Neoplasia: Definition, Classification, and Diagnosis PDF

Topics to be covered Neoplasia: definition, classification and diagnosis Gillian Hall Consultant Head and Neck Pathology 4th Floor Definition of neoplasia Differentiation Tumour behaviour – benign and malignant lesions Tumour classification Tumour spread Metastatic cascade Factors which may affect p...

Topics to be covered Neoplasia: definition, classification and diagnosis Gillian Hall Consultant Head and Neck Pathology 4th Floor Definition of neoplasia Differentiation Tumour behaviour – benign and malignant lesions Tumour classification Tumour spread Metastatic cascade Factors which may affect prognosis Non-malignant effect of tumours Diagnosis Staging and grading Essential terminology Essential terminology: classification of tumours Neoplasia Neoplasia: a tissue state characterised by a permanently altered growth pattern New growth A tissue state characterised by a permanently altered growth pattern Abnormal mass of tissue, the growth of which is uncoordinated with that of normal tissues and persists after the stimulus is removed Behaviour Cell type of origin (major categories) *Benign / malignant Tumour Swelling, generally without inflammation, caused by an abnormal growth of tissue whether benign or malignant Essential terminology: tumour differentiation/ grade In general The extent to which a tumour resembles its normal counterpart, both morphologically and functionally Grade 1 / well differentiated In general terms well differentiated lesions are less proliferative and less aggressive with less potential for metastatic spread than their poorly differentiated counterparts Grade 2 / moderately differentiated Epithelium Connective tissue Lymphoid / haematopoietic tissue Germ cells Grade 3 / poorly differentiated There are exceptions There are tumours for which no normal cell of origin can be determined: unable to comment therefore on differentiation 1 Abnormalities of growth / differentiation Examples Hyperplasia: Bone marrow cells in people living at high altitudes Hypertrophy: Bodybuilders / athletes Atrophy: Muscle atrophy in a dis-used limb Involution: Breast tissue on cessation of breastfeeding Metaplasia: Barrett’s oesophagus Dysplasia: Cervical screening Hyperplasia: Increase in the number of cells in a tissue Hypertrophy: Increased in the size of cells in a tissue Atrophy: Reduction in the size of cells in a tissue Involution: Decrease in the number of cells in a tissue Metaplasia: A change from one to another normal differentiated cell type within a tissue Dysplasia: A state in some tissues which denotes an increased risk of malignant change (*) Neoplasia: A tissue state characterised by a permanently altered growth pattern *fibrous dysplasia: abnormal development Barrett’s oesophagus Neoplasia: Benign v malignant Benign Malignant Well differentiated, likely to resemble tissue of origin Slow growth Mitotic figures rare and normal Well demarcated Expansible growth Do not metastasise Spectrum of differentiation from well to poorly differentiated Growth rate variable and less predicable Mitotic figures may be numerous and atypical Poorly demarcated Locally invasive Regional and distant metastasis Ameloblastoma Benign Malignant Basal cell carcinoma Acinic cell carcinoma 2 Tumour nomenclature (1) Tissue Tumour nomenclature (2) Benign Malignant Squamous Glandular Squamous cell papilloma Adenoma Squamous cell carcinoma Adenocarcinoma Smooth muscle Skeletal muscle Fat Bone Cartilage Blood vessels (endothelial) Leiomyoma Rhabdomyoma Lipoma Osteoma Chondroma Haemangioma Leiomyosarcoma Rhabdomyosarcoma Liposarcoma Osteosarcoma Chondrosarcoma Angiosarcoma Epithelial Mesenchymal Lymphoma Melanoma Leukaemia Teratoma Tumours of the lymphoid system Malignant tumour of melanocytes. Tumour of bone marrow cells A tumour which includes elements of all 3 embryonic germ layers Hamartoma A developmental anomaly 3 Significance of the tumour microenvironment A. A tumour of lymph nodes B. A tumour seen in Africa which has an aetiological agent in common with infectious mononucleosis Genetic predisposition 1. Burkitt 2. Ewing C. An odontogenic tumour 3. Hodgkin D. A tumour seen as a feature of HIV / AIDS 4. Kaposi E. A tumour of bone in children and young adults 5. Pindborg Tumour Surrounding tissues e.g. inflammation Environment / social / infectious Epidemiologists have for long known that for most cancers, environmental factors have highly attributable risks (as high as 95% for some cancers in some Western populations) Christiani DC et al. NEJM 2011; 364(9): 791-92 Cancers caused by viruses? Cancers associated with infection / inflammation? Cervical, oropharyngeal and anal squamous cell carcinoma: high risk HPV “Oropharyngeal HPV associated squamous cell carcinoma” Hepatitis and liver cancer (hepatocellular carcinoma) Nasopharyngeal carcinoma and Burkitts lymphoma: EBV Pancreatitis and pancreatic cancer (adenocarcinoma) H pylori and gastric cancer (adenocarcinoma) Kaposi sarcoma: HHV-8 (human herpes virus 8) Spread of malignant tumours Spread of malignant tumours – local infiltration Mode of spread Notes Squamous epithelium Direct Local infiltration Lymphatic To regional lymph nodes Haematogenous Lungs, liver, bone Peri-neural Salivary tumours Trans-coelomic Pleura, pericardium, peritoneal Where it is and it’s function It’s structure Squamous epithelium Basement membrane Lamina propria 4 Spread of malignant tumours – local infiltration Squamous cells Lose tight attachments Disrupt / dissolve the basement membrane Enter connective tissues / acquire mobility Surface epithelium Infiltrating islands of tumour Inflamed lamina propria Muscle Spread of malignant tumours – local infiltration Spread of malignant tumours – local infiltration Nerve infiltration Nerve involvement and intracranial extension Sensory loss Loss of motor function Parotid mass 5 Spread of malignant tumours – lymphatic spread Spread of malignant tumours – lymphatic spread Cross reference Lymphatic drainage of the head and neck Clinical anatomy of the cervical chain of nodes Clinical examination of the lymph nodes Distant metastasis SMG What primary tumour is likely to have given rise to these metastatic deposits? Metastatic cascade Angiogenesis Detachment Invasion of connective tissues towards blood vessels and lymphatic channels Evasion of host defences Migration through vessel wall Formation of tumour embolus, further evasion of host defences Adhesion to vessel wall Extravasation Invasion of new host tissue Angiogenesis What do cancer and inflammation have in common? 6 Non-malignant effects of tumours Paraneoplastic phenomenon Set of signs and symptoms that are a consequence of the presence of the tumour but not directly attributable to it Increased tendency to thrombosis e.g secretion of hormones and other substances that wouldn’t normally be secreted by the tumour cell type Cellular over activity Factors affecting prognosis (1) Tumour type Site and size; resectability Differentiation Degree of cellular atypia Depth and extent of invasion Mitotic index and degree of mitotic atypia Regional lymph node involvement Distant metastasis e.g. overproduction of a hormone that would be expected to be produced by that particular tumour cell type, such as parathyroid adenoma or carcinoma Well differentiated Intercellular bridges Moderately differentiated Poorly differentiated Factors affecting prognosis (2) Subjective observation Differentiation/ atypia Objective observation Depth and extent of invasion, mitotic count 7 Prognostic indices: melanoma Prognostic indices: Dukes for colorectal cancer Dukes A: Confined to bowel wall Dukes B: Invading into the muscularis propria layer or beyond, lymph node negative Breslow thickness Dukes C: Lymph node metastases Tumour Depth 4 mm Approximate 5 year survival 95-100% 80-96% 60-75% 50% Prognostic indices: mitotic count Dukes D: Distant metastases Diagnosis You need a tissue sample for diagnosis of presence of a tumour and also to sub-type it Radiology can help to define size, extent and structures involved and might give some clues as to the tumour type Tissue Fine needle aspirate (FNA) Histology (biopsy) Immunohistochemistry and genetic testing of tumours Refer to laboratory diagnosis of disease lecture Screening The systematic search for cancer in people who have no signs or symptoms of cancer Two issues False positives Over diagnosis 8 Well established screening programs US data Cervical Breast Colorectal Lung: CT screening 70-90% patients had 1 false positive result Why not… Lung? Prostate? Thyroid? Prostate: PSA screening 25-30% of patients had 1 false positive result * typically each test has 5-10% false positive risk, but screening is repetitive and these can add up Lung: CT screening 70-90% patients had 1 false positive result – remember radiological examination does not diagnose cancer and consider the radiation dose for a CT chest Early 2000’s South Korea and USA Prostate: PSA screening 25-30% of patients had 1 false positive result – equally a simple blood test cannot differentiate a hyperplastic prostate from a malignant one * typically each test has 5-10% false positive risk, but screening is repetitive and these can add up Thyroid Thyroid 9 Staging Oral cancer screening? Understand the difference between grading (tumour differentiation) and staging T N M Things to go and look up / read about What is the grading system for prostate cancer? A few different types of paraneoplastic phenomena TNM staging for oral cavity cancer (TNM 8 is the most current version) An example of a tumour whose cell of origin is uncertain (clue, one is mentioned somewhere in this lecture) An example of a head and neck benign tumour that has the potential to become malignant, especially when present for long periods of time Further lectures Tutorials Practical class 10