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Professor Adrienne M Flanagan

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1 Professor Adrienne M Flanagan
Pathology Cancer Professor Adrienne M Flanagan

2 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

3 Diagnosis determines treatment
Grade of tumour Stage of tumour Fully excised

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

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

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

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9 Germline Or Somatic?

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

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

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

14 Staging

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

16 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

17 Sarcoma

18 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

19 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

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

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27 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

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

30 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

31 The End


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