Renal Neoplasia

Question 1

What is an angiomyolipoma?

Answer 1

hamartoma comprised of blood vessels, smooth muscle, and adipose tissue.
*Increased frequency in pts with TUBEROUS SCLEROSIS.

Question 2

** What is a renal cell carcinoma?

Answer 2

• malignant epithelial tumor arising from PCT kidney tubules due to loss of VHL (3p tumor suprressor gene) leading to increased IGF-1 and increaed HIF transcription factor (increases VEGF and PDGF).
• presents with classic triad of hematuria, palpable mass, and flank pain (rarely all present together).
• can produce multiple PARANEOPLASTIC SYNDROMES (could release EPO= POLYCYTHEMIA, renin= HTN, parathyroid hormone related peptide= HYPERCALCEMIA, or ACTH= CUSHINGS).

Question 3

What rarely can happen in renal cell carcinoma on the left side of the renal vein?

Answer 3

left-sided varicocele (enlargement of veins in the scrotum, due to the involvement of the left renal vein by carcinoma blocking drainage of the left spermatic/testicular vein).

Question 4

What does a gross exam reveal with a renal cell carcinoma?

Answer 4

yellow mass and microscopically, the most common variant will exhibit clear cytoplasm (clear cell type).

Question 5

What are the 2 classic pathways to develop renal cell carcinoma?

Answer 5

1. sporadic= single tumor in upper pole (usually older males due to cigarette smoking).
2. hereditary= bilateral tumors often in younger adults.
   * Remember both of these pathways involve loss of the VHL tumor suppressor gene.

Question 6

What is an example of a hereditary syndrome that can result in renal cell carcinoma?

Answer 6

Von Hippel-Lindau disease= autosomal dominant disorder associated with inactivation of teh VHL gene leading to increased risk for hemangioblastoma of the cerebellum and renal cell carcinoma.

Question 7

How is renal cell carcinoma staged?

Answer 7

• T= based on tumor size and involvement of the RENAL VEIN (increases risk of hematogenous spread to lungs (CANNONBALL LIKE lesions on chest x-ray) and bone).
• N= can also spread to RETROPERITONEAL lymph nodes.

Question 8

** What is Wilms Tumor?

Answer 8

• malignant kidney tumor comprised of BLASTEMA (immature kidney mesenchyme), primitive glomeruli and tubules, and stomal cells.
• loss of WT1 tumor suppressor gene (esp. syndromic cases).
• MOST COMMON malignant renal tumor in CHILDREN!

Question 9

How do children with Wilms Tumor present?

Answer 9

large, unilateral flank mass with hematuria and HTN (due to renin secretion).

Question 10

*** What are 3 specific high yield examples of Wilms tumor syndromic cases?

Answer 10

1. WAGR syndrome:
   - Wilms tumor
   - Aniridia (absence of iris)
   - Genital abnormalities
   - Retardation
2. Beckwith-Wiedemann syndrome:
   - Wilms tumor
   - neonatal hypoglycemia, muscular hemihypertrophy
   - organomegaly (including tongue).
3. Denys-Drash syndrome:
   - Wilms tumor
   - progressive glomerular disease
   - male pseudohermaphroditism

Question 11

What are the 3 types of lower urinary tract carcinomas?

Answer 11

1. urothelial (transitional cell) carcinoma
2. squamous cell carcinoma
3. adenocarcinoma

Question 12

** What is a urothelial (transitional cell) carcinoma?

Answer 12

• malignant tumor arising from the urothelial lining of the renal pelvis, ureter, bladder, or urethra.
• MOST COMMON type of lower urinary tract cancer.

Question 13

What are the risk factors for urothelial carcinoma?

Answer 13

• cigarette smoke (#1)
• azo dyes (hair dressers from dying hair)
• long term cyclophosphamide or phenacetin (analgesic).

Question 14

How does urothelial carcinoma present?

Answer 14

painless hematuria in older adults

Question 15

What are the 2 pathways by which urothelial carcinoma can present?

Answer 15

1. flat= develops as a high grade flat tumor then invades. Associated with p53 mutations.
2. papillary= progresses from low to high grade and then invades (associated with KERATIN 7). NOT associated with p53.
   * Tumors are often multifocal and recur (field defect).

Question 16

** What is squamous cell carcinoma of the lower urinary tract?

Answer 16

• malignant proliferation of squamous cells, usually involving the bladder. Remember the lower urinary tract does not normally have any squamous epithelium. Thus, this arises in a background of squamous metaplasia, which would progress to dysplasia, and then carcinoma!

Question 17

What are the risk factors for squamous cell carcinoma?

Answer 17

• chronic cystitis (older woman)
• Schistosoma haematobium (middle-eastern male)
• long-standing nephrolithiasis
• all due to chronic inflammation

Question 18

** What is adenocarcinoma of the lower urinary tract?

Answer 18

• malignant proliferation of glands, usually involving the bladder. Remember, glandular epithelium normally does NOT line the bladder.

Question 19

*** What are risk factors for adenocarcinoma?

Answer 19

• URACHAL REMNANT (tumor develops at the DOME of the BLADDER; high yield).
• cystitis glandularis
• exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls).

Question 20

*** What is an Onocytoma?

Answer 20

• solid, mahogany brown tumor with a CENTRAL STELLATE SCAR. Will see NESTING of cells.
• Lacks 3p abnormalities.

Question 21

*** What is a sarcomatoid spindle cell carcinoma?

Answer 21

Rare KERATIN positive, high grade, high stage tumor with poor prognosis.