Malignant stuff

Question 1

Classic triad of RCC?

Is this common?

Answer 1

palpable mass
hematuria
flank pain

• uncommon; < 15%

Question 2

The majority of RCC’s are _____, while the 3 most common subtypes are ___, ___, and ___.

Answer 2

Adenocarcinomas

Subtypes are:

1. Clear cell (75%)
2. Papillary (10-15%)
3. Chromophobe (5%)

Question 3

On average, what percentage of patients present with metastatic disease?

Answer 3

1/4 to 1/3 (25-33%

Question 4

What are 3 histologic good prognostic signs?

Answer 4

1. Increased CA-IX (carbonic anhydrase factor 9)
   - low CA-IX expression is bad
2. Low vimentin
   - vimentin is a mesenchymal intermediate filament; low expression means less differentiation/mutation
3. Low p53
   - high p53 means more aggressive cancer

Question 5

Any variant of RCC with ______ features has poor prognosis.

Answer 5

Sarcomatoid

Question 6

All familial RCC disorders are autosomal recessive or dominant?

Answer 6

Dominant

Question 7

What is the subtype of RCC that is most common in kids?

Answer 7

Papillary (still rare to see RCC in kids though)

Question 8

What is the subtype of RCC that is most common in ESRD/dialysis (acquired cystic renal disease)?

How many years after being on dialysis is it recommended to start annual US screening?

Answer 8

Papillary RCC most common in ESRD/acquired cystic disease

Get screening US after 5 years of dialysis

Question 9

A patient has a rapid development of right sided varicocele, what are you suspicious for?

Answer 9

Right sided RCC tumor venous invasion

Question 10

When do you consider renal biopsy? Why?

Answer 10

Small renal masses < 4 cm

Why small?

• B/c 20% benign, 60% indolent malignancy, 20% aggressive malignancy.
• Low false negative rate (1%), low complication rate (<2%), and needle tract seeding is extremely rare (one case report)

Question 11

Classically, what are the indications for renal biopsy?

Answer 11

Small renal masses < 4cm
Concern about metastasis
Abcess
Concern about lymphoma

Question 12

What is the treatment for renal lymphoma?

Answer 12

Chemotherapy

Question 13

What imaging workup should be pursued in patients with RCC?

Answer 13

CT scan: contrast enhancement >20 HU’s (i.e. no fat/AML)
MRI scan if renal vein or IVC involvement
CXR in all patients; CT chest if CXR inconclusive
CT brain if neurologic findings
Bone scan if elevated ALP, bone pain, or pathologic fracture
Mammogram in all women to r/o metastatic primary breast cancer

Question 14

This is a subtype of RCC in which there is a purely cystic tumor lined by RCC clear cells (no solid component).

What is it associated with?

Treatment?

Answer 14

Multilocular Cystic RCC

Associated with VHL

Tx with surgical removal.
**no recurrence or metastasis reported after resection

Question 15

Genetics of clear cell RCC?

Answer 15

mutated tumor suppression gene of VHL at 3p25-26

Question 16

Clear cell RCC arises from which part of the nephron?

Answer 16

proximal tubules

Question 17

What does the VHL gene normally suppress?

Answer 17

Hypoxia Inducible Factor-1 (HIF-1)

Question 18

What is the normal physiological function of HIF-1?

Answer 18

under hypoxic situations, HIF-1 stimulates angiogenesis, glucose transport, and autocrine growth stimulation by activating the pathways of VEGF, PDGF, and Glut1

• therefore, if VHL is mutated, HIF-1 is intrinsically active and tumorigenesis proceeds
• • these pathways are what the Tyrosine kinase, mTOR, and VEGF inhibitors target

Question 19

Genetics of Papillary Type 1 RCC?

Answer 19

mutated proto-oncogene of cMet gene at 7q31

**this is the ONLY familial RCC proto-oncogene

Question 20

What is the physiological function of cMet?

Answer 20

aka scatter factor, in regulates proliferation and differentiation of renal epithelial and endothelial cells

Question 21

Papillary type 1 RCC arises from which part of the nephron?

Answer 21

proximal tubules

Question 22

Histologically, papillary type 1 RCC appears?

Answer 22

Basophillic (blue) and low grade

Question 23

Genetics of Papillary Type 2 RCC?

Answer 23

mutated tumor suppressor gene of fumarate hydratase at 1q42-44

*fumarate hydratase is a Krebs cycle enzyme, so if mutated, cells will continue to make ATP and grow

Question 24

Papillary type 2 RCC arises from which part of the nephron?

Answer 24

Proximal tubules

Question 25

Histologically, papillary type 2 RCC appears?

Answer 25

Eosinophilic (pink), high grade (more aggressive)

Question 26

Which RCC subtypes arise from the proximal tubule?

Answer 26

Clear cell, papillary type 1, papillary type 2

Question 27

Genetics of chromophobe RCC?

Answer 27

mutated tumor suppressor gene of Folliculin at 17p11.2

*this is the same gene mutated in Birt-Hogg-Dube syndrome

Question 28

Chromophobe RCC arises from which part of the nephron?

What does chromophobe RCC closely resemble?

Answer 28

Distal tubule

Closely resemble oncocytomas, and it is believed both are on a spectrum of distal tubule tumors

Question 29

Histologic appearance of chromophobe RCC?

Answer 29

Perinuclear halo (Koilocyte-like) with raisinoid nuclei

*Hale’s Colloidal + (blue stain)

Diffuse CK7 staining (vs. oncocytoma, which is sparse for CK7 staining)

**Few mitochondria and many microvesicles (vs. oncocytoma, which has many mitochondria and few microvesicles)

Question 30

This is a very rare subtype of RCC, found in young AA’s with sickle cell disease. Usually locally advanced or metastatic at presentation and highly aggressive, with mean 12-15 months survival.

Answer 30

Renal medullary carcinoma

Question 31

What is the most common metastatic lesion to the kidney?

What are other common sources?

Answer 31

lung cancer is MC

other sources: contralateral kidney, breast, GI

Question 32

Most common RCC metastatic sites?

Answer 32

1. Lung
2. Bone (elevated ALP)
3. Liver