(Iteceived for publication December 3, 1915)

Transcription

1 TRANSPLANTABLE SARCOMATA OF THE RAT LIVER ARISING IN THE WALLS OF PARASITIC CYSTS G. L. ROHDENBURG, M.D., AND F. D. BULLOCK, M.D. From Colurnbia University, George Crocker Special Re-search Fund, F. C. Wood, Director (Iteceived for publication December 3, 1915) An earlier paper' recorded the occurrence of a primary sarcoma in the wall of a cestode cyst of the liver of a rat. The malignant nature of this small tumor was not recognized in the gross and consequently no attempt was made to propagate the growth.* The present report presents two tumors of the liver of rats, arising from the cyst wall of a Tenia crassicola, but differing from the first in their extensive growth and widespread metastases. As the gross appearance of these neoplasms was diagnostic of malignancy, the tumors were transplanted. Crocker rat sarcoma No. 7. The host was afull grown female white rat of unknown age. Upon opening the abdomen a mass measuring about 2 x 3 cm. was found near the left border of the right lobe of the liver. Section through this mass showed an infiltrating growth with a central yellowish core. The pancreas, which was not adherent to the tumor, contained numerous small secondary nodules, chiefly at the splenic end. The lower third of the spleen was replaced by a large metastasis. The right kidney was represented by a large necrotic mass. The mesentery and the peritoneal surface of the small intestine and colon were studded with numerous small metastatic nodules. The omentum was almost entirely replaced by neoplastic tissue, and metastases were found also in the diaphragm and in the tissues 1 Bullock, F. D., and Rohdenburg, G. L.: Jour. Med. Research, 1913, xxviii, 477. Similar tumors have been recorded by Borrel (Bull. Inst. Pasteur, 1907, v, 497), Bridr6 (Compt. rend. SOC. Biol., 1909, lxvi, 376), and others. 87

2 88 G. L. ROHDENBURG AND F. D. BULLOCK about the ovaries and the adrenal glands. No gross metastases were demonstrable in the lungs or in the lymph nodes outside the peritoneal cavity. Histologically the hepatic tumor was a small spindle-cell sarcoma, composed of cells of irregular size, many of which showed mitotic figures (fig. 1). The center of the tumor contained a dead parasite (fig. 2) surrounded by necrotic tissue. In certain portions of the neoplasm isolated strands of liver cells and bile FIG. I. Sarcoma in wall of cyst about a parasitic worm. X 250. ducts were abundant; in still other areas the tumor was exceedingly vascular. The secondary deposits in the various organs (fig. 3) were identical in structure with the hepatic tumor. The site of origin of the growth is indicated by the central location of the parasite and the surrounding necrosis. Cultures of the necrotic material replacing the right kidney were sterile. The tumor on transplantation behaved like other transplantable rat sarcomata. As will be noted in the appended Table I,

3 TRANSPLANTABLE SARCOMATA OF THE RAT LIVER 89 the inoculation percentage of the tumor is high and growth is rapid, although the majority of the tumors undergo spontaneous absorption. The growth is now in the 10th generation, with an inoculation percentage of 100 and an absorption percentage FIG. 2. Parasitic worm in liver surrounded by sarcomatous tissue. X 25. of 95. An attempt was made to propagate the tumor, using dried tumor powder and a Berkefeld filtrate after the method of Rous. The outcome of the experiments, however, was negative. Croclcer rat sarcoma No. 8. A full grown white male rat was the bearer of this tumor. The primary growth occupied the

4 90 G. L. ROHDENBURG AND F. D. BULLOCK upper and lower poles and the upper posterior wall of a rather large cyst which was attached to the Spigelian lobe of the liver by a short, broad pedicle. The liver itself apparently was only slightly involved in the malignant process. The mass, consisting of cyst and tumor tissue (fig. 4), was ovoid in shape, somewhat nodular on its anterior and posterior surfaces, and measured 1.5 x 1.5 x 2 cm. Cross section, after fixation, showed that the upper pole and a part of the cyst wall were replaced by tumor tissue which encroached upon the cyst cavity, and formed the somewhat nodular surface of the cyst. The growth in the upper pole measured 1 cm. at its thickest portion. A part of the lower pole of the cyst was composed of tumor tissue and had a maximum TABLE I NO. OF GENERATION NO. INOCULATED PERCENTAOE TAKE1 PERCENTAOE BPONTANEOUB DIB- APPEARANCE A... 2B... 2 c... 3A... 3B per cent per cent thickness of 3 mm. The portions of the cyst wall lying between the tumors were apparently slightly thicker than the usual thickness of these cysts. The cyst cavity was filled with a large cestode worm. Many small, round, secondary nodules were found scattered throughout the omentum, mesentery, and upon the serous coats of the small intestine; the omental metastases were by far the most abundant. The diaphragm contained a small tumor, but the thoracic viscera showed no gross metastasis. Microscopically (fig. 5) the upper tumor was composed of a rather compact mass of cells which, in general, showed no definite arrangement, although in particular areas the cells tended to form in parallel rows or in groups. Variations in size and polymorphism were characteristic features of the cells. They were

5 TRANSPLANTABLE SARCOMATA OF THE RAT LIVER 91 FIG. 3. Metastatic nodule of sarcoma in splenic portion of pancreas. X 150. FIG. 4. Gross appearance of Crocker rat sarcoma No. 8. Scale in millimeters.

6 92 G. L. ROHDENBURG AND F. D. BULLOCK round, polygonal, sometimes oval or spindle in shape, and possessed an indistinct outline. The nuclei showed a corresponding variability in shape and size, and mitotic figures were numerous. Scattered freely through the tumor were many small and large multinucleated cells. The scanty stroma of the tumor consisted mainly of fine spindle cells with a few delicate connective tissue FIG. 5. Microscopical appearance of tumor at lower pole. fibrils. The tumor was richly supplied with blood furnished in large part by capihries which were especially abundant where the cells were arranged in rows, and here apparently supplied the only stroma. Other tumor cells armnged in groups were partially or comgletply surrounded by, Nood capillaries. Degenerative changes and hemorrhage were observed in certain

7 TRANSPLANTABLE SARCOMATA OF THE RAT LIVER 93 areas. A few bile ducts and an occasional liver cell were found in the portion of the tumor bordering the cyst cavity. The lower tumor differed from the upper in the preponderance of giant cells, in the greater degree of cell degeneration, and in an utter lack of any definite cell arrangement. FIQ. 6. Cyst showing tumors at upper and lower pole and the relation of the tenia. LOW power. The cyst wall between the upper and lower tumors was very vascular and contained many cells, chiefly of the spindle type.

8 94 G. L. ROHDENBURG AND F. D. BULLOCK Eosinophiles were numerous. Giant cells and cells resembling those of the tumor were found in the cyst wall at a remote distance from the tumor. Lining the cyst cavity were cylindrical cells showing degenerative changes, which reached the stage of complete necrosis where they lay beneath the tumors. The metastatic tumors presented the general appearance of the primary growth except that the cells showed more regularity in shape and size, and fewer giant ceils were found. The tumor on transplantation differed from tumor No. 7 in the smaller percentage of takes. The good staining qualities of the tissues of the tenia (fig. 6) is an indication that the parasite was alive when the tumor was discovered; this fact was not noted before as the specimen was fixed in toto. These two cases of the association of parasite and tumor are not presented as an argument in favor of the parasitic hypothesis of the origin of malignant neoplasms, but rather as additional examples of malignant tumors following chronic irritation.