Renal Cell Carcinoma And Colon Cancer Flashcards
Types of RCC
Clear cell carcinoma
Papillary
Chromophobe
Features of RCC
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
Clear cell carcinoma why is it called this
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
Types of clear cell carcinoma
Familial - Von hippel lindau syndrome
Sporadic
Metastatic carcinoma with unknown primary
Von hippel lindau
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
What is the VHL protein involved in
HIF
Hypoxia inducible factor pathway
Do VHL tumours form just at the kidneys
No Brain spinal cord Retinal haemangioblastoma and cysts Adrenal - phaechromocytoma Renal cysts Pancreatic cysts and cystadenomas Epididymal cystadenomas
VHL mutation causes
Accumulation of HIF alpha
VEGF
PDGF
TGF alpha
Sporadic clear cell RCC
Commonest type
Mean age 61years
Abhorrent VHL gene - found in 75% of sporadic cases
Loss of VHL function important during RCC pathogenesis
RCC common infiltrates
Renal vein
Treatment
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
Happens when tumour becomes high grade?
Change in morphology
-> sarcomatoid clear cell
Spindle like
Histology report on nephrectomy specimen
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
Staging stage 1
<4 cm partial nephrectomy
>4cm or multiple - radical nephrectomy
Stage 2,3
Normal contralateral kidney -> radical nephrectomy
Solitary kidney -> partial nephrectomy
Stage 4
Immunotherapy -> clinical response -> nephrectomy?
RCC in adults
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
Colon cancer clinical signs and investigations
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
Tissue biopsy results
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
CT exam results
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
Treatment
Remove diseased part of the colon right hemicolectomy
Tumour is analysed when removed from the patient
Analysis
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
TNM staging T
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
N stage
PN0 no lumps nose metastasis
PN1 metastasis in up to 3 nodes
PN2 metastasis in 4 or more nodes
M stage
PM0 no distant metastasis
PM1 distant metastasis present
Dukes classification
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
Histology
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
Molecular prognostic factors
Micro satellite stable/in stable
Majority MSS (micro satellite stable) tumour show chromosomal instability
Aneuploidy, allelic losses, amplification, translocation, mutation of APC, KRas, TP53
Mismatch repair genes
Indications
Young age multiple colonic tumours, cancer in other organs, family history
Immunohistochemistry
-MLH1, MSH2, MSH6, PMS2
MSI-H tumour
Proximal colon
Poorly differentiated
Mucinous histology
Increased lymphocytic infiltration
What is the clinical importance of MSI-H tumours
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
Lynch syndrome -
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
Loss of MSH2 and MSH6 what is diagnosed
Lynch syndrome
Refer to geneticist
Loss of MLH1
BRAF not mutated
No MLH1 promoter methylation
Diagnoses ?
Lynch syndrome
Refer to geneticist
Loss of MLH1
BRAF mutated
MLH1 promoter methylated
Sporadic
Not genetics referall
Mutations involved ? Can they be targeted with immunotherapy
RAS and BRAF
Mab can be used
Ras mutations
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
BRAF mutation
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
