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From THE JOURNAL OF EXPERIMENTAL MEDICINE Vol. I, No. 4, 1896 ^ pi'J'F Vt^^fi'W*;^ "T^^ vs-gjp^?* TWO CASES OF SAKCOMATOSIS WITH PURPURA HiEMORRHAGICA By C. F. MAETIN, M. D., AND W. F. HAMILTON, M.D, (From the Pathological Laboratory, Royal Victoria Hospital, Montreal.) PLATE8 XXI, XXn, AND XXIII. Cases of sarcoma in which purpura hsemorrhagica has been pres- ent as a concurrent condition are comparatively rare. The volumes at our disposal contain references on the subject only by Hilton Fagge* and Railton.f According to the latter author, the subject has also been studied by Kingsford and Anderson, though we could obtain no evidence of their work in the literature. Fagge, in an interesting article published more than fifteen years 50, gives six records taken from the Gm/s Hospital Rejpm'ts. In these cases purpura and sarcomatous tumours were coincident, so far as macroscopic appearances and clinical observations could verify the conditions. In four of the cases, however, no microscopic examina- tion was made, while in the two remaining instances the pathological reports and microscopic examinations are, to say the least, unsatis- factory. The most interesting of all thciae is perhaps Case I, in which the purpura was present about the chest and abdomen, the hsemorrhagic infiltration appearing in the form of narrow rings surrounding round, elevated, aard nodules, the conditions being evidently identical with those found in our second case. There were also the same tendency of the cells to infiltrate the adipose tissue and the same visceral haem- orrhages. The main growth, which began in the ileum, was made up of small round cells. * Hilton Fagge, Ouy''8 Hospital Reports, vol. xxv. t Bailton, British Medical Journal, May 18, 1895. COFTBIOBT, 1896, BT D. APPLBTON AND COMPANT. 2 Two Cases 0/ Sarcomatosis with Purpura Hmmorrlmgica In three of the other cases there were no nodules in the skin. In one instance in which no autopsy was obtained the multiple growths in the skin and glands appeared as flattened thickenings in the brownish-stained skin. The purpura seems to have formed chiefly around the hair follicles. In the last case of all, where no micro- scopic examination was made, the skin presented many swellings, which on section seemed to contain merely fibrin and blood. Out of all six cases, then, a microscopic examination of the skin was made in but one instance, and even in this no report of the con- dition of the vessels is recorded. In his concluding remarks the au- thor suggests the possibility that the prevalence of purpura having been first noted in these cases, the hospital records of instances of so-called Werlhofs's disease may in reality refer to conditions of sar- comatous origin, the primary growth, perhaps, remaining obscured in the medulla of the bones or elsewhere. From the fact, however, that in three of his cases the onset was ushered in with a chill, and that there had been a previous exposure to wet, Fagge regards this factor as a possible direct cause of sarcoma, in which case the multi- ple tumours would have to be considered not as metastases, but rather as a uniform development of numerous growths, each in itself pri- mary. Fagge advances sevonil i)ossible explanations of the relationship between sarcoma and purpura. The first, as has been already indi- cated, supposes that a minute development of sarcomatous tissue, with vessels made up of embryonic cells, takes place at each eft'used spot, apart from any infection or appearance of metastases, and that the conditions are somewhat analogous to those which occur in mol- luscum fibrosum. The second explanation is based upon the embolic theory, the sarcoma cells reaching the capillary vessels. Thirdly, Fagge deems it not impossible that the condition of cachexia, with its altered blood state, which is of frequent occurrence in sarcoma, might of itself suffice to produce the purpuric condition, the sequence of events being analogous to that which characterizes the grave anae- mias. In the case recorded by Railton the skin of the head was mainly . C. F. Martin and W. F. Hamilton 3 affected, large sarcomatous nodules existing in this region, with li£emorrhages in tlieir immediate vicinity. There were elsewhere no cutaneous effusions. The liver and retroperitoneal glands were the only organs showing sarcomatous infiltration. The cases which have come under our notice are as follov/s: Cask 1. — Janet JL. ajiod tliirty-fivo years, was admitted to Prof. James Stewart's wards in the Hoyal N'ietoria Hospital on May ii, 1895, complain- ing of anorexia, great thirst, which had existed for one week previously, with pain in the epigastrium, increased by pressure. For the past two months she had been losing flesh. Two days prior to admission she ob- served a discoloured patch on the right forearm about the size of a twenty- five-cent piece, and had also some bleeding from the gums. On the fol- lowing day she vomited a cupful of dark-coloured bloody fluid; the bleed- ing from the gums continued, and further areas of subcutaneous hfem- orrhage appeared; these rapidly increased in size and number up to the day of admission. Slie was a Canadian, with previous good health, and accustomed to good diet. There was a family history of tuberculosis. Menstruation had always been regular an unaccompanied with pain. Cuiiditioii (III Admiftsidii. — The patient was stout and powerfully built, ahliongh rather anaemic; the gums were somewhat swollen and ha^mor- rluigic; the tongue was coated and fissured, and showed hemorrhages upon the dorsum. Nimierous subcutaneous hasniorrhages of various sizes existed over all parts of the body. Some were bright red, others brown- ish; whereas many were diffuse, extensive, irregular, and not elevated, others were smaller, firmer, distinctly nodular on deep pressure, and pain- ful. There was no evidence of glandular enlargement. The teeth were loosened in the alveolar processes, with blood oozing about them. The breath was foul, the appetite poor, and there was great thirst. No evidence of abdominal pain or tenderness. The liver and spleen were apparently normal in size. The urine was very acid (specific gravity 1017), and contained some albumin, a few casts, and a heavy de- posit of amorphous urates and uric-acid crystals. Blood examination showed 3.300,000 red corpuscles; moderate leuco- cytosis, with forty-five per cent of haemoglobin. In stained preparations there were present a few eosinophiles and free eosinophilous granules. The siibsequent history was that of rapid failure up to death, which occurred within ten days. During this period the patient vomited sev- 4 2\oo Cases of iSanwnatosls ^oith Purparn ILvmoi'rhagica eral times, losing in all more than three pints of a grumous bloody fluid. An ascaris lumbricoides was present in one vomitus. The diagnosis was reserved; scurvy was suspected. Autopsy (Performed three hours and a half after death; notes by Prof. Adami). — The body was that of a stout, broadly built adult woman, 18G centimetres long, nearly 50 centimetres across the hips. The face approached the negro type, and the complexion was swarthy. Gums ancemic, slightly swollen around the bases of the teeth, and pre- senting here a fine line of exiided blood. The upper and lower in- cisors and bicuspids loose. A small, deep haemorrhage in the lobe of the left ear. Numerous punctiform petechiae upon the neck. Ou the arms the skin was discoloured in patches, some areas measuriiig as much as 10.5 centimetres ir diameter. These patches were irregu- larly distributed over the arms, but showed no elevations whatever. In both axillary regions there were clusters of petechise. On the trimk there were very many punctate hannorrh ges, forming a zone around the body above the umbilicus. There were no signs of haem- orrhage in the exposed mucous membranes of the vagina. The legs were affected similarly to the arms. In some places the haemorrhages existed definitely at the roots of the hairs, while in other places there seemed to be no relation between the purpuric spots and the hair folli- cles. Ahdomhial Cavitij. — !Massive panniculus, nearly 8 centimetres thick; very numerous petechise in the parietal peritonaeum. The omentum large and fatty, and presenting numerous small haemor- rhages in its substance. The serous coat of the intestine and the appendices epiploicae showed multiple punctate ecchymoses. There were about 20 cubic centimetres of turbid, faintly blood-stained fluid in the abdominal cavity. SpUen. — Very large and heavy, measuring 18.3 X 11 X 4 centi- metres, and weighing 630 grammes. The edges were rounded and without notches. It was firm to the feel, and the surface pre- sented a coarsely mottled appearance, with distinct yellowish areas not projecting from the deep red groundwork of splenic substance. These areas varied in size up to that of a split pea, and Avere not well C. F. Martin and W. F. Hamilton circumscribed. On section the organ was very firm, presenting throughout its substance the same ycliovvish areas of new tissue, Hilum normal. Kidneys. — The right kidney slightly enlarged; the easily peeled- off capsule revealed a pale-yellow smooth surface, upon which could be seen a few small grayish-yellow nodules, resembling those in the spleen. On section it presented evidence of much fatty change, and a few minute new growths were distributed throughout the cortex. The pelvis and ureters were normal. The left kidney resembU >l the right. RhuUhr. — Mucosa pale; upon it were numerous rounded, slightly projecting masses about 1 millimetre in diameter, around which there were punctate heemorrhages. Vayina. — Normal and without ecchymoses. Uterus and Adiuuiu. — Enlarged; the wall greatly thickened and for the most part firm, though posteriorly there could be seen softer areas. The cervical portion especially enlarged, owing to the presence of a new growth, which appeared as a large rounded infiltrating mass, chiefly on the posterior portion. The mass was not sharply limited on all sides, but was continuous with tissue of a similar character in the body of the uterus itself. There were a few minute cysts centrally situated. The growth measured about 8 or 9 centimetres in its great- est diameter, and projected backward and somewhat upward, so that its superior part lay behind the body of the uterus itself. It was fairly firm on section, and free from juice. From the posterior por- tion of the fundus there was given off a firm pedunculated, subserous fibroid tumour, slightly lobulated, the greatest diameter of which measured 3.5 centimetres. The right Fallopian tube was slightly enlarged, and was partially bound down by a few adhesions to the surrounding tissues. The fim- briated extremity was free. The right ovary was much enlarged, and contained a cyst 6 centimetres in diameter, with delicate trans- parent walls and thin, greenish mucoid contents. The solid tissue remaining was dense and uniform, measuring about 2.5 centimetres in thickness. The left tube was tortuous from old adhesions and en- 6 Tvjo Canes of SnrconiatoaiH with J*urj»tr/eeu measured 14x10x4 centimetres; weight, 340 grammes; large, smooth, of a uniform bluish-red colour, fairly soft on section, with apparent increase of pulp. ^NEalpighian bodies indistinct. T/te I'idneys gave evidence of an acute nephritis, with engorge- ment of the medullary vessels. Beneath the mucosa of the pelvis and some of the calices of the left kidney there was some diffuse recent hsemorrhage. In the right kidney there was moderate hydro- nephrosis, some thickening of the ureter and narrowing of its lumen halfway down to the bladder. The Madder showed a pale mucosa, with two or three punctifonn hasmorrhnges beneath it. T/te liver was small and somewhat friable; its colour brownish. C. F. Martin and W. F. Hamilton 11 t The ufen/s was of abont normal size; walls firm, especially at the cei'vix. Tubes apparently normal. T/ie ovaricfi were both converted into large more or less solid tinnours; the left, which was reniform, measured 9x5x4 centi- metres; it was in the main solid, though fluctuating in parts. The surface, though somewliat nodular, was smooth and glistening, and presented some STibperitoncal haemorrhages. On section the solid part was homogeneous, free from juices, and contained a few minute haem- orrhages. The fluctuating mass contained a clear, thin fluid. The right mass was slightly more rounded and larger; it Aveighed 60 grammes. It was more fluctiiating than the left, owing to the pres- ence of smooth-walled cysts and caA'ities containing hoBmorrhagic detritus, as well as other degenerated material. The vessels in the neighbourhood appeared free, and there was elsewhere no evidence of abnormality in the pelvic organs. Thoracic Cavity. — In both pleural cavities there were about 100 cubic centimetres of a thin, turbid, reddish-brown fluid. On removal of the sternum, the lungs retracted in part only, being held fixed by loose adhesions at apex and base and by firmer adhesions in the cen- tral portions. Tbe left lung showed, in addition to moderate oedema and anthracosis, some minute recent hoemorrhages into its substance; the larger blood vessels were free, the bronchi reddened. The right lung was similar in general character to the left, the haemorrhages being likewise minute, and distributed more at the base than at the apex. Th<- IL'nii. — The iiericardial cavity contained about 30 cubic centimetres of clear yellow serum. The surface was smooth and glis- tening. Beneath the visceral pericardium and over different areas of the heart there wore numerous haemorrhagic patches of a bright- red colour, none of them appearing old or of long duration; these were distributed most markedly over the left ventricle, almost cover- ing its entire surface. In the various chambers of the heart there was a small quantity of blood. The various orifices and valves were normal. Beneath the endocardium of both the right and left sides of the heart there were likewise haemorrhages of small size, and within \'2 Two Cases of SafComatosls with J'lirjmra IIa'mo7'7'/uujica the heart muscle interstitial eccliymoscs. There was early atheroma of the aorta. The jieribronohial glands were normal. 2/ic hraln was free from haemorrhages, and showed no abnor- mality beyond some congestion. The thyroid (jluml showed bilateral enlargement with colloid degeneration, but no luemorrhages. The remaining organs of the neck were normal. Cultures on glycerin agar from the heart's blood, spleen, and ii/er remained sterile. Microscopic Examination. — The orarhi/i tumours -pYesenied the characteristics of small-spindle-celled sarcomata, with a generous ad- mixture of small round cells. There were large, irregular patches of haemorrhage and great engorgement of the veins. A considerable amount of myxomatous change had supervened, while in other parts a kind of hyaline degeneration was apparent. The blood vessels, and especially the arteries, were in many cases seen to be packed with small spindle cells, even in directly transverse sections of the vessels. 27ie lymphatic ylands in the region of the stomach and pancreas had but little of their lymphoid structure left, the specimens show- ■ng great infiltration, with small spindle cells arranged in the maimer usual in sarcomatous growths. The spleen showed great congestion; the Malpighian bodies were not very distinct, and the fibrous tissue was about normal in amount. There was no sign of new growth, nor evidence of haemorrhage. The kidneys were congested; the glomeruli apparently normal; the convoluted tubules in some cases showed cloudy swelling, in others advanced degeneration. In the sections cut there was no evidence of hajmorrhage. The Stomach. — Sections cut through the haemorrhagic portion showed both old and recent pigment. In the neighbourhood of some of the haemorrhages there was distinct evidence of necrosis in the mucosa, submucosa, and muscular coat. There was, in addition, a small amount of cellular infiltration, with great congestion of the submucosa. The vessels of the stomach, and especially the arteries, showed in many places the lumina filled with spindle cells. In some C. F. Martin and W. F. Hamilton IS of them, cut transversely, blood-corpuscles and numerous spindle cells were irregularly intermingled. From the large number of these cells, and from the fact that they were massed together to such an extent as in many cases to occlude compL: ■^'" *he lumen, it is hardly likely that they were endothelial cells; ana, noreover, their outlines presented the characters of young connective-tissue cells rather than those of endothelial cells. (Plate XXIII, Figs. 5 and 6.) The small inteatine showed great congestion and haemorrhages of moderate degree, with superficial necrosis of the mucosa; in addition, a considerable amount of small round-celled infiltration was apparent between the glandular structures. The liver showed brown atrophy of the cells, but no evidence of haemorrhages. In certain irregular areas in the periphery of the lobule there was a moderate amount of small-round-celled infiltration. None of the vessels contained emboli. Heart Mnscle. — In the subpericardial fat there was a large amount of recently extravasated blood, and there was also very much cellular infiltration, the cells infiltrating the tissues between the fat globules and being closely packed together. In many places the haemorrhage and the cellular infiltration existed side by side. Within the heart substance there were many patches of recent haemorrhage, with slight necrosis of the muscle fibres. In the vessels there were many spindle cells, while outside the adventitia of many arteries there were fairly large collections of small spindle cells closely packed together. The lungs showed in some parts thin septa, whereas in other por- tions the meshes of tissue composing the septa were widely separated, apparently from oedema. There was but little cellular exudate in the alveoli, but here and there many patches of haemorrhage were apparent. Tlie blood vessels in the neighbourhood did not present very much abnormality, though in some of the arteries could be seen collections of small spindle cells, the signs here being apparently merely those of a desquamative angeiitis. The Sl'ln. — Sections were taken not only from parts distinctly nodular in appearance, but also from the more diffuse haemorrhages. In the nodular haemorrhagic portions the epidermis and papillae were 14 Two Canes of' Sarcotnatosis with Purpura HcBmorrhagioa fairly well marked in some places, while in others there was distinct flattening of the papillse. The subcutaneous tissue seemed thickened, the meshes being in some portions widely separated, as though from oedema. The sudoriparous glands and hair follicles presented no abnormality, there being but a small amount of cellular infiltration in their vicinity. The haemorrhages were for the most part deeply situated in the subcutaneous tissue. Many of the vessels in the neigh- bourhood were plugged with spindle cells, though in the vicinity of these there was no sign of sarcomatous growth, and the tissues stained poorly, being necrosed. The conditions present in the latter case, therefore, show primary sarcoma of the pelvic organs, which had, to some extent at all events, advanced by way of the lymphatic system, and involved the glands in the neighbourhood of the coeliac axis, as is apparent both from the macroscopic and microscopic examinations. A more minute ex- amination of the primary seat showed involvement of the vessels in the tumour, spindle cells filling their lumina. In the other tissues, moreover, and especially in those parts where haemorrhage existed, the perivascular lymphatics appear to have conveyed the cellular elements, for on examination of some of the various affected tissues there were found in the perivascular spaces accumulations of spindle cells, with a moderate amount of haemorrhage in their immediate vicinity. General Conclusions. The purpura accompanying the two foregoing cases of sarcoma- tosis would seem to find its explanation in the coexistence of several factors, the main feature being an involvement of the vascular system bv the sarcomatous elements. There existed in Case I a direct lesion of the vessel wall whereby the sarcoma cells invaJed directly the various coats, and were found mainly between the intima and the adventitia, dissecting their way, as it were, along these tracts in the vessel walls. There was further an extensive involvement of the perivascular lymphatics, from which point, indeed, it would seem that the sarcoma cells had invaded the walls of the vessels themselves. C. F. Martin and W. ?. Hamilton 15 In Case II, moreover, not only was there a definite invasion of the lymph spaces near the vessels, bnt, furthermore, there was un- doubted evidence of tlie existence of emboli of sarcoma cells in the lumina of the blood vessels; and in the immediate vicinity of such conditions hremorrliages were invariably found. While some vessels, and indeed a great niany, were quite free from such emboli, in others the lumina were completely occluded by spindle cells, so as to pre- clude the possibility that these were merely a collection of desqua- mated endothelial cells, such as is frequently found as the result of post-mortem changes. That such an embolic condition can exist is by no means an unreasonable supposition, and, while it is generally recognised that nniltii)le sarcomata are usually made up of small round cells, in this case we have an undoubted example of sarcoma- tosis of the spindle-celled variety. There are numerous instances of this " embolic purpura," as it may be called, especially in French and German literature, the condition being associated with rheumatism, valvular lesions of the heart, and other diseases which induce di- rectly or indirectly the formation of emboli. Krauss,* Gimard,f Leloir,:}: and others have insisted with considerable emphasis on the embolic origin of many purpuric conditions, and in some instances they have verified their observations by histological examination. Leloir assumes that, in addition to the presence of the ordinary omboli and the changes in the vessel walls with desquamative endar- teritis, the blood itself may be much altered chemically, and that in tlie cachectic conditions clots may be thrown down from the circu- lating blood and be carried onward to form capillary emboli, with resulting hsemorrhagic infarctions. Krogerer,''* some ten years ago, in examining the skin removed from patients with symptomatic piirpura, found definite thromboses in tlie smaller veins, and even in the arteries. According to his view, the alterations in the vessel walls gave rise to slowed circulation and tendency to thrombosis, bringing about a liability to haemorrhages. * E. Krauss, Ueber Purpura, Heidelberg", 1883. t Gimard, Arch. gin. de. m€d., October, 1383. t Leloir, Annates dc deniiatolngie vt de sypMligraphie, 2. ser., t. v, p. 1, 1884. «Krogerer, Zeitsclirift ftir klin. Medictn, 1885, Bd. x, Hft. 3. 16 Two Cases of Sarcomatosis tnith Purpura ILvmorrhagica His plates bear out his theories regarding the thrombi, many of which show considerable organization. But a careful examination of the piirpuric areas shows further that a mere invasion of the vascular system by sarcoma cells can not explain all the varioiis blood effusions present. On examining the skin, for instance, in those a?*eas where large irregular hsemorrhages had occurred, there was but little evidence of vascular invasion, while the emboli, on the other hand, seemed to exist mainly in the localized smaller and more circumscribed patches. One must therefore con- clude that in such instances a combination of factors will alone afford a rational explanation of the purpura, and that in the general con- dition of the patient we shall find another cause for the enormous effusions of blood. In both of our cases there were high fever, ca- chexia, and a rapid progressive asthenia, all being the results of a sarcomatosis, and implying also grave alterations in the composition of the blood. From this we may infer an altered condition of the vessel walls, and hence probably a combination of circumstances suf- ficient to explain the incidence of haimorrhage. The raised cutaneous nodules in our second case, some of which were hsemorrhagic, can not be regarded as pure sarcomatous metas- tases, for on microscopic examination they merely revealed haemor- rhage or necrosis, or both, and sometimes plugging of the vessels. There was nowhere in these nodules evidence of new growths. Such elevations, then, must have been produced rather by a temporary serous or cellular exudation coincident with or following upon the haemorrhage — a probability which is emphasized by the fact that during the last days of the patient's illness many of the nodules dimin- ished in size. Whether the oedema and infiltration were secondary to the embolic process in the subcutaneous vessels or whether they were merely coincident with the haemorrhage would be difficult to decide. The ringlike spots, however, are of special interest, inasmuch as it has been shown that they have been present in more than one case of sarcoma. It is not impossible that such spots may be definitely related either to the embolic processes or to a direct invasion of the C. F, Martin and W. F. Hamilton 17 cutaneous vessels, though, so far as we know, there do not exist any experimental proofs to bear out sucii a theory. From what has been said, however, it is evident that the cutaneous vessels were plugged during the last few days of the illness, at a time when the walls of the smaller vessels and capillaries were already greatly enfeebled. The result of the embolic formation may therefore mean a decided deficiency in the supply of nutriment to the involved area, the col- lateral circulation naturally being poor under the circumstances. As soon, then, as the vessels h*- ' become plugged, the surrounding blood supply would be poured in to a limited extent, and, on meeting the enieebled vessels, might possibly break through their thin walls, thus producing a zone of haemorrhage around the area deprived of its nor- mal nutrition. In other words, the condition may be regarded as in many respects analogous to that presented in embolic infarcts in regions with end arteries, central necrosis with peripheral congestion and haemorrhage being induced, the latter being chiefly limited to the outer zone of the necrotic area. The cutaneous vessels under such circumstances may be regarded as end arteries in a functional sense, since the collateral circulation would be so diminished under the altered conditions that no complete nourishment could be afforded to the area supplied normally by the plugged vessel. Von Reckling- hausen * has directed especial attention to the occurrence of cutaneous haemorrhages following embolic or thrombotic occlusion of peripheral arteries. The possibility of some toxic condition as a factor in the produc- tion of the purpura in our cases may also be suggested ; but while we would not exclude this possibility, we are unable to find any positive evidence in its favour. Focal necroses, which are often associated with toxic and infectious processes, were present only in direct associ- ation with the haemorrhages, and were not distributed in the liver, spleen, and kidneys in the manner characteristic of toxic infections. Nevertheless the absence of these necroses does not exclude the pos- sibility of the existence of some form of toxaemia. Infection demon- * Von Secklihghausen, Handbuch der allg". Pathologie d. Kreislaufs u. der Ernahrung, p. 160, Stuttgart, 1883. 18 Two Cases qf' iSa/rcomaioH is with J*urjntra Ihvtaorrhctgioa Btrable by bacteriological examination was absent, and there is no reason to regard our cases as allied to tlie infectious purpuras. The thermic theory suggested by Fagge at all events finds no place in the production of the multiple tumours in our cases, inas- much as in each instance extensive visceral growths had given rise to the metastases. In conclusion, we would express our gratitude to Prof. J. Stewart for permission freely granted to record the cases, as also to Prof. Adami, the director of the laboratory, who not only gave us much assistance in the preparation of this paper, but kindly undertook the entire work connected with the appended illustrations. DESCKirTlON OF PlATES XXI, XXII, AND XXIII. Fig. 1. — Spleen from Case I. Low power, X 55. Masses of small round sarcoma cells are seen apparently lining the sinuses of the spleen. The other structures visible in this specimen are normal. Fig. 2. — Fart of the same under high power, X 240. This section shows the sarcoma cells on the inner margin of the splenic sinuses; they are sep- arated from the lumen of the sinus by a thin layer of endothelial cells, E. At one portion the cells are seen iniiltratlng between the fibrils of the sinus wall, I. M, the main wall of the sinus; P, the spleen parenchyma; S, sar- coma cells. Fig. 3. — Liver from Case I. Low power, X 40. The section shows a mod- erate small round-celled infiltration in the periphery of the hepatic lobule, following mainly the portal sheath. Fig. 4. — Part of the same section under high power, X 240. The small round sarcoma cells are infiltrating the portal sheath, and may be seen covered by a thin layer of endothelial cells; the condition is similar to that seen in the spleen. A, H, arteria hepatica; B, D, bile duct; L, liver cells; V, P, vena portse. Fig. 5. — Section through the stomach wall from Case II. Low power, X 40. The arteries of the submucous coat are seen plugged with spindle cells, and in their immediate vicinity there are old and recent blood ex- travasations. H, hssmorrhage; N, necrosis; E, embolus of sarcoma cells. Fig. 6. — The same under high power, X 180. B, blood-corpuscles; E, em- bolus of sarcoma cells; N, necrosed tissue. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. I PLATE XXIII. r^ r If ^H;, THE JOURNAL O^ EXPERIMENTAL MEDICINE. VOL. I PLATE XXI. THE JOURNAL OF EXPERIMENTAL MEDICINE. VOL. I .;>;.-tf r •» .»^ ■NTAL MEDICINE. VOL. I PLATE XXII THE JOURNAL OF EXPERIMENTAL MEDIOINE. VOL. I PLATE XXIII. J,' ■■■■^>: %' ( -f#iis>. ' ''''^^^''\ s f]SP^»'