Renal and Urinary Tract Neoplasms CORBETT Flashcards
What are the two main BENIGN renal neoplasms?
- ANGIOMYOLIPOMA
2. ONCOCYTOMA
ANGIOMYOLIPOMA: Are majority of the cases sporadic or hereditary? If hereditary, what disease is it most associated with?
80% (majority) - SPORADIC
20% - Hereditary: TUBEROUS SCLEROSIS (Autosomal Dominant HAMARTOMA)
Are most clinical manifestations of TUBEROUS SCLEROSIS COMPLEX renal? List out HAMARTOMA mnemonic
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
In pts with TUBEROUS SCLEROSIS COMPLEX, what are the possible renal manifestations? What is the most common manifestation?
- RENAL ANGIOLIPOMAS (A) - ANGIOMYOLIPOMA = most common
- RENAL CELL CARCINOMA
- RENAL CYSTS
Describe the most common characteristics of ONCOCYTOMA. Unilateral/Bilateral? Sporadic/Hereditary? Small/Large mass? Homogenous/Heterogenous?
MAJORITY - UNILATERAL, SINGLE SPORADIC LARGE (up to 12cm) oncytomas, Relatively HOMOGENEOUS
What is the origin of RENAL ONCOCYTOMAS?
INTERCALATED cells of the LATE DISTAL TUBULE/COLLECTING DUCT
What are the 3 microscopic features of ONCOCYTOMAS?
- LARGE EOSINOPHILIC CELLS
- NUMEROUS MITOCHONDRIA
- Benign nuclei with LARGE NUCLEOLI
What is the most common age population affected by RENAL CELL CARCINOMA? Age, Sex
OLDER (Avg Age: 60) MALE SMOKERS
What are the risk factors of RENAL CELL CARCINOMA? What is the most significant one?
*SMOKING - Increases x2,
OBESITY (Especially in women)
HTN
What is the majority subtype of RCC (sporadic or hereditary)? Which genetic disorder is most commonly associated with HEREDITARY RCC?
*>95 - SPORADIC RCC
3% HEREDITARY RCC - most commonly associated with VON HIPPEL-LANDAU Disease
What are the 3 variants of RCC? Which is the most common one?
- *CLEAR CELL CARCINOMA - most common
- PAPILLARY CARCINOMA
- CHROMOPHOBE CARCINOMA
What is the most common pathogenesis of RCC CLEAR CELL CARCINOMA variant?
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
What is generally the origin of RCC (Clear cell variant - most common)?
UPPER POLE of kidney - PROXIMAL TUBULAR EPITHELIUM
Is CLEAR CELL CARCINOMA mostly sporadic or hereditary?
SPORADIC (95%) - Thus mostly SOLITARY and SINGULAR tumor
How does HEREDITARY CLEAR CELL CARCINOMA (CCC) differ from the more common SPORADIC CCC?
Hereditary - VHL syndrome related + BILATERAL/MULTIFOCAL TUMOR
Is PAPILLARY CELL CARCINOMA (RCC variant 2) mostly sporadic or hereditary? What syndromes are associated with familial PCC?
MOSTLY HEREDITARY - Thus mostly BILATERAL/MULTIFOCAL
Type 1 - Low Grade - Linked to MET mutation
Type 2 (H) - High Grade - Linked to fumarate Hydrase
What may be the pathogenesis of HEREDITARY PAPILLARY CELL CARCINOMA? Which is the most common one?
TRISOMY 7*- most common
Trisomy 17, Loss of Y chromosome
How does CHROMOPHOBE CARCINOMA (RCC Variant 3) differ from the other variants CLEAR CELL and PAPILLARY? [Think origin, pathogenesis, and prognosis]
***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)
How does hematuria of RENAL and URINARY/BLADDER CARCINOMAS differ from hematuria of other renal pathology involving the GLOMERULUS?
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)
What are NEPHROGENIC RESTS? What are they indicative of in terms of renal pathology?
NEPHROGENIC RESTS = Blastema cells (primitive renal mesenchyme) + Stromal cells + Primitive glomeruli/tubular
WILM’S TUMOR
What is the pathogenesis of WILM’S TUMOR?
EARLY BLOCK in NEPHROGENIC process: Gets arrested in the primitive stage -> Thus hallmark cell of nephrogenic rests are BLASTEMA CELLS
How do you CONFIRM the diagnosis of WILM’S TUMOR? When do you do this test in relation to treatment?
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
What is the most common urinary system malignancy? What is the most common age population and sex? Are most cases hereditary or sporadic?
BLADDER CANCER
Mostly ELDERLY (avg age: 70) MEN (3:1 M:F)
MOSTLY SPORADIC
RENAL MALIGNANCIES vs URINARY MALIGNACIES - Account for genetics or environment (i.e. familial or sporadic)
Majority of BOTH system malignancies are SPORADIC.
Renal malignancies do have a strong HEREDITARY correlation, whereas urinary malignancies are mostly ENVIRONMENTAL-related
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?
NO, Non-invasive
FLAT - HG
PAPILLARY - LG or HG
