TRANSPLANTABLE SARCOMATA OF THE RAT LIVER
ARISING I N THE WALLS OF PARASITIC CYSTS
G. L. ROHDENBURG, M.D.,
AND
F. D. BULLOCK, M.D.
From Colurnbia University, George Crocker Special Re-search F u n d , 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. T h e
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
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,
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
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. a t its thickest portion. A part of the lower
pole of the cyst was composed of tumor tissue and had a maximum
TABLE I
N O . OF GENERATION
1.....................
2 A. . . . . . . . . . . . . . . . . . .
2 B...................
2 c. . . . . . . . . . . . . . . . . . .
3 A ...................
3 B. . . . . . . . . . . . . . . . .
NO. INOCULATED
365
36
36
48
36
36
PERCENTAOE TAKE1
PERCENTAOE
BPONTANEOUB DIBAPPEARANCE
per cent
per cent
70
100
100
75
79
80
89
77
66
65
69
75
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
TRANSPLANTABLE SARCOMATA O F T H E RAT L I V E R
FIG.3. Metastatic nodule of sarcoma in splenic portion of pancreas.
91
X 150.
FIG.4. Gross appearance of Crocker r a t sarcoma No. 8. Scale in millimeters.
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
TRANSPLANTABLE SARCOMATA O F 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. LOWpower.
The cyst wall between the upper and lower tumors was very
vascular and contained many cells, chiefly of the spindle type.
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.