Renal Cell Carcinoma And Colon Cancer

Question 1

Types of RCC

Answer 1

Clear cell carcinoma
Papillary
Chromophobe

Question 2

Features of RCC

Answer 2

Kidneys are retroperitoneal present late 
Haematuria 
Flank pain 
Abdominal mass
Those are triad of features 
More common but less specific features include 
Weight loss 
anaemia 
Fever symptoms related to metastasis

Question 3

Clear cell carcinoma why is it called this

Answer 3

Small masses of cells separated by capillaries
Clear cytoplasm - cytoplasm originally contained lipid this was dissolved when being processed
Cells not processed are yellow due to lipid presence
Some cells black due to haemorrhage

Question 4

Types of clear cell carcinoma

Answer 4

Familial - Von hippel lindau syndrome
Sporadic
Metastatic carcinoma with unknown primary

Question 5

Von hippel lindau

Answer 5

Autosomal dominant
Occurs 1 in 36000
Mean age of presentation 37years
Haemangioblastomas of CNS and retina, pancreatic and renal cysts and renal tumors
Germ line mutation of the VHL tumour suppressor gene

Question 6

What is the VHL protein involved in

Answer 6

HIF

Hypoxia inducible factor pathway

Question 7

Do VHL tumours form just at the kidneys

Answer 7

No 
Brain spinal cord
Retinal haemangioblastoma and cysts 
Adrenal - phaechromocytoma
Renal cysts 
Pancreatic cysts and cystadenomas 
Epididymal cystadenomas

Question 8

VHL mutation causes

Answer 8

Accumulation of HIF alpha
VEGF
PDGF
TGF alpha

Question 9

Sporadic clear cell RCC

Answer 9

Commonest type
Mean age 61years
Abhorrent VHL gene - found in 75% of sporadic cases
Loss of VHL function important during RCC pathogenesis

Question 10

RCC common infiltrates

Answer 10

Renal vein

Question 11

Treatment

Answer 11

Radical nephrectomy 
Remove kidney 
Perinephric fat 
Adrenal glands and blood vessel 
Done because primary tumour can extend to the adrenals not a met just grew that far

Question 12

Happens when tumour becomes high grade?

Answer 12

Change in morphology
-> sarcomatoid clear cell
Spindle like

Question 13

Histology report on nephrectomy specimen

Answer 13

Type of renal cell carcinoma 
Fuhrman nuclear grading
Tumour necrosis 
Local spread- insinus or perinephric fat 
Vascular main renal vein invasion 
Completeness of resection 
Final TNM staging - pTNM
Prognostic indicators

Question 14

Staging stage 1

Answer 14

<4 cm partial nephrectomy

>4cm or multiple - radical nephrectomy

Question 15

Stage 2,3

Answer 15

Normal contralateral kidney -> radical nephrectomy

Solitary kidney -> partial nephrectomy

Question 16

Stage 4

Answer 16

Immunotherapy -> clinical response -> nephrectomy?

Question 17

RCC in adults

Answer 17

Mortality rate 40-50%
20% patients present with locally advanced or metastatic disease
30% who undergo surgery will develop mets
Currently available for advanced RCC is immunotherapy with IL 2 and INF alpha with small survival benefit at the price of significant toxicity

Question 18

Colon cancer clinical signs and investigations

Answer 18

Malaise
Weakness
Weight loss
Altered bowel habits
Anaemia
Upper GI endoscopy -normal if no oesophageal or stomach lesion
Colonoscopy exam- exophytic ulcerative mass in the colon
Exophytic - proliferating on the exterior or surface epithelium of an organ or other structure in which the growth originated
Lesion is partially obstructing the lumen of the bowel

Question 19

Tissue biopsy results

Answer 19

Abnormal tortuous colonic glands
Glands are arranged haphazardly around the tissue
Fibrotic stroma - pink
Cells look blue - nuclei stained blue -> enough to diagnose colon cancer

Question 20

CT exam results

Answer 20

Bulky circumferential tumour in colon
Tumour shows pericolic streaking
Haziness around wall of colon tumour is in = tumour is perforating the fat around the colon

Question 21

Treatment

Answer 21

Remove diseased part of the colon right hemicolectomy

Tumour is analysed when removed from the patient

Question 22

Analysis

Answer 22

Reaches the outer bowel wall surface
Polyps present - pre neoplastic benign but may become cancerous
Enlarged lymph nodes - tumour metastasised to regions lymph nodes
Abnormal glands - larger nuclei
Highly differentiated glands - can be clearly seen well defined
Moderately diff - not as easy to see les well defined
Poor diff - diff to see poorly defined

Question 23

TNM staging T

Answer 23

PT1 tumour invades submucosa 
PT2 tumour invades muscularis propria
PT3 tumour invades through the muscle into subserosa 
PT4a tumour invades adjacent organs 
PT4b tumour invades visceral peritoneum

Question 24

N stage

Answer 24

PN0 no lumps nose metastasis
PN1 metastasis in up to 3 nodes
PN2 metastasis in 4 or more nodes

Question 25

M stage

Answer 25

PM0 no distant metastasis | PM1 distant metastasis present

Question 26

Dukes classification

Answer 26

A tumour confined to bowel wall node neg B tumour spread beyond muscle node neg C1 tumour lymph node pos highest node spared C2 highest node involved

Question 27

Histology

Answer 27

Invasive adenocarcinoma poorly differentiated Invading through the wall reaching serosal surface, pT4 Lymphovascular and perineural invasion 12/25 met nodes pN2 Apical node positive dukes C2

Question 28

Molecular prognostic factors

Answer 28

Micro satellite stable/in stable Majority MSS (micro satellite stable) tumour show chromosomal instability Aneuploidy, allelic losses, amplification, translocation, mutation of APC, KRas, TP53

Question 29

Mismatch repair genes

Answer 29

Indications Young age multiple colonic tumours, cancer in other organs, family history Immunohistochemistry -MLH1, MSH2, MSH6, PMS2

Question 30

MSI-H tumour

Answer 30

Proximal colon Poorly differentiated Mucinous histology Increased lymphocytic infiltration

Question 31

What is the clinical importance of MSI-H tumours

Answer 31

Sporadic 15%, less aggressive tumours Microsatellite status should be assessed in all pT3N0 tumours to decide on adjuvant chemotherapy Lynch syndrome alert patient and blood relatives Healthy relatives tested - clinically /direct DNA sequencing of MMR genes Monitor patients for other cancers

Question 32

Lynch syndrome -

Answer 32

Autosomal dominant Germline mutations of one of the MMR genes Germline mutations identified by sequencing - genetic test requires patients consent Young age Right colon Assciated with cancers in endometrium, ovary, renal pelvis, ureter, small bowel, stomach and pancreas

Question 33

Loss of MSH2 and MSH6 what is diagnosed

Answer 33

Lynch syndrome | Refer to geneticist

Question 34

Loss of MLH1 BRAF not mutated No MLH1 promoter methylation Diagnoses ?

Answer 34

Lynch syndrome | Refer to geneticist

Question 35

Loss of MLH1 BRAF mutated MLH1 promoter methylated

Answer 35

Sporadic | Not genetics referall

Question 36

Mutations involved ? Can they be targeted with immunotherapy

Answer 36

RAS and BRAF | Mab can be used

Question 37

Ras mutations

Answer 37

KRas NRAS Found in 40-45% of colorectal tumours Mutations occur in codon 12, 13, 61, 117, 146. Result in constructive activation of the protein Unlikely to benefit from EGFR mab treatment

Question 38

BRAF mutation

Answer 38

8% colorectal cancers Commonest p.V600E mutation within the kinase activation domain Poor prognosis if not associated with MSI H status Not regarded as a negative predictive marker for anti EGFR1 therapy currently