Professor Adrienne M Flanagan Pathology Cancer Professor Adrienne M Flanagan

What is the role of the pathologist? Postmortem? Tissue diagnosis – benign vs malignant (cancer) What type of cancer Carcinoma - epithelium Lymphoma - lymphoreticular Leukaemia – circulating malignant lymphoreticular cells Sarcoma – 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 from pathological examination? Tumour type Tumour grade Tumours stage Excision margins Other features of prognostic value

What information is acquired from pathological examination? Tumour type Tumour grade Tumours stage Excision margins Other features of prognostic value

Type of tumour Benign Vs Malignant vs low malignant potential Macroscopic Microscopic

Germline Or Somatic?

What are the microscopic features that distinguish benign from malignant tumours? Architecture Cell morphology – pleomorphism - mitotic figures

Endometrial carcinoma Tumour type Breast carcinoma Ductal Lobular Tubular Endometrial carcinoma Endometrioid Papillary carcinoma others

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

Staging

Tumour Stage Extent of Disease 2cm Pathological Staging: Size Lymph Node status Radiology Clinical

C erb B2 CerbB2 overexpressed in approx 25% of breast cancers TK 185-kd transmembrane glycoprotein receptor p185 HER2 Correlates with poor outcome in node+ and node- ve disease Recombinant humanised anti-Her2 monoclonal antobody [Herceptin] Signal 1 Signal 2 Cobleigh et al. J Clin Oncol 222 with metastatic disease & previous chemotherapy 9 CR, 37 PR [total 22%] Median duration of survival 13 months Toxicity Fevers, chills 4.7% cardiac dysfunction

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

Cancer of the large bowel 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

Cervical intraepithelial neoplasia Dysplasia grade 1, 2, 3 Cervical intraepithelial neoplasia Carcinoma in situ

Determines treatment 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 cervix Stage II – 75% - beyond cervix Stage III – 35% - into pelvic side wall Determines treatment

Typing histologically is essential Polyps Typing histologically is essential Epithelial Hyperplastic Adenomatous Smooth muscle Vascular

Multi-Step Carcinogenesis (eg, Colon Cancer) Normal epithelium Hyper- proliferative Early adenoma Late Carcinoma Metastasis Loss of APC Activation of K-ras 18q DCC p53 Other alterations Fearon ER. Cell 61:759, 1990 Inter- mediate DCC – deletado no câncer de colon

The End