Renal cancer

Question 1

Renal papillary adenomas mostly occur in the (1)

Answer 1

1. renal cortex

Question 2

Angiomyolipoma of the kidney is a tumor composed of an admixture of ?

Answer 2

smooth muscle, blood vessels and fatty tissue

Question 3

Angiomyolipoma of the kidney originate from ?

Answer 3

perivascular epithelioid cells

Question 4

Angiomyolipoma of the kidney frequently seen (up to 50%) in cases of (1), loss of function mutation of TSC1 or the TSC2 tumor suppressor gene

Answer 4

tuberous sclerosis

Question 5

While they are histologically benign, angiomyolipomas of the kidney are important because of their propensity for (1) due to their increased vasculature

Answer 5

1. spontaneous hemorrhage

Question 6

Renal oncocytoma, is thought to arise from the (1); it accounts for up to 15% of all renal neoplasms.

Answer 6

1. collecting ducts

Question 7

The Renal oncocytoma tumors are (1) in appearance and frequently show (2). The tumor cells are strongly (3) and their cytoplasm demonstrates numerous (4) when viewed with the electron microscope

Answer 7

1. tan
2. a central scarred area
3. eosinophilic
4. mitochondria

Question 8

The common benign renal neoplasms are ?

Answer 8

renal papillary adenoma, angiomyolipoma and renal oncyctoma

Question 9

(1) is the biggest risk factor for renal cancer

Answer 9

1. Tobacco smoking

Question 10

Risk factors for renal cancer besides tobacco smoking

Answer 10

Hypertension, exposure to heavy metals, asbestosis exposure and chronic kidney disease are additional risk factors along with a history of long term dialysis(acquired cystic disease).

Question 11

(1) accounts for 80% of renal cancers.

Answer 11

1. Clear cell renal cell carcinoma

Question 12

Both familial and sporadic types of clear cell renal cell carcinoma are associated with (1) of function of the (2) gene on chromosome (3)

Answer 12

1. loss
2. VHL tumor suppressor
3. 3

Question 13

(1) gene encodes for proteins involved in the ubiquitin ligase complex which is involved in protein degradation. One protein regulated by this complex is (2) This is a factor promoting cell growth and angiogenesis.

Answer 13

1. VHL
2. HIF-1 (hypoxia inducible factor).

refers to clear cell renal cell carcinoma

Question 14

When (1) is inactivated the activity of (2) goes unregulated thus increasing cell growth and proliferation and tumor development

Answer 14

1. VHL
2. HIF-1 (hypoxia inducible factor).

refers to clear cell renal cell carcinoma

Question 15

Papillary renal cell carcinoma sporadic cases show (1) and loss of (2).

Answer 15

1. trisomy 7 and trisomy 17

2. Y chromosome in males

Question 16

Familial forms of papillary renal cell carcinoma feature (3)

Answer 16

3. trisomy chromosome 7.

Question 17

Both familial and sporadic forms of papillary renal cell carcinoma in addition feature (1) mutations.

Answer 17

1. activating MET

Question 18

Clinical features of renal cell carcinoma are (1). Constitutional symptoms of (2) are often also present.

Answer 18

1. costovertebral angle pain, presence of a palpable mass and often hematuria (intermittent)
2. fever, malaise and weight loss

Question 19

Renal cell carcinomas can produce a diverse number of symptoms from abnormal hormone production such as (1) which may confuse the diagnosis.

Answer 19

1. polycythemia, HTN, hypercalcemia and Cushing’s syndrome

Question 20

Frequent metastatic sites of renal cell carcinomas are ?

Answer 20

lungs and bone

Question 21

Tumor extension to involve perirenal or the presence of tumor within (1) are signs of poor prognosis

Answer 21

1. renal veins (renal vein invasion)

Question 22

(1) are the mainstays of treatment along with (2) drugs

Answer 22

1. Radical or partial nephrectomy (for smaller tumors) and chemotherapy
2. VEGF and tyrosine kinase inhibitor

Question 23

Urothelial carcinoma originates from the (1). (2) is a frequent presenting symptom. Larger tumors may produce (3)

Answer 23

1. urothelial lining cells of the renal pelvis
2. Hematuria
3. hydro nephrosis

Question 24

Urothelial carcinoma may frequently be present in other portions of the (1)

Answer 24

renal pelvis, ureters or bladder

Question 25

(1) is the most common primary kidney tumor in children (1 in 10,000 children) and the fourth most common pediatric malignancy. Tumors are bilateral in up to 10% of cases.

Answer 25

1. Wilms tumor or nephroblastoma

Question 26

Wager syndrome patients (1) have a >30% lifetime risk of developing a Wilms tumor

Answer 26

1. aniridia, genital abnormalities, mental retardation

Question 27

Wager syndrome features germline deletions of (1) and studies of these patients led to the identification of the (2).

Answer 27

1. 11p13 | 2. Wilms tumor associated gene (WT1)

Question 28

(1) is crucial to the proper development of the kidneys and gonadal development.

Answer 28

1. The WT1 gene

Question 29

Denys-Drash syndrome patients (1) have a 90% lifetime risk of developing a Wilms tumor. These patients have a (2) mutation of the (3) ( this interferes with the proper function of the remaining wild type allele).

Answer 29

1. gonadal dysgenesis, early onset nephropathy with renal failure 2. dominant negative inactivating 3. WT1 gene

Question 30

Beskwith-Wiedmann syndrome patients (1) also have an increased incidence of Wilms tumors.

Answer 30

1. enlargement of individual body parts or body segments

Question 31

Beskwith-Wiedmann syndrome is an example of a disorder of (2) whereby certain genes are inactivated during gametogenesis.

Answer 31

2. genomic imprinting

Question 32

The area of interest is an area of at least 10 genes distal to the WT1 locus and although the exact gene has not been identified the area is now called the (3). (4) is one of the genes in this area and it normally is only expressed by the paternal allele and the maternal gene is “imprinted” (inactivated normally”).

Answer 32

3. “WT2 gene”. 4. IGF-2 refers to Beskwith-Wiedmann syndrome

Question 33

Loss of imprinting of the (1) gene is believed to occur allowing for overexpression of (2) thus promoting organ enlargement or tumor development in (3)

Answer 33

1. maternal 2. IGF-2 3. Beskwith-Wiedmann syndrome

Question 34

often come to light due to presence of an easily palpated very large abdominal mass that may even extend into the pelvic area

Answer 34

Wilms tumors

Question 35

Wilms tumors may produce what s/s?

Answer 35

intestinal obstruction, hematuria, fever and weight loss.

Question 36

Three groupings of congenital malformations feature an increased risk for the development of Wilms tumor

Answer 36

Wager syndrome patients (aniridia, genital abnormalities, mental retardation) Denys-Drash syndrome patients (gonadal dysgenesis, early onset nephropathy with renal failure) Beskwith-Wiedmann syndrome patients (enlargement of individual body parts or body segments)

Question 37

Angiomyolipoma ``` Lesion with 1) Origin is from 2) 25‐50% of 3) patients have them Loss of suppressor function in TSC1 or TSC2 genes Significant because risk of 4) ```

Answer 37

1) fat, smooth muscle and blood vessels 2) perivascular epithelioid cells 3) Tuberous Sclerosis 4) spontaneous hemorrhage

Question 38

Renal ocnocytoma--> gross hallmark

Answer 38

central scarring

Question 39

Clear cell carcinoma VHL encodes protein for _____ promoting degradation of ______ which promotes cell growth and ____

Answer 39

ubiquitin ligase complex HIF‐1 (hypoxia inducible factor ) angiogenesis

Question 40

halo around nucleus

Answer 40

Chromophobe type renal cell carcinoma

Question 41

``` Diverse symptoms from hormone production (systemic symptoms unrelated to the kidney itself) Polycythemia HTN Hypercalcemia Cushing’s syndrome ```

Answer 41

Renal cell carcinoma clinical features

Question 42

Treatment options for renal neoplasms: | 3 things

Answer 42

``` Radical nephrectomy Partial nephrectomy ( smaller tumors) VEGF and tyrosine kinase inhibitors if metastatic disease present ```

Question 43

aniridia, genital abnormalities, mental retardation‐33% lifetime risk

Answer 43

Wager syndrome

Question 44

Germline deletions of 11p13 (WT1 gene); | Two hit hypothesis

Answer 44

Wager syndrome

Question 45

Dominant negative inactivating mutation of WT1 gene

Answer 45

Denys‐Drash syndrome

Question 46

gonadal dysgenesis, renal abnormalities‐90% lifetime risk

Answer 46

Denys‐Drash syndrome

Question 47

Denys‐Drash syndrome 1) mutation of WT1 gene Interferes with function of the remaining wild type allele Bi‐allelic WT1 inactivation leads to tumor development

Answer 47

1) Dominant negative inactivating

Question 48

Triphasic combination of elements in WILMS tumor | 1, 2, 3

Answer 48

blastemal stroma; epithelial cell types(abortive tubules or glomeruli)