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13.1 Explain the key processes and cellular types involved in inflammation and cancer
ANSWER
INFLAMMATION
• Inflammation is the protective response to foreign agents such as microorganisms and facilitates the repair of damaged tissue Following minor injury, inflammation is transient and is followed by resolution However, in some instances the inflammatory response can have harmful effects on the tissue/organ and causes the signs and symptoms of disease.
• Inflammation is a complex reaction orchestrated by chemical mediators secreted by a variety of different cells. Initially, there are changes in blood vessels—transient contraction and then prolonged dilatation is followed by the vessels becoming ‘leaky’. These events slow the flow of blood and protein-rich fluid escapes from the vessel into the area of damaged tissue. White blood cells (leucocytes) stick to the walls of capillaries and leave the vasculature, migrating to the area of tissue damage. The protein-rich fluid containing leucocytes is called the inflammatory exudate. Inflammation is classified into acute and chronic types.
• Acute inflammation is usually of relatively short duration, lasting up to a few days, and is characterized by the accumulation of neutrophils (the principal acute inflammatory cell). Sometimes acute inflammation leads to the formation of pus, which essentially comprises tissue fluid, dead neutrophils and microorganisms. The formation of pus is called suppuration.
• Chronic inflammation is of longer duration and is defined by the accumulation of specialized immune cells such as B and T lymphocytes, plasma cells that secrete immunoglobulin, and macrophages. It occurs due to persistent infections (which can cause delayed hypersensitivity and/or granulomatous inflammatory reaction), prolonged exposure to toxins and autoimmunity. Following removal of the cause of inflammation the body repairs the damaged tissue. The process of repair involves the growth of many new blood vessels and the deposition of fibrous repair tissue, and is termed granulation tissue. Sometimes an excessive amount of fibrous tissue is laid down and this leads to fibrosis, which can impair the function of the tissue/organ.
• The clinical signs of inflammation (the cardinal signs) are redness, heat, swelling, pain and loss of function. Redness is caused by increased blood flow to the inflamed tissue. In skin, the increased blood flow warms the skin surface. In addition, inflammatory mediators cause an increase in body temperature (pyrexia). The development of swelling occurs as a result of the accumulation of tissue fluid (oedema). The inflammatory response produces symptoms of pain because there is distortion and stretching of the tissues, and inflammatory mediators sensitize pain receptors in the affected tissue. Loss of function is caused by the increasing pain and swelling.
• In general, the terms used to describe inflammation affecting different organs and tissues are formulated by adding the suffix ‘itis’
• The key cell types involved include neutrophils, monocytes, lymphocytes, plasma cells, eosinophils, basophils, macrophages and mast cells.
NEOPLASIA
• Neoplasia means new growth (Greek: neo new, plassein to form). A neoplasm has an inherent ability to grow and continues to enlarge unless it is treated. The term tumour is sometimes used instead of neoplasm, but the literal meaning of tumour is swelling. Neoplasms are -classified into benign and malignant types depending on their clinical presentation, histological appearance and biological behaviour (see Table 1.3 Typical features of benign and malignant neoplasms.). A general term used for a malignant neoplasm is cancer, a word that is often associated with pain, suffering and death.
• Benign neoplasms tend to be small, but large benign neoplasms can occasionally develop because they do not cause symptoms or the patient does not seek medical help. Benign tumours usually have a well-defined edge and are separated from adjacent tissues by a -capsule of compressed fibrous tissue. Benign tumours are composed of mature tissue that resembles the site of origin. The growth rate is slow and mitotic figures are infrequent. By definition, benign neoplasms remain localized and do not spread to form new growths at other sites in the body.
• Malignant neoplasms tend to be large at diagnosis unless identified at an early stage, or those detected within the many screening programmes available. Typically, they show ill-defined borders because they invade and destroy adjacent tissue. They are often hard to the touch (indurated) and stuck down to adjacent tissues. Malignant neoplasms show varying degrees of resemblance to their tissue of origin and are graded depending on degree of differentiation (i.e. well differentiated [resembles tissue of origin], moderately differentiated [some resemblance to tissue of origin], and poorly differentiated [little or no resemblance to tissue of origin]). They tend to grow rapidly, mitotic figures are usually easily identified and growth sometimes is so rapid that the tumour outstrips its blood supply, leading to necrosis (tumour death). Malignant cells have the ability to invade lymphatic channels or blood vessels, termed ‘vascular invasion’, and this is associated with the spread of malignant cells to other parts of the body, a process called metastasis. Malignant cell spread through lymphatic channels usually results in the development of lymph node metastases, whereas spread through blood vessels results in metastases to distant organs (e.g. lung, liver, brain and bone).
• Neoplasms are classified according to their behaviour and the tissue that they most resemble (histogenesis). All neoplasms share the common suffix ‘oma’. Benign epithelial neoplasms are eithercan be papillomas (originating from surface epithelium) or adenomas (originating from glandular epithelium). In the case of benign mesenchymal neoplasms, a prefix is used to denote histogenesis; for example, a benign neoplasm of fibrous tissue is called a fibroma. Malignant epithelial neoplasms are termed carcinomas and malignant mesenchymal neoplasms are sarcomas Classification of benign and malignant neoplasms.). However, there are a couple of exceptions where the name suggests a benign tumour but the disease is malignant. Melanomas are highly aggressive malignant skin tumours and lymphomas are malignant neoplasms of the haematopoietic system.
• It is estimated that one person in three will develop cancer and many die as a consequence of their disease. The vast majority of cancers are diagnosed in elderly patients. Cancers occur in children but they are uncommon. There are over 200 different types of cancer. In the UK the most common cancers are those of breast, lung, colon and prostate. These four cancers account for over half of all new cases each year (breast 15%, lung 13%, bowel 13%, prostate 12%; Cancer Research UK, 2007; http://info.cancerresearchuk.org/)
• The key cells types include squamous cells, glandular derived cells, melanocytes, soft tissue cells and cells from the haemato-lymphoid lineage.
13.2 Discuss the importance of the histopathology report and its significance in the patient management pathway
ANSWER
Include the following points in relation to the content of a histopathology report:
• Clinical suspected diagnosis and associated patient history
• Clinicians signature and authorisation
• Macro or gross description
• Microscopic description
• Diagnosis ex tumour type/ cancer grade (details on how abnormal the cells appear under the microscope and indicators of how rapidly the tumour is likely to grow or spread)
• Tumour size or depth of invasion (metric measurement) often with prognostic significance
• Tumour margins: There are three outcomes when whole tumours are removed clinically A) Positive margins, meaning tumour cells remain at the edge of the tissue removed B) Negative margins, meaning clear or free tumour margins ie there are no cancer cells found at the outer edges and deep margins of the removed tissue. C) Close margins, this indicates that the cancer cells are very close to the margins of the tissue taken.
• Information pertaining to other investigative tests on additional samples taken this may constitute a supplementary report encompassing such tests that are molecular in nature ie T cell gene re-arrangement assessments to confirm clonality and confirm cancer.
• Diagnostic code or SNOMED CODE
• Histopathologist’s signature and details of affiliations/qualifications. Information on departmental contact information.
• Information on data sets
• All this information is useful when reviewing the patient’s management in MDM discussions and also to review progress with expected outcomes for patients with protracted disease outcomes.
13.3 The photomicrograph below shows a particular type of chronic inflammation. The section is taken from a white/cream nodule with central cavitation from the lung of an elderly, homeless, frail and malnourished man.
a) What is the name given to this type of chronic inflammation?
b) What cell types can you see in the photomicrograph?
c) What is the most likely cause in this case?
d) What other causes can lead to this type of inflammation?
ANSWERS
a) Granulomatous inflammation
b) Langhans’ giant cell, histiocytes, macrophages, lymphocytes
c) Pulmonary tuberculosis (given history and macroscopic appearances)
d) Sarcoidosis, other mycobacterial infections, fungal infections, foreign body type and drug reactions, Crohn’s disease in the gastrointestinal tract, granuloma annulare in the skin/soft tissues