal chest radiograph
79. Biopsy of the primary tumor and/or potential metastatic sites is also
selectively required as part of the staging process.
80. Five years survival
Upto 7 cm size within renal capsule is 90-100%
>10 cm upto 70%
Invasion of IVC above diaphragm <40%
Adrenal medulla involvement or Gerota fascia involvement < 20%
Systemic mets <10%
81.
82. Active surveillance and ablative therapies
Radiofrequency ablation (RFA) and cryotherapy
Preferred in elderly or competing health risk
If tumor is > 3-4 cm or >0.5 cm/year
Can be done laparoscopically, percutaneous, CT or USG guided
Local recurrence rate is high
83. Medical Management
Tyrosine kinase inhibitors targeting the VEGF – vascular tumor
• Approved as first line and second line for metastatic RCC
• Example, sorafenib, sunitinib
Anti-VEGF monoclonal antibody: bevacizumab, is approved for use with
interferon-α.
mTOR inhibitor severolimus and temsirolimus, 2nd line agents
Avg duration of disease control: 1st line 8-9 mo and 2nd line 5-6 mo
84. Surgical management
Nephron sparing surgery or partial nephrectomy
• Open
• Minimally invasive/ laparoscopic
Radical nephrectomy
• Open
• Minimally invasive/ laparoscopic
Approach
• Flank approach
• Anterior approach
85.
86. Flank/Thoracoabdominal approach
Flank approach for open surgery as it enables an extraperitoneal
dissection
Best for adrenal gland and upper pole of the kidney
Incision is made from the interspace between the 10th and 11th ribs, and
directed toward an area 1 cm above the umbilicus
This entails placing the patient with the ipsilateral abdomen tilted up 45
degrees
87. A. Position of
the patient for the
flank approach. B. The
incision is lined up
between the 11th and
12th ribs, going from
the midaxillary line to
the edge of the rectus,
and aimed at a position
1 cm above the
umbilicus. C
88. Anterior Transabdominal Approach
Transabdominal approaches to nephrectomy include chevron or
subcostal incisions. Not good for upper pole and adrenals
These incisions primarily when a transperitoneal laparoscopic procedure
requires conversion to open
Chevron incision: access to bilateral kidneys; renal hilar structures;
leftsided tumor thrombus case
89.
90. Subcostal incision is made from the tip of the 11th rib anteriorly toward
the xiphoid process, about 2 fingerbreadths below the costal margin
The white line of Toldt is incised to medialize the ascending or
descending colon off of the anterior surface of Gerota’s fascia
depending on laterality
91.
92. Right side duodenum is found and need to be kocherized carefully
On the left side reflection of colon proceed with awareness of pancreas
and splenic vessels which should be avoided
93.
94. Open Radical Nephrectomy (ORN)
Radical nephrectomy traditionally has included all components within
Gerota’s fascia, including kidney, perirenal fat, and adrenal gland.
If tumor <5 cm on the lower pole adrenals can be spared
Lymph node dissection depends on clinically positive nodes on CT
95. Kidney is mobilized in the following sequence (Flank approach):
Lateral dissection: Ligasure can be used
Posterior dissection: bluntly to separate the posterior surface of Gerota’s
fascia from the psoas
Superior dissection: lienorenal ligaments on the left and hepatorenal
ligaments on the right
96. The hilar structures last
Renal artery ligated first after dissecting it to sufficient length.
It is ligated as proximal as possible
After release of the artery, the renal vein is ligated in similar fashion.
97. Venous extension of RCC
Staging of IVC thrombus:
Level I adjacent to renal vein ostium
Level II extending into IVC upto lower aspect of liver
Level III Infrahepatic portion of IVC below diaghragm
Level IV extending above the diaghragm
98.
99.
100. Kidney is mobilized except for the renal vein and cava is widely
exposed
If thrombus extends partly into the renal vein then there is sufficient
margin to control the vein on the cava side
Cava may need to be side-clamped, and the vein with a cuff of cava
resected. If less <50% decrease in diameter than cava is repaired
primarily with 4-0 prolene
101. If the thrombus extends cephalad into the cava, the cava need to be
exposed above and below and portion of cava may require resection
along with the specimen
Primary repair can again be performed (if lumen >50%),
Or patch graft repair with bovine pericardium or expanded
polytetrafluoroethylene (ePTFE) for narrow lumen
103. Open partial nephrectomy (OPN)
Requires cold ischemia
OPN requires entering into the gerota’s fascia to identify tumor
Margin of at least few millimeters is required
For multiple lesions or solitary well circumscribed tumor enucleation
can be done to minimize vital adjacent damage
104. Intra-op USG is needed for endophytic tumors
Renal capsule is exposed circumferentially
Intended line of resection is marked with cautery
Capsule is left intact for suture repair later because renal parenchyma is
easy to tear
105. Renal hilum is exposed for temporary clamping
Vessels and ureter is marked with color coded vessel loops (art vein)
Before clamping 12.5 g of iv mannitol and 20 mg iv Lasix to avoid
reperfusion injury
Bulldog clamp is placed on the renal artery and vein
106. Ice packing is done
Resection is done circumferentially with 3 mm of margin
Base of defect is oversewn by figure-of-8 fashion with 3-0 vicryl or
chromic.
Electrocautery can be done for bleeders on the base
107. Defect is closed with mattress sutures at 90 degree angle with 2-0 vicryl
Clamp is removed from the hilum with venous clamp removed first
108.
109. Upper tract urothelial cancer (UTUC)
An upper tract urothelial cancer (UTUC) is essentially any neoplastic
growth of urothelium from renal calices to distal ureter.
4:1 Male:Female ratio
Whites > African americans
110. ETIOLOGY
Hereditary UTUC is associated with hereditary nonpolyposis colorectal
carcinoma (HNPCC), or Lynch syndrome
Mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6,
and PMS2
May develop colonic, urothelial, gastric, pancreatic, uterine, sebaceous,
and ovarian carcinomas.
111. Aristolochic Acid Nephropathy/Chinese herb nephropathy: aristolochic
acid, which is found in plants Aristolochia fangchi. Present in most of
the Chinese herbs.
Results in degenerative interstitial nephropathy
High prevalence of UTUC in Taiwan and china because of it.
112. Smoking: more commonly related to ureteric then renal pelvis tumors
Coffee: increased incidence of UTUC but relationship is confounded
Analgesics: with phenacetin abuse. Papillary scarring and basement
membrane thickening
Arsenic: Taiwan population
113. Occupation: aromatic hydrocarbons, especially those used in chemical,
petroleum, and plastic industries
Chronic Inflammation, Infection, or Iatrogenesis: The development of
squamous cell cancer (and less commonly adenocarcinoma) has been
shown to be related to chronic bacterial infection associated with
urinary stones and obstruction
115. UTUC is associated with poor prognosis
At the time of diagnosis the disease is already metastatic
The disease is more often invasive and poorly differentiated
116. Ureteric tumors are more common in the lower part
Upper ureter: 5%
Mid-ureter: 25%
Lower-ureter: 70%
High grade tumors are mostly metasynchronus and multifocal CIS
40% eventually present with metasynchronus bladder cancer
25% are reduced with single dose of mitomycin-C
117. Dissemination of Disease
Direct extension seen in 95% cases
Vascular seen in 83%
Invasion seen in 77%
Lympatic: from upper to the lower ureter --renal hilar, para-aortic,
paracaval, interaortocaval, and ipsilateral common iliac and pelvic
lymph nodes
118. Hematogenous: liver, lung, and bone
Epithelial: this malignancy is known for synchronous (< 6mo from pri)
and metasynchronus (>6mo of pri)
Two theories: 1. Monoclonal epithelial cells migrate thus all sites are
derived from single genetic neoplastic cell
2. Urothelium to diffusely form unrelated de novo tumors called as
“field effect”
119. Upper tract transitional cell
carcinoma (UTTCC)
Constitutes 5-10% of the urinary tract tumors (risk is similar for bladder
cancer)
Most of them present late with metastasis
120. Urothelial carcinomas make up more than 90% of upper urinary tract
tumors. They may manifest as flat (CIS), papillary or sessile lesions,
and may be unifocal or multifocal
Vary in appearance from a whitish plaque to epithelial hyperplasia,
velvety red patch as a result of increased submucosal vascularity
Relative thinness of the muscle coat invasion into the renal parenchyma
or adventitial tissues may occur
121. Squamous cell, glandular, sarcomatoid, micropapillary, neuroendocrine,
and lymphoepithelial and can be seen in as high as 25% of UTUCs
These variants are considered aggressive tumors
122. Clinical presentation
Hematuria (visible or non-visible) is the most common (56% - 98%)
Flank pain typically dull 2nd most common (30%) due to gradual
development of obstruction and hydronephrosis
At time pain maybe colicky due to passage of clot
123. Localized disease (hematuria, dysuria)
Advanced upper tract tumors (weight loss, fatigue, anemia, bone pain,
flank or abdominal mass)
About 15% of patients are asymptomatic at presentation and are
diagnosed when an incidental lesion
124. Evaluation
CT scan is the investigation of choice 100% sensitivity and 60% specificity
Radiolucent filling defects or incomplete filling of the upper part, or non-
visualization of the collecting system
D/D: blood clot, stones, overlying bowel gas, external compression, sloughed
papilla, and fungus ball.
Urothelial cancer 10-70 Hounsfield units (HU) density
Urinary tract stone 80-250 HU
125. Evaluation of the contralateral kidney because of possible bilaterality of the
disease
Cystoscopy: Because upper urinary tract tumors are often associated with
bladder cancers, cystoscopy is mandatory
Ureteroscopic Evaluation and Biopsy
Urine Cytology:Overall accuracy estimates of the sensitivity of cytology have
ranged from about 20% for grade 1 tumors to 45% and 75% for grade 2 and
grade 3 tumors, respectively
127. Surgical management
Radical nephroureterectomy with excision of a bladder cuff is the gold
standard for large, high-grade, suspected invasive tumors of the renal
pelvis and proximal ureter
128. Standard treatment is nephroureterectomy
If higher up tumor: laparoscopic mobilization of the kidney and ureter
can be combined with endoscopic resection of the ipsilateral intramural
ureter
distal ureter is usually
dissected out using a lower midline incision and opening the bladder –
with again laparoscopic mobilisation of the kidney which is then
delivered through the open incision