Lecture 8.1 - Neoplasia 1 PDF

What is a neoplasm?: ◦Neoplasm - an abnormal growth of cells that persists after the initial stimulus is removed ◦Malignant neoplasm - an abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with potential to spread to...

What is a neoplasm?: ◦Neoplasm - an abnormal growth of cells that persists after the initial stimulus is removed ◦Malignant neoplasm - an abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue with potential to spread to distant sites Terms - tumour, cancer, metastasis: ◦Tumour - any clinically detectable lump or swelling. A neoplasm is just one type of tumour ◦Cancer - any malignant neoplasm ◦Metastasis - a malignant neoplasm that has spread from its original site to a new non-contiguous site. The original location is the primary site and the place to which it has spread is a secondary site. ◦Dysplasia - a pre-neoplastic alteration in which cells show disordered tissue organisation. It is not neoplastic because the change is reversible Benign and malignant neoplasms: ◦Benign neoplasms remain confined to their site of origin and do not not produce metastases ◦Malignant neoplasms have the potential to metastasise ◦Benign tumours grow in a confined local area and so have a pushing outer margin. This is why they are so rarely dangerous ◦Malignant tumours have an irregular outer margin and shape and may show areas of necrosis and ulceration (if on a surface) Neoplasms under the microscope: ◦Benign neoplasms have cells that closely resemble the parent tissue i.e. they are well differentiated ◦Malignant neoplasms range from well to poorly differentiated. Cells with no resemblance to any tissue are called anaplastic  ◦With progressing differentiation individual cells have increasing nuclear size and nuclear to cytoplasmic ratio, increased nucleus staining (hyperchromasia), more mitotic figures and increasing variation in size and shape of cells and nuclei, which is called pleomorphism Modified Bloom-Richardson Grading system: Neoplasms under the microscope: ◦The term grade is used to indicate differentiation, high grade being poorly differentiated ◦Dysplasia also represents altered differentiation. Mild, moderate and severe dysplasia indicates worsening differentiation Benign and malignant (invasive) tumour:  Evolution of a squamous cell carcinoma: Characteristics of benign and malignant tumours: The hallmarks of cancer: Neoplastic transformation: ◦Genetic alterations - mutations, deletions, amplifications, translocations, rearrangements ◦Epigenetic changes - DNA methylation, chromatin modifications Oncogenes and tumour suppressors:  Oncogenes: Control of the cell cycle: Neoplasms are monoclonal: ◦A collection of cells is monoclonal if they all originated from a single founding cell ◦Evidence that neoplasms are monoclonal came from the study of the X-linked gene for the enzyme glucose-6-phosphate dehydrogenase (G6PD) in tumour tissue from women ◦The gene has several alleles encoding different isoenzymes How do we know neoplasms are monoclonal: Intratumoural heterogeneity - non-clonal and clonal:  Intratumour and inter and intra-metastatic heterogeneity: How to name neoplasms: ◦Confusing mixture of an organised system that follows rules and a traditional system that often disobeys the rules ◦Takes into account a neoplasm's site of origin, whether it is benign or malignant, the type of tissue the tumour forms and sometimes the gross morphology (e.g. cyst or papilloma) ◦Benign neoplasms ends in -oma ◦Malignant ones end in -carcinoma, if it is an epithelial malignant neoplasms, which constitute 90% malignant tumours, or -sarcoma if it is a stromal malignant neoplasm Characterisitics of carcinomas and sarcomas: How to name neoplasms - epithelial neoplasms - benign: ◦Stratified squamous: ‣ Squamous cell papilloma (any tumour with finger-like projections) e.g. skin, buccal mucosa ◦Transitional: ‣ Transitional cell papilloma e.g. bladder mucosa ◦Glandular: ‣ Adenoma - e.g. adenomatous polyp of the colon ‣ Cystadenoma - e.g. ovary How to name neoplasms - epithelial neoplasms - malignant: ◦Epithelial = carcinoma (90% of cancers are carcinomas) ◦Stratified squamous: ‣ Squamous cell carcinoma: skin, larynx, oesophagus, lung, others ◦Transitional: ‣ Transitional cell carcinoma: bladder, ureters ◦Glandular: ‣ Adenocarcinoma: stomach, colon, lung, prostate, breast, pancreas, oesophagus, others  ◦Other: ‣ Basal cell carcinoma: skin Tumour nomenclature: How to name neoplasms - lymphoid and haemotopoietic neoplasms: ◦All malignant ◦Haematopoietic = acute and chronic leukaemia ‣ Occurs in bone marrow and abnormal cells then enter blood ◦Lymphoid = lymphoma (B and T) ‣ Occurs in lymphoid tissue, usually in lymph nodes ‣ Hodgkins and non hodgkins lymphomas ◦Myeloma (multiple myeloma) ‣ Occurs in the bone marrow plasma cells ‣ Can affect several areas of the body How to name neoplasms - germ cell neoplasms: ◦Testis ‣ Seminoma (malignant neoplasm) ‣ Non-seminomas (malignant teratoma) ◦Ovary ‣ Benign teratoma - dermoid cyst ‣ Malignant germ cell ovarian tumours Embryonal tumours - blastomas: ◦Retinoblastoma - Rb ◦Nephroblastoma - Wilm's tumour ◦Neuroblastoma ◦Medulloblastoma ◦Hepatoblastoma How to name neoplasms - neuroendocrine tumours: ◦Includes: ‣ Carcinoid tumours (various organs) ‣ Phaeochromocytoma (adrenal) ‣ Small cell carcinoma of bronchus  Hamartomas and cysts: ◦Hamartomas: ‣ Benign ‣ Usually consist of two or more mature cell types normally found in the organ in which the lesion arises. E.g. adenochondroma: cartilage and bronchial type epithelium ‣ May be mistaken for malignant neoplasms on a chest X-ray ‣ Hamartomas are sometimes associated with clinical syndromes e.g. in tuberous sclerosis ◦Cysts: ‣ A fluid-filled space lined by epitherlium ‣ Some could be neoplastic, but many are not Neoplastic (e.g. cystadenoma, cystadenocarcinoma, cystic teratoma) Congenital (e.g. branchial and thryoglossal cysts due to embryological defects) Parasitic (e.g. hydatid cysts due to Echinococcus granulosus) Retention (e.g. epidermoid and pilar cysts of the skin) Implantation (e.g. a result of surgical or accidental implantation of epidermis