Neoplasia

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Chapter 6 Neoplasia

Non-Neoplastic Proliferation 115

Neoplastic Proliferation 116

Neoplasms – Classification 117

Benign Tumours – Histology 118

Malignant Tumours – Histology 119

Benign Epithelial Tumours 120–122

Benign Connective Tissue Tumours 123, 124

Malignant Epithelial Tumours 125

Types of Carcinoma 126, 127

Malignant Connective Tissue Tumours 128

Sarcomas 129, 130

Other Tumour Types 131–134

Spread of Tumours 135

Lymphatic Spread 136, 137

Blood Spread 138, 139

Other Modes of Spread of Tumours 140

Effects of Tumours 141

Tumour Markers 142

Diagnosis of Tumours Immunocytochemistry 143

Pre-Malignancy 144

Carcinoma in situ (Intraepithelial Neoplasia) 145

Carcinogenesis 146–149

Carcinogenesis – Viruses 150

Carcinogenesis – Heredity 151

Oncogenes and Tumour Suppressor Genes 152

Tumour Suppressor Genes 154

Carcinogenesis – Summary 155

Neoplasia

Cancer is the second commonest cause of death (25%) in the Western world after heart disease. Knowledge of non-neoplastic proliferation is helpful in understanding neoplasia.

Physiological proliferation occurs:

1. In somatic growth during fetal development.

2. In tissues where constant proliferation is needed in RAPID CELL TURNOVER from stem cells (p.48) e.g. in:

3. Proliferation at a much slower rate occurs in tissues where cell turnover is low, e.g. LIVER, but will increase rapidly following injury.

ENLARGEMENT of an organ due to increase in the parenchymal cell mass may be due to:

(1) an increase in the size of the individual cells – hypertrophy

or (2) an increase in the number of cells – hyperplasia

or (3) commonly a combination of (1) and (2).

The stimuli responsible are:

(a) increase in functional demand

(b) increased trophic hormonal activity.

Physiological enlargement of organs is common and well illustrated by the increase in muscle bulk consequent upon training and the enlargement of uterus and breasts in pregnancy. Pathological enlargement is the result of disease processes.

Hypertrophy

Enlargement of the heart as a result of hypertension is a good example of hypertrophy: the result of the increased functional demands to maintain the high blood pressure is an increase in the size of the myocardial cells.

Neoplasms – Classification

Tumours may be classified in two ways: 1. clinical behaviour and 2. histological origin.

1. CLINICAL BEHAVIOUR

The tumour is classified according to its morbid anatomy and behaviour. Two main groups are recognised – benign (simple) and malignant. The contrast between these two groups is as follows:

	BENIGN	MALIGNANT
Spread (the most important feature)	Remains localised	Cells transferred via lymphatics, blood vessels, tissue planes and serous cavities to set up satellite tumours (metastases)
Rate of Growth	Usually slow	Usually rapid
Boundaries	Circumscribed, often encapsulated	Irregular, ill-defined and non-encapsulated
Relationship to surrounding tissues	Compresses normal tissue	Invades and destroys normal tissues
Effects	Produced by pressure on vessels, tubes, nerves, organs, and by excess production of substances, e.g. hormones. Removal will alleviate these	Destroys structures, causes bleeding, forms strictures

In practice, there is a spectrum of malignancy. Some tumours may grow locally and invade normal tissues but never produce metastases. Others will produce metastases only after a very considerable time while, at the other end of the spectrum, there are tumours which metastasise very early in their development.

2. HISTOLOGICAL ORIGIN

Tumours may arise from any tissue in the body and they can be conveniently accommodated in five groups.

2. Mesenchymal tissues including fibrous tissue, bone, cartilage and vessels.

3. Neuroectoderm.

4. Haemopoietic and lymphoid cells.

The commonest tumours arise from tissues which have a rapid turnover of cells and which are exposed to environmental mutagens, e.g. epithelium of mucous membranes, skin, breast and reproductive organs and lymphoid and haemopoietic tissues.

Malignant Tumours – Histology

The cells of malignant tumours tend to be less well-differentiated than those of benign tumours.

There is a spectrum within malignant neoplasms from slowly growing well differentiated examples to rapidly growing undifferentiated highly malignant tumours.

Benign Epithelial Tumours

Benign epithelial tumours are essentially of two types: 1. papillomas and 2. adenomas.

Papilloma

Papillomas take origin from an epithelial surface. As the epithelium proliferates it is thrown into folds which become increasingly complex.

The epithelial proliferation is accompanied by a corresponding growth of supporting connective tissue and blood vessels.

Typical examples are found in the skin, e.g. the common wart.

In these benign tumours:

(a) The normal arrangement of epithelial cells is maintained, e.g. in skin papillomas the surface cells are squamous and proliferation is confined to the deepest layers.

(b) The relationship of epithelium to connective tissue is normal.

(c) Blood vessels are well formed.

Adenoma

Adenomas are derived from the ducts and acini of glands, although the name is also used to cover simple tumours arising in solid epithelial organs.

Again the proliferation of epithelium of a gland causes the formation of tubules which ramify and become compound. The original communication with the parent gland duct or acinus tends to become lost.

In the case of a hollow viscus, such as the intestine, the adenomatous proliferation, instead of growing down into the underlying connective tissue, is usually pushed upwards into the lumen of the viscus.

The growth therefore combines the features of a papilloma and an adenoma. The term adenomatous polyp is often applied in such a case.

In the type which grows into the subjacent connective tissue, the progressive budding of the epithelium results in new acini which become nipped off from the parent acini.

In cases in which retention of secretion is marked, a cyst forms and the tumour is then called a CYSTADENOMA which may reach an enormous size, e.g. some cystadenomas of the ovary may be 30–40 cm in diameter, particularly those which secrete mucus.

As in a hollow viscus, the proliferating epithelium may be heaped to form papillomas and the tumour then becomes a PAPILLARY CYSTADENOMA. These are also common in the ovary (see p.511).

Fibroadenoma

In the breast the term is clinically useful for a small nodule consisting of a mixture of acinar elements and prominent supporting fibrous tissue. The histological appearances are variable depending on the distribution of the fibrous tissue (see also p.520). This is not now considered to be a true neoplasm.

Benign Connective Tissue Tumours

Benign connective tissue tumours are composed of mature connective tissues – fat, cartilage, bone and blood vessels. They tend to form encapsulated rounded or lobulated masses which compress the surrounding tissues.

Lipoma

Circumscribed masses of fat are commonly found in the subcutaneous tissue of the arms, shoulders and buttocks. Less commonly they occur in the deep soft tissues of the limbs or retroperitoneum, but at these sites they must be carefully distinguished from low grade liposarcomas. Lipomas very rarely arise from the viscera.

Chondroma

A chondroma usually arises within the medullary cavity of the tubular bones of the hands and feet; it grows slowly, causing gradual expansion of the bone. Less commonly it occurs in long bones. Rarely multiple enchondromas appear in children and are associated with deformity: they occasionally become malignant.

Osteoma

This tumour is mainly found in the bones of the skull, although it may occur in long bones. Osteomas are relatively small but may produce severe symptoms because of their situation.

Leiomyoma (Fibroid)

The majority of benign smooth muscle tumours occur in the wall of the uterus where they are extremely common, but may lie within the uterine cavity or attached to the serosa. They are firm, rounded masses which usually begin in the myometrium.

Tumours of Fibrous Tissue

So-called fibromas are rare but tumour-like growths are fairly common. An example is a FIBROMATOSIS.

Palmar fibromatosis, at first nodular, causes flexion deformities of fingers (Dupuytren’s contracture) due to contraction of fibrous tissue within the palmar fascia. A similar condition may affect the plantar fascia. Deeply located fibromatoses behave in a locally aggressive manner.

Benign tumours of peripheral nerve and of vessels are described on pages 579 and 580.

Malignant Epithelial Tumours

Malignant epithelial tumours are known as CARCINOMAS (Greek ‘karkinos’: a crab), referring to the typical irregular jagged shape. This is due to invasion into adjacent normal tissues (p.135).

Types of Carcinoma

Like benign epithelial tumours, carcinomas can arise from squamous or glandular epithelium.

Squamous Cell Carcinoma

This is commonly found on the skin, especially exposed surfaces, but also develops in other sites covered by stratified squamous epithelium, e.g. lips, tongue, pharynx, oesophagus and vagina. In addition, it may occur on surfaces covered by glandular type epithelium through metaplastic transformation as in the bronchus, gall bladder and uterine cervix. It frequently arises from areas of carcinoma-in-situ (p.144).

1. It starts as a small papular mass

2. The surface breaks down and a characteristic irregular ulcer is produced.

Histologically, it is composed of irregular strands and columns of invading epithelium which infiltrate the underlying connective tissue. If well differentiated, the central cells of the invading masses show conversion into eosinophilic keratin, while the outer layer consists of young basophilic cells. In cross-section, the appearance is typical.

Squamous carcinoma of skin is typically well differentiated and slow growing. In contrast, uterine cervical carcinomas are poorly differentiated and spread early to draining lymph nodes.

Types of Carcinoma

Basal Cell Carcinoma (Rodent Ulcer)

This tumour may arise in any part of the skin but is most common in the face, near the eyes and nose.

First Stage

It starts as a flattened papilloma which slowly enlarges over months or perhaps a year or two.

Second Stage

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