renal cell carcinoma

RENAL CELL CARCINOMA

AJM

A 60 yr old man presents with a feeling of fullness in his abdomen and 5kg weight loss over the past 6 months. Physical examination in entirely normal. Lab studies show Hb is 8.2g/dl, haematocrit is 24% and MCV is 70, Urine analysis shows haematuria(+++), but no protein, glucose or leucocytes. An abdominal CT scan shows a 11cm mass at the upper pole of the right Kidney. Right nephrectomy was performed and upon gross examination renal vein is seen distended by the tumor

1. What is your diagnosis?2. What are the Clinical manifestations of

the disease?.3. What are the gross and microscopic

features?.4. What is the prognosis .

Renal Cell Carcinoma(RCC). The diagnosis was based on the– Age of the patient– Chronic nature of his complaints– Massive haematuria– The detection of the mass on Abdominal CT

examination– Invasion of the renal vein*– Significant weight loss*

WHAT IS THE DIAGNOSIS?

• Classification of renal cell carcinoma is based on cytogenetic, genetic and histological features.

• The major types of tumors are1. CLEAR CELL CARCINOMA2. PAPILLARY CARCINOMA3. CHROMOPHOBE RENAL CARCINOMA4. COLLECTING DUCT CARCINOMA

CLEAR CELL CARCINOMA• Most common• Loss of sequences on short arm of chromosome

3 (3p12 to 3p26).• This region harbors the VHL gene(3p25.3), which

acts as a tumor suppressor gene in familial and sporadic forms.

• It codes for pVHL which plays a role in ubiquination of proteins, and hence protein degradation.

• HIF-1 is an important target of pVHL, when it is mutated high levels of HIF-1 are maintained.

• Insulin like growth factor another target of pVHL is also upregulated.

WHAT ARE THE GROSS AND MORPHOLOGICAL FEATURES?

MORPHOLOGY:1. Arise from proximal tubular

epithelium.2. Solitary unilateral lesions. 3. Well defined margins and confined

to the renal capsule4. Spherical masses 5. Variegated areas that distorts the

renal outline.6. Large areas of *ischemic, *opaque,

gray-white necrosis, *foci of haemorrhagic discolouration and *areas of softening.

MICROSCOPY:1.Nests cells are seen. Nonpapillary pattern is

seen2.Cells are rounded or polygonal shape3.Abundant clear or granular

cytoplasm(vacuolated).4.Tumors have delicate branching fibro vascular

septae5.Well differentiated ,but some show marked

nuclear atypia.

PAPILLARY CARCINOMA

• Papillary growth pattern • Occurs in both familial and sporadic forms.• Unlike clear cell carcinomas, papillary

carcinomas are multifocal in origin.

MORPHOLOGY:1. They are thought to arise

from the DCT’s,2. Multifocal and B/L.3. They are typically

haemorrhagic and cystic, especially when large.

4. Fungate through the walls of the collecting tubules to enter the ureter.

5. Invade the renal veins.

WHAT ARE THE CLINICAL FEATURES?

* In 10% of cases a triad of1. COSTOVERTEBRAL PAIN2. A PALPABLE MASS3. HAEMTURIA

are seen.• The are generalised symptoms of fever

malaise, weakness and weight loss.

• More than 10 cm in diameter when it is clinically detected.

• RCC gives several false localising symptoms.• RCC can give rise to several paraneoplastic

entities.• Metastasize widely before giving rise to any

local symptoms or signs.

The common sites of metastasis areLungs > Bones > LN’s > Liver > Adrenals > Brain

STAGING AND PROGNOSIS• Stage I: <7cms – Confined to the kidney.• Stage II: >=7cms – Conifined to the kidney.• Stage III: Tumors extend through the renal capsule but are confined to Gerotas fascia

(IIIa).• Stage IV: Invaded adjacent organs(excluding kidney) or multile LN’s or distant

metastasis

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• The 5-year survival rate varies by stage:– >90%- Stage I– 85% - Stage II– 60% - Stage III– 10% - Stage IV