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.
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 carcinoma.
Macroscopically, squamous cell carcinomas are either proliferative or ulcerative. On section solid masses of polyhedral cells are seen, which invade the deeper structures. ‘Cell-nests’ are usually apparent in slowly growing cases, and are due to deeper cells becoming flattened and undergoing keratinisation. ‘Prickle’ (acanthotic) cells are characteristic, and resemble those present in the epidermis.
Basal-celled (syn. rodent ulcer)
Glandular carcinoma commonly occurs in the alimentary tract, breast and uterus, and less frequently in the kidney, prostate, gall bladder and thyroid. Three types of glandular carcinoma may be recognised:
• carcinoma simplex, in which the cells are arranged in circumscribed groups, no glandular structure being recognisable. This type commonly occurs in the breast, and the majority of cells are spheroidal or polygonal in shape;
• adenocarcinoma, so called from the tendency of the cells to form acini, which resemble those of the gland from which they are derived. The alveoli are ductless, and the walls are composed of layers of cells which invade the surrounding tissues. The cells of the primary growth, and even of the metastases, sometimes retain secretory powers; bronchial adenocarcinomas are well known for this;
• colloid (mucoid) is a degenerative process which develops in tumours arising from mucin-secreting cells. The mucin permeates the stroma of the growth, which appears as a gelatinous mass and is typically seen in the colon and stomach.
Glandular carcinoma is also subdivided into various types,e.g. encephaloid (soft), scirrhous (hard) and atrophic scirrhous (stony-hard). These distinctions depend clinically on their rate of growth, and pathologically on the relative proportions of fibrous tissue and gland elements. Examples occur in the breast. All these glandular types of cancer are best regarded as adenocarcinomas.
Methods of spread
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 (Chapter 13), 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, free-floating 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
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. This is a detailed clinical staging which is arrived at simply by the clinician ascertaining the following points. What is the extent of the primary Tumour? Are any lymph Nodes affected? Are there any Metastases? The information so obtained is scored, e.g. ii carcinoma of the breast, as follows:
Tumour Nodes Metastasis
T1 2 cm or less. N0 No nodes M0 No metastasis
No skin fixation
T2 More than 2 cm, N1 Axillary nodes M1 Metastases are
but less than 5 cm. movable (a) not present including
Skin tethered or significant, involvement of skit
dimpled. No (b) significant beyond breast, and
pectoral fixation contralateral nodes
T3 More than 5 cm, N2 Axillary
but less than 10 cm. nodes fixed
Skin infiltrated or
T4More than 10 cm. N3 Supraclavicular
Skin involved but nodes. Oedema
not beyond breast, of arm
(i) Thus, for example, one patient may have an early carcinoma which is T1N0M0, while in another late case the extent of the disease may be T2N2M1.
(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 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).
The macroscopic appearance of a sarcoma varies considerably. As the word implies, most tumours appear as a fleshy mass, but their consistency depends on the relative proportion of fibrous and vascular tissue. Haemorrhage commonly occurs owing to the very thin walls of the veins, which in some places are represented merely by venous spaces.
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.
Fibrosarcoma is composed of spindle cells of varying lengths (the rounder they are the more malignant they are), and occurs in muscle sheaths, scars and as a fibrous epulis. A fibrosarcoma of a muscle sheath presents as an elastic or firm and slowly growing swelling. Dilated veins over the tumour suggest malignancy, and if not obvious they may be demonstrated by infrared photography. On palpation the tumour often feels warm and pulsation may even be detected. Fibrosarcomas not uncommonly arise in scar tissue, sometimes many years after the scar developed. Sir James Paget described this as a ‘recurrent fibroid’.
Treatment of sarcoma
The spread of a fibrosarcoma 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, a fibrosarcoma eventually fungates through the skin. 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 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.
This rather uncommon tumour may arise in any synovial joint or tendon sheath, especially those of the hand. It appears as a soft, painless swelling, and sarcomatous changes can occur. The diagnosis can only be established by excision and biopsy of the tumour.
Naevus and melanoma
The endothelial linings of blood vessels, lymphatic spaces and serous membranes occasionally give rise to neoplasms. They can be malignant. They arise from the pleura (Chapter 47) and rarely from the pericardium or peritoneum. Asbestos inhalation may provoke their development. ‘Blue’ asbestos fibres especially have been shown to be a cause. The original cells are flattened, but they become spheroidal or cuboidal when neop]astic changes occur. The ‘endothelioma’ (meningioma) of the dura mater is thought to arise from the arachnoid membrane, which is not an endothelial structure .
Peritheliomas are tumours arising in the endothelial lining of small blood vessels or lymphatics. Carotid body tumours are probably of this nature .
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