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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 .
WHAT IS THE DIAGNOSIS?
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*
• Classification of renal cell carcinoma is
  based on cytogenetic, genetic and
  histological features.
• The major types of tumors are
  1.   CLEAR CELL CARCINOMA
  2.   PAPILLARY CARCINOMA
  3.   CHROMOPHOBE RENAL CARCINOMA
  4.   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 capsule
4. 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
  seen
2.Cells are rounded or polygonal shape
3.Abundant clear or granular
  cytoplasm(vacuolated).
4.Tumors have delicate branching fibro vascular
  septae
5.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 of
  1. COSTOVERTEBRAL PAIN
  2. A PALPABLE MASS
  3. 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 are
Lungs > 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
• The 5-year survival rate varies by stage:
  – >90%- Stage I
  – 85% - Stage II
  – 60% - Stage III
  – 10% - Stage IV

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Renal cell carcinoma

  • 2. 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
  • 3.
  • 4. 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 .
  • 5. WHAT IS THE DIAGNOSIS? 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*
  • 6. • Classification of renal cell carcinoma is based on cytogenetic, genetic and histological features. • The major types of tumors are 1. CLEAR CELL CARCINOMA 2. PAPILLARY CARCINOMA 3. CHROMOPHOBE RENAL CARCINOMA 4. COLLECTING DUCT CARCINOMA
  • 7. 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.
  • 8. • 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.
  • 9. WHAT ARE THE GROSS AND MORPHOLOGICAL FEATURES?
  • 10. MORPHOLOGY: 1. Arise from proximal tubular epithelium. 2. Solitary unilateral lesions. 3. Well defined margins and confined to the renal capsule 4. 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.
  • 11. MICROSCOPY: 1.Nests cells are seen. Nonpapillary pattern is seen 2.Cells are rounded or polygonal shape 3.Abundant clear or granular cytoplasm(vacuolated). 4.Tumors have delicate branching fibro vascular septae 5.Well differentiated ,but some show marked nuclear atypia.
  • 12.
  • 13. PAPILLARY CARCINOMA • Papillary growth pattern • Occurs in both familial and sporadic forms. • Unlike clear cell carcinomas, papillary carcinomas are multifocal in origin.
  • 14. 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.
  • 15.
  • 16.
  • 17. WHAT ARE THE CLINICAL FEATURES? * In 10% of cases a triad of 1. COSTOVERTEBRAL PAIN 2. A PALPABLE MASS 3. HAEMTURIA are seen. • The are generalised symptoms of fever malaise, weakness and weight loss.
  • 18. • 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.
  • 19. The common sites of metastasis are Lungs > Bones > LN’s > Liver > Adrenals > Brain
  • 20. 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
  • 21. • The 5-year survival rate varies by stage: – >90%- Stage I – 85% - Stage II – 60% - Stage III – 10% - Stage IV