Kidney Malignancies

Question 0

Most common renal cancer in adults? Where is it located?

Answer 0

Renal cell carcinoma.

This neoplasm originates in the cortex.

Question 1

Where are “urothelial neoplasms”?

Answer 1

In the epithelium of the renal pelvis and below.

Question 2

Most common renal cancer in children?

Answer 2

Nephroblastoma (Wilm’s tumor)

Question 3

Major risk factors for renal cell carcinoma?

Answer 3

Tobacco use
Heavy metal and petroleum exposure
HTN, obesity, estrogen, etc.
(majority are sporadic, not linked to genetics)

Question 4

Typical presentation of renal cell carcinoma?

What’s the classic triad of signs/symptoms?

Answer 4

Generalized symptoms: fever, weight loss, malaise.
Classic triad: hematuria, flank pain, and renal mass.
(hematuria is most sensitive, but only 10% of pts have all 3. Of people who have all 3, 50% already have mets)

Question 5

How can renal cell carcinoma mimic many other diseases?

Answer 5

A lot of paraneoplastic processes can occur... E.g.:
Polycythemia via EPO production.
Anemia.
Hypercalcemia via PTH-related protein.
Hypertension via renin.

Question 6

3 most common histologic variants of renal cell carcinoma (RCC)?

Answer 6

Clear cell - 70% of all RCC.
Papillary.
Chromophobe.

Question 7

With what heritable syndrome is clear cell RCC associated? (sporadic clear cell RCC pts have mutations in the same gene - it takes 2 hits to get RCC)

Answer 7

Von Hippel Lindau syndrome - mutation in VHL.

Question 8

Must RCC be large in order to metastasize?

Answer 8

No. It can metastasize when <1cm, but this is rare.

Question 9

Gross appearance of RCC? (how does this correspond to histological appearance)

Answer 9

Pseudocapsule
Yellow (lots of lipid… which is washed out during fixation, making the cells look “clear”)
Hemorrhage and necrosis

Question 10

How vascular are RCC tumors?

Answer 10

Very vascular. You can see capillaries running throughout them on histology.

Question 11

What is grading of clear cell RCC based upon? (Fuhrman grading)

Answer 11

Nucleus morphology - small, dense like a lymphocyte is good.

Large, open chromatin with nucleoli is bad.

Question 12

What factor does VHL suppress?

Answer 12

HIF, under normoxic conditions.

If VHL isn’t present HIF activity -> very vascular tumors.

Question 13

4 examples of genes turned on by HIF that promote tumorigenesis?

Answer 13

VEGF
PDGF
TGF-alpha
GLUT-1 (insulin-independent glucose transporter)

Question 14

Most frequent site of metastasis from RCC?

Answer 14

Lungs, then bone - but they can go “unusual” places.

it can travel along renal vein -> vena cava -> heart -> lung

Question 15

Clear cell RCC responds poorly to chemotherapy.. what are 2 interesting more specific therapies being investigated for RCC?

Answer 15

VEGF inhibitors.

mTOR inhibitors

Question 16

Where do nephroblastomas come from?

Answer 16

They’re embryological remnants - “nephrogenic blastema cells”

Question 17

Does nephroblastoma have an association with any genetic syndromes?

Answer 17

Yes. 10% of nephroblastomas are associated with dysmorphic syndromes (WAGR, Beckwith-Wideman, Denys-Drash… don’t worry about knowing these)

Question 18

Clinical presentation of nephroblastoma?

Answer 18

Abdominal mass (commonly incidentally discovered by parent).
Abdominal pain, hematuria, HTN, and acute abdominal crisis (due to trauma).
Rarely, kidney-related paraneoplastic stuff: anemia, HTN (from renin), polycythemia (from EPO)

Question 19

Gross appearance of nephroblastoma?

Answer 19

Sharply-deliniated.
Tan, commonly with hemorrhage and necrosis.
(these can get quite big - photo showed one dwarfing the remnant normal kidney)

Question 20

What the characteristic histology of nephroblastoma?

Answer 20

Renal tumor with 3 components:

Epithelium, blastema, and stroma.

Question 21

What constitutes unfavorable histology in nephroblastoma?

Answer 21

Anaplasia (ugly cells with ugly nuclei)

Question 22

Prognosis for nephroblastoma?

Answer 22

Very good (as far as these things go…)- 90% survival at 2 years, and 2 year survival usually means cure.

Question 23

What gene is responsible for nephroblastoma/ Wilm’s tumor?

Answer 23

WT-1, a tumor supressor.

Question 24

Where do the majority of urothelial cancers in the kidney originate?

Answer 24

Most actually originate in the bladder.

Question 25

Risk factors for urothelial carcinoma?

Answer 25

Smoking.

Impaired ability to detoxify carcinogens (“slow acetylators”)

Question 26

Most common presenting sign/symptom of urothelial carcinoma?

Answer 26

Painless hematuria -90% of cases

Question 27

2 morphological categories of urothelial carcinoma?

Why is this difference important?

Answer 27

Papillary.
Flat.
Either can invade, but all flat urothelial carcinomas are high grade and present a risk for invasion.

Question 28

How do papillary urothelial carcinomas look in histology?

Answer 28

More layers of cells in the epithelium.

Higher grade lesions have… uglier cells/nuclei (no different from all the other cancers we’ve looked at).

Question 29

What does flat urothelial carcinoma look like in histology?

Answer 29

Normal epithelial thickness, but with atypical cells with messed up polarity, malignant-looking nuclei.

Question 30

What can microscopy of urine show in uroepithelial carcinoma?

Answer 30

Casts of shed carcinoma cells.

Question 31

What technique can easily tell you that epithelial cells in found in the urine likely come form a urothelial carcinoma?

Answer 31

FISH -> aneusomic cells (duplicated chromosomes, translocations)

Question 32

It’s bad when urothelial carcnioma invades the lamina propria / kidney parenchyma.

Answer 32

yes it is.

Question 33

Common chromosomal aberrations seen in urothelial carcinoma?

Answer 33

Los of heterozygosity of chromosome 9 and/or 17p.

more aberrations -> more aggressive

Question 34

Treatment of urothelial carcinoma?

Answer 34

Depends on stage.

If advanced in the bladder, cystectomy often done.