Robbins, Chapter 20, Congenital Defects and Neoplasia

Question 1

A newborn with bilateral agenesis of the kidney, think what

Answer 1

Incompatible with life

Question 2

Above pelvic brim or within the pelvis, think what congenital disorder?

Answer 2

Ectopic localization

Question 3

Where is the renal angle?

Answer 3

Between the lower border of the 12th rib and lateral border of erector spinae muscle

Question 4

What am I?
Hereditary disorder characterized by multiple expanding cysts of both kidneys that ULTIMATELY destroy renal parenchyma, taking over the entire cortex, and result in renal failure (ultimately, unless patient dies of something else first).
Am I universally uni or bilateral?

Answer 4

Autosomal Dominant (adult) Polycystic Kidney Disease
ADPKD

Bilateral

Question 5

PKD1 and PKD2 genes:
What overall disease?
What chromosomes, respectively?
What protein does each code for?
Which is more aggressive, faster onset, and worse prognosis/higher likelihood of developing ESRF?

Answer 5

ADPKD
PKD1 - Polycystin 1, an integral membrane glycoprotein, ch16
PKD2 - Polycystin 2, a Ca2+ permeable cation channel, ch4 (ADPKD disrupts regulation of intracellular Ca2+.
PKD1 has worse prognosis than PKD2 - more aggressive, faster onset, more likely to develop ESRF

Question 6

What renal damage do cysts cause?

In ADPKD, are cysts always intrarenal? If extrarenal, where and what percentage of pts have cysts here?

Answer 6

Glomerular, vascular damage
Interstitial inflammation/fibrosis
No - they can be found in the LIVER (40% have here), lungs, or spleen with mitral valve prolapse in the heart (25%).

Question 7

What am I?
May be asymptomatic until renal insufficiency announces presence.
Flank pain may be indicative of hemorrhage into cysts.
Hematuria is sometimes found with large, palpable abdominal masses.
Associated with African American, M>F, and concomitant HTN.
82% prevalence of diverticular disease of colon in patients with this.

Answer 7

ADPKD

Question 8

Subarachnoid hemorrhage secondary to intracranial berry aneurysms account for 10% of deaths in what hereditary kidney disease?
How many

Answer 8

ADPKD

Question 9

PKD1 chromosome# on childhood ARPKD v. adult ADPKD

Are signs of renal failure present in ARPKD and/or ADPKD?

Answer 9

ARPKD - ch6, coding for fibrocystin.
ADPKD - ch16, coding for Polycystin 1.

ARPKD has obvious renal failure, but ADPKD may be asymptomatic.

Question 10

What am I?
Slighly enlarged kidneys exhibiting numerous small (1-2mm) linear/radial arrayed cysts derived from dilated collecting ducts. Elongated cysts along cortex and medulla, perpendicular to cortical surface. BILATERAL.

What age group?
Good prognosis?

Answer 10

ARPKD

Children!
Bad prognosis - death.

Question 11

What are the four subtypes of ARPKD?
Which is most common?
Which has most (and least) % of cystic CD?
Time for survival.
Which is associated with LIVER dysfunction (portal HTN, systemic HTN, HEPATIC FIBROSIS)?
Which is associated with PROGRESSIVE hepatic fibrosis and esophageal varicies?

Answer 11

(1) Perinatal - Most common
90% CD cystic
(2) Neonatal
60% CD cystic
(3) Infantile - hepatic fibrosis, portal HTN, systemic HTN
20% CD cystic
(4) Juvenile - PROGRESSIVE hepatic fibrosis with esophageal varicies
10% CD cystic

Question 12

Time for survival of the four subtypes of ARPKD - which is only a few hours (and death due to what?). Which survives months (death due to what?), which die in early childhood?

Answer 12

(1) Perinatal - live hours, death due to hypoplastic lungs
(2) Neonatal - live for months, death due to renal failure
(3) Infantile - 90% survive neonatal, but almost all die in early childhood

Question 13

What am I?

Obvious renal failure in all cases. survivors develop congenital hepatic fibrosis with HTN and SM.

Answer 13

ARPKD

Question 14

What are the two diseases of the renal medulla - the Medullary Cystic Diseases? Which is more, which is less severe?

Answer 14

(1) Medullary sponge kidney - less severe (innocuous)

2) Nephronophthisis cystic disease - more severe (malicious

Question 15

What am I?
Occur in adults, innocuous medullary cystic disease. Found on radiograph. Person has increased risk for STONES, hematuria, infection. Cysts consist of cuboidal epithelium from collecting tubules.

Answer 15

Medullary Sponge Kidney

Question 16

What am I?
The person will present with POLYURIA and POLYDYPSIA.
5-10 years later, the person will have renal failure (due to what?). In children patients, family history has unexplained renal failure - mutations in MCKD1 and MCKD2 (adult) NPHP (kid) are identified as cause.
MEDULLARY CYSTS LOCALIZED TO THE CORTICOMEDULLARY JUNCTION and medulla.

Answer 16

Nephronophthisis-Medullary Cystic Disease

While medullary cysts are present, cortical tubulointerstitial damage is the cause of renal insufficiency.

Question 17

Why are the first signs of Nephronophthisis - polyuria and polydipsia? What does it mean the kidney cannot do?

Answer 17

It reflects the person’s inability to concentrate urine.

Question 18

Tubular disorders all generally initially present with what, clinically?

Answer 18

Polyuria and polydipsia

Question 19

What am I?
Caused by ESRD with PROLONGED DIALYSIS. Cortex and Medulla may have numerous, small cysts that contain clear fluid. RCC associated with this.

Answer 19

Acquired (Dialysis Associated) Cystic Disease

Question 20

How can you tell the difference between a renal cyst and tumor on ultrasonography?

Answer 20

Renal cysts are smooth and avascular, giving fluid signals.

Renal tumors are more irregular and solid.

Question 21

What am I?
Kidneys normal sized.
RENAL FUNCTION IS NOT AFFECTED.
Usually single, SMALL, on renal CORTEX surface, filled with clear fluid, common post-mortem finding.
Person may have sudden distention and pain, if HEMORRHAGE (possibly DUE TO TRAUMA) into cyst.

Answer 21

Simple (Localized) Renal Cyst

Question 22

What am I?
Extremely large kidneys (mass in the PERINATAL period, oligohydraminos!). Absent ureter, ureteropelvic obstruction or other lower GU anomalies.
Multiple, large cysts that are surrounded by undifferentiated mesenchyme and immature collecting ducts. Disorganzied lobar architecture.
Non-familial.

Answer 22

Multicystic Renal Dysplasia

Question 23

What type of Urinary Tract Obstruction does this describe?
Pain from rapid dilation of area immediately proximal.
Stones cause colic from ureter/capsule distention.
Prostate causes bladder symptoms.

Answer 23

Acute Obstruction

Question 24

What type of Urinary Tract Obstruction does this describe?
Asymptomatic leading to preventable hydronephrosis, atrophy, and loss of renal function.
Identify with ultrasonography so damage doesn’t occur.

Answer 24

Unilateral or Incomplete Obstruction

Question 25

What type of Urinary Tract Obstruction does this describe? Person presents with inability to concentrate urine reflected by polyuria and nocturia. Result of tubular atrophy and scarring associated with tubular interstitial nephritis.

Answer 25

Bilateral Partial Obstruction

Question 26

What type of Urinary Tract Obstruction does this describe? | Inability to produce urine (ANURIA). When obstruction removed, massive salt concentrated diuresis occurs.

Answer 26

Complete Bilateral Obstruction

Question 27

Hyperparathyroidism (due to progressive kidney failure) can lead to hypercalciuria (idipoathic most common cause) with hypercalcemia, leading to what type of stone? RADIO-OPAQUE

Answer 27

Calcium oxalate stone

Question 28

Nucleation of what type of crystal leads to ___ stone formation? RADIOLUSCENT

Answer 28

Uric Acid

Question 29

Infection by urea splitting bacteria such as PROTEUS can lead to what type of stone? RADIO-OPAQUE What size of stone?

Answer 29

``` Struvite Stone (Magnesium Ammonium Phosphate) Largest of stones ```

Question 30

Staghorn Caliculi = what stone

Answer 30

Struvite Stone

Question 31

Gout or chemo for leukemia is associated with what type of stone due to high or low urinary pH?

Answer 31

Uric Acid Stones | low pH

Question 32

What am I? | Intermittent renal colic, sharp flak pain that radiates to groin. Hematuria due to shredded ureter.

Answer 32

Stones

Question 33

What are these - benign or malignant renal tumors? Respective sizes that differentiates benign from malignant? Renal Papillary Adenoma Renal Fibroma or Hamartoma Oncocytoma

Answer 33

Types of Benign Renal Tumors (3) | Benign is less than 1cm diameter

Question 34

What type of benign tumor am I? Gross: CORTICAL nodules that are yellow-grey, discrete EM - resembles Low Grade Papillary RCC Papillomatous structures with numerous complex folds Cytogenetics - trisomy 7 and 17

Answer 34

Renal Papillary Adenoma!

Question 35

What type of benign tumor am I? Epithelial tumor composed of large, eosinophilic cells with benign-looking nuclei and monster nuclei. EM - MASSIVE AMOUNTS OF MITOCHONDRIA Gross - mahogany brown and central stellate scar May closely simulate RCC, especially CHROMOPHOBE variant. While benign, can cause compressive syndromes due to size (up to 12cm).

Answer 35

Renal Oncocytoma

Question 36

Where do Renal Oncocytomas arise form?

Answer 36

type A intercalated cells of renal cortical collecting ducts

Question 37

What benign tumor am I? A middle aged female presents with SHOCK due to tumor spontaneously rupturing, with massive RETROPERITONEAL/intra-abdominal HEMORRHAGE. Associated with TUBEROUS SCLEROSIS 25-50% of all of this tumor type arise in TS patients).

Answer 37

Renal angiomyolipoma

Question 38

What malignant tumor am I? Black or white (1:1) male, 60+yo with hx of smoking cigarettes and exposure to asbestos, petroleum, heavy metals - often asymptomatic, but can present with weight loss, malaise, weakness, fever, and.... any combo of TRIAD of symptoms: HEMATURIA (most common), FLANK/costovertebral PAIN, and PALPABLE FLANK MASS.

Answer 38

RCC

Question 39

What paraneoplastic syndromes are associated with RCC?

Answer 39

polycythemia (Epo), Hypercalcemia (PTH), HTN (Ald, Renin), Cushings (ACTH), Feminization (Androgens)

Question 40

Why is RCC dangerous, where does it metastasize to?

Answer 40

Reach massive sizes before symptoms set in. | 25% have metastasized prior to discovery - 50% lung, 1/3 to bone, etc.

Question 41

What RCC am I? 98% have 3p deletion = mutation in VHL tumor suppressor gene, causes multiple bi-lateral tumors if VHL. Sporadic HIF Kidney is the most common site of origin of this metastatic cancer (arises from Proximal Tubule Epithelium)! See CLEAR CYTOPLASM, dilated thrombosed renal vein. UNILATERAL, one spot, YELLOW masses. Average prognosis

Answer 41

Clear Cell Carcinoma

Question 42

What RCC am I? Trisomy 7, 16, 17, lost Y (familial form, mapped to MET proto oncogene) Usually BILATERAL, mutiple spots arising from Distal Tubule Hemorrhagic and cystic, papillary pattern. Better prognosis

Answer 42

Papillary Carcinoma

Question 43

What RCC am I? Eosinophilic cytoplasm, perinuclear HALO, faintly granular. Localized to vasculature. Grown from type B Intercalated calls of renal cortex collecting ducts (like oncocytoma). Better prognosis

Answer 43

Chromophobe

Question 44

What RCC am I? | Young patient with TFE3 gene translocation on chromosome 11

Answer 44

Xp11 translocation carcinoma

Question 45

What RCC am i? arise form CD cells in medulla, forming "hoblike pattern". Malignant cells enmeshed within a prominent fibrotic stroma. Good or poor prognosis? What is morphologically similar to this, but seen in sickle cell patients? Heavily infiltrated by neuts. Worse prognosis for both

Answer 45

Collecting (Bellini) Duct carcinoma. Poor prognosis Medullary carcinoma

Question 46

What is the typical mode of spread of RCC and where is early invasion? Rank the prognoses of the 6 types of RCC:

Answer 46

Hematologic mode (not lymphatic) with early Renal Vein invasion. Best - Papillary and chromophobe Average - Clear cell Worst - CDCarcinoma, Sarcomatoid RCC, medullary

Question 47

What grade of tumor is recommended for partial nephrectomy?

Answer 47

T1a - less than 4cm

Question 48

What has Oil Red O+ stain? What does this neoplasm elaborate? What accumulates in the cytoplasm?

Answer 48

Clear cell carcinoma Lipids elaborated Lipids and glycogen accumulate

Question 49

What tumors often have concomitant bladder tumors (50% have)? Associated with analgesic and Balkan (tubulo-interstitial) nephropathy.

Answer 49

Urothelial Carcinoma of the Renal Pelvis

Question 50

What neoplasm am I? | Person has hematuria, hydronephrosis, and flank pain.

Answer 50

Urothelial Carcinoma of the Renal Pelvis

Question 51

Tumors of the urothelium of the renal pelvis make up what percent of primary renal tumors? The wall of what two areas are common sites infiltration?

Answer 51

5-10% Pelvis and calyces

Question 52

What neoplasm am I? A 2yo Asian child presents with LARGE ABDOMINAL MASS, HTN/Nausa/Hematuria. 90% of the time the masses are unilateral. Well circumscribed margins, tan to gray color with tumor in lower pole of the kidney.

Answer 52

Wilms

Question 53

If nephrogenic rests (precurosor lesions) are identified, what do you think of?

Answer 53

Wilms

Question 54

What is the triphasic pattern of Wilms? What does it mimic?

Answer 54

It mimics germinal development of normal kidney Stromal component - spindle shpaed cells Epithelial component - immature tubule Blastemal component - densely packed small blue cells

Question 55

What is the most critical prognostic element in Wilms tumor? What is an unfavorable histomorphlogy? What gene association? Also, is older or younger better? Is Wilms curable?

Answer 55

Absence or presence of DIFFUSE ANAPLASIA. Presence of diffuse anaplasia=always unfavorable. Presence of focal anaplasia is NOT ALWAYS a poor prognosis. p53 mutation and resistance to chemo Older = better Px Yes, curable in 90% of chidlren

Question 56

What percent of Wilms Tumor patients have WT1 mutations? What are the rest? WT1 mutation associated with what syndromes that include Wilms? What has possible WT2 involvement?

Answer 56

10%WT1 mutation, the rest are previously healthy children. Group 1: WAGR (Wilms-Anidirida-Gential-Retardation) Group 2: Denys-Drash Syndrome (gonadal and renal tumors) Group 3:Beckwith-Wiedeman syndrome (hemihypertrophy syndrome)

Question 57

Most common sites of origin of metastasis TO the kidney (5).

Answer 57

LUNG! melanoma, breast, GI, pancreas

Question 58

FH gene mutation

Answer 58

Autosomal dominant | Cutaneous and uterine leiyomyomas (skin and uterine tumors)

Question 59

MET mutation

Answer 59

Autosomal Dominant | Bilateral, multiple tumors (papillary?)

Question 60

BHD mutation

Answer 60

AD folliculitis - BHD Syndrome Skin, pulmonary, and renal tumors

Question 61

VHL deletions >> HIF-1 hyperactive >> VEGF and IGF 1 active unifocal Sporadic type

Answer 61

CCC

Question 62

Trisomy 7, 17, no Y (male) Mutated, active MET mutifocal

Answer 62

Papillary carcinoma

Question 63

VHL gene, ch 3 | Familial type

Answer 63

CCC