Tumours
A tumour is a new growth of tissue (a mass) which can refer to an
inflammatory swelling such as Pott’s puffy tumour (Chapter 35) or to a
neoplastic growth. A neoplastic tumour is an uncontrolled proliferation of a
clone of cells without useful function.
Causation
Cancer is a disease of genes. The cell is the basic unit of organisation
and control. The genetic code is contained within the deoxyribonucleic acid
(DNA) molecule present within the cell nucleus. Genes make proteins which govern
the function and structure of a cell. There are around 100 000 genes (human
genome) representing approximately 10 per cent of the DNA; each cell expresses 5—150
000 genes. Since all genes are present in each cell nucleus, any gene may be
expressed if the gene promoter is switched on, as occurs in neoplasia. Cancer is
caused by disease of genes which control production of daughter cells from stem
cells, cell proliferation, terminal differentiation and programmed cell death
(apoptosis); from the Greek — shedding of autumn leaves. There are three
important classes of genes involved in cancer:
• oncogenes, which promote cell proliferation by increasing
signalling activity from the cell surface to the transcription apparatus on gene
promoters (KRAS, ERBB2, C-MYC);
• growth factors and their receptors which are switched on by
oncogenes or switched off by tumour suppressor genes (EGF, TGFa, IGF, FGF).
Environmental
cofactors are also important. Helicobacten pylori is linked to the
development of gastric cancer by an unknown mechanism. A diet high in calories
and rich in saturated fats (from red meat) is implicated in many cancers
including those of the colorectum and
Definitions
• Hypertrophy is an increase in the size of an organ
without an increase in cell numbers.
• Hyperplasia is an increase in the size of an organ due to
an increase in cell numbers.
• Metaplasia. The epithelium from which the tumour grows
has already changed its characteristics: bladder transitional epithelium to
squamous epithelium, gallbladder columnar to squamous epithelium, bronchial
columnar to squamous epithelium, gastric columnar epithelial pattern to
intestinal epithelial pattern and oesophageal squamous to columnar epithelium
(Barrett’s oesophagus).
• Dysplasia. This represents the earliest changes of neoplastic
transformation than can be detected at the microstructural level (e.g. by light
microscopy). In fact, genetic mutations are detectable at an earlier stage.
Alterations in intracellular organisation, the individual size and shape of the
nucleus, cellular size and shape and intercellular three-dimensional
organisation indicate dysplasia. These changes may be classified as mild,
moderate or severe dysplasia. Any grade of dysplasia may revert to normal due to
elimination of the neoplastic clone, but is least likely with severe dysplasia.
• Carcinoma in situ. Severe dysplasia may progress to carcinoma
in situ: the cellular, nuclear and three-dimensional architecture
resemble cancer but without invasion into the extracellular matrix.
• Genotype. This is the molecular structure of any cell. A malignant
genotype will have losses and mutations of tumour suppresser genes and the
presence of oncogenes.
• Phenotype. This is the appearance of a cell at a
microstructural level (microscopic phenotype) and its functional state
(biological phenotype). A changed genotype will always precede a particular
phenotype: for a
• Differentiation. Depending on the degree to which the cells and
organisation (morphology) of tumours resemble the parent tissue they are
divided into well-differentiated, moderately differentiated and poorly
differentiated forms.
• Anaplasia. Tumours are usually composed of cells which resemble
those of the tissue from which they arise. Complete loss of differentiation (anaplasia)
is associated with an aggressive cancer.
• Teratomas arise from embryonic stem cells containing representative
cells from all three embryonic layers: ectoderm, endoderm, mesoderrn (Fig.
12.4). Teratomatous dermoids contain hair and teeth, muscle and gland tissue. An
unusual type is the sacrococcygeal teratoma (Fig. 12.5),
which can be
considered as foetus in foeto (an ‘included’ foetus).
• Blastomas develop from ‘unipotent’ cells, and arise from any one
of the three embryonic layers (e.g. neuroblastoma).
• Dermoid cysts. ‘Dermoid’ is a loose term given to cysts lined by
squamous epithelium occurring in various parts of the body. Sebaceous cysts are
lined by superficial squamous cells and should more accurately be called ‘epiderrnoid’.
—
Teratomatous dermoids (see above) are found in the ovary, testis
retroperitoneum, superior mediastinurn and the presacral area. Malignant change
(carcinomatous or sarcomatous) can occur.
—
Sequestration dermoids (see Cysts, below) are not new growths, but
are formed by the inclusion of epithelial ‘nests’ beneath the surface at
places where lines of developing skin meet and join: midline, external angular
process (Fig.12.6), root of nose (Chapter 37), branchial cysts (Chapter 43).
—
Implantation dermoids (see Cysts, below) may follow puncture
wounds, commonly of the fingers, when living epithelial cells are implanted
beneath the surface.
• Benign tumour. A benign tumour is usually encapsulated, and does not
disseminate or recur after complete removal. Symptoms and effects, which can be
harmful, are due to its size, position, and pressure. Certain adenomas secrete
a hormone which
may affect bodily functions. Benign tumours are often multiple.
• Malignant tumour. The characteristics of malignancy are:
—
invasion of surrounding tissues;
—
pleomorphism (variable shapes) of cells and nuclei;
—
rapid growth;
—
the tendency to spread to other parts of the body (metastasis) by the
lymphatics, the bloodstream, along nerve sheaths and across body cavities;
—
general weight loss (cachexia in advanced disease).
At an early stage, evidence of invasion is the most important sign of
malignancy. Many cells of a malignant tumour have an abnormal number of
chromosomes which is not a multiple of the usual haploid number (= ‘aneuploidy’).
It
has been suggested that the division of tumours into these two major groups
imposes a concept which is too rigid (Walter). A third group of intermediate tumors
exists which includes some carcinoid tumours, adenoma of the bronchus,
‘mixed’ salivary tumours and basal-cell carcinoma. These intermediate types
invade locally, but are much less inclined to lymphatic or especially vascular
dissemination.