Galyl, luargol, and other preparations act in the same way as the "606" and "914" groups.

The "606" preparations may be introduced into the veins by injection or by means of an apparatus which allows the solution to flow in by gravity. The left median basilic vein is selected, and a platino-iridium needle with a short point and a bore larger than that of the ordinary hypodermic syringe is used. The needle is passed for a few millimetres along the vein, and the solution is then slowly introduced; before withdrawing the needle some saline is run in to diminish the risk of thrombosis.

The "914" preparations may be injected either into the subcutaneous tissue of the buttock or into the substance of the gluteus muscle. The part is then massaged for a few minutes, and the massage is repeated daily for a few days.

No hard-and-fast rules can be laid down as to what constitutes a complete course of treatment. Harrison recommends as a minimum course of one of the "914" preparations in early primary cases an initial dose of 0.45 grm. given intra-muscularly or into the deep subcutaneous tissue; the same dose a week later; 0.6 grm. the following week; then miss a week and give 9.6 grms. on two successive weeks; then miss two weeks and give 0.6 grm. on two more successive weeks.

When a positive Wassermann reaction is present before treatment is commenced, the above course is prolonged as follows: for three weeks is given a course of potassium iodide, after which four more weekly injections of 0.6 grm. of "914" are given.

With each injection of "914" after the first, throughout the whole course 1 grain of mercury is injected intra-muscularly.

In the course of a few hours, there is usually some indisposition, with a feeling of chilliness and slight rise of temperature; these symptoms pass off within twenty-four hours, and in a few days there is a decided improvement of health. Three or four days after an intra-muscular injection there may be pain and stiffness in the gluteal region.

These preparations are the most efficient therapeutic agents that have yet been employed in the treatment of syphilis.

The manifestations of the disease disappear with remarkable rapidity. Observations show that the spirochaetes lose their capacity for movement within an hour or two of the administration, and usually disappear altogether in from twenty-four to thirty-six hours. Wassermann's reaction usually yields a negative result in from three weeks to two months, but later may again become positive. Subsequent doses of the arsenical preparation are therefore usually indicated, and should be given in from 7 to 21 days according to the dose.

When syphilis occurs in a pregnant woman, she should be given in the early months an ordinary course of "914," followed by 10-grain doses of potassium iodide twice daily. The injections may be repeated two months later, and during the remainder of the pregnancy 2-grain mercury pills are given twice daily (A. Campbell). The presence of albumen in the urine contra-indicates arsenical treatment.

It need scarcely be pointed out that the use of powerful drugs like "606" and "914" is not free from risk; it may be mentioned that each dose contains nearly three grains of arsenic. Before the administration the patient must be overhauled; its administration is contra-indicated in the presence of disease of the heart and blood vessels, especially a combination of syphilitic aortitis and sclerosis of the coronary arteries, with degeneration of the heart muscle; in affections of the central nervous system, especially advanced paralysis, and in such disturbances of metabolism as are associated with diabetes and Bright's disease. Its use is not contra-indicated in any lesion of active syphilis.

The administration is controlled by the systematic examination of the urine for arsenic.

The Administration of Mercury.—The success of the arsenical preparations has diminished the importance of mercury in the treatment of syphilis, but it is still used to supplement the effect of the injections. The amount of mercury to be given in any case must be proportioned to the idiosyncrasies of the patient, and it is advisable, before commencing the treatment, to test his urine and record his body-weight. The small amount of mercury given at the outset is gradually increased. If the body-weight falls, or if the gums become sore and the breath foul, the mercury should be stopped for a time. If salivation occurs, the drinking of hot water and the taking of hot baths should be insisted upon, and half-dram doses of the alkaline sulphates prescribed.

Methods of Administering Mercury.—(1) By the Mouth.—This was for long the most popular method in this country, the preparation usually employed being grey powder, in pills or tablets, each of which contains one grain of the powder. Three of these are given daily in the first instance, and the daily dose is increased to five or even seven grains till the standard for the individual patient is arrived at. As the grey powder alone sometimes causes irritation of the bowels, it should be combined with iron, as in the following formula: Hydrarg. c. cret. gr. 1; ferri sulph. exsiccat. gr. 1 or 2.

(2) By Inunction.—Inunction consists in rubbing into the pores of the skin an ointment composed of equal parts of 20 per cent. oleate of mercury and lanolin. Every night after a hot bath, a dram of the ointment (made up by the chemist in paper packets) is rubbed for fifteen minutes into the skin where it is soft and comparatively free from hairs. When the patient has been brought under the influence of the mercury, inunction may be replaced by one of the other methods, of administering the drug.

(3) By Intra-muscular Injection.—This consists in introducing the drug by means of a hypodermic syringe into the substance of the gluteal muscles. The syringe is made of glass, and has a solid glass piston; the needle of platino-iridium should be 5 cm. long and of a larger calibre than the ordinary hypodermic needle. The preparation usually employed consists of: metallic mercury or calomel 1 dram, lanolin and olive oil each 2 drams; it must be warmed to allow of its passage through the needle. Five minims—containing one grain of metallic mercury—represent a dose, and this is injected into the muscles above and behind the great trochanter once a week. The contents of the syringe are slowly expressed, and, after withdrawing the needle, gentle massage of the buttock should be employed. Four courses each of ten injections are given the first year, three courses of the same number during the second and third years, and two courses during the fourth year (Lambkin).

The General Health.—The patient must lead a regular life and cultivate the fresh-air habit, which is as beneficial in syphilis as in tuberculosis. Anaemia, malaria, and other sources of debility must receive appropriate treatment. The diet should be simple and easily digested, and should include a full supply of milk. Alcohol is prohibited. The excretory organs are encouraged to act by the liberal drinking of hot water between meals, say five or six tumblerfuls in the twenty-four hours. The functions of the skin are further aided by frequent hot baths, and by the wearing of warm underclothing. While the patient should avoid exposure to cold, and taxing his energies by undue exertion, he should be advised to take exercise in the open air. On account of the liability to lesions of the mouth and throat, he should use tobacco in moderation, his teeth should be thoroughly overhauled by the dentist, and he should brush them after every meal, using an antiseptic tooth powder or wash. The mouth and throat should be rinsed out night and morning with a solution of chlorate of potash and alum, or with peroxide of hydrogen.

Treatment of the Local Manifestations.—The skin lesions are treated on the same lines as similar eruptions of other origin. As local applications, preparations of mercury are usually selected, notably the ointments of the red oxide of mercury, ammoniated mercury, or oleate of mercury (5 per cent.), or the mercurial plaster introduced by Unna. In the treatment of condylomata the greatest attention must be paid to cleanliness and dryness. After washing and drying the affected patches, they are dusted with a powder consisting of equal parts of calomel and carbonate of zinc; and apposed skin surfaces, such as the nates or labia, are separated by sublimate wool. In the ulcers of later secondary syphilis, crusts are got rid of in the first instance by means of a boracic poultice, after which a piece of lint or gauze cut to the size of the ulcer and soaked in black wash is applied and covered with oil-silk. If the ulcer tends to spread in area or in depth, it should be scraped with a sharp spoon, and painted over with acid nitrate of mercury, or a local hyperaemia may be induced by Klapp's suction apparatus.

In lesions of the mouth and throat, the teeth should be attended to; the best local application is a solution of chromic acid—10 grains to the ounce—painted on with a brush once daily. If this fails, the lesions may be dusted with calomel the last thing at night. For deep ulcers of the throat the patient should gargle frequently with chlorine water or with perchloride of mercury (1 in 2000); if the ulcer continues to spread it should be painted with acid nitrate of mercury.

In the treatment of iritis the eyes are shaded from the light and completely rested, and the pupil is well dilated by atropin to prevent adhesions. If there is much pain, a blister may be applied to the temple.

The Relations of Syphilis to Marriage.—Before the introduction of the Ehrlich-Hata treatment no patient was allowed to marry until three years had elapsed after the disappearance of the last manifestation. While marriage might be entered upon under these conditions without risk of the husband infecting the wife, the possibility of his conveying the disease to the offspring cannot be absolutely excluded. It is recommended, as a precautionary measure, to give a further mercurial course of two or three months' duration before marriage, and an intravenous injection of an arsenical preparation.

Intermediate Stage.—After the dying away of the secondary manifestations and before the appearance of tertiary lesions, the patient may present certain symptoms which Hutchinson called reminders. These usually consist of relapses of certain of the affections of the skin, mouth, or throat, already described. In the skin, they may assume the form of peeling patches in the palms, or may appear as spreading and confluent circles of a scaly papular eruption, which if neglected may lead to the formation of fissures and superficial ulcers. Less frequently there is a relapse of the eye affections, or of paralytic symptoms from disease of the cerebral arteries.

Tertiary Syphilis.—While the manifestations of primary and secondary syphilis are common, those of the tertiary period are by comparison rare, and are observed chiefly in those who have either neglected treatment or who have had their powers of resistance lowered by privation, by alcoholic indulgence, or by tropical disease.

It is to be borne in mind that in a certain proportion of men and in a larger proportion of women, the patient has no knowledge of having suffered from syphilis. Certain slight but important signs may give the clue in a number of cases, such as irregularity of the pupils or failure to react to light, abnormality of the reflexes, and the discovery of patches of leucoplakia on the tongue, cheek, or palate.

The general character of tertiary manifestations may be stated as follows: They attack by preference the tissues derived from the mesoblastic layer of the embryo—the cellular tissue, bones, muscles, and viscera. They are often localised to one particular tissue or organ, such, for example, as the subcutaneous cellular tissue, the bones, or the liver, and they are rarely symmetrical. They are usually aggressive and persistent, with little tendency to natural cure, and they may be dangerous to life, because of the destructive changes produced in such organs as the brain or the larynx. They are remarkably amenable to treatment if instituted before the stage which is attended with destruction of tissue is reached. Early tertiary lesions may be infective, and the disease may be transmitted by the discharges from them; but the later the lesions the less is the risk of their containing an infective virus.

The most prominent feature of tertiary syphilis consists in the formation of granulation tissue, and this takes place on a scale considerably larger than that observed in lesions of the secondary period. The granulation tissue frequently forms a definite swelling or tumour-like mass (syphiloma), which, from its peculiar elastic consistence, is known as a gumma. In its early stages a gumma is a firm, semi-translucent greyish or greyish-red mass of tissue; later it becomes opaque, yellow, and caseous, with a tendency to soften and liquefy. The gumma does harm by displacing and replacing the normal tissue elements of the part affected, and by involving these in the degenerative changes, of the nature of caseation and necrosis, which produce the destructive lesions of the skin, mucous membranes, and internal organs. This is true not only of the circumscribed gumma, but of the condition known as gummatous infiltration or syphilitic cirrhosis, in which the granulation tissue is diffused throughout the connective-tissue framework of such organs as the tongue or liver. Both the gummatous lesions and the fibrosis of tertiary syphilis are directly excited by the spirochaetes.

The life-history of an untreated gumma varies with its environment. When protected from injury and irritation in the substance of an internal organ such as the liver, it may become encapsulated by fibrous tissue, and persist in this condition for an indefinite period, or it may be absorbed and leave in its place a fibrous cicatrix. In the interior of a long bone it may replace the rigid framework of the shaft to such an extent as to lead to pathological fracture. If it is near the surface of the body—as, for example, in the subcutaneous or submucous cellular tissue, or in the periosteum of a superficial bone, such as the palate, the skull, or the tibia—the tissue of which it is composed is apt to undergo necrosis, in which the overlying skin or mucous membrane frequently participates, the result being an ulcer—the tertiary syphilitic ulcer (Figs. 40 and 41).

Tertiary Lesions of the Skin and Subcutaneous Cellular Tissue.—The clinical features of a subcutaneous gumma are those of an indolent, painless, elastic swelling, varying in size from a pea to an almond or walnut. After a variable period it usually softens in the centre, the skin over it becomes livid and dusky, and finally separates as a slough, exposing the tissue of the gumma, which sometimes appears as a mucoid, yellowish, honey-like substance, more frequently as a sodden, caseated tissue resembling wash-leather. The caseated tissue of a gumma differs from that of a tuberculous lesion in being tough and firm, of a buff colour like wash-leather, or whitish, like boiled fish. The degenerated tissue separates slowly and gradually, and in untreated cases may be visible for weeks in the floor of the ulcer.



The tertiary ulcer may be situated anywhere, but is most frequently met with on the leg, especially in the region of the knee (Fig. 42) and over the calf. There may be one or more ulcers, and also scars of antecedent ulcers. The edges are sharply cut, as if punched out; the margins are rounded in outline, firm, and congested; the base is occupied by gummatous tissue, or, if this has already separated and sloughed out, by unhealthy granulations and a thick purulent discharge. When the ulcer has healed it leaves a scar which is depressed, and if over a bone, is adherent to it. The features of the tertiary ulcer, however, are not always so characteristic as the above description would imply. It is to be diagnosed from the "leg ulcer," which occurs almost exclusively on the lower third of the leg; from Bazin's disease (p. 74); from the ulcers that result from certain forms of malignant disease, such as rodent cancer, and from those met with in chronic glanders.

Gummatous Infiltration of the Skin ("Syphilitic Lupus").—This is a lesion, met with chiefly on the face and in the region of the external genitals, in which the skin becomes infiltrated with granulation tissue so that it is thickened, raised above the surface, and of a brownish-red colour. It appears as isolated nodules, which may fuse together; the epidermis becomes scaly and is shed, giving rise to superficial ulcers which are usually covered by crusted discharge. The disease tends to spread, creeping over the skin with a serpiginous, crescentic, or horse-shoe margin, while the central portion may heal and leave a scar. From the fact of its healing in the centre while it spreads at the margin, it may resemble tuberculous disease of the skin. It can usually be differentiated by observing that the infiltration is on a larger scale; the progress is much more rapid, involving in the course of months an area which in the case of tuberculosis would require as many years; the scars are sounder and are less liable to break down again; and the disease rapidly yields to anti-syphilitic treatment.



Tertiary lesions of mucous membrane and of the submucous cellular tissue are met with chiefly in the tongue, nose, throat, larynx, and rectum. They originate as gummata or as gummatous infiltrations, which are liable to break down and lead to the formation of ulcers which may prove locally destructive, and, in such situations as the larynx, even dangerous to life. In the tongue the tertiary ulcer may prove the starting-point of cancer; and in the larynx or rectum the healing of the ulcer may lead to cicatricial stenosis.

Tertiary lesions of the bones and joints, of the muscles, and of the internal organs, will be described under these heads. The part played by syphilis in the production of disease of arteries and of aneurysm will be referred to along with diseases of blood vessels.



Treatment.—The most valuable drugs for the treatment of the manifestations of the tertiary period are the arsenical preparations and the iodides of sodium and potassium. On account of their depressing effects, the latter are frequently prescribed along with carbonate of ammonium. The dose is usually a matter of experiment in each individual case; 5 grains three times a day may suffice, or it may be necessary to increase each dose to 20 or 25 grains. The symptoms of iodism which may follow from the smaller doses usually disappear on giving a larger amount of the drug. It should be taken after meals, with abundant water or other fluid, especially if given in tablet form. It is advisable to continue the iodides for from one to three months after the lesions for which they are given have cleared up. If the potassium salt is not tolerated, it may be replaced by the ammonium or sodium iodide.

Local Treatment.—The absorption of a subcutaneous gumma is often hastened by the application of a fly-blister. When a gumma has broken on the surface and caused an ulcer, this is treated on general principles, with a preference, however, for applications containing mercury or iodine, or both. If a wet dressing is required to cleanse the ulcer, black wash may be used; if a powder to promote dryness, one containing iodoform; if an ointment is indicated, the choice lies between the red oxide of mercury or the dilute nitrate of mercury ointment, and one consisting of equal parts of lanolin and vaselin with 2 per cent. of iodine. Deep ulcers, and obstinate lesions of the bones, larynx, and other parts may be treated by excision or scraping with the sharp spoon.

Second Attacks of Syphilis.—Instances of re-infection of syphilis have been recorded with greater frequency since the more general introduction of arsenical treatment. A remarkable feature in such cases is the shortness of the interval between the original infection and the alleged re-infection; in a recent series of twenty-eight cases, this interval was less than a year. Another feature of interest is that when patients in the tertiary stage of syphilis are inoculated with the virus from lesions from these in the primary and secondary stage lesions of the tertiary type are produced.

Reference may be made to the relapsing false indurated chancre, described by Hutchinson and by Fournier, as it may be the source of difficulty in diagnosis. A patient who has had an infecting chancre one or more years before, may present a slightly raised induration on the penis at or close to the site of his original sore. This relapsed induration is often so like that of a primary chancre that it is impossible to distinguish between them, except by the history. If there has been a recent exposure to venereal infection, it is liable to be regarded as the primary lesion of a second attack of syphilis, but the further progress shows that neither bullet-buboes nor secondary manifestations develop. These facts, together with the disappearance of the induration under treatment, make it very likely that the lesion is really gummatous in character.

INHERITED SYPHILIS

One of the most striking features of syphilis is that it may be transmitted from infected parents to their offspring, the children exhibiting the manifestations that characterise the acquired form of the disease.

The more recent the syphilis in the parent, the greater is the risk of the disease being communicated to the offspring; so that if either parent suffers from secondary syphilis the infection is almost inevitably transmitted.

While it is certain that either parent may be responsible for transmitting the disease to the next generation, the method of transmission is not known. In the case of a syphilitic mother it is most probable that the infection is conveyed to the foetus by the placental circulation. In the case of a syphilitic father, it is commonly believed that the infection is conveyed to the ovum through the seminal fluid at the moment of conception. If a series of children, one after the other, suffer from inherited syphilis, it is almost invariably the case that the mother has been infected.

In contrast to the acquired form, inherited syphilis is remarkable for the absence of any primary stage, the infection being a general one from the outset. The spirochaete is demonstrated in incredible numbers in the liver, spleen, lung, and other organs, and in the nasal secretion, and, from any of these, successful inoculations in monkeys can readily be made. The manifestations differ in degree rather than in kind from those of the acquired disease; the difference is partly due to the fact that the virus is attacking developing instead of fully formed tissues.

The virus exercises an injurious influence on the foetus, which in many cases dies during the early months of intra-uterine life, so that miscarriage results, and this may take place in repeated pregnancies, the date at which the miscarriage occurs becoming later as the virus in the mother becomes attenuated. Eventually a child is carried to full term, and it may be still-born, or, if born alive, may suffer from syphilitic manifestations. It is difficult to explain such vagaries of syphilitic inheritance as the infection of one twin and the escape of the other.

Clinical Features.—We are not here concerned with the severe forms of the disease which prove fatal, but with the milder forms in which the infant is apparently healthy when born, but after from two to six weeks begins to show evidence of the syphilitic taint.

The usual phenomena are that the child ceases to thrive, becomes thin and sallow, and suffers from eruptions on the skin and mucous membranes. There is frequently a condition known as snuffles, in which the nasal passages are obstructed by an accumulation of thin muco-purulent discharge which causes the breathing to be noisy. It usually begins within a month after birth and before the eruptions on the skin appear. When long continued it is liable to interfere with the development of the nasal bones, so that when the child grows up there results a condition known as the "saddle-nose" deformity (Figs. 43 and 44).



Affections of the Skin.—Although all types of skin affection are met with in the inherited disease, the most important is a papular eruption, the papules being of large size, with a smooth shining top and of a reddish-brown colour. It affects chiefly the buttocks and thighs, the genitals, and other parts which are constantly moist. It is necessary to distinguish this specific eruption from a form of eczema which occurs in these situations in non-syphilitic children, the points that characterise the syphilitic condition being the infiltration of the skin and the coppery colour of the eruption. At the anus the papules acquire the characters of condylomata, also at the angles of the mouth, where they often ulcerate and leave radiating scars.

Affections of the Mucous Membranes.—The inflammation of the nasal mucous membrane that causes snuffles has already been referred to. There may be mucous patches in the mouth, or a stomatitis which is of importance, because it results in interference with the development of the permanent teeth. The mucous membrane of the larynx may be the seat of mucous patches or of catarrh, and as a result the child's cry is hoarse.

Affections of the Bones.—Swellings at the ends of the long bones, due to inflammation at the epiphysial junctions, are most often observed at the upper end of the humerus and in the bones in the region of the elbow. Partial displacement and mobility at the ossifying junction may be observed. The infant cries when the part is touched; and as it does not move the limb voluntarily, the condition is spoken of as the pseudo-paralysis of syphilis. Recovery takes place under anti-syphilitic treatment and immobilisation of the limb.

Diffuse thickening of the shafts of the long bones, due to a deposit of new bone by the periosteum, is sometimes met with.



The conditions of the skull known as Parrot's nodes or bosses, and craniotabes, were formerly believed to be characteristic of inherited syphilis, but they are now known to occur, particularly in rickety children, from other causes. The bosses result from the heaping up of new spongy bone beneath the pericranium, and they may be grouped symmetrically around the anterior fontanelle, or may extend along either side of the sagittal suture, which appears as a deep groove—the "natiform skull." The bosses disappear in time, but the skull may remain permanently altered in shape, the frontal and parietal eminences appearing unduly prominent. The term craniotabes is applied when the bone becomes thin and soft, reverting to its original membranous condition, so that the affected areas dimple under the finger like parchment or thin cardboard; its localisation in the posterior parts of the skull suggests that the disappearance of the osseous tissue is influenced by the pressure of the head on the pillow. Craniotabes is recovered from as the child improves in health.

Between the ages of three and six months, certain other phenomena may be met with, such as effusion into the joints, especially the knees; iritis, in one or in both eyes, and enlargement of the spleen and liver.

In the majority of cases the child recovers from these early manifestations, especially when efficiently treated, and may enjoy an indefinite period of good health. On the other hand, when it attains the age of from two to four years, it may begin to manifest lesions which correspond to those of the tertiary period of acquired syphilis.

Later Lesions.—In the skin and subcutaneous tissue, the later manifestations may take the form of localised gummata, which tend to break down and form ulcers, on the leg for example, or of a spreading gummatous infiltration which is also liable to ulcerate, leaving disfiguring scars, especially on the face. The palate and fauces may be destroyed by ulceration. In the nose, especially when the ulcerative process is associated with a putrid discharge—ozaena—the destruction of tissue may be considerable and result in unsightly deformity. The entire palatal portions of the upper jaws, the vomer, turbinate, and other bones bounding the nasal and oral cavities, may disappear, so that on looking into the mouth the base of the skull is readily seen. Gummatous disease is frequently observed also in the flat bones of the skull, in the bones of the hand, as syphilitic dactylitis, and in the bones of the forearm and leg. When the tibia is affected the disease is frequently bilateral, and may assume the form of gummatous ulcers and sinuses. In later years the tibia may present alterations in shape resulting from antecedent gummatous disease—for example, nodular thickenings of the shaft, flattening of the crest, or a more uniform increase in thickness and length of the shaft of the bone, which, when it is curved in addition, is described as the "sabre-blade" deformity. Among lesions of the viscera, mention should be made of gumma of the testis, which causes the organ to become enlarged, uneven, and indurated. This has even been observed in infants a few months old.

Occasionally a syphilitic child suffers from a succession of these gummatous lesions with resulting ill-health, and, it may be, waxy disease of the internal organs; on the other hand, it may recover and present no further manifestations of the inherited taint.

Affections of the Eyes.—At or near puberty there is frequently observed an affection of the eyes, known as chronic interstitial keratitis, the relationship of which to inherited syphilis was first established by Hutchinson. It occurs between the ages of six and sixteen years, and usually affects one eye before the other. It commences as a diffuse haziness or steaminess near the centre of the cornea, and as it spreads the entire cornea assumes the appearance of ground glass. The chief complaint is of dimness of sight, which may almost amount to blindness, but there is little pain or photophobia; a certain amount of conjunctival and ciliary congestion is usually present, and there may be iritis in addition. The cornea, or parts of it, may become of a deep pink or salmon colour from the formation in it of new blood vessels. The affection may last for from eighteen months to two years. Complete recovery usually takes place, but slight opacities, especially in the site of former salmon patches, may persist, and the disease occasionally relapses. Choroiditis and retinitis may also occur, and leave permanent changes easily recognised on examination with the ophthalmoscope.

Among the rarer and more serious lesions of the inherited disease may be mentioned gummatous disease in the larynx and trachea, attended with ulceration and resulting in stenosis; and lesions of the nervous system which may result in convulsions, paralysis, or dementia.

In a limited number of cases, about the period of puberty there may develop deafness, which is usually bilateral and may become absolute.

Changes in the Permanent Teeth.—These affect specially the upper central incisors, which are dwarfed and stand somewhat apart in the gum, with their free edges converging towards one another. They are tapering or peg-shaped, and present at their cutting margin a deep semilunar notch. These appearances are commonly associated with the name of Hutchinson, who first described them. Affecting as they do the permanent teeth, they are not available for diagnosis until the child is over eight years of age. Henry Moon drew attention to a change in the first molars; these are reduced in size and dome-shaped through dwarfing of the central tubercle of each cusp.

Diagnosis of Inherited Syphilis.—When there is a typical eruption on the buttocks and snuffles there is no difficulty in recognising the disease. When, however, the rash is scanty or is obscured by co-existing eczema, most reliance should be placed on the distribution of the eruption, on the brown stains which are left after it has passed off, on the presence of condylomata, and of fissuring and scarring at the angles of the mouth. The history of the mother relative to repeated miscarriages and still-born children may afford confirmatory evidence. In doubtful cases, the diagnosis may be aided by the Wassermann test and by noting the therapeutic effects of grey powder, which, in syphilitic infants, usually effects a marked and rapid improvement both in the symptoms and in the general health.

While a considerable number of syphilitic children grow up without showing any trace of their syphilitic inheritance, the majority retain throughout life one or more of the following characteristics, which may therefore be described as permanent signs of the inherited disease: Dwarfing of stature from interference with growth at the epiphysial junctions; the forehead low and vertical, and the parietal and frontal eminences unduly prominent; the bridge of the nose sunken and rounded; radiating scars at the angles of the mouth; perforation or destruction of the hard palate; Hutchinson's teeth; opacities of the cornea from antecedent keratitis; alterations in the fundus oculi from choroiditis; deafness; depressed scars or nodes on the bones from previous gummata; "sabre-blade" or other deformity of the tibiae.

The Contagiousness of Inherited Syphilis.—In 1837, Colles of Dublin stated his belief that, while a syphilitic infant may convey the disease to a healthy wet nurse, it is incapable of infecting its own mother if nursed by her, even although she may never have shown symptoms of the disease. This doctrine, which is known as Colles' law, is generally accepted in spite of the alleged occurrence of occasional exceptions. The older the child, the less risk there is of its communicating the disease to others, until eventually the tendency dies out altogether, as it does in the tertiary period of acquired syphilis. It should be added, however, that the contagiousness of inherited syphilis is denied by some observers, who affirm that, when syphilitic infants prove infective, the disease has been really acquired at or soon after birth.

There is general agreement that the subjects of inherited syphilis cannot transmit the disease by inheritance to their offspring, and that, although they very rarely acquire the disease de novo, it is possible for them to do so.

Prognosis of Inherited Syphilis.—Although inherited syphilis is responsible for a large but apparently diminishing mortality in infancy, the subjects of this disease may grow up to be as strong and healthy as their neighbours. Hutchinson insisted on the fact that there is little bad health in the general community that can be attributed to inherited syphilis.

Treatment.—Arsenical injections are as beneficial in the inherited as in the acquired disease. An infant the subject of inherited syphilis should, if possible, be nursed by its mother, and failing this it should be fed by hand. In infants at the breast, the drug may be given to the mother; in others, it is administered in the same manner as already described—only in smaller doses. On the first appearance of syphilitic manifestations it should be given 0.05 grm, novarsenbillon, injected into the deep subcutaneous tissues every week for six weeks, followed by one year's mercurial inunction—a piece of mercurial ointment the size of a pea being inserted under the infant's binder. In older children the dose is proportionately increased. The general health should be improved in every possible direction; considerable benefit may be derived from the use of cod-liver oil, and from preparations containing iron and calcium. Surgical interference may be required in the destructive gummatous lesions of the nose, throat, larynx, and bones, either with the object of arresting the spread of the disease, or of removing or alleviating the resulting deformities. In children suffering from keratitis, the eyes should be protected from the light by smoked or coloured glasses, and the pupils should be dilated with atropin from time to time, especially in cases complicated with iritis.

Acquired Syphilis in Infants and Young Children.—When syphilis is met with in infants and young children, it is apt to be taken for granted that the disease has been inherited. It is possible, however, for them to acquire the disease—as, for example, while passing through the maternal passages during birth, through being nursed or kissed by infected women, or through the rite of circumcision. The risk of infection which formerly existed by the arm-to-arm method of vaccination has been abolished by the use of calf lymph.

The clinical features of the acquired disease in infants and young children are similar to those observed in the adult, with a tendency, however, to be more severe, probably because the disease is often late in being recognised and treated.



CHAPTER X

TUMOURS[2]

Definition—Etiology—General characters of innocent and malignant tumours. CLASSIFICATION OF TUMOURS: I. Connective-tissue tumours: (1) Innocent: Lipoma, Xanthoma, Chondroma, Osteoma, Odontoma, Fibroma, Myxoma, Endothelioma, etc.; (2) Malignant: Sarcoma—II. Epithelial tumours: (1) Innocent: Papilloma, Adenoma, Cystic Adenoma; (2) Malignant: Epithelioma, Glandular Cancer, Rodent Cancer, Melanotic Cancer—III. Dermoids—IV. Teratoma. Cysts: Retention, Exudation, Implantation, Parasitic, Lymphatic or Serous. Ganglion.

[2] For the histology of tumours the reader is referred to a text-book of pathology.

A tumour or neoplasm is a localised swelling composed of newly formed tissue which fulfils no physiological function. Tumours increase in size quite independently of the growth of the body, and there is no natural termination to their growth. They are to be distinguished from such over-growths as are of the nature of simple hypertrophy or local giantism, and also from inflammatory swellings, which usually develop under the influence of a definite cause, have a natural termination, and tend to disappear when the cause ceases to act.

The etiology of tumours is imperfectly understood. Various factors, acting either singly or in combination, may be concerned in their development. Certain tumours, for example, are the result of some congenital malformation of the particular tissue from which they take origin. This would appear to be the case in many tumours of blood vessels (angioma), of cartilage (chondroma), of bone (osteoma), and of secreting gland tissue (adenoma). The theory that tumours originate from foetal residues or "rests," is associated with the name of Cohnheim. These rests are supposed to be undifferentiated embryonic cells which remain embedded amongst fully formed tissue elements, and lie dormant until they are excited into active growth and give rise to a tumour. This mode of origin is illustrated by the development of dermoids from sequestrated portions of epidermis.

Among the local factors concerned in the development of tumours, reference must be made to the influence of irritation. This is probably an important agent in the causation of many of the tumours met with in the skin and in mucous membranes—for example, cancer of the skin, of the lip, and of the tongue. The part played by injury is doubtful. It not infrequently happens that the development of a tumour is preceded by an injury of the part in which it grows, but it does not necessarily follow that the injury and the tumour are related as cause and effect. It is possible that an injury may stimulate into active growth undifferentiated tissue elements or "rests," and so determine the growth of a tumour, or that it may alter the characters of a tumour which already exists, causing it to grow more rapidly.

The popular belief that there is some constitutional peculiarity concerned in the causation of tumours is largely based on the fact that certain forms of new growth—for example, cancer—are known to occur with undue frequency in certain families. The same influence is more striking in the case of certain innocent tumours—particularly multiple osteomas and lipomas—which are hereditary in the same sense as supernumerary or webbed fingers, and appear in members of the same family through several generations.

INNOCENT AND MALIGNANT TUMOURS

For clinical purposes, tumours are arbitrarily divided into two classes—the innocent and the malignant. The outstanding difference between them is, that while the evil effects of innocent tumours are entirely local and depend for their severity on the environment of the growth, malignant tumours wherever situated, in addition to producing similar local effects, injure the general health and ultimately cause death.

Innocent, benign, or simple tumours present a close structural resemblance to the normal tissues of the body. They grow slowly, and are usually definitely circumscribed by a fibrous capsule, from which they are easily enucleated, and they do not tend to recur after removal. In their growth they merely push aside and compress adjacent parts, and they present no tendency to ulcerate and bleed unless the overlying skin or mucous membrane is injured. Although usually solitary, some are multiple from the outset—for example, fatty, fibrous, and bony tumours, warts, and fibroid tumours of the uterus. They produce no constitutional disturbance. They only threaten life when growing in the vicinity of vital organs, and then only in virtue of their situation—for example, death may result from an innocent tumour in the air-passage causing suffocation, in the intestine causing obstruction of the bowels, or in the vertebral canal causing pressure on the spinal medulla.

Malignant tumours usually show a marked departure from the structure and arrangement of the normal tissues of the body. Although the cells of which they are composed are derived from normal tissue cells, they tend to take on a lower, more vegetative form; they may be regarded as parasites living at the expense of the organism, multiplying indefinitely and destroying everything with which they come in contact.

Malignant tumours grow more rapidly than innocent tumours, and tend to infiltrate their surroundings by sending out prolongations or offshoots; they are therefore liable to recur after an operation which is restricted to the removal of the main tumour. They are not encapsulated, although they may appear to be circumscribed by condensation of the surrounding tissues; they are rarely multiple at the outset, but show a marked tendency to spread to other parts of the body. Fragments of the parent tumour may become separated and be carried off in the lymph or blood-stream and deposited in other parts of the body, where they give rise to secondary growths. Malignant tumours tend to invade and destroy the overlying skin or mucous membrane, and thus give rise to bleeding ulcers; if the tumour tissue protrudes through the gap in the skin, it is said to fungate. In course of time they give rise to a condition of ill-health or cachexia, the patient becoming pale, sallow, feverish, and emaciated, probably as a result of chronic poisoning from the absorption of toxic products from the tumour. They ultimately destroy life, it may be by their local effects, such as ulceration and haemorrhage, by favouring the entrance of septic infection, by interfering with the function of organs which are essential to life, by cachexia, or by a combination of these effects.

The situation of a malignant tumour exercises considerable influence on the rapidity, as well as on the mode, in which it causes death. Some cancers, such as that known as "rodent," show malignant features which are entirely local, while others, such as melanotic cancer, exhibit a malignancy characterised by rapid generalisation of growths throughout the body. Tumours that are structurally alike may show variations in malignancy, according to their situation and to the age of the patient, as well as to other factors which are as yet unknown.

In attempting to arrive at a conclusion as to the innocence or malignancy of any tumour, too much reliance must not be placed on its histological features; its situation, rate of growth, and other clinical features must also be taken into consideration. It cannot be too emphatically stated that there is no hard-and-fast line between innocent and malignant growths; there is an indefinite transition from one to the other. The possibility of the transformation of a benign into a malignant tumour must be admitted. Such a transformation implies a change in the structure of the growth, and has been observed especially in fibrous and cartilaginous tumours, in tumours of the thyreoid gland, and in uterine fibroids. The alteration in character may take place under the influence of injury, prolonged or repeated irritation, incomplete removal of the benign tumour by operation, or the altered physiological conditions of the tissues which attend upon advancing years.

After a tumour has been removed by operation it should as a routine measure be subjected to microscopical examination; the results are often instructive and sometimes other than what was expected.

Varieties of Tumours.—In the following description, tumours are classified on an anatomical basis, taking in order first the connective-tissue group and subsequently those that originate in epithelium.

INNOCENT CONNECTIVE-TISSUE TUMOURS

Lipoma.—A lipoma is composed of fat resembling that normally present in the body. The commonest variety is the subcutaneous lipoma, which grows from the subcutaneous fat, and forms a soft, irregularly lobulated tumour (Fig. 45). The fat is arranged in lobules separated by connective-tissue septa, which are continuous with the capsule surrounding the tumour and with the overlying skin, which becomes dimpled or puckered when an attempt is made to pinch it up. As the fat is almost fluid at the body temperature, fluctuation can usually be detected. These tumours vary greatly in size, occur at all ages, grow slowly, and, while generally solitary, are sometimes multiple. They are most commonly met with on the shoulder, buttock, or back. In certain situations, such as the thigh and perineum, they tend to become pedunculated (Fig. 46).

A fatty tumour is to be diagnosed from a cold abscess and from a cyst. The distinguishing features of the lipoma are the tacking down and dimpling of the overlying skin, the lobulation of the tumour, which is recognised when it is pressed upon with the flat of the hand, and, more reliable than either of these, the mobility, the tumour slipping away when pressed upon at its margin.



The prognosis is more favourable than in any other tumour as it never changes its characters; the only reasons for its removal by operation are its unsightliness and its probable increase in size in the course of years. The operation consists in dividing the skin and capsule over the tumour and shelling it out. Care must be taken that none of the outlying lobules are left behind. If the overlying skin is damaged or closely adherent, it should be removed along with the tumour.



Multiple subcutaneous lipomas are frequently symmetrical, and in a certain group of cases, met with chiefly in women, pain is a prominent symptom, hence the term adiposis dolorosa (Dercum). These multiple tumours show little or no tendency to increase in size, and the pain which attends their development does not persist.

In the neck, axilla, and pubes a diffuse overgrowth of the subcutaneous fat is sometimes met with, forming symmetrical tumour-like masses, known as diffuse lipoma. As this is not, strictly speaking, a tumour, the term diffuse lipomatosis is to be preferred. A similar condition was described by Jonathan Hutchinson as being met with in the domestic animals. If causing disfigurement, the mass of fat may be removed by operation.



Lipoma in other Situations.—The periosteal lipoma is usually congenital, and is most often met with in the hand; it forms a projecting lobulated tumour, which, when situated in the palm, resembles an angioma or a lymphangioma. The subserous lipoma arises from the extra-peritoneal fat in the posterior abdominal wall, in which case it tends to grow forwards between the layers of the mesentery and to give rise to an abdominal tumour; or it may grow from the extra-peritoneal fat in the anterior abdominal wall and protrude from one of the hernial openings or through an abnormal opening in the parietes, constituting a fatty hernia. A subsynovial lipoma grows from the fat surrounding the synovial membrane of a joint, and projects into its interior, giving rise to the symptoms of loose body. Lipomas are also met with growing from the adipose connective tissue between or in the substance of muscles, and, when situated beneath the deep fascia, such as the fascia lata of the thigh, the characteristic signs are obscured and a differential diagnosis is difficult. It may be differentiated from a cold abscess by puncture with an exploring needle.



Zanthoma is a rare but interesting form of tumour, composed of a fibrous and fatty tissue, containing a granular orange-yellow pigment, resembling that of the corpus luteum. It originates in the corium and presents two clinical varieties. In the first of these, it occurs in the form of raised yellow patches, usually in the skin of the eyelids of persons after middle life, and in many instances is associated with chronic jaundice; the patches are often symmetrical, and as they increase in size they tend to fuse with another.

The second form occurs in children and adolescents; it may affect several generations of the same family, and is often multiple, there being a combination of thickened yellow patches of skin and projecting tumours, some of which may attain a considerable size (Figs. 48 and 49). On section, the tumour tissue presents a brilliant orange or saffron colour.

There is no indication for removing the tumours unless for the deformity which they cause; exposure to the X-rays is to be preferred to operation.



Chondroma.—A chondroma is mainly composed of cartilage. Processes of vascular connective tissue pass in between the nodules of cartilage composing the tumour from the fibrous capsule which surrounds it. On section it is of a greyish-blue colour and semi-translucent. The tumour is firm and elastic in consistence, but certain portions may be densely hard from calcification or ossification, while other portions may be soft and fluctuating as a result of myxomatous degeneration and liquefaction. These tumours grow slowly and painlessly, and may surround nerves and arteries without injuring them. They may cause a deep hollow in the bone from which they originate. All intermediate forms between the innocent chondroma and the malignant chondro-sarcoma are met with. Chondroma may occur in a multiple form, especially in relation to the phalanges and metacarpal bones. When growing in the interior of a bone it causes a spindle-shaped enlargement of the shaft, which in the case of a phalanx or metacarpal bone may resemble the dactylitis resulting from tubercle or syphilis. A chondroma appears as a clear area in a skiagram.

A skiagram of a bone in which there is a chondroma shows a clear rounded area in the position of the tumour, which must be differentiated from similar clear areas due to other kinds of tumour, especially the myeloma; when it has undergone calcification or ossification, it gives a shadow as dark as bone.



Treatment.—In view of the unstable quality of the chondroma, especially of its liability to become malignant, it should be removed as soon as it is recognised. In those projecting from the surface of a bone, both the tumour and its capsule should be removed. If in the interior, a sufficient amount of the cortex should be removed to allow of the tumour being scraped out, and care must be taken that no nodules of cartilage are left behind. In multiple chondromas of the hand, when the fingers are crippled and useless, exposure to the X-rays should be given a trial, and in extreme cases the question of amputation may have to be considered. When a cartilaginous tumour takes on active growth, it must be treated as malignant.

The chondromas that are met with at the ends of the long bones in children and young adults form a group by themselves. They are usually related to the epiphysial cartilage, and it was suggested by Virchow that they take origin from islands of cartilage which have not been used up in the process of ossification. They are believed to occur more frequently in those who have suffered from rickets. They have no malignant tendencies and tend to undergo ossification concurrently with the epiphysial cartilage from which they take origin, and constitute what are known as cartilaginous exostoses. These are sometimes met with in a multiple form, and may occur in several generations of the same family. They are considered in greater detail in the chapter dealing with tumours of bone.

Minute nodules of cartilage sometimes form in the synovial membrane of joints and lining of tendon sheaths and bursae: they tend to become detached from the membrane and constitute loose bodies; they also undergo a variable amount of calcification and ossification, so as to be visible in skiagrams. They are further considered with loose bodies in joints.

Cartilaginous tumours in the parotid, submaxillary gland, and testicle belong to a class of "mixed tumours" that will be referred to later.

Osteoma.—The true osteoma is composed of bony tissue, and originates from the skeleton. Two varieties are recognised—the spongy or cancellous, and the ivory or compact. The spongy or cancellous osteoma is really an ossified chondroma, and is met with at the ends of the long bones (Fig. 52). From the fact that it projects from the surface of the bone it is often spoken of as an exostosis. It grows slowly, and rarely causes any discomfort unless it presses upon a nerve-trunk or upon a bursa which has developed over it. The Rontgen rays show a dark shadow corresponding to the ossified portion of the tumour, and continuous with that of the bone from which it is growing (Fig. 138). Operative interference is only indicated when the tumour is giving rise to inconvenience. It is then removed, its base or neck being divided by means of the chisel. The multiple variety of osteoma is considered with the diseases of bone.

The bony outgrowth from the terminal phalanx of the great toe—known as the subungual exostosis—is described and figured on p. 404. Bony projections or "spurs" sometimes occur on the under surface of the calcaneus, and, projecting downwards and forwards from the greater process, cause pain on putting the heel to the ground.



The ivory or compact osteoma is composed of dense bone, and usually grows from the skull. It is generally sessile and solitary, and may grow into the interior of the skull, into the frontal sinus, into the cavity of the orbit or nose, or may fill up the external auditory meatus, causing most unsightly deformity and interference with sight, breathing, and hearing.

Bony formations occur in muscles and tendons, especially at their points of attachment to the skeleton, and are known as false exostoses; they are described with the diseases of muscles.

Odontoma.—An odontoma is composed of dental tissues in varying proportions and different degrees of development, arising from tooth-germs or from teeth still in process of growth (Bland Sutton). Odontomas resemble teeth in so far that during their development they remain hidden below the mucous membrane and give no evidence of their existence. There then succeeds, usually between the twentieth and twenty-fifth years, an eruptive stage, which is often attended with suppuration, and this may be the means of drawing attention to the tumour. Following Bland Sutton, several varieties of odontoma may be distinguished according to the part of the tooth-germ concerned in their formation.

The epithelial odontoma is derived from persistent portions of the epithelium of the enamel organ, and constitutes a multilocular cystic tumour which is chiefly met with in the mandible. The cystic spaces of the tumour contain a brownish glairy fluid. These tumours have been described by Eve under the name of multilocular cystic epithelial tumours of the jaw.

The follicular odontoma, also known as a dentigerous cyst, is derived from the distension of a tooth follicle. It constitutes a cyst containing a viscid fluid, and an imperfectly formed tooth is often found embedded in its wall. The cyst usually forms in relation to one of the permanent molars, and may attain considerable dimensions.

The fibrous odontoma is the result of an overgrowth of fibrous tissue surrounding the tooth sac, which encapsulates the tooth and prevents its eruption. The thickened tooth sac is usually mistaken for a fibrous tumour, until, after removal, the tooth is recognised in its interior.

Composite Odontoma.—This is a convenient term to apply to certain hard dental tumours which are met with in the jaws, and consist of enamel, dentine, and cement. The tumour is to be regarded as being derived from an abnormal growth of all the elements of a tooth germ, or of two or more tooth germs, indiscriminately fused with one another. It may appear in childhood, and form a smooth unyielding tumour, often of considerable size, replacing the corresponding permanent tooth. It may cause a purulent discharge, and in some cases it has been extruded after sloughing of the overlying soft parts. Many examples of this variety of odontoma, growing in the nasal cavity or in the maxillary sinus, have been erroneously regarded as osteomas even after removal.

On section, the tumour is usually laminated, and is seen to consist mainly of dentine with a partial covering of enamel and cement.

Diagnosis.—Odontomas are often only diagnosed after removal. When attended with suppuration, the condition has been mistaken for disease of the jaw. Fibrous odontomas have been mistaken for sarcoma, and portions of the maxilla removed unnecessarily. Any circumscribed tumour of the jaw, particularly when met with in a young adult, should suggest the possibility of an odontoma. Skiagrams often give useful information both for diagnosis and for treatment.

Treatment.—The solid varieties of odontoma can usually be shelled out after dividing the overlying soft parts. In the follicular variety, it is usually sufficient to excise a portion of the wall, scrape out the interior, and remove any tooth that may be present. The cavity is then packed and allowed to heal from the bottom.

Fibroma.—A fibroma is a tumour composed of fibrous connective tissue. A distinction may be made between the soft fibroma, which is comparatively rich in cells and blood vessels, and in which the fibres are arranged loosely; and the hard fibroma, which is composed of closely packed bundles of fibres often arranged in a concentric fashion around the blood vessels. The cut surface of the soft fibroma presents a pinkish-white, fleshy appearance, resembling the slowly growing forms of sarcoma; that of a hard fibroma presents a dry, glistening appearance, aptly compared to watered silk. The soft variety grows much more rapidly than the hard. In certain fibromas—in those, for example, which grow from the periosteum of the base of the skull and project into the naso-pharynx—the blood vessels are dilated into sinuses and have no proper sheaths; they therefore tend to remain open when divided, and to bleed excessively. Transition forms between soft fibroma and sarcoma are met with, so that in operating for their removal it is safer to take away the capsule along with the tumour, and the patient should be kept under observation in view of the risk of recurrence.

The skin—especially the skin of the buttock—is one of the favourite seats of fibroma, and it may occur in a multiple form. It is met with also in the subcutaneous and intermuscular cellular tissue, and in the abdominal wall, where it sometimes attains considerable dimensions. Various forms of fibroma are met with in the mamma and are described with diseases of that organ. The fibrous overgrowths in the skin, known as keloid and molluscum fibrosum, and those met with in the sheaths of nerves, are described elsewhere. Fibroid tumours of the uterus are described with myoma.

Diffuse fibroma or Fibromatosis, analogous to lipomatosis, is met with in the connective tissue of the skin and sheaths of nerves, and constitutes one form of neuro-fibromatosis; a similar change is also met with in the stomach and colon.

Myxoma.—A myxoma is composed of tissue of a soft gelatinous, semifluid consistence. The pure myxoma is extremely rare, and clinically resembles the lipoma. Myxomatous tissue is, however, frequently found in other connective-tissue tumours as a result of degeneration, for example, in cartilaginous tumours and in sarcomas. Myxomatous tissue is also a prominent constituent of the "innocent parotid tumour." Mucous polypus of the nose, which is often described as a myxoma, is merely a pendulous process of oedematous mucous membrane.



Myeloma.—A myeloma is composed of large multinuclear giant cells surrounded by round and spindle cells. The cut surface of the tumour presents a deep red or maroon colour. While occasionally met with in tendon sheaths and bursae, and is then of an orange-yellow colour, the myeloma occurs most frequently in the cancellous tissue at the ends of the long bones, its favourite site being the upper end of the tibia. Although formerly classified as a sarcoma, it is the exception for it to present malignant features, and it can usually be extirpated by local measures without fear of recurrence. The diagnosis, X-ray appearances, and the method of removal are considered with the diseases of bone. Sometimes the myeloma is met with in multiple form in the skeleton, in association with an unusual form of protein in the urine (Bence Jones).

Myoma.—A myoma is composed of non-striped muscle fibres. A pure myoma is very rare, and is met with in organs possessed of non-striped muscle, such as the stomach, intestine, urinary bladder, and prostate. In the uterus, which is the most common situation, these tumours contain a considerable admixture of fibrous tissue, and are known as fibroids or fibro-myomas. They present on section a fasciculated appearance, which may resemble that of a section of balls of cotton (Fig. 54). They are encapsulated and vascular, frequently attain a large size, and may be single or multiple. While they may occasion neither inconvenience nor suffering, they frequently give rise to profuse haemorrhage from the uterus, and may cause serious symptoms by pressing injuriously on the ureters or the intestine, or by complicating pregnancy and parturition.

The Rhabdomyoma is an extremely rare form of tumour, met with in the kidney, uterus, and testicle. It contains striped muscle fibres, and is supposed to originate from a residue of muscular tissue which has become sequestrated during development.



Glioma.—A glioma is a tumour composed of neuroglia. It is met with exclusively in the central nervous system, retina, and optic nerve. It is a slowly growing, soft, ill-defined tumour, which displaces the adjacent nerve centres and nerve tracts, and is liable to become the seat of haemorrhage and thus to give rise to pressure symptoms resembling apoplexy. The glioma of the retina tends to grow into the vitreous humour and to perforate the globe. It is usually of the nature of a glio-sarcoma and is highly malignant.

Endotheliomas take origin from the endothelium of lymph vessels and blood vessels, and serous cavities. They show great variation in type, partly because of the number of different kinds of endothelium from which they are derived, and partly because the new connective tissue which is formed is liable to undergo transformation into other tissues. They may be soft or hard, solid or cystic, diffuse or circumscribed; they grow very slowly, and are almost always innocent, although recurrence has been occasionally observed. Cases of multiple endotheliomata of the skin have recently been described by Wise.

Angioma, lymphangioma, and neuroma are described with the disease of the individual tissues.

MALIGNANT CONNECTIVE-TISSUE TUMOURS—SARCOMA

The term sarcoma is applied to any connective-tissue tumour which exhibits malignant characters. The essential structural feature is the predominance of the cellular elements over the intercellular substance or stroma, in which respect a sarcoma resembles the connective tissue of the embryo. The typical sarcoma consists chiefly of immature or embryonic connective tissue. It most frequently originates from fascia, intermuscular connective tissue, periosteum, bone-marrow, and skin, and forms a rounded or nodulated tumour which appears to be encapsulated, but the capsule merely consists of the condensed surrounding tissues, and usually contains sarcomatous elements. The consistence of the tumour depends on the nature and amount of the stroma, and on the presence of degenerative changes. The softer medullary forms are composed almost exclusively of cells; while the harder forms—such as the fibro-, chondro-, and osteo-sarcoma—are provided with an abundant stroma and are relatively poor in cells. Degenerative changes may produce areas of softening or liquefaction which result in the formation of cystic cavities in the interior of the tumour. The colour depends on the amount of blood in the tumour, and on the presence of the products of degeneration.

The blood vessels are usually represented by mere chinks or spaces between the cells. This peculiarity accounts for the facility with which haemorrhage takes place into the substance of the tumour, the persistence of the bleeding when it is incised or ulcerates through the skin, and the readiness with which the sarcomatous cells are carried off and infect distant parts through the blood-stream. Sarcomas are devoid of lymphatics, and unless originating in lymphatic structures—for example, in the tonsil—they rarely infect the lymph glands. Minute portions of the tumour grow into the small veins, and, becoming detached, are transported by the blood-current to distant organs, where they are arrested in the capillaries and give rise to secondary growths. These are most frequently situated in the lungs, except when the primary growth lies within the territory of the portal circulation, in which case they occur in the liver. The secondary growths closely resemble the parent tumour. Sarcoma may invade an adjacent vein on such a scale that if the invading portion becomes detached it may constitute a dangerous embolus. This may be observed in sarcoma of the kidney, the growth taking place along the renal vein until it projects into the vena cava.



In its growth, a sarcoma compresses and destroys neighbouring parts, surrounds vessels and nerves, and may lead to destruction of the skin, either by invading it, or more commonly by causing sloughing from pressure. Inflammatory and suppurative changes may take place as a result of pyogenic infection following upon sloughing of the overlying skin or upon an exploratory incision. Once the skin is broken the tumour fungates through the opening. Sarcomas vary in malignancy, especially as regards rapidity of growth and capacity for dissemination. Certain of them, such as the so-called "recurrent fibroid of Paget," grow comparatively slowly, and are only malignant in the sense that they tend to recur locally after removal; others—especially the more cellular ones—grow with extreme rapidity, and are early disseminated throughout the body, resembling in these respects the most malignant forms of cancer. They are usually solitary in the first instance, although primary multiple growths are occasionally met with in the skin and in the bones.

Many varieties of sarcoma are recognised, according to its structural peculiarities. Thus, in virtue of the size and character of the cells, we have the small round-celled and the large round-celled sarcoma, the small and the large spindle-celled, the giant-celled and the mixed-celled sarcoma. The lympho-sarcoma presents a structure similar to that of lymph-follicular tissue, and the alveolar sarcoma an arrangement of cells in alveoli resembling that seen in cancers. When there is a considerable amount of intercellular fibrous tissue, the tumour is called a fibro-sarcoma.



The term lymphangio-sarcoma is applied when the cells of the tumour are derived from the endothelium of lymph spaces and vessels. The angio-sarcomas are those in which blood vessels form a prominent element in the structure of the tumour. They are sometimes derived from innocent angiomas, and they may be so vascular as to pulsate and on auscultation yield a blowing murmur like an aneurysm. The glio-sarcoma, myxo-sarcoma, chondro-sarcoma, and myo-sarcoma are mixed forms which usually develop in pre-existing innocent tumours. The osteo-sarcoma is characterised by the formation in the tumour of bone, the medullary spaces being occupied by sarcomatous cells in place of marrow. The osteoid sarcoma is characterised by the formation of a tissue resembling bone but deficient in lime salts, and the petrifying sarcoma by the formation of calcified areas in the stroma. These varieties, although met with chiefly in the bones, may occur in soft tissues such as muscle, and in such organs as the mamma. The pigmented varieties include the chloroma, which is of a light-green colour, and the melanotic sarcoma, which is brown or black. The psammoma is a sarcoma containing a material resembling sand; it is chiefly met with in the membranes of the brain. The chordoma is a rare form of tumour originating from the remains of the notochord in the region of the spheno-occipital synchondrosis or in the sacro-coccygeal region.

Diagnosis of Sarcoma.—A sarcoma is to be differentiated from an inflammatory swelling such as results from tubercle, actinomycosis, or syphilis, from an innocent tumour, and from a cancer. The points on which the diagnosis is founded are discussed with the different tissues and organs.

Treatment.—The removal of the tumour by operation is the most reliable method of treatment; in order to be successful it must be undertaken before dissemination has taken place, and a considerable area of healthy tissue beyond the apparent margin of the growth must be removed, and in tumours near the surface of the body, the overlying skin also.

In order to prevent recurrence, a tube of radium, to which a silk thread is attached, is inserted into the space from which the tumour was removed; the thread is brought out at the drain-opening, and at the end of a week or ten days the tube of radium is removed by pulling on the thread. Radium causes a reaction in the tissues attended with exudation from the vessels, for the escape of which provision must be made. If radium is not available, the affected area is repeatedly exposed to the action of the X-rays as soon as the wound has healed. The employment of these measures has diminished to a remarkable degree the recurrence of sarcoma after operation.

It will readily be understood that the less thoroughly or radically the growth has been removed, the more do we depend upon radium or the X-rays for bringing about a permanent cure, and that in advanced cases of sarcoma and in cases in which, on account of their anatomical situation, removal by operation is necessarily incomplete, the prospect of cure is still more dependent on the use of radium or of the X-rays. Finally, there are cases in which removal by operation is impossible, the so-called inoperable sarcoma; a tube of radium, to which a silk thread is attached, is inserted into the substance of the tumour, either through an opening made by a large trocar, or, when necessary, by open dissection. A second tube of radium is placed upon the skin over the tumour and is secured there by a stitch or by a strip of plaster, thus securing a cross-fire action of the radium rays, both from within and without, as this is found to be much more efficacious in destroying or inhibiting the cellular elements of the growth. The tubes of radium are left in situ for from eight to fourteen days, according to the power of the radium employed, but are moved about every second day or so in order that every part of the tumour may be efficiently radiated. If the tumour shrinks in size after the use of radium and becomes operable, it should be removed before time is given it to resume its growth. It will depend upon the subsequent course of the disease, whether or not a second, or it may be even a third, application of radium will be required.

Where neither radium nor X-rays is available or applicable, recourse may be had to the injection of Coley's fluid, a preparation containing the mixed toxins of the streptococcus of erysipelas and the bacillus prodigiosus; or of selenium.

EPITHELIAL TUMOURS

An excessive and erratic growth of epithelium is the essential and distinguishing feature of these tumours. The innocent forms are the papilloma and the adenoma; the malignant, the carcinoma or cancer.

Papilloma.—A papilloma is a tumour which projects from a cutaneous or mucous surface, and consists of a central axis of vascular fibrous tissue with a covering of epithelium resembling that of the surface from which the tumour grows. In the papillomas of the skin—commonly known as warts—the covering consists of epidermis; in those growing from mucous surfaces it consists of the epithelium covering the mucous membrane. When the surface epithelium projects as filiform processes, the tumour is called a villous papilloma, the best-known example of which is met with in the urinary bladder. Papillomatous growths are also met with in the larynx, in the ducts of the breast, and in the interior of certain cystic tumours of the breast and of the ovary. Although papillomas are primarily innocent, they may become the starting-point of cancer, especially in persons past middle life and if the papilloma has been subjected to irritation and has ulcerated. The clinical features and treatment of the various forms of papilloma are considered with the individual tissues and organs.

Adenoma.—An adenoma is a tumour constructed on the type of, and growing in connection with, a secreting gland. In the substance of such glands as the mamma, parotid, thyreoid, and prostate, adenomas are met with as encapsulated tumours. When they originate from the glands of the skin or of a mucous membrane, they tend to project from the surface, and form pedunculated tumours or polypi.

Adenomas may be single or multiple, and they vary greatly in size. The tumour is seldom composed entirely of gland tissue; it usually contains a considerable proportion of fibrous tissue, and is then called a fibro-adenoma. When it contains myxomatous tissue it is called a myxo-adenoma, and when the gland spaces of the tumour become distended with accumulated secretion, a cystic adenoma, the best examples of which are met with in the mamma and ovary. A characteristic feature of the cystic variety is the tendency the tumour tissue exhibits to project into the interior of the cysts, constituting what are known as intracystic growths. They are essentially innocent, but intracystic growths, especially in the mamma of women over fifty, should be regarded with suspicion and therefore should be removed on radical lines. Transition forms between adenoma and carcinoma are also met with in the rectum and large intestine, and these should be treated on the same lines as cancer.

CARCINOMA OR CANCER

A cancer is a malignant tumour which originates in epithelium. The cancer cells are derived by proliferation from already existing epithelium, and they invade the sub-epithelial connective tissue in the form of simple or branching columns. These columns are enclosed in spaces—termed alveoli—which are probably dilated lymph spaces, and which communicate freely with the lymph vessels. The cells composing the columns and filling the alveoli vary with the character of the epithelium in which the cancer originates. The malignancy of cancer depends on the tendency which the epithelium has of invading the tissues in its neighbourhood, and on the capacity of the cells, when transported elsewhere by the lymph or blood-stream, of giving rise to secondary growths.

Cancer may arise on any surface covered by epithelium or in any of the secreting glands of the body, but it is much more common in some situations than in others. It is frequently met with, for example, in the skin, in the stomach and large intestine, in the breast, the uterus, and the external genitals; less frequently in the gall-bladder, larynx, thyreoid, prostate, and urinary bladder.

Tissues appear to be most liable to cancer when, having attained maturity, they enter upon the phase of decadence or involution, and this phase is reached by different tissues at different periods. It is not so much, therefore, the age of the person in whom it occurs, as the age of the tissue in which it arises, that determines the maximum incidence of cancer. Cancer of the stomach appears and attains a maximum frequency earlier than cancer of the skin; cancer of the uterus and mamma is more frequent towards the decline of reproductive activity than in the later years of life; rectal cancer is not infrequently met with during the second and third decades. There is evidence that the irritation caused by alcohol and tobacco plays a part in the causation of cancer, in the fact that a large proportion of those who become the subjects of cancer of the mouth are excessive drinkers and smokers.

A cancer may appear as a papillary growth on a mucous or a skin surface, as a nodule in the substance of an organ, or as a diffuse thickening of a tubular organ such as the stomach or intestine. The absence of definition in cancerous tumours explains the difficulty of completely removing them by surgical measures, and has led to the practice of complete extirpation of cancerous organs wherever this is possible. The boundaries of the affected organ, moreover, are frequently transgressed by the disease, and the epithelial infiltration implicates the surrounding parts. In cancer of the breast, for example, the disease often extends to the adjacent skin, fat, and muscle; in cancer of the lip or tongue, to the mandible; in cancer of the uterus or intestine, to the investing peritoneum.

In addition to its tendency to infiltrate adjacent tissues and organs, cancer is also liable to give rise to secondary growths. These are most often met with in the nearest lymph glands; those in the neck, for example, becoming infected from cancer of the lip, tongue, or throat; those in the axilla, from cancer of the breast; those along the curvatures of the stomach, from cancer of the pylorus; and those in the groin, from cancer of the external genitals. In lymph vessels the cancer cells may merely accumulate so as to fill the lumen and form indurated cords, or they may proliferate and give rise to secondary nodules along the course of the vessels. When the lymphatic network in the skin is diffusely infected, the appearance is either that of a multitude of secondary nodules or of a diffuse thickening, so that the skin comes to resemble coarse leather. On the wall of the chest this condition is known as cancer en cuirasse. Although the cancer cells constantly attack the walls of the adjacent veins and spread into their interior at a comparatively early period, secondary growths due to dissemination by the blood-stream rarely show themselves clinically until late in the course of the disease. It is probable that many of the cancer cells which are carried away in the blood or lymph stream undergo necrosis and fail to give rise to secondary growths. Secondary growths present a faithful reproduction of the structure of the primary tumour. Apart from the lymph glands, the chief seats of secondary growths are the liver, lungs, serous membranes, and bone marrow.

It is generally believed that the secondary growths in cancer that develop at a distance from the primary tumour, those, for example, in the medullary canal of the femur or in the diploe of the skull occurring in advanced cases of cancer of the breast, are the result of dissemination of cancer cells by way of the blood-stream and are to be regarded as emboli. Sampson Handley disagrees with this view; he believes that the dissemination is accomplished in a more subtle way, namely, by the actual growth of cancer cells along the finer vessels of the lymph plexuses that ramify in the deep fascia, a method of spread which he calls permeation. It is maintained also that permeation occurs as readily against the lymph stream as with it. He compares the spread of cancer to that of an invisible annular ringworm. The growing edge extends in a wider and wider circle, within which a healing process may occur, so that the area of permeation is a ring, rather than a disc. Healing occurs by a process of "peri-lymphatic fibrosis," but as the natural process of healing may fail at isolated points, nodules of cancer appear, which, although apparently separate from the primary growth, have developed in continuity with it, peri-lymphatic fibrosis having destroyed the cancer chain connecting the nodule with the primary growth. This centrifugal spread of cancer is clearly seen in the distribution of the subcutaneous secondary nodules so frequently met with in the late stages of mammary cancer. The area within which the secondary nodules occur is a circle of continually increasing diameter with the primary growth in the centre.

In the rare cases in which the skin of the greater part of the body is affected, the nodules rarely appear below the level of the deltoid or the middle third of the thigh, the patient dying before the spread can reach the distal portions of the limbs.

Handley argues against the embolic origin of the metastases in the bones because of the rarity of these in the bones of the distal parts of the limbs, because of the fact that secondary cancer of the femur nearly always commences in the upper third of the shaft, which harmonises with the intimate connection of the deep fascia with the periosteum over the great trochanter, thus favouring invasion of the bone marrow when permeation has spread thus far. He claims support for the permeation theory from the fact that the humerus is rarely involved below the insertion of the deltoid, and that spontaneous fracture of the femur is three times more common on the side on which the breast cancer is situated.

The tumour tissue may undergo necrosis, and when the overlying skin or mucous membrane gives way an ulcer is formed. The margins of a cancerous ulcer (Fig. 57) are made up of tumour tissue which has not broken down. Usually they are irregular, nodularly thickened or indurated; sometimes they are raised and crater-like. The floor of the ulcer is smooth and glazed, or occupied by necrosed tissue, and the discharge is watery and blood-stained, and as a result of putrefactive changes may become offensive. Haemorrhage is rarely a prominent feature, but discharge of blood may constitute a symptom of considerable diagnostic importance in cancer of internal organs such as the rectum, the bladder, or the uterus.



The Contagiousness of Cancer.—A limited number of cases are on record in which a cancer appears to have been transferred by contact, as from the lower to the upper lip, from one labium majus to the other, from the tongue to the cheek, and from one vocal cord to the other; these being all examples of cancer involving surfaces which are constantly or frequently in contact. The transference of cancer from one human being to another, whether by accident, as in the case of a surgeon wounding his finger while operating for cancer, or by the deliberate introduction of a portion of cancerous tumour into the tissues, has never been known to occur. It is by no means infrequent, however, that when recurrence takes place after an operation for the removal of cancer, the recurrent nodules make their appearance in the main scar or in the scars of stitches in its neighbourhood. In the lower animals the grafting of cancer only succeeds in animals of the same species; for example, a cancer taken from a mouse will not grow in the tissues of a rat, but only in a mouse of the same variety as that from which the graft was taken.

While cancer cannot be regarded as either contagious or infectious, it is important to bear in mind the possibility of infection of a wound with cancer when operating for the disease. A cancer should not be cut into unless this is essential for purposes of diagnosis, and the wound made for exploration should be tightly closed by stitches before the curative operation is proceeded with; the instruments used for the exploration must not be used again until they have been boiled. The greatest care should be taken that a cancer which has softened or broken down is not opened into during the operation.

Investigations regarding the cause of cancer have been prosecuted with great energy during recent years, but as yet without positive result. It is recognised that there are a number of conditions which favour the development of cancer, such as prolonged irritation, and a considerable number of cases have been recorded in which cancer of the skin of the hands has followed prolonged and repeated exposure to the Rontgen rays.

The Alleged Increase of Cancer.—Regarding the alleged increase of cancer, it may be pointed out that it is impossible to ascertain how much of the apparent increase is due to more accurate diagnosis and improved registration. It is probable also that some increase has taken place in consequence of the increased average duration of life; a larger proportion of persons now reach the age at which cancer is frequent.

The prognosis largely depends on the variety of cancer and on its situation. Certain varieties—such as the atrophic cancer of the breast which occurs in old people, and some forms of cancer in the rectum—are so indolent in their progress that they can scarcely be said to shorten life; while others—such as the softer varieties of mammary cancer occurring in young women—are among the most malignant of tumours. The mode in which cancer causes death depends to a large extent upon its situation. In the gullet, for example, it usually causes death by starvation; in the larynx or thyreoid, by suffocation; in the intestine, by obstruction of the bowels; in the uterus, prostate, and bladder, by haemorrhage or by implication of the ureters and kidneys. Independently of their situation, however, cancers frequently cause death by giving rise to a progressive impairment of health known as the cancerous cachexia, a condition which is due to the continued absorption of poisonous products from the tumour. The patient loses appetite, becomes emaciated, pale, and feverish, and gradually loses strength until he dies. In many cases, especially those in which ulceration has occurred, the addition of pyogenic infection may also be concerned in the failure of health.

Treatment.—Removal by surgical means affords the best prospect of cure. If carcinomatous disease is to be rooted out, its mode of spread by means of the lymph vessels must be borne in mind, and as this occurs at an early stage, and is not evident on examination, a wide area must be included in the operation. The organ from which the original growth springs should, if practicable, be altogether removed, because its lymph vessels generally communicate freely with each other, and secondary deposits have probably already taken place in various parts of it. In addition, the nearest chain of lymph glands must also be removed, even though they may not be noticeably enlarged, and in some cases—in cancer of the breast, for example—the intervening lymph vessels should be removed at the same time.

The treatment of cancer by other than operative methods has received a great deal of attention within recent years, and many agents have been put to the test, e.g. colloidal suspensions of selenium, but without any positive results. Most benefit has resulted from the use of radium and of the X-rays, and one or other should be employed as a routine measure after every operation for cancer.

It has been demonstrated that cancer cells are more sensitive to radium and to the Rontgen rays than the normal cells of the body, and are more easily killed. The effect varies a good deal with the nature and seat of the tumour. In rodent cancers of the skin, for example, both radium and X-ray treatment are very successful, and are to be preferred to operation because they yield a better cosmetic result. While small epitheliomas of the skin may be cured by means of the rays, they are not so amenable as rodent cancers.

Cancers of mucous membranes are less amenable to ray treatment because they are less circumscribed and are difficult of access. In cancers under the skin, the Rontgen rays are less efficient; if radium is employed, the tube containing it should be inserted into the substance of the tumour after the method described in connection with sarcoma—and another tube should be placed on the overlying skin.

In the employment of X-rays and of radium in the treatment of cancer, experience is required, not only to obtain the maximum effect of the rays, but to avoid damage to the adjacent and overlying tissues.

Ray treatment is not to be looked upon as a rival but as a powerful supplement to the operative treatment of cancer.

VARIETIES OF CANCER

The varieties of cancer are distinguished according to the character and arrangement of the epithelial cells.

The squamous epithelial cancer or epithelioma originates from a surface covered by squamous epithelium, such as the skin, or the mucous membrane of the mouth, gullet, or larynx. The cancer cells retain the characters of squamous epithelium, and, being confined within the lymph spaces of the sub-epithelial connective tissue, become compressed and undergo a horny change. This results in the formation of concentrically laminated masses known as cell nests.

The clinical features are those of a slowly growing indurated tumour, which nearly always ulcerates; there is a characteristic induration of the edges and floor of the ulcer, and its surface is often covered with warty or cauliflower-like outgrowths (Fig. 58). The infection of the lymph glands is early and constant, and constitutes the most dangerous feature of the disease; the secondary growths in the glands exhibit the characteristic induration, and may themselves break down and lead to the formation of ulcers.



Epithelioma frequently originates in long-standing ulcers or sinuses, and in scars, and probably results from the displacement and sequestration of epithelial cells during the process of cicatrisation.

The columnar epithelial cancer or columnar epithelioma originates in mucous membranes covered with columnar epithelium, and is chiefly met with in the stomach and intestine. As it resembles an adenoma in structure it is sometimes described as a malignant adenoma. Its malignancy is shown by the proliferating epithelium invading the other coats of the stomach or intestine, and by the development of secondary growths.

Glandular carcinoma originates in organs such as the breast, and in the glands of mucous membranes and skin. The epithelial cells are not arranged on any definite plan, but are closely packed in irregularly shaped alveoli. If the alveoli are large and the intervening stroma is scanty and delicate, the tumour is soft and brain-like, and is described as a medullary or encephaloid cancer. If the alveoli are small and the intervening stroma is abundant and composed of dense fibrous tissue, the tumour is hard, and is known as a scirrhous cancer—a form which is most frequently met with in the breast. If the cells undergo degeneration and absorption and the stroma contracts, the tumour becomes still harder, and tends to shrink and to draw in the surrounding parts, leading, in the breast, to retraction of the nipple and overlying skin, and in the stomach and colon to narrowing of the lumen. When the cells of the tumour undergo colloid degeneration, a colloid cancer results; if the degeneration is complete, as may occur in the breast, the malignancy is thereby greatly diminished; if only partial, as is more common in rectal cancer, the malignancy is not appreciably affected. Melanin pigment is formed in relation to the cells and stroma of certain epithelial tumours, giving rise to melanotic cancer, one of the most malignant of all new growths. Cyst-like spaces may form in the tumour by the accumulation of the secretion of the epithelial cells, or as a result of their degeneration—cystic carcinoma. This is met with chiefly in the breast and ovary, and the tumour resembles the cystic adenoma, but it tends to infect its surroundings and gives rise to secondary growths.