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Tumours
A tumour is a new growth of tissue (a •
mass) which can refer to an
inflammatory swelling 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 which control production of
daughter cells from stem cells, cell proliferation, terminal
differentiation and programmed cell death (apoptosis.
There are three important classes of genes involved in
cancer:
• 1-tumour suppressor genes, which control the cell cycle
by slowing down the cycle or triggering apoptosis (TP53, P16,
APC, RB1).
•2-oncogenes, which promote cell proliferation by
increasing signaling activity from the cell surface to the
transcription apparatus on gene promoters (KRAS, ERBB2, CMYC).
•3-growth factors and their receptors which are switched
on by oncogenes or switched off by tumour suppressor
genes (EGF, TGFa, IGF, FGF).
Chemical carcinogens
probably account for the majority of sporadic
(acquired) cancers. Natives of Kashmir are
prone to cancer of the skin of the thighs and
lower abdomen.
This is due to their habit of keeping warm by
squatting and hugging earthenware pots
containing glowing charcoal.
• DNA strand breaks are induced by ultraviolet and ionising radiation which,
if not repaired, lead to cancer.
• Cellular instability from ageing of stem cell-lines (many common cancers)
or chronic inflammation leads to increased cell proliferation and reduced
apoptosis. This results in malignant transformation. Squamous cell
carcinoma occasionally occurs in a chronic ulcer (Marjolin’s ulcer’). A
fibrosarcoma also may arise in a scar. At least 20 per cent of cancers
world-wide are caused by oncogenic viruses.
• 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
pancreas.
• In viral carcinogenesis there are specific cofactors for different cancers:
malaria (Burkitt’s lymphoma), immunosuppression (post-transport
lymphomatous proliferative disease — PTLPD), human immunodeficiency
virus (Kaposi’s sarcoma), smoking (cervical cancer) and aflatoxins (liver
cancer).
• A benign tumour grows by expansion without
invasion of the extra-cellular matrix.
• A malignant tumour (cancer) grows by
invasion into the extracellular matrix; most
solid tumours also invade the basement
membrane of endothelium and metastasize.
• The unit of cancer is the altered malignant
cell which proliferates (clone).
• Different clones usually arise with different
characteristics, such as the ability to
metastasize via blood vessels or lymphatics.
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. Alterations in intracellular organisation, the individual size and
shape of the nucleus, cellular size and shape and intercellular threedimensional 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.
• 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.
• The characteristics of malignancy are
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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).
• Many cells of a malignant tumour have an
abnormal number of chromosomes which is not a
multiple of the usual haploid number (aneuploidy).
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.
Hamartoma
• The term hamartoma is roughly translated from
the Greek as a ‘fault’, and its original meaning
was ‘missing the mark in spear throwing’.
• It is a developmental malformation consisting of
overgrowth of tissue or tissues proper to the
part.
• Common lesions that are hamartomas are
benign pigmented moles, and the majority of
angiomas and neurofibromas.
• On rare occasions a malignant change occurs in a
hamartoma, but for practical purposes the
lesion is benign .
Malignant tumours
• Carcinomas arise from cells which are
ectodermal or endodermal in origin, and they
are classified squamous, basal-celled or
glandular (adenocarcinomas).
• Sarcomas occur in connection with structures
of mesoblastic origin, hence fibrosarcoma,
osteosarcoma.
• Germ cell tumours arise from germ cells
(teratoma, seminoma, thecoma). Ovarian cancer
is an adenocarcinoma: it does not arise from
oocytes.
Carcinoma
•
Squamous cancer arises from surfaces covered by
squamous epithelium, particularly as a result of ultraviolet
or ionising radiation and chronic irritation.
• Chronic irritation of transitional cells (e.g. by a stone in
the renal pelvis) or columnar cells (e.g. the gall bladder)
will cause a change in these cells to a squamous type
(squamous metaplasia), which may lead on to carcinoma.
• The regional lymph nodes are likely to be invaded, and
may also be infected from the sepsis attendant upon the
primary growth. Blood-borne metastases occur, but
uncommonly from skin squamous cell
carcinomaGlandular.
• Glandular carcinoma commonly occurs in the alimentary
tract, breast and uterus, and less frequently in the kidney,
prostate, gall bladder and thyroid.
Methods of spread
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Direct spread (local extension). Invasion takes place readily along
connective tissue planes, but no structures are resistant. Veins are
invaded commonly. Arteries are rarely invaded. Muscle is less
susceptible to invasion or metastatic deposits than other tissues.
Fascia also limits direct extension, e.g. Denonvillier’s fascia for
rectal carcinoma.
Lymphatics by invasion and by embolism.
• Invasion. The malignant cells grow along the lymphatic vessels
from the primary growth (permeation).
This may even occur in a retrograde direction. The cancer cells
stimulate perilymphatic fibrosis, but this does not stop the
advance of the disease. In some instances, notably malignant
melanoma , groups of cells may so overcome the surrounding
fibrosis that they give rise to intermediate deposits between the
primary growth and the lymph nodes.
• Embolism. Cancer cells which invade a lymphatic vessel can
break away and are carried by the lymph circulation to a regional
node, so that nodes comparatively distant from the tumour may
be involved in the early stages.
• Blood stream. Cancer cells may be detected in the venous blood draining an
organ involved in carcinoma. A carcinoma of the kidney may invade the renal vein
and grow inside the lumen into the vena cava. Malignant emboli may be arrested
in the lungs, liver and bone marrow (secondary deposits — metastases). Thyroid,
breast and bronchial cancers also commonly disseminate via the blood stream.
• Implantation. Implantation of carcinoma has been observed in situations where
skin or mucous membrane is in close contact with a primary growth. Examples of
this ‘kiss cancer’ are carcinoma of the lower lip affecting the upper, and
carcinoma of the labium majus giving rise to a similar growth on the opposite
side of the vulva. Recurrence after operation is occasionally due to implantation
of malignant cells in the wound. Examples of this mischance are the appearance
of a malignant deposit in the scar after suprapubic removal of a primary
carcinoma of the bladder, and nodules of carcinoma in the scar of the incision
after mastectomy for a carcinoma of the breast. When a cavity is involved, freefloating cells from a carcinoma may spread like snowflakes all over its serous
surface. For the abdomen, transcoelomic spread is specially notable when cells
from a colloid carcinoma of the stomach gravitate on to an active ovary and give
rise to malignant ovarian tumours (Krukenberg’s tumour); intracavitary
dissemination can also take place within the pleura and cerebrospinal spaces.
• Nerve sheaths. Adenocarcinomas, especially pancreas, may disseminate along
nerve sheaths
• Grading and staging are used to assess the degree of malignancy of the
tumour as an indication of the prognosis, and may be used as a guide to
determine the type and the extent of the treatment which is required.
Advanced staging and grading may indicate the need for adjuvant
methods of treatment, e.g. by chemotherapy or irradiation.
• Grading.
• Grading predicts the aggressiveness of a malignant neoplasm by
characterising its microscopic appearance taking into account the
degree of differentiation, nuclear and cellular appearance, architectural
integrity and the proportion of active mitoses.
• •Grade 1: well differentiated;
• •Grade 2: moderately well differentiated;
• •Grade 3: poorly differentiated.
• Staging.
(i) TNM classification. This has been adopted by the International Union
against Cancer (UICC) and has been extended to many sites of cancer e.g.
• carcinoma of the breast.
(ii) Manchester staging. This is a method of staging clinical spread of
carcinoma of the breast.
(iii) Dukes’ staging. This is a method of classifying the spread of
carcinoma of the rectum and colon .
Sarcomas
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Sarcomas differ from carcinomas, not only in their derivation, but in their earlier
age incidence, as they are most common during the first and second decades.
Sarcomas often grow rapidly and dissemination occurs early via the bloodstream
(e.g. ‘cannon-ball’ secondary deposits in the lung from an osteogenic sarcoma).
Sarcomatous cells may reproduce tissue similar to that from which the tumour
originated, e.g. osteosarcoma or chondrosarcoma. Sometimes a sarcoma develops
in preexisting benign tumours, such as fibroma or a uterine fibroid, and also in
bones which are affected by osteitis deformans.
Treatment of sarcoma
The spread of a sarcoma is hastened by incomplete removal. The moral is that wide
excision with surrounding healthy tissues should be practised in all cases. This may
mean amputation in the case of a limb. If untreated or if wide local excision is
unsuccessful. Metastases are widely scattered and, unfortunately, radiotherapy has
but little effect on either the primary growth or the secondary deposits. Sarcomas
are often susceptible to anticancer drugs, but fibrosarcomas are more resistant
than other types. Sarcoma of bone is sensitive to radiotherapy, which is used in
some cases as an alternative to amputation .
Lymphomas
Lymphomas arise in lymph nodes, tonsils, Peyer’s patches or lymph nodules in the
intestines. Lymph nodes of the neck or mediastinum are most commonly affected .
They have a bad prognosis.
Benign to malignant transformation
Certain benign neoplasms are prone to undergo malignant
changes, and it is important, for both treatment and prognosis, to
realise when this occurs. Some or all of the following changes
may be recognized:
• increase in size: comparatively rapid enlargement is always
suspicious, e.g. a neurofibroma which is becoming sarcomatous.
• increased vascularity: dilated cutaneous veins, ulceration and
bleeding in the case of a superficial growth (e.g. melanoma).
•fixity: due to invasion of surrounding structures.
•involvement of adjacent structures: e.g. facial palsy suggests
malignant change in an otherwise longstanding parotid
pleomorphic adenoma.
•dissemination: discovery of secondary deposits.