VIII. Summary The type of fungus infection of the extremities known as mycetoma is comparatively rare in North America. It is relatively more common in the tropics and sub-tropics then in the temperate zone, and apparently more common in semi arid regions than elsewhere. The majority of the reported cases have occurred among Mexicans (probably Indians). Its onset may occur at any age period, though it is most common between the ages of twenty and thirty. The occurrence of a case in a woman is very unusual. Most of the cases are laborers by occupation, and of these the majority are engaged in agricultural pursuits. The other cases regardless of occupation, appear to have lead quite active lives out of doors. The extent to which the patients habitually went barefooted is very striking. Associated with habitual barefootedness, a large proportion of patients received injuries to the affected foot, either of the nature of contusions or incisions, before the onset of the disease. Presumptively the trauma either inoculated the fungus into the subcutaneous tissues or otherwise favored invasion. Usually the earliest sign of invasion consists in the appearance of one or more fungating nodules on the skin, sometimes at the site of the previous trauma, which sooner or later are crowned with a discharging sinus. Early swelling of the foot is another common symptom, at first local and later general, which may or may not be painful. Less frequently the first symptoms may be variously (1) the formation of vesicles, or (2) an abscess, or (3) a pigmentation of the skin. In all except one case the feet were the site of invasion, the left foot being more commonly attacked than the right. In one instance both feet were involved. The hand was only involved once. The disease tends to run a slowly progressive course extending over a considerable period of years (as long as sixteen years) with apparently no tendency to self limitation, though but slight spread beyond the affected extremity is noted. The affected member may be swollen to several times the normal size, which may seriously interfere with locomotion. There is an absence of any definite systemic reaction. Marked weakness associated with emaciation is common. Over the skin of the invaded area are invariably present a variable number of discharging sinuses. If nodules are present the sinuses open on the nodule summits. Nodules are not invariably present, and there is some suggestion that their presence or absence varies with the causative organism. From the sinuses is discharged a scanty volume of a thin sero-sanguinolent fluid, in which may be occasionally noted the characteristic granules. The nodules are most in evidence on the dorsum of the foot and may either be discrete or confluent. The activity of any given sinus is apparently of rather short duration, and where nodules exist, their formation precedes the appearance of a sinus. Internally, there is very extensive disorganization of all the tissues of the invaded area. Fatty tissue disappears and the muscles disintegrate. There is a marked hyperplasia of dense connective tissue which tends to undergo an early hyaline degeneration which may account for the purplish color quite characteristic of the invaded areas. The invaded area is penetrated in every direction by fistulous channels or sinuses, which open externally through the nodules noted. These sinuses are lined by granulation tissue infiltrated with round cells and in their lumen may be found either necrotic debris, serous fluid, extravasated blood and a varying number of the characteristic granules which usually lie in cavernous expansions in the sinus. These sinuses may extend to the bones and granules may lie in excavations in the bony tissue. The bones of the invaded area undergo a rarifying and hyperplastic osteitis and may become very spongy. Joint involvement is apparently rare. The process appears to show a tendency to spread along fascial planes. Histologically, the most characteristic feature appears to be the proliferation of fibroblasts, either with the granulation tissue which lines the sinuses and which tends constantly to effect their closure, or independantly of the granulation tissue. There is but a limited accumulation of polymorphonuclear leucocytes, which are chiefly found in the immediate vicinity of a granule. No evidence of phagocytosis of the fungus by any type of cell was noted. Round or oval multinucleated giant cells are common. Russell's bodies are frequently seen. The changes in the skin are solely secondary to those taking place within the foot. The development of a nodule appears to be due to the internal pressure in the subcutaneous tissues produced by an extending sinus. The skin does not present any change of note. The extensive production of granulation tissue is responsible for the frequency with which blood appears in the discharge from a sinus, as well as the evidences of a past and recent hemorrhage into the tissues. The granules are dense circumscribed colonies of the causative organism, which was not found apart from these aggregations. They are visible to the naked eye, and may vary from black, to white or pale ocher in color. The light colored grains are soft in consistency. According to the type of fungus producing the grains, the North American cases may be divided into three groups. The first group includes but a single case. This is the sole case in which the granules were black in color and from which were cultivated a hyphomycete probably identical with Madurella mycetoma, Laveran, a recognized cause of black grained mycetoma in India, Africa and Italy. The tissue reaction in this case differed from that presented by the other cases. In addition to the hyperplasia of dense connective tissue, there was an abundance of a peculiar type of giant cell, frequently in contact with the granule, a proliferation of endothelial cells so that tubercle like structures were formed and very little...