A CYSTICERCUS CARCINO-OSTEOCHONDRO- SARCOMA OF THE RAT LIVER WITH MULTIPLE CYSTICERCUS SARCOMATA

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1 A CYSTICERCUS CARCINO-OSTEOCHONDRO- SARCOMA OF THE RAT LIVER WITH MULTIPLE CYSTICERCUS SARCOMATA 1. D. BUIJIJOCK AND M. 11. CUIlTIs (Proin fhe Ztulitute of Cancor Research, Francis C. Wood, Director) It is remarkable that among more than 2,100 rats in our colony which from July 30, 1920, to April 12, 1928, developed cysticercus tumors of the liver following experimental infestation with Cysticercus fasciolaris, the larva of the cat tapeworm Taenia crassicollis, there was not a single carcinoma whose origin could in any way be attributed to the stimulation by the parasite. In a previous study (1) of cysticercus tumors of 1,400 rats (1) the writers found that all these tumors were of mesothelial origin and all except one were malignant. Two of the neoplasms contained hyaline cartilage and two contained both cartilage and osteoid tissue or bone. Of these four tumors one was an osteoid chondroma, one a chondrosarcoma, one an osteo-chondrosarcoma, and the other a mixed cell sarcoma containing islands of cartilage. Since the publication of this article we have encountered another Cysticercus chondroma or chondrosarcoma and the interesting mixed tumor which is the subject of this report. In addition to these, two rats developed benign cystadenomata which apparently originated in isolated bile ducts in the walls of Cysticercus cysts. Excluding the tumor which will be presented in this paper, these two adenomata were the only epithelial growths which have arisen in the walls of parasitic cysts among more than 2100 rats bearing Cysticercus tumors. Two explanations present, themselves for the failure of the epithelium of the liver to participate more frequently in the neoplastic process inaugurated by the Cysticercus. (1) The 328

2 CYSTICERCUS CARCINO-OSTEOCHONDRO-SARCOMA OF RAT 327 liver cells and bile ducts may be more or less protected from the irritant elaborated by the parasite by the fibrous cyst wall which encloses the larva. It is true that the outer parts of the wall of many cysts contain bile ducts and isolated liver cells or groups of cells, but these are more or less remote from the cyst cavity. As the sarcomatous process progresses the barrier FIG. 1. AN AREA FROM ONI OF THE TWO ORDINARY POLYMORPHOUS CELL TUMORS IItS between liver and larva is correspondingly strengthened by t'he increased amount of tissue separating them, whether the sarcoma arises from the cells lining the cyst or the deeper lying cells in the cyst wall. Yet the fact that some sarcomata do originate in the outer part of the cyst wall suggests that the irritant sometimes comes in contact with the outlying connective tissue cells of the wall and probably with the epithelial

3 328 F. D. BULLOCK AND M. R. cuxm cells included therein. (2) The hepatic cells and bile duct epithelium may be more or less resistant to the proliferative action of the parasite or these cells possess little or no predisposition to neoplastic changes from my form of irritation. Yet t,he liver cells are not irresponsive to stiniulation by the parasite in its early stage of development, but participate actively in the proliferative process engendered by this organism. At this time the liver cells are exposed to the direct action of the parasite. The infrequency of spontaneous epithelial tumors of the liver of rats speaks for the relative insusceptibility of the hepatic epithelium to neoplastic changes. In man, on the contrary, the liver cells are highly susceptible to the irritant of another type of worm-puragonirnus, as is shown by the great frequency of primary liver carcinoma among those infested.

4 CYSTICERCUS CARCINO-OSTEOCHONDRO-SARCOMA OF RAT 329 Although it is doubtful if either of these explanations suffices to account for the paucity of Cysticercus epithelial tumors, it is not improbable that both the indisposition of the hepatic epithelium to neoplastic pro1iferat)ion and the protection afforded the epithelium by the cyst wall are important factors. FIG. 3. AREA OF OYTEO-SARCOMA IN MIXED ~ UMOR 1RS 2177 In this paper we wish to record a malignant Cysticercus tumor which in part originated from the bile ducts in the wall of a Cysticercus cyst. The host was a Copenhagen male rat 638 days of age which was fed Taenia eggs 37 days after birth. The tumor, IRS 2177 occupied the cranial half of the caudal division of the right lateral lobe and measured 4.5 em. X 3.3 em. X 2.7 em. It was very firm in consistency and contained spicules of calcareous material or bone. There was extensive

5 330 F. D. BULLOCK AND M. R. CURTIS necrosis with pinkish-white healthy areas at the periphery. Embedded in the tumor near the surface were five cysts containing Taenia larvae, the longest measuring 45 em. and the shortest 31 em. The same liver lobe presented two additional tumors of approximately the same size as the above. One of these was attached to the caudal tip of the caudal division of the FIG. 4. AN AREA OF CARCINO-OSTEOSARCOMA FROM THE MIXED TUMOR IRS lobe by a slender pedicle. It was firm and tough in consistency but contained no tissue resembling bone or cartilage. Although no parasite was found in this tumor, it contained an empty cyst-like space and there was a necrotic worm in the scrota1 sac. The other tumor involved the caudal tip of the cranial division of the lobe and was much softer than either of the other two tumors. At the liver margin of the tumor was a cyst containing

6 CYSTICERCUS CARCINO-OSTEOCHONDRO-SARCOMA OF RAT 331 a healthy intact worm 45 cm. in length. There were generalized peritoneal metastases and a moderate amount of straw-colored fluid in the peritoneal cavity. In addition to the cysts in the tumor the liver contained 19 cysts and 18 of these showed small secondary tumor nodules on the outer walls. Microscopically the last two tumors (Fig. 1) were polymorphous cell sarcomata FIG. 5. AN AREA OF CARCINO-SARCOMA FROM THE MIXED TUMOR IRS identical in structure with many other Cysticercus sarcomata. The first mentioned tumor, however, showed a morphology which was unique among Cysticercus tumors. The bulk of the tumor was an osteo-chondrosarcoma of a rather diversified structure and contained a large quantity of cartilage, osteoid tissue and bone, the bone being of the trabeculated type without lamellations (Figs. 2 and 3). The intercellular substance was of

7 332 I?, 11. BTTLLOCK AND M. R. CURTIS several different kinds embracing fibrillar, hyahe, osteoid, cartilaginous, and osseous material. Intermingled with the intercellular substance were tumor cells in different stages of differentiation. These cells showed wide variation in size from very small compressed elongated cells in the dense less cellular areas to large and sometimes multinucleated cells in some of the more cellular areas. A part of the sarcoma consisted of compact structureless masses of rather small cells of irregular outline imbedded in a very scanty fibrillar matrix. In some of these masses were scattered islands of cartilage. Other parts of the growth consisted solely of large polymorphous cells. The

8 CYSTICERCUS CARCINO-OSTEOCHONDRO-SARCOMA OF RAT 333 tumor was rich in thin-walled blood vessels, many of these of large calibre. In spite of its great vascularity a large part of the tumor was necrotic or in an advanced stage of degeneration, the healthy tissue being confined to particular areas in the outer part of the growth. Toward the periphery of the tumor the sarcoma merged into carcinomatous tissue (Figs. 4, 5) which comprised the minor part of the tumor mass and formed the greater part of the healthy portion of its surface. Where the two types of tissue came together it was sometimes impossible to distinguish carcinoma cells from sarcoma cells. The carcinoma was composed for the most part of rather small deeply staining cells of polyhedral or cuboidal form which showed a tendency to arrange themselves into alveoli, small groups or strands or occasionally to form the lining of small acini (Fig. 6). In localized areas the epithelial cells were of very small size and were spread out in diffuse masses. In one part of the growth there was a broad sheet of small hyperchromatic fusiform cells which were probably epithelial in origin, though they resembled sarcoma. Included in the tumor were nests and cylinders of squamous epithelium showing often central cornification or necrosis. Mitotic figures were observed in some of the cells though they were not abundant. The stroma was relatively scanty and was well vascularized. The carcinoma had infiltrated the liver and had replaced a part of the wall of one of the cysts on the surface of the tumor mass. This cyst showed emboli of carcinoma cells in the blood vessels of the wall and many bile ducts in the uninvolved part. Of the numerous secondary abdominal tumors only a diaphragmatic metastasis was submitted to microscopic examination. This showed the structure of a polymorphous cell sarcoma and contained a few scattered islands of osteoid tissue and bone. Lumph nodes from the superior mediastinum showed a number of polymorphous cells resembling tumor cells in the sinuses. The three tumors considered in this paper which arose in the same lobe of the liver of a rat were approximately of equal size and probably were of independent origin. It seems likely that the two types of tumor in the carcino-sarcoma also arose 23

9 334 F. D. BULLOCK AND M. R. CURTIS independently of one another since there was no evidence to show that the sarcoma resulted from the malignant transformation of the stroma of the carcinoma, a process which has been observed in this laboratory in some of the spontaneous carcinosarcomata of the skin, breast and uterus of rats. REFERENCE (1) BULLOCK, F. D., AND CURTIS, M. R.: J. Crtncer Res., 1925, ix, 425.