Renal cell carcinoma for students

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Causes, pathogenesis, Morphology, stages and prognosis

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Renal Cell Carcinoma

Lecturer 53

Tumors of the Kidney

Adenocarcinoma of the Kidney

Hypernephroma

HYPERNEPHROMA- RCC• Because of their gross yellow color and the

resemblance of the tumor cells to clear cells of the adrenal cortex, they were at one time

called Hypernephroma.

Renal Adenocarcinoma

• It is now clear that all these tumors arise from tubular epithelium and are therefore

RENAL ADENOCARCINOMAS.

Epidemiology• Male predominance (1.6:1.0 M:F)• Highest incidence between age 60-80-Median age of diagnosis is 66 years-Median age of death 70 years• Highest incidence in Scandinavia and North

America, lowest in Africa

Risk Factors

Causes/ Risk Factors

• There is also an increased incidence in

patients with chronic renal failure and acquired cystic disease and in

tuberous sclerosis.

RCC•Most renal cancer is

sporadic, but unusual forms of

autosomal dominant familial cancers occur, usually in

younger individuals.

Classification of RCCThe major types of RCC are as follows:• 1. Clear cell carcinoma -70-80%, 95%

Sporadic• 2. Papillary carcinoma- 10-15%• 3. Chromophobe renal carcinoma- 5%• 4. Collecting duct (Bellini duct) carcinoma-

1% 0r less

Pathogenesis of VHL• Von Hippel-Lindau protein, product of VHL gene,

is a tumor suppressor • VHL inhibits hypoxia-inducible genes involved in

angiogenesis such as VEGF, TGF-a, GLUT-1• VHL destabilizes and promotes ubiquination of

HIF-a (hypoxia-inducible factor) • Loss of VHL results in tumor angiogenesis, tumor-

cell proliferation, epithelial cell proliferationGlucose transporter 1Ubiquination: a small polypeptide, found in most eukaryotic cells, that combines with other proteins to

make them susceptible to degradation

Morphology•Renal cell carcinomas may

arise in any portion of the kidney, but more commonly affects the

poles.

RCC Morphology• One of the striking

characteristics of renal cell carcinoma is its tendency to invade the renal vein and grow as a solid column of cells within this vessel.

Clear cell Carcinomas

Morphology- Papillary Carcinomas

• Papillary carcinomas are the most common type of renal cancer in patients who develop dialysis-associated cystic disease.

Microscopy- Papillary Carcinoma

• Papillary carcinoma is composed of cuboidal or low columnar cells arranged in papillary formations.

• Interstitial foam cells are common in the papillary cores.

• Psammoma bodies may be present. • The stroma is usually scanty but highly

vascularized.

Chromophobe renal carcinoma• Chromophobe renal carcinoma is made up of

pale eosinophilic cells, often with a

perinuclear halo, arranged in

solid sheets with a concentration of

the largest cells around blood vessels.

Collecting duct carcinoma

• Collecting duct carcinoma is a rare variant showing irregular channels lined by highly atypical epithelium with a hobnail pattern.

RCC•Sarcomatoid changes

arise infrequently in all types of renal cell carcinoma and are a decidedly

ominous feature.

Renal cell carcinoma. Typical cross-section of yellowish, spherical neoplasm in one pole of the kidney. Note the tumor in the dilated thrombosed renal vein.

Paraneoplastic Syndromes

1. Polycythemia, 2. Hypercalcemia,3. Hypertension,4. Hepatic dysfunction, 5. Feminization or masculinization, 6. Cushing syndrome, 7. Eosinophilia, 8. Leukemoid reactions, and9. Amyloidosis.

RCC

Clinical Presentation• Most asymptomatic • Hematuria present 40% of patients• Classic triad: flank pain, hematuria, palpable

abdominal mass occur in 9% of patients• 45% present with localized disease, • 25% with locally advanced disease,• 30% with metastatic disease

Treatment•Nephrectomy has been the

treatment of choice, but

•Partial nephrectomy to preserve renal function is being done with increasing frequency and similar outcome.

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