CVPR Week 8: Cystic disease and renal neoplasia Flashcards by Jay Sandoval

Types of cystic diseases of the kidney

8 listed

Multicystic renal dysplasia
Polycystic kidney disease
Medullary cystic disease
Acquired (dialysis-associated) cystic disease
Localized (simple) renal cysts
Renal cysts in hereditary malformation syndromes (tuberous sclerosis)
Glomerulocystic disease
Extraparenchymal renal cysts (pyelocalyceal cysts, hilar lymphangitic cysts)

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Types of polycystic kidney disease

2 listed

Autosomal dominant (adult) polycystic disease
Autosomal recessive (childhood) polycystic disease

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Types of medullary cystic disease

2 listed

Medullary sponge kidney
nephronophthisis

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ADPKD AKA

Autosomal dominant polycystic kidney disease

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ADPKD etiology

Autosomal dominant mutation of PDK1 or PDK2 genes

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ADPKD epidemiology

1 of every 400-1000 live births

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ADPKD clinical features and complications

5 listed

hematuria
flank pain
TUI
Renal stones
HTN

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ADPKD pathologic features

Large multicystic kidneys
liver cysts
berry aneurysms

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ADPKD prognosis

Chronic renal failure beginning at age 40-60 requiring transplant or dialysis

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ADPKD gross histological features

Bilateral enlarged
can weigh as high as 4 Kg each kidney
up to 3-4 cm, no intervening parenchyma

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ADPKD Gross histological features

Bilateral enlarged
can weigh as high as 4 Kg each kidney
up to 3-4 cm, no intervening parenchyma

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ADPKD gross histological features

Bilateral enlarged
can weigh as high as 4 Kg each kidney
up to 3-4 cm, no intervening parenchyma

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ADPKD histological features

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PDK1 gene genome location

Chromosome 16p13.3

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PDK1 gene encodes

Polycystin-1, a large (460KD0 integral membrane protein)

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PDK1 gene gross location

Localized to tubular epithelial cells particularly those of the distal nephron

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PDK1 gene function

not yet clear but it contains domains involved in cell-cell and cell-matrix interactions

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PDK2 gene genome location

Chromosome 4p21

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PDK2 gene encodes

plycystin-2 which is an integral membrane protein

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PDK2 gene gross location

localized to all segments of renal tubules

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PDK2 gene function

Functions as a Ca2+ permeable cation channel

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Possible mechanism of ADPKD

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ARPKD AKA

Autosomal recessive polycystic kidney disease

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ARPKD etiology

Autosomal recessive mutation of PKHD1 gene

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ARPKD pathologic features

enlarge cystic kidneys at birth (infantile polycystic kidney disease)

ARPKD clinical features and complications

hepatic fibrosis

ARPKD prognosis

viable death in in infancy or childhood

ARPKD gross histologic features

* 1-2 cm uniformly distributed * spongy appearance * in utero, oligohydramnios or anhydramnios

ARPKD gross histologic features

* 1-2 cm uniformly distributed * spongy appearance * in utero, oligohydramnios or anhydramnios

ARPKD histologic features

PKHD1 gene genome location

chromosome 6p21-23

PKHD1 gene encodes

a large protein fibrocystin (447-KD) integral membrane protein

Fibrocystin location

localized to the primary cilium of tubular cells similar to polycystin 1 and 2 encoded by PKHD1

PKHD1 gene possible mutations?

a wide range of possible mutations

Multicystic renal dysplasia prevalence

More common than ARPKD

Multicystic renal dysplasia etiology

* no inheritance pattern * part of a malformation complex

Multicystic renal dysplasia unilateral/bilateral

often unilateral but bilateral cases are often asymmetric

Multicystic renal dysplasia clinical manifestations and complications

A/W urinary tract anomalies (uteropelvic obstruction, ureteral agenesis atresia)

Multicystic renal dysplasia gross histological features

Multicystic renal dysplasia histological features

Medullary sponge kidney cyst size

1-7mm cysts in the medulla

Medullary sponge kidney unilateral/bilateral

Typically bilateral and incidental finding on imaging

Medullary sponge kidney clinical manifestations and complications

* Renal function is usually normal (cortex is not involved) * Renal calculi-obstruction and infection (pyelonephritis) and hematuria * some have Marfan, Ehler-Danlos syndrome and Caroli disease

Medullary sponge kidney gross histological features

Medullary cystic disease/Nephronophthisis etiology

* Hereditary form of tubulointerstitial disease secondary to mutations in cilliary proteins * Mutations in NPHP1 accounts for ~85% of NPHP type 1 which maps in chromosome 2q13 * NPHP2 encodes for inversin responsible for NPHP type II and maps to chromosome 9p22-31 * NPHP3 encodes for nephrocystin-3 responsible for NPHP type III

Medullary cystic disease/Nephronophthisis subtypes

* Divided into NPHP types I (juvenile), II (infantile), III (Adolescent) by the onset of ESRD

NPHP1 genome location

chromosome 2q13

NPHP2 genome location

chromosome 9p22-31

NPHP3 gene encodes

encodes nephrocystin-3

NPHP2 gene encodes

inversin

NPHP1 gene encodes

nephrocystin-1

NPHP3 gene location

3q22.1

Phenotypic spectrum of children with nephronophthisis

Nephronophthisis gross histological features

Identify

Tumors of the kidney

* Clear cell renal cell carcinoma * Papillary renal cell carcinoma * Chromophobe renal cell carcinoma

% of kidney tumors that are clear cell renal cell carcinoma

70-80%

% or kidney tumors that are Papillary renal cell carcinoma

10-15%

% of kidney tumors that are chromophobe renal cell carcinoma

Risk factors for tumors of the kidney

smoking

Common etiology of kidney tumors

* most are sporadic * some are autosomal dominant (4%) * some deletion of 3p

What % of kidney tumors are autosomal dominant?

What percentage of Von Hippel-Lindau (VHL) develop clear cell RCC

* 2/3 to 1/2 * Even hereditary clear cell RCC without a VHL manifestation involves VHL related genes

The common cause of papillary RCC

Hereditary papillary RCC

Chromophobe RCC cause

multiple chromosome losses and hypodiploidy

Renal cell carcinomas are often associated with?

* Polycythemia from the elaboration of erythropoietin * Hypercalcemia with tumor production of parathormone-related peptide * Steroid hormone release with Cushing syndrome, feminization, or masculinization

Identify

Causes of sporadic papillary RCC

* Trisomy 7, 16 and 17 * Loss of Y * Mutated activated MET t(X;1) -\> PRCC oncogenes * TFE on X transfusion with PRCC on chromosome 1 * clear cell papillary RCC

Causes of hereditary papillary RCC

* Trisomy 7 * Mutated, activated MET

Causes of sporadic Clear cell RCC

* Translocations 3;6, 3;8, 3;11 * deletions on chromosome 3 (3p21)

Causes of hereditary clear cell RCC

* Loss of VHL * Inactivated, mutated VHL * Hypermethylation of VHL

Clear cell renal carcinoma gross histological features

Most common type of RCC

Clear cell renal cell carcinoma

Clear cell renal cell carcinoma histological features

Papillary RCC gross histological features

Papillary RCC histological features

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RCCs

Wilms tumor AKA

Nephroblastoma

What is the most common childhood tumor?

Wilms tumor (nephroblastoma)

Wilms tumor clinical manifestations and complications

* abdominal pain * fever * anemia * hematuria * hypertension (25-30% of children)

Wilms tumor diagnosis

diagnosis can only be made on the histologic assessment of the tumor

Wilms tumor genetics

Germline genetic and epigenetic variants in Wilms tumor involve WT1 and the 11p15.5 locus

WT1 mutations

* in Wilms tumor with aniridia, genitourinary malformations and mental retardation (WAGR)-syndrome patients * Patient with WAGR syndrome have an earlier age of Wilms tumor diagnosis and more frequent occurence of bilateral disease

Denys-Drash Syndrome

(DDS) characterized by diffuse mesangial sclerosis leading to early-onset renal failure, intersex disorders that can range from ambiguous to normal-appearing female in both XY & XX individuals and a high-risk of Wilms tumor (some report 74%)

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