PathologyPathology

CancerCancer

Professor Adrienne M FlanaganProfessor Adrienne M Flanagan

What is the role of the pathologist?

Postmortem?

Tissue diagnosis – benign vs malignant (cancer)

What type of cancer

Carcinoma - epitheliumLymphoma - lymphoreticular

Leukaemia – circulating malignant lymphoreticular cellsSarcoma – connective tissue / muscle (smooth & skeletal) bone,

cartilage, endothelium, fibroblasts, fat, tendon/ligament

Diagnosis determines treatment

Grade of tumour Stage of tumour

Fully excised

What information is acquired What information is acquired from pathological examination?from pathological examination?

Tumour typeTumour type

Tumour gradeTumour grade

Tumours stageTumours stage

Excision marginsExcision margins

Other features of prognostic valueOther features of prognostic value

What information is acquired What information is acquired from pathological examination?from pathological examination?

Tumour typeTumour type

Tumour gradeTumour grade

Tumours stageTumours stage

Excision marginsExcision margins

Other features of prognostic valueOther features of prognostic value

Type of tumourType of tumour

Benign Vs Malignant Benign Vs Malignant vs low malignant potentialvs low malignant potential

MacroscopicMacroscopic

MicroscopicMicroscopic

Germline

Or

Somatic?

What are the microscopic features What are the microscopic features that distinguish benign from that distinguish benign from

malignant tumours?malignant tumours?

•ArchitectureArchitecture•Cell morphologyCell morphology – pleomorphism – pleomorphism

- mitotic figures- mitotic figures

Tumour type

•Breast carcinoma

DuctalLobularTubular

•Endometrial carcinoma

Endometrioid Papillary carcinoma

others

Tumour GradeTumour Grade

How closely a tumour How closely a tumour resembles resembles its tissue of origin?its tissue of origin?

Staging

Tumour StageTumour Stage Extent of DiseaseExtent of Disease

Pathological Staging:Pathological Staging:SizeSizeLymph Node statusLymph Node status

RadiologyRadiology

ClinicalClinical

2cm

TK

185-kd transmembrane185-kd transmembraneglycoprotein glycoprotein receptor p185 receptor p185 HER2HER2

Signal 1 Signal 2

CerbB2 overexpressed inCerbB2 overexpressed inapprox 25% of breast cancersapprox 25% of breast cancers

Correlates with poor outcomeCorrelates with poor outcomein node+ and node- ve diseasein node+ and node- ve disease

Recombinant humanised anti-Her2Recombinant humanised anti-Her2monoclonal antobody [Herceptin]monoclonal antobody [Herceptin]

Cobleigh et al. J Clin OncolCobleigh et al. J Clin Oncol222 with metastatic disease & 222 with metastatic disease & previous chemotherapyprevious chemotherapy

9 CR, 37 PR [total 22%]9 CR, 37 PR [total 22%]

Median duration of survival 13 monthsMedian duration of survival 13 months

ToxicityToxicityFevers, chillsFevers, chills4.7% cardiac dysfunction4.7% cardiac dysfunction

C erb B2C erb B2

Sarcoma

Why is it useful to have all of this information?

Prevention – screen, cervical and breast cancer

Early diagnosis

Choose best treatment

Provide a useful prognosis

Ways in which pathologists can and have contributed to understanding the

progression of cancer

Compare outcome

Identify the genetic changes which are associated with progression of disease

Cancer of the large bowel

Dysplasia grade 1, 2, 3Cervical intraepithelial neoplasia

Carcinoma in situ

Cervical carcinoma

If cancer invades less than 3mm deep from the surface, it is likely to be curable if resected (stage 1a)

Less than1% of people will have lymph node deposits

Stage 1b - 90% survival – still within cervixStage II – 75% - beyond cervix

Stage III – 35% - into pelvic side wall

Determines treatment

Polyps

Typing histologically is essential

•Epithelial Hyperplastic

Adenomatous

•Smooth muscle•Vascular

Normal Normal epitheliumepithelium

Hyper-Hyper-proliferativeproliferativeepitheliumepithelium

EarlyEarlyadenomaadenoma

LateLateadenomaadenoma CarcinomaCarcinoma MetastasisMetastasis

Loss ofLoss ofAPCAPC

ActivationActivationof of K-rasK-ras

Loss ofLoss of18q18q

DCCDCC

Loss ofLoss ofp53p53

Other Other alterationsalterations

Fearon ER. Fearon ER. CellCell 61:759, 1990 61:759, 1990

Inter-Inter-mediatemediate

adenomaadenoma

Multi-Step Carcinogenesis (eg, Colon Cancer)

The End