2. How do we proceed ?
• Definition (if applicable)
• Epidemiology
• Etiology / Risk factors
• Pathology
– Pathogenesis
– Gross pathology
– Microscopic pathology
• Clinical presentation
• Investigations:
– To confirm diagnosis
– To evaluate extent of disease
– To assess co-morbidities
– To evaluate patient’s fitness for undergoing treatment
– Staging
3. Epidemiology: general
• Increasing incidence worldwide (including India)
• Males are more frequently affected
• Females more likely to have benign tumours
• Blacks may have slightly higher incidence than whites
9. Benign tumours
Tumor Type Distinctive Features
Benign renal
cyst
Commonest renal SOL: Typically asymptomatic
Water density and homogeneous
Renal cortical
adenoma
Commonly found at autopsy
Small (<1 cm), well circumscribed, low grade, and papillary
More commonly found with papillary RCC and in end-stage renal failure Cannot be
differentiated from RCC by clinical or radiographic means
Metanephric
adenoma
Incidental presentation, peak incidence is fifth decade
May be related to Wilms' tumor or papillary RCC
Paraneoplastic syndrome-polycythemia
Cannot be differentiated from RCC by clinical or radiographic means
Oncocytoma Commonest benign solid renal SOL
Tan and homogeneous in gross appearance central stellate scar
Eosinophilic with nested or organoid appearance
Multiple mitochondria on electron microscopy
Cannot be differentiated from RCC by clinical or radiographic means
10. Cont…
Tumor Type Distinctive Features
Angio-
myolipoma
Sporadic or associated with tuberous sclerosis syndrome
Fat density found with CT; hyperechoic on ultrasonography
Wunderlich's syndrome
Typically intervene if symptomatic or large (>4 cm)
Options for management: selective embolization, partial nephrectomy
Cystic
nephroma
Bimodal age distribution: Middle-aged women or young males
Herniation into collecting system can be clinical clue
Difficult to differentiate from cystic malignancy
Partial nephrectomy if diagnosis suspected
MESTK Perimenopausal women, typically with history of hormonal manipulation
Often stains for estrogen or progesterone receptors
Leiomyoma Often arises from the capsule
Reninoma Derived from juxtaglomerular cells
Secretes renin; associated with hypertension and hypokalemia
17. RCC (Hypernephroma Radiologist tumour, INTERNIST.Tumour).
Epidemiology
• RCC accounts for 2% to 3% of all adult malignant
neoplasms.
• Incidence is increasing by 3-4 % per year.
– ? ↑ Incidental diagnosis
• Male : female ratio is 3:2
• Typical presentation in 6th -7th decade
• Higher in blacks by 10-20%
• Familial: 4%, sporadic 96%
18. Etiology
• Environmental
– Tobacco exposure: in any form
• Congenital
1. von Hippel–Lindau
2. Birt-Hogg-Dubé
3. Hereditary papillary RCC [HPRCC] syndrome
4. Hereditary leiomyomatosis and RCC [HLRCC] syndrome
19. Risk factors
• Modifiable
– Chemical
• Aromatic hydrocarbons, Lead compounds,
Thiochlorethylene,,Thorotrast.
– Irradiation: therapeutic
– End-stage renal disease
– Hypertension
– Obesity
– Low socioeconomic status with urban background
• Unmodifiable
– Affected 1st or 2nd degree relative
– Sickle cell disease
– H/O Wilm’s tumor in childhood
20.
21. Von Hippel–Lindau disease
vHL gene is located on
chromosome 3p25-26
Autosomal dominant pattern of
inheritance
Overall penetrance for renal
tumors is about 50%
Age at onset: 3rd-5th decade
Bilateral and multifocal
involvement.
Major manifestations:
RCC (Clear cell type)
Pheochromocytoma
Retinal angiomas
Benign hemangioblastomas of:
Brain stem
Cerebellum
Spinal cord
Islet cell tumour of pancreas
Epididymal cystadenoma
22. Birt-Hogg-Dubé syndrome
*BHD1 gene located on
chromosome 17p11.2
*Autosomal dominant
pattern of inheritance
*Overall penetrance for
renal tumors is about
20% to 30%
Often bilateral and
multifocal
Major manifestations:
Cutaneous fibrofolliculomas
Lung cysts
spontaneous
pneumothoraces
Renal tumors primarily
derived from the distal
nephron:
*chromophobe RCC
*Oncocytomas
*hybrid or transitional
tumors
23. Tumour biology
Immunogenicity
CA-9 and other antigens
High degree of immune tolerance on trial of
immunotherapy
Angiogenesis
One of the most vascular of cancers
Distinctive neovascular pattern
PDGF
Multi-drug resistance
P-glycoprotein (MDR-1 protein)
Production of a variety of systemically-active
agents:
1,25-dihydroxycholecalciferol
Renin
Erythropoietin
Various Prostaglandins
Parathyroid hormone-like peptides
Lupus-type anticoagulant
β - human chorionic gonadotropin
Insulin
Various cytokines & inflammatory mediators
Normal
Pathological
24. Pathology: Gross
• Round to ovoid
• Usually unifocal and unilateral (except in familial forms)
• Usually circumscribed
– Pseudocapsule of compressed parenchyma and fibrous tissue
rather than a true histologic capsule.
– Not grossly infiltrative, unlike upper tract transitional cell
carcinomas.
– Exception:
• collecting duct RCC , sarcomatoid variants
• Cut surface:
– Yellow, tan, or brown tumor
– Interspersed with: Fibrotic,Necrotic,and Hemorrhagic areas
26. Pathology: Microscopic
• By definition all RCC are adenocarcinomas:
– derived from renal tubular epithelial cells
• Tissue architecture:
– Loss of cellular polarity with disorganized cell clusters
– Microscopic villous invasion into surrounding normal tissues
through the psuedocapsule
• Ultrastructure:
– surface microvilli
– complex intracellular junctions
– normal proximal tubular cells
• There are no reliable histologic or ultrastructural criteria
27. Histological classification: Kovacs
Histology Subtypes Characteristics
Conventional 70-80%
• Clear cell
• Granular
• Mixed
• Derived from PCT
• Hypervascular
• von Hippel-Lindau syndrome
Chromophilic
(papillary)
10-15%
• Type 1 [HPRCC]
• Type 2 [HLRCC]
• Derived from PCT
• Typically hypovascular
• Usually multicentric / bilateral
Chromophobic 3-5%
• Type 1
-classic
• Type 2
-eosinophilic
• Derived from intercalated cells of CD
• Birt-Hogg-Dubé syndrome
• Better prognosis
Collecting duct 1%
• Medullary cell
is one variant
• Derived from collecting duct
• Centrally located / Infiltrative
• Poor prognosis, Hobnail growth.
Unclassified 1%
• Origin not defined
• Poor prognosis
28. 1)Clear cell RCC
• MC type, sporadic, arises from
PCT(Cortical)
• Both sporadic & hereditory assoc.with
loss of sequnce on
chr.n0.3(3;6,3;8,3;11) OR deletion.
• Solitarry
unilateral,pseudoencapsulated. well
diffrentiated.
• Tumour cell are clear & contained
glycogen&lipid
30. 3)CHROMOPHOBE RCC
*Composed of cells with
prominent cell
memb.,eosinophilic
cytoplasm & perinuclear
halo.
*Exhibit.multiple chr.
Abnormalities& extreme
hypodiploidy.
Best prognosis
*Arises from intercaleted
cells of collecting duct.
31. Rare types
5) Renal medullary carcinoma
– Occurs almost exclusively in association with the sickle cell trait
– It is typically diagnosed in young African Americans, 3rd decade
– Thought to arise from the calyceal epithelium near the renal papillae
– The site of origin (renal papillae) and association with sickle cell trait suggest
that a relatively hypoxic environment may contribute to tumorigenesis.
– Highly infiltrative:
• Many cases are both locally advanced and metastatic at the time of
diagnosis
– Most patients do not respond to therapy and succumb to their disease in a
few to several months
32. 6) Sarcomatoid variants
– Poorly differentiated regions of other histologic subtypes of RCC
– found in 1% to 5% of RCCs,
• most commonly in association with conventional or chromophobic RCC
– It is characterized by spindle cell histology, positive staining for vimentin,
infiltrative growth pattern, aggressive local and metastatic behavior, and poor
prognosis
– Invasion of adjacent organs is common
– Median survival has been less than 1 year in most series
36. Robson's modification of the system of Flocks
and Kadesky,
• Stage I
– Tumour within capsule
• Stage II
– Invasion of perinephric
fat
(but confined within
Gerota’s fascia)
• Stage III
– Involvement of:
• Renal vein
• IVC
• Regional LN (IIIb)
37. Clinical feature
• Asymptomatic until the late disease stages.
• Incidental;- > 50% of RCCs .
• Symptoms associated with RCC can be due to
A)Local tumor growth;-
• Hematuria Perirenal hematoma
• Flank pain;-due to hemorrhage and clot obstruction, can
also occurs with locally advanced or invasive disease.
• Abdominal mass.
38. B) Metastatic disease ;-
• Persistent cough
• Bone pain
• Cervical lymphadenopathy
• Constitutional symptoms
• Weight loss/fever/malaise
C) Obstruction of the Inferior Vena Cava
• Bilateral lower extremity edema
• Nonreducing or right-sided varicocele
40. Investigations: to confirm diagnosis
• Imaging
– MRI: most sensitive
– CECT
• Helical / multiplanar
• Conventional
– USG: limited sensitivity and specificity
– PET: using isotope labelled antibodies against CA-9
• Imaging guided pathological sampling (only in selected
cases)
– Trucut biopsy
– FNAC
41. CECT
Provides information on:(LE: 3).
• Function and morphology of the contralateral kidney
• Primary tumour extension;
• Venous involvement;
• Enlargement of locoregional lymph nodes;
• Condition of the adrenal glands and other solid organs .
• A change of 15 or more HUs demonstrates enhancement .
• To maximise differential diagnosis and detection, the
evaluation should include images from the nephrographic
phase for best depiction of renal masses, which do not
44. Bosniak class II hyperdense cyst.
A, Unenhanced CT scan shows small, smooth-walled, high-density left renal cyst.
B, CT scan after administration of contrast material shows no
enhancement of the cyst.
46. MRI
Indication;-(LE-3)
• Allergy to intravenous CT contrast medium
• Pregnancy without renal failure
• Indeterminate result on CECT.
• Patients of hereditary RCC who are worried about the
radiation exposure of frequent CT scans.
Provide additional information on:
• venous involvement if the extent of an inferior vena cava
(IVC) tumour thrombus is poorly defined on CT
• Doppler US is less accurate for identifying the extent of a
52. Renal tumour biopsy
• Can reveal histology of radiologically indeterminate renal
masses.
• It should be considered
1) to select patients with small masses for active surveillance,
2) to obtain histology before ablative treatments
3) to select the most suitable form of medical and surgical
treatment strategy in the setting of metastatic disease.
4) Suspicion of lymphoma:
• Very large para-aortic nodes,Lymphadenopathy in other LN
fields,Splenomegaly
• 5.)Suspicion of abscess:-Flank pain,Tender lump,Fever
1. Metastatic lump: known other primary
53. • Performed with US or CT guidance, in LA, with a
similar diagnostic yield (LE: 2b).
• Types;-
1) Fine needle aspiration (FNA)
2)Needle core biopsy (18 G Coaxial cannula technique)
*0-22.6% of core biopsies are non-diagnostic.
*should be preferred for the characterization of solid
renal masses (LE: 2b).
• The ideal number and location of core biopsies are
undefined. However, at least two good quality cores
54. • Peripheral biopsies are preferable for larger
tumours, to avoid areas of central necrosis.
• low diagnostic yield for cystic masses and are not
recommended alone, unless areas with a solid
pattern are present (Bosniak IV cysts).
• If a biopsy is non-diagnostic, and radiologic
findings are suspicious for malignancy, a further
biopsy or surgical exploration should be
considered (LE: 4).
Complication;-low morbidity .
• Spontaneously resolving subcapsular/ perinephric
55. Investigations: to evaluate extent
• T-staging
– MRI or helical CECT
– Vena-cavography:
• equivocal MRI findings
• patients who cannot tolerate or have other contraindications to MRI
• N-staging
– MRI or CECT
– Diagnostic laparoscopy
• M-staging
– X-ray chest PA view CECT Chest
– Pelvic CECT
– MRI Brain
56. • Most of bone and brain metastases are
symptomatic at diagnosis, thus routine bone or
brain imaging is not generally indicated. Howeve
they may be used in the presence of specific
clinical or laboratory signs and symptoms(LE: 3).
• The value of positron-emission tomography (PET)
in the diagnosis and follow-up of RCC remains to
be determined, and PET is not currently
recommended (LE: 3).
58. Investigations: to evaluate patient’s fitness to
undergo treatment
• Urine examination:
– Physical
– Chemical
– Microscopic
– Culture and sensitivity
• Complete hemogram:
– Hb, TLC, DLC, PCV, RBC count
• Biochemical assay
– KFT: Blood urea, serum creatinine
– LFT: SB (T, D & ID), AST, ALT, SAP, GGT, Total protein, Sr. albumin
– Serum electrolytes: Na+, K+, Ca2+, Cl‾, HCO3‾
– Blood sugar: fasting and post-prandial
• Coagulation profile:
– BT, CT, PT ( INR), aPTT, platelet count
• IVU: to assess function of contralateral kidney
59. Renal scientigraphy;-
• Split renal function should be estimated in the following
situations (LE: 2b):
1 ) when renal function is compromised
2) when renal function is clinically important - e.g., in
patients with a solitary kidney or multiple or bilateral
tumours.
• Renal scintigraphy is an additional diagnostic option in
patients at risk of future renal impairment due to
comorbid disorders.
