48. Renal tumours (oncocytoma, renocellular cancer, Wilms tumor, urothelial carcinoma of the renal pelvis)

Most common tumors of urinary tract?

- Oncocytoma

- Renal cell carcinoma

Benign renal cell tumors?

- Oncocytoma

- Angiomyolipoma

- Papillary adenoma

Oncocytoma?

Benign renal tumor

- Originates from intercalated cells of the tubules -> "oncocytes"

Tumor is brown on macroscopy

- Can be hard to differentiate from chromophobe RCC (must use cytogenetics)

Oncocytes?

Cells with large eosinophilic cytoplasm -> due to high content of mitochondria

Angiomyolipoma?

Hamartoma of the kidney

Comprised of:

- Blood vessels, smooth m.m. and adipose tissue

More frequent in patients with tuberous sclerosis

What is a hamartoma?

Disorganized tissue that is composed of correct tissue for the location

- Not dysplastic

- Not cancerous

Papillary adenoma?

Small (5mm) and grey benign tumor of the kidney

- Always within the cortex

Renal cell carcinoma?

Malignant epithelial tumor

- Arising from kidney tubules

- Represents 80% of all primary malignant tumors of the kidney

Classic triad of RCC?

- Hematuria (with normal RBCs)

- Flank pain

- Palpable mass on flank

(also... non-specific symptoms like fever & weight loss)

Most important risk factors for RCC are?

- Smoking

- Cystic disease of kidney

- Obesity

- Hypertension

Types of RCC according to histology?

- Clear cell RCC - 65%

- Papillary RCC - 10%

- Chromophobe RCC - 5%

- Cystic RCC - 2,5%

- Collecting duct RCC - 1%

Clear cell RCC?

Clear cytoplasm of tumor cells

= High fat content of cell -> why tumor looks yellow on macro

- Can have capsule -> can mimic benign tumor

- Occurs on lower pole

- Clear cell carcinoma has worse prognosis than the next 2

Genetics of clear cell RCC?

Loss of tumor-suppressor VHL on chromosome 3p25

- Either sporadic or hereditary as is the case in von Hippel-Lindau disease

- 50% with this disease develop clear RCC

- Often multiple & bilateral tumors in VHL-disease

Papillary RCC?

Papillary growth pattern

- Tumors appear in multiple foci and bilaterally

Genetics of papillary RCC?

MET proto-oncogene on chromosome 7q31

- is associated - both in hereditary and sporadic forms

Chromophobe RCC?

Tumor cells stain darkly

- Tumor cells have usually lost multiple chromosomes -> making them hypoploid

- Good prognosis

Hypoploid?

Fewer than the normal chromosome number

Cystic RCC?

Rare type of RCC that is commonly misdiagnosed as a benign renal cyst

- Excellent prognosis after surgical removal

Collecting duct RCC?

Very rare subtype

- Very aggressive

- BAD prognosis

Paraneoplastic syndromes of RCC?

- Hypertension (can produce renin)

- Hypercalcemia (Produce PTH-related-protein)

- Polycythemia - (EPO production)

- Secondary hypercortisolism - as it can produce ACTH (Cushing)

What can RCC cause in the scrotum?

Left-sided varicoele

- Pathological dilation of the venous plexus of the scrotum

Where does RCC spread?

Spreads locally to the renal vein

- Can block the point where left testicular vein drains into the renal vein

= Pressure builds up in the venous plexus of the scrotum -> soft lump

Metastasis of RCC?

- Lung

- Bones

most frequently

As it commonly grows to renal vein and IVC -> it can extend as far to the heart

Lymphatic spread:

- To retroperitoneal lymph nodes

Diagnosis of RCC?

Does not cause symptoms until later stages

- Often found incidentally

Up to 25% have already distant metastasis at diagnosis

Furhman system?

Grading system for kidney tumors

- Based on how prominent the nucleoli is

= More prominent -> the higher the grade is

A grade IV RCC ?

Has sarcomatoid or rhabdoid appearance

(Rod-shaped)

TNM staging of kidney tumors?

Depends on:

- Size of tumor

- Renal vein involvement

- Local invasion

• Kidney tumors commonly infiltrate the adipose capsule -> T3

• If they infiltrate beyond renal fascia -> T4 (inoperable)

Wilms tumor?

Nephroblastoma

- Most common malignant renal tumor in children

- Age of diagnosis: 3 y/o

- Rarely occurs in adults

What is Wilms tumor comprised of?

Blastema:

- Embryological tissue that the normal kidney develops from

- Tumor may have primitive glomeruli and tubules

Genetics of Wilms tumor?

Mutation of WT1 - a tumor suppressor gene

- This mutation often occurs in WAGR syndrome

WT1?

Regulates transcription of insulin-like growth factor, E-cadherin and PDGF

Is essential for renal & gonadal development

WAGR syndrome?

- Wilms tumor

- Aniridia

- Genital abnormalities

- Retardation

Syndrome is with germ-line deletion of WT1

- 1/3 will acquire "second hit" -> developing Wilms tumor

Denys-Drash syndrome?

Germ-line mutation (NOT deletion) in one allele of WT1

- Have 90% chance of developing Wilms tumor

They also have:

- Gonadal dysgenesis

- Early nephropathy

Histology of Wilms tumor?

Triphasic tumor - has 3 different parts:

1. Epithelial part

2. Stromal part

3. Blastema part -> has most clinical relevance. The more of this part, the poorer diagnosis