B5.081 Prework 1: Renal Tumors

Question 1

most common kidney neoplasms

Answer 1

1. RCC (3 subtypes)
2. wilms tumor
3. urothelial tumors of renal pelvis

Question 2

epidemiology of RCC

Answer 2

30,000 new cases/year in US
typically older patients (60s-70s)
2:1 M:F

Question 3

where does RCC arise from

Answer 3

arise from renal tubular epithelium

Question 4

risks factors for RCC

Answer 4

tobacco**
obesity, HTN, asbestos, petroleum, heavy metals
renal failure (long term dialysis)
tuberous sclerosis
vHL

Question 5

rare familial variants of RCC

Answer 5

autosomal dominant
von Hippel Lindau (vHL)
hereditary papillary carcinoma

Question 6

von Hippel Lindau

Answer 6

RCC occurs in 2/3 of patients with vHL
often bilateral
loss of vHL tumor suppressor gene

Question 7

hereditary papillary carcinoma

Answer 7

multiple bilateral tumors

mutated MET proto-oncogene

Question 8

most common type of RCC

Answer 8

clear cell carcinoma

Question 9

description of clear cell carcinoma

Answer 9

70-80% of renal cell cancers
proximal tubule origin
clear or granular cytoplasm
95% are sporadic

Question 10

gross appearance of clear cell carcinoma

Answer 10

well circumscribed, tan mass

arises in parenchyma

Question 11

histo appearance of clear cell carcinoma

Answer 11

multiple small cells with clear cytoplasm

blood vessels scattered throughout

Question 12

cytogenetics associated with clear cell carcinoma

Answer 12

loss of sequences on short arm of chromosome 3 OR unbalanced translocation with loss of part of 3p

Question 13

description of papillary carcinoma

Answer 13

10-15% of renal cell cancer
distal convoluted tubule origin
most common subtype found in dialysis patients

Question 14

histo appearance of papillary carcinoma

Answer 14

papillary growth (tubular formations with blood vessels in the middle)
cells with pink cytoplasm
interstitial foam cells (macrophages)

Question 15

genetics associated with papillary carcinoma

Answer 15

familial and sporadic
associated with trisomy of 7 and 17 and loss of Y
chromosome 7: MET locus (proto-oncogene) mediates cell growth, invasion

Question 16

description of chromophobe renal cell carcinoma

Answer 16

5% of renal cell cancer
intercalated cell of collecting duct origin
excellent prognosis

Question 17

histo appearance of chromophobe renal cell carcinoma

Answer 17

cells with prominent cell membranes and pale cytoplasm “vegetable cells”
halo around nucleus

Question 18

genetics associated with chromophobe RCC

Answer 18

multiple chromosome losses and hypodiploidy

no characteristic abnormalities

Question 19

clinical presentation of RCC

Answer 19

classic triad: costovertebral (flank) pain, palpable mass, hematuria
increased incidental discovery due to imaging for other reasons
produced a variety of systemic symptoms: polycythemia, hypertension, hypercalcemia

Question 20

severity of RCC

Answer 20

often metastasizes before any symptoms: lungs, bones most common
tends to invade renal vein, can grow continuously and reach vena cava/ right heart

Question 21

prognosis and treatment of RCC

Answer 21

5 year survival average : 70 %
if localized : 95%
renal vein invasion or perinephric fat invasion : 60%
nephrectomy or partial nephrectomy
chemo if metastatic

Question 22

gross description of urothelial carcinoma of the renal pelvis

Answer 22

well circumscribed mass confined to renal pelvis

Question 23

description of UCC renal pelvis

Answer 23

5-10% of primary renal tumors
present earlier than RCC due to location: hematuria, urinary obstruction
50% have previous or concurrent bladder tumor

Question 24

risk factors for UCC renal pelvis

Answer 24

analgesic nephropathy

Lynch Syndrome

Question 25

prognosis of UCC renal pelvis

Answer 25

50-100% 5 year survival with low grade non-invasion | 10% 5 year survival with invasion

Question 26

epidemiology of wilms tumor

Answer 26

most common primary pediatric renal tumor incidence: 1/10,000 2-5 years old 5-10% bilateral

Question 27

prognosis of wilms tumor

Answer 27

90% 5 year survival anaplastic histology key determinant survivors at increased risk for secondary tumors (sarcoma, leukemia, lymphoma)

Question 28

gross appearance of wilms tumor

Answer 28

well circumscribed, bulging tumor | "squishes" out normal kidney

Question 29

genetic associations with wilms tumor

Answer 29

sporadic much more common BUT 10% are syndromic

Question 30

syndromes associated with wilms tumor

Answer 30

WAGR Denys-Drash Syndrome Beckwith Wiedemann Syndrome

Question 31

what is WAGR

Answer 31

wilms (33% chance) aniridia genital anomalies mental retardation

Question 32

genetic mutation in WAGR

Answer 32

germline deletion of 11p13 WT1 gene PAX6 gene

Question 33

what is the WT1 protein

Answer 33

critical for normal renal and gonadal development encodes DNA binding transcription factors tumor suppressor gene

Question 34

what is Denys Drash Syndrome

Answer 34

``` 90% risk for wilms gonadal dysgenesis early onset nephropathy diffuse mesangial sclerosis increases risk of gonadoblastoma ```

Question 35

genetic mutation in Denys-Drash

Answer 35

germline mutations in WT1 | missense mutation in region that affect DNA binding properties

Question 36

what is Beckwith-Wiedemann syndrome

Answer 36

organomegaly macroglossia omphalocele adrenal cytomegaly

Question 37

other tumors that appear in Beckwith-Wiedemann syndrome

Answer 37

``` wilms hepatoblastoma pancreatoblastoma adrenal cortical tumors rhabdomyosarcomas ```

Question 38

genetic mutation associated with Beckwith-Wiedemann syndrome

Answer 38

genomic imprinting in 11p15.5, WT2 gene loss of imprinting (re-expression of normally silenced maternal IGF2 allele) OR deletion of imprinted maternal allele/supplication of active paternal allele

Question 39

histology of wilms tumor

Answer 39

triphasic: blastemal cells, stromal cells, epithelial cells possible anaplasia in 5% of tumors -large pleomorphic cells with abnormal mitoses -p53 mutations, resistant to chemo = worse prognosis

Question 40

appearance of blasternal cells in wilms

Answer 40

small, blue cells | form clumps together

Question 41

appearance of stromal cells in wilms

Answer 41

fibrous or myxoid spindle cells skeletal muscle

Question 42

appearance of epithelial cells in wilms

Answer 42

abortive tubules or glomeruli (gland looking)

Question 43

precursor lesions to wilms

Answer 43

nephrogenic rests seen in renal parenchyma adjacent to tumor in 25-40% of cases share genetic abnormalities with adjacent tumor increased risk of wilms in other kidney if present

Question 44

clinical presentation of wilms

Answer 44

``` large abdominal mass (often felt by parent) hematuria abdominal pain intestinal obstruction HTN pulmonary mets ```