THE BENIGN–MALIGNANT BOUNDARY AND CANCER
It will have become obvious that, although there are some benign tumours that never become malignant and some that very rarely do the boundary between the two is not very clear. Can we clarify things by looking at the underlying molecular biology? If cancers arise because of mutations in genes, maybe benign tumours are mutation free and simply arise because of a local imbalance in growth factors. There’s much less information available for benign lesions compared with tumours but a quick glance dashes any hopes of a simple answer.
Some benign tumours never become malignant yet carry mutations in genes that in other tissues are associated with malignancy. On the other hand, there are tissues in which mutations occur in both benign and malignant tumour forms, albeit sometimes with quite different frequency. Table 1 contrasts mutation patterns in a number of benign and malignant tumours.
We’re stuck with a typical cancer problem. The distinction between benign and malignant tumours is crucial: one of them can kill you. Unfortunately, even the power of modern molecular biology cannot identify what it is that converts a relatively harmless form of abnormal growth into the fatal variety.
Cancers can be divided into two broad classes: solid and liquid tumours. Most human and animal solid tumours. Approximately 85% are carcinomas (strictly ‘carcinomata’) – malignant tumours of epithelial cells – which includes malignant tumours of glandular epithelial tissue that are termed adenocarcinomas. Carcinoma in situ is a pre-malignant change in which cells proliferate abnormally (hyperplasia) within their normal location. The epithelium (particularly of the cervix or skin) shows many malignant changes but does not invade the underlying tissue. Carcinoma in situ is a feature of many cancers. For example, ductal carcinoma in situ (DCIS) is one of the two forms of mammary ductal carcinoma, the most common type of breast cancer, characterised by hyperplasia in the wall of the milk ducts. It carries a risk of developing into the invasive ductal carcinoma (IDC) form in which the cells have become malignant.
Most other cancers are sarcomas, tumours of tissue derived from the mesenchymal layer (connective tissue, bone, cartilage, muscle, fat, blood vessels) that are often highly malignant. Sarcomas are therefore relatively rare and they are not thought to have a premalignant (in situ) phase.
The remaining ~3% of human cancers are leukaemias and lymphomas that arise from the abnormal white blood cells or, very rarely, of red blood cell precursors. White cells, together with red cells (erythrocytes), make up the population of cells that continuously circulates in the bloodstream. Because leukaemias and lymphomas arise in the blood and the tissues where blood cells develop they are collectively named haematological neoplasms. The word leukaemia comes from the Greek words for white and blood (leukos λευκός and aima αίμα) and refers to cancers arising from the abnormal proliferation of white blood cells in the bone marrow. These cells are sometimes called leucocytes but, as that term covers all white blood cells including lymphocytes, it’s apt to be a bit confusing. Lymphomas are cancers of lymphocytes, the cells of the adaptive immune system that fall into the two main classes of T cells and B cells. The two major divisions of this cancer are Hodgkin’s disease (Hodgkin’s lymphoma) and non-Hodgkin’s lymphomas.