Renal and Urinary Tract Neoplasms CORBETT

Question 1

What are the two main BENIGN renal neoplasms?

Answer 1

1. ANGIOMYOLIPOMA

2. ONCOCYTOMA

Question 2

ANGIOMYOLIPOMA: Are majority of the cases sporadic or hereditary? If hereditary, what disease is it most associated with?

Answer 2

80% (majority) - SPORADIC

20% - Hereditary: TUBEROUS SCLEROSIS (Autosomal Dominant HAMARTOMA)

Question 3

Are most clinical manifestations of TUBEROUS SCLEROSIS COMPLEX renal? List out HAMARTOMA mnemonic

Answer 3

No, most are CNS-related
H-hamartoma (CNS/skin), A-angiofibroma, M-mitral regurgitation, A-ash leaf spots, R-Rhabomyoma, T-empty, O-Autosomal dOminant, M-mental disability, A-renal angiomyolipoma

Question 4

In pts with TUBEROUS SCLEROSIS COMPLEX, what are the possible renal manifestations? What is the most common manifestation?

Answer 4

1. RENAL ANGIOLIPOMAS (A) - ANGIOMYOLIPOMA = most common
2. RENAL CELL CARCINOMA
3. RENAL CYSTS

Question 4

Describe the most common characteristics of ONCOCYTOMA. Unilateral/Bilateral? Sporadic/Hereditary? Small/Large mass? Homogenous/Heterogenous?

Answer 4

MAJORITY - UNILATERAL, SINGLE SPORADIC LARGE (up to 12cm) oncytomas, Relatively HOMOGENEOUS

Question 5

What is the origin of RENAL ONCOCYTOMAS?

Answer 5

INTERCALATED cells of the LATE DISTAL TUBULE/COLLECTING DUCT

Question 6

What are the 3 microscopic features of ONCOCYTOMAS?

Answer 6

1. LARGE EOSINOPHILIC CELLS
2. NUMEROUS MITOCHONDRIA
3. Benign nuclei with LARGE NUCLEOLI

Question 7

What is the most common age population affected by RENAL CELL CARCINOMA? Age, Sex

Answer 7

OLDER (Avg Age: 60) MALE SMOKERS

Question 8

What are the risk factors of RENAL CELL CARCINOMA? What is the most significant one?

Answer 8

*SMOKING - Increases x2,
OBESITY (Especially in women)
HTN

Question 9

What is the majority subtype of RCC (sporadic or hereditary)? Which genetic disorder is most commonly associated with HEREDITARY RCC?

Answer 9

*>95 - SPORADIC RCC

3% HEREDITARY RCC - most commonly associated with VON HIPPEL-LANDAU Disease

Question 10

What are the 3 variants of RCC? Which is the most common one?

Answer 10

1. *CLEAR CELL CARCINOMA - most common
2. PAPILLARY CARCINOMA
3. CHROMOPHOBE CARCINOMA

Question 11

What is the most common pathogenesis of RCC CLEAR CELL CARCINOMA variant?

Answer 11

3- ‘RCC:VHL:Chrom 3Del’
CHROM 3 DELETION containing the VHL tumor suppressor gene - VHL normally allows for ubiquitination of IGF-1 and HIF-1. No VHL = No ubiquitination = No protein degradation = Accumulated IGF-1/HIF-1 = Growth and angiogenesis

Question 12

What is generally the origin of RCC (Clear cell variant - most common)?

Answer 12

UPPER POLE of kidney - PROXIMAL TUBULAR EPITHELIUM

Question 13

Is CLEAR CELL CARCINOMA mostly sporadic or hereditary?

Answer 13

SPORADIC (95%) - Thus mostly SOLITARY and SINGULAR tumor

Question 14

How does HEREDITARY CLEAR CELL CARCINOMA (CCC) differ from the more common SPORADIC CCC?

Answer 14

Hereditary - VHL syndrome related + BILATERAL/MULTIFOCAL TUMOR

Question 15

Is PAPILLARY CELL CARCINOMA (RCC variant 2) mostly sporadic or hereditary? What syndromes are associated with familial PCC?

Answer 15

MOSTLY HEREDITARY - Thus mostly BILATERAL/MULTIFOCAL
Type 1 - Low Grade - Linked to MET mutation
Type 2 (H) - High Grade - Linked to fumarate Hydrase

Question 16

What may be the pathogenesis of HEREDITARY PAPILLARY CELL CARCINOMA? Which is the most common one?

Answer 16

TRISOMY 7*- most common

Trisomy 17, Loss of Y chromosome

Question 17

How does CHROMOPHOBE CARCINOMA (RCC Variant 3) differ from the other variants CLEAR CELL and PAPILLARY? [Think origin, pathogenesis, and prognosis]

Answer 17

***EXCELLENT PROGNOSIS (other RCC are highly dependent on Staging - T/N)
Origin = INTERCALATED CELLS of COLLECTING DUCT (others are PCT epithelium)
Pathogenesis = MULTIPLE chromosomal losses (others are DEL/Trisomy)

Question 18

How does hematuria of RENAL and URINARY/BLADDER CARCINOMAS differ from hematuria of other renal pathology involving the GLOMERULUS?

Answer 18

CARCINOMAS - Hematuria: RBC look NORMAL because they’re bleeding directly into the tubular lumen due to damage of epithelium (AFTER GLOMERULUS)
GLOMERULAR DISEASE - Hematuria: RBC look DYSMORPHIC or RBC CASTS due to glomerular damage (AT GLOMERULUS)

Question 19

What are NEPHROGENIC RESTS? What are they indicative of in terms of renal pathology?

Answer 19

NEPHROGENIC RESTS = Blastema cells (primitive renal mesenchyme) + Stromal cells + Primitive glomeruli/tubular
WILM’S TUMOR

Question 20

What is the pathogenesis of WILM’S TUMOR?

Answer 20

EARLY BLOCK in NEPHROGENIC process: Gets arrested in the primitive stage -> Thus hallmark cell of nephrogenic rests are BLASTEMA CELLS

Question 21

How do you CONFIRM the diagnosis of WILM’S TUMOR? When do you do this test in relation to treatment?

Answer 21

Do confirmatory BIOPSY AFTER excision of the tumor after detecting HETEROGENOUS tumor on scan
Can NOT put a needle in mass bec it will change the staging

Question 22

What is the most common urinary system malignancy? What is the most common age population and sex? Are most cases hereditary or sporadic?

Answer 22

BLADDER CANCER
Mostly ELDERLY (avg age: 70) MEN (3:1 M:F)
MOSTLY SPORADIC

Question 23

RENAL MALIGNANCIES vs URINARY MALIGNACIES - Account for genetics or environment (i.e. familial or sporadic)

Answer 23

Majority of BOTH system malignancies are SPORADIC.
Renal malignancies do have a strong HEREDITARY correlation, whereas urinary malignancies are mostly ENVIRONMENTAL-related

Question 24

Are PAPILLARY and(or) FLAT UROTHELIAL (TRANSITIONAL CELL) Carcinomas INVASIVE? Which one can be Low grade only, low grade only or high grade, or only high grade?

Answer 24

NO, Non-invasive
FLAT - HG
PAPILLARY - LG or HG