Pathology is the scientific study of disease and the science behind the cure. It forms the backbone of evidence based clinical medicine.
Pathology evolved in the early-nineteenth century as a single discipline, based mainly on cellular (anatomical) pathology. Medicine was revolutionised by the application of microscopy to the study of diseased tissues. The German pathologist Rudolf Virchow, an ardent advocate of the microscope, was the first to recognise that the cell was the smallest viable constituent unit of the body. He contrived a new and lasting set of ideas about disease, which has formed the basis of cellular pathology from the mid-nineteenth century to the present time.
Today, many subspecialties including anatomical pathology (histopathology, cytopathology and post-mortem pathology), medical microbiology, clinical and laboratory haematology, chemical pathology, immunology, genetics, molecular pathology and forensic pathology exist within the discipline. The divergence of specialties was largely on the basis of the different techniques used in each area.
The boundaries between these subspecialties are increasingly becoming blurred, as modern techniques especially those resulting from molecular biology are applied to all.
Cellular pathology remains a critical part of the clinical evaluation of a patient prior to definitive treatment being offered. Both the clinician and patient want to know the diagnosis, so that appropriate management can be planned and instituted. For example, such information in the case of a neoplasm would include type of tumour, estimate of its biology (grade), extent of its spread (stage) and whether it has been completely excised or not. Additional information regarding the various prognostic and predictive markers is also sought in certain instances.
Major streams of Anatomical Pathology
- Surgical Pathology
Surgical pathology relies on the examination of solid tissues, obtained during a surgical procedure, by utilising light microscopy. Biopsy material is fixed and processed to obtain thin sections. The sections are stained by simple tinctorial techniques, utilising vegetable dyes such as haematoxylin and eosin to allow distinction between different components of the tissue. Normal histology and the basic disease processes of inflammation, repair, degeneration and neoplasia are defined from such sections. Advances in optics and computers are allowing pathologists to interpret images obtained by microscopy and from these images deduce information about the diagnosis and cause of the disease. Recommendation regarding treatment and prediction about the likely outcome are then made.
Unlike surgical pathology where assessment relies primarily on tissue architecture, in cytology, the characteristics of the individual cells are of most value. Although the relationship between adjacent cells can be appreciated to some extent, the nuclear and cytoplasmic features are of utmost importance. In screening practice, such as cervical cancer programs, the identification of abnormal cells representing an earlier stage, which gives a warning of incipient cancerous changes, are sought.
The technique of immunohistochemistry evolved in the 1980s, and gained a major boost from the development of monoclonal antibodies. It depends on the property of antibodies to bind specifically to cell associated antigens. Tagging such an antibody with a fluorescent, enzymatic or radioactive label allows specific substances to be identified and localised in tissue sections or cytological preparations.
- Electron Microscopy
Utilisation of electron beams rather than visible light became available in the form of electron microscopy in the 1960s. This method allowed identification of and ultrastructural definition of cellular organelles. Electron microscopy allowed more precise diagnosis of tumour types. The structure of proteins such as amyloid was determined by this technique. Today electron microscopy has a limited place in tumour characterisation but still has a central role in the study of renal disease.
- Molecular Pathology
Rather than attempt to identify proteins within a cell by immunohistochemistry, expression of the genes responsible could be identified if appropriate mRNA could be extracted from the cell or localised to them by in-situ hybridisation techniques was the logical next step. Identification of the expression of abnormal genes, some of which appear to be responsible for neoplastic proliferation can be routinely performed today. These techniques allow precise typing of tumour and selection of specific targeted therapies.
- Post mortem pathology
The popular image of a pathologist is of an individual who determines the cause of death, especially when foul play is suspected. From the early days of pathology, the post-mortem examination has been of importance in understanding disease mechanisms, and in explaining the nature of the individual's final illness. However, advances in imaging, and a cultural move not to accept post-mortem examination in many countries, have significantly reduced the number of post-mortems performed other than those carried out for legal reasons.
Enormous advances in imaging techniques specially computerised tomography and magnetic resonance imaging, when coupled with targeted needle biopsies has to some extent diminished the need for post-mortem examination. However, publications continue to show that post-mortems uncover unsuspected conditions. The post-mortem examination remains the final arbiter of the cause of death in many cases, the key technique in the forensic investigation of unexplained death and potentially an essential part of medical audit.
Meticulous post-mortem examination has helped clarify the disease mechanism in some of the recently emerged diseases such as AIDS, SARS and Mad Cow Disease.