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without definite arrangement; in other areas they formed distinct cords, parallel
to an empty channel re.sembling a liver sinusoid. The liver substance adjacent
to the hepatoma was compressed and not infiltrated by the tumor.

From these data hepatoma of the chicken appears to be a rather uncommon
neoplasm. Its benign character is indicated by the fact that all of the cases were
incidental findings.

Cholangioma

The diagnosis of cholangioma or adenoma of the bile duct was a problem m
several cases. The difficult}- arose because of the marked connective tissue and
polyblastic response that occurred in many of the cases diagnosed as cholangioma.
Instances of cirrhosis, hepatitis, and cholangitis were seen in which there was an
active fibrosis in the periportal areas coupled with a proliferation of the bile
ducts. In some, the proliferation was so extensive as to suggest a neoplastic
state. One case of a fibrosarcoma of the liver is described in another section with
a similar reaction of the bile ducts. The basis upon which a pathologist may
separate a neoplastic from a granuloblastic process is rather arbitrary under such
conditions. It is, of course, "possible that the neoplastic condition might arise
from a process that in the beginning was only a granuloma. Except for the
reports of Goss (11) and Eber and Malke (4), biliary carcinoma of the chicken is
not often discussed in the literature. Unfortunately no description is given of
the cases mentioned in these reports. It is worth while, therefore, to present a brief
description of the four cases of cholangioma found in this collection.



NEOPLASTIC DISEASES IN CHICKENS 31

1. T 143. An 8-month-oId pullet affected with chicken pox was killed for
examination. The liver was moderatel}' enlarged by the presence of numerous
areas of hemorrhage, particularh- common in the right lobe. The hemorrhages
were not fresh and were only partl\- organized. The largest area of hemorrhage
was approximately 2 cm. in diameter. In the substance of the right lobe of the
liver was an oval mass of firm, gray tissue measuring 9X5 mm. Histologically
this mass was composed of numerous irregular acini of bile duct epithelium
between which were arranged bundles of fibroblasts and irregular areas of myelo-
cytes and "polyblasts. The other necropsx' findings were essentially negative
except for a few shallow, chronic ulcers in the ileum. No explanation for the
hemorrhages in the liver could be found. Fowl leukosis was suspected but the
bone marrow though somewhat scant in amount was in a hyperplastic and not
neoplastic state.

2. T 286. A 33-week-old pullet was found dead. In the right lobe of the
liver was a gray-red-brown mass rather sharply defined and somewhat firmer
than the adjacent hepatic tissue. The mass measured 20 X 22 X 25 mm. and
consisted of irregular acini and tubules of low cuboidal epithelium between which
were niany lymphoid cells and a few connective tissue fibers (Plate XI, Figure 3).
There was a rather marked degree of fatty metamorphosis in the neighboring
hepatic cells.

3. Case 283. This bird died at the age of 61 days with erythroblastic leukosis
induced by inoculation with material of a transmissible strain of the disease.
A small gray nodule of tumor tissue was found in the substance of the right
liver lobe. The tumor was composed of epithelial cells, which for the most part
were without definite arrangement, although in some areas irregular acini were
formed.

4. T 242. A 12-month-old pullet with fowl pox was killed for examination.
The pox lesions involved a rather extensive area over the abdomen and sternum.
Pathology of the visceral organs was limited to the liver in which were several
irregular areas of gray tissue scattered in both lobes. Only one mass in the
right lobe was apparent in the intact specimen. The others were found upon
cross section. The tumor masses were intimately associated with the larger
blood vessels. The largest mass was 10 mm. in diameter. Numerous acini and
irregular tubules of bile duct cells were found in the tumor. Between the epithelial
elements was a dense infiltration with lymphoid cells and a light, scattered in-
filtration with heterophils. A rather marked fatty metamorphosis of the liver
cells was found.

Cholangiomas in these cases were either single or nmlliple. All were found In
female chickens but the number is so small that this fact has little significance.
The ages of the birds at the time of examination ranged from two months to a
year. From the data, it would seem that cholangiomas are benign neoplasms.
Although the cholangioma found in Case 4 must be considered an incidental
finding, its multiple nature suggests that with more time for development it
might have been a primary cause of death.

Thymoma

Two cases of tumor were diagnosed as thymoma. There was a distinct sim-
ilarity of the macroscopic and microscopic features in both cases.

1. T 19. A 9-month-old pullet was found dead with a marked swelling of
the throat in the region of the crop. Upon necropsy the swelling was found to be
due to an irregular tumor mass at the base of the neck on the left side. The
mass measured approximately 8X5X3 cm. and was relatively firm and grayish
pink in color. The tumor lay in the left jugular furrow, infiltrated the adjacent
soft structures, and closely enveloped both the trachea and esophagus. In
general the tumor seemed to grow upward in the neck although there was a small
projection beginning to enter the thoracic aperture. Deposits of urate crystals
were found in the pericardial sac, and both kidneys were slightly swollen and pale
in color, suggesting that death may have been due to a kidney insutificiency rather
than to the tumor. Other visceral organs were essentially normal. Microscopic
study indicated that the principal components of the tumor were polymorphous
cells larger than the thymic lymphocytes seen in a normal thymus. These cells



32 MASS. EXPERIMENT STATION BULLETIN 391

were round, ov^al, or polyhedral and possessed a relatively large vesicular nucleus
in many of which nucleoli could be distinguished. The polymorphous cells were
supported by a well-developed framework of anastomosing reticulum cells similar
to those seen in a normal thymus. Scattered throughout the tumor were peculiar
large cells with an opaque acidophilic cytoplasm and relatively small vesicular
nuclei. Their appearance was that of giant cells, although multinucleated forms
could not be found. In a few places the reticular stroma cells clumped them-
selves together in such a manner as to suggest an attempt to form a structure
like a Hassell's corpuscle.

Although the tumor was well supported by fibroblasts, it was not confined
by a capsule. It readily infiltrated the adjacent soft tissues including the mus-
culature. The muscles of the trachea were infiltrated but the annular cartilages
seemed to be an effective barrier to further invasion of the structure.

2. T 306. A very fat year-and-a-half-old hen was found dead. Death was
apparently due to hermorrhage from rupture of the liver capsule, the cause of
which could not be determined. A tumor mass was found in the right jugular
furrow in the mid-cervical region and was apparenth' derived from the thymic
node of that location. The tumor measured 3X ^ X 2.5 cm., was reddish gray-
white in color, and was relativeh' firm. On cross section, small cysts filled with
clear fluid were noted. Other nodes of the thymic chain were fairly well de-
veloped and a representative node anterior to the tumor measured 10 X 5 X 2
mm. No other significant pathology was found. The histology of the tumor
was similar to that described in the first case (Plate IX, Figure 2). The cyst-like
structures were interpreted as obstructed and distended hmph channels.

A thymoma of the chicken has been described by Feldman (6) and the two
cases above seem very similar to his. These tumors of the chicken show a gran-
ulomatous character coupled with the invasiveness of a neoplasm, which leads
to the question of whether or not they should be considered as a neoplasm.
Ewing (5) discusses this question uith regard to thymomas ol man and comes to
the conclusion that they should be regarded as infectious granulomas.



Hemangioma

Neoplasia classified as hemangionia was found in five instances. The t\pe
cell of a hemangioma is the angioblast, whiih teiuls to lorm new blood spaces
or channels. Sometimes the channels formed b\- the tumor are ol capillary size
and the term "capillary hemangioma" is descriptive. At other times the tumor
tends to form large blood spaces, for which condition the term "cavernous heman-
gioma" is used. Some authors favor the term "hemangio-endothelioma" in pref-
erence to hemangioma (Feldman 7). Both capillary and cavernous forms of
hemangioma were found in this collection. Although certain data on the cases
are presented in Table 16, a brief description of each will provide a better con-
ception of the cases.

1. Case 444. Some details of this case have been described previously
(Olson 23). The chicken was found dead in its pen. Examination of the blood
made 46 days previously had shown no significant changes. A slight relative
eosinophilia was noted 39 da\s previous to death; and 25 da>s preceding death a
moderate, relative, heterophil leukocytosis was observed. A swelling of the
left foot pad was noted about a week before the bird died, and on the day before
death the chicken was wealc, dull, and listless. The carcass was emaciated. The
swelling of the left foot pad was soft and fluctuating and on section was found to
be composed of clotted blood and what appeared upon gross examination to be
granulation tissue. The liver was slightly swollen, was red brown in color, and
contained numerous foci of clotted blood under the capsule and deep in the sub-
stance of the organ. Similar foci of accunmlated blood were present in the kidneys,
lungs, heart, and spleen. The spleen was enlarged (2 cm. diameter) and consisted
principally of an ancient blood clot. Splenic tissue was confined to a narrow
crescentic border along one edge of the mass representing the spleen. The foci
of blood in the heart muscle and in the kidney seemed to have a thin though
distinct surrounding membrane. The blood in the heart chambers was not
clotted. No pathological changes could be noted in a smear prepared from the



NEOPLASTIC DISEASES IX CHICKENS



33



heart's blood. The histology of the tumor was portra\ed best in foci in the heart
and lung. The t\pe cell was the angioblast. In some areas these were compact
and in others they tended to form small spaces which were filled with blood.
The lining of the larger blood spaces was stretched thin. In many of the larger
blood spaces the blood was coagulated and varying degrees of organization were
apparent. Although no section was made of the tissue surrounding the blood
clot in the left foot pad it is possible that this lesion represented a focus of tumor.

2. Case T 291. The bird was thin and inactive when killed for necropsy. The
liver was markedh" enlarged, with a somewhat greater relative enlargement of
the right lobe. Numerous areas of coagulated blood of variable size were scat-
tered throughout the substance of the organ. A few similar masses of clotted
blood were found in the anterior pole of the right kidney. Sections prepared
from the liver revealed a histology so altered that the tissue could scarcely be
recognized as liver. The bulk of the parench\ma was replaced by neoplastic
cells which tended to form walls enclosing masses of blood. In some areas the
tumor cells were in a sheetlike, s^ncitial arrangement without definite order.
An irregular, patchy granulocytic infiltration was evident throughout the liver.
Neoplastic angioblasts were found around the blood clots in the kidney. The
bone marrow and spleen were found negative upon histological examination.

3. Case T 46. A tumor mass was found in a bird which the owner had killed
and dressed for food. The carcass was in good flesh and the bird had shown no
symptoms of disease. The tumor mass, which measured 35 X 25 X 20 mm.
and weighed 150 grams, was found attached to the ovary. The ovarian tissue
itself was inactive and appeared normal. The tumor was dark red with irregular
yellow areas. The colors were obviously due to coagulated masses of blood in
v^arious stages of organization. Upon section, the masses of blood were found
surrounded b\' a membrane formed of a thin, stretched angioblast type of cell.
Between the large masses of blood, the tunTor cells tended to form small capil-
laries, some of which did not contain blood in the lumen. Histological section
of the normal-appearing part of the ovar\- revealed no pathology.

4. Case T 98. A bird with a respiratory infection was killed for examination.
An incidental finding was a small (2 mm. in diameter), gra\' nodule beneath the
capsule of the left lobe of the liver. This nodule was made up of imperfectly
formed capillaries, a few of which contained blood cells in their lumens. Inter-
spersed between the vessels were many granulocytes.

5. Case T 280. The bird providing material for this case was affected with
histiocytic sarcoma and is described in the section dealing with that form of
neoplasia. The histiocytic sarcoma was confined to the subcutis of the pectoral
region and both lungs. A small gray mass was noted beneath the capsule of the
liver. On section, this proved to be an area composed of angioblasts forming
fairly well developed capillaries (Plate XI, Figure 2).

Three of the five cases of hemangioma described may be considered as the
cavernous form and the other two as the capillary form (Table 16). Only two
of the cases (Cases 444 and T 291) were malignant as indicated by extent of the
tumor growth. Both of the cases regarded as malignant were of the cavernous
form, and in these birds the lesions were responsible for serious illness. The small



Table 16. — Dat.\ on Five Cases of HEMANG:ci:A.



Case

No.



Age
(Weeks)



Location of Tunic



Form of Tumor



444 *D 22 Female Li\er, kidne\s, lungs, heart, spleen Cavernous

T 291 K 28 Female Liver, kidney Cavernous

T 46 K 52 Female Ovar)- Cavernous

T 98 K 32 Female Liver Capillary

T 280 K 28 Female Liver Capillary



*D indicates that bird died; K, that it was killed for examination.



34 MASS. EXPERIMENT STATION BULLETIN 391

lesion in the liver of two of the cases might easily have been overlooked. It is
of interest to note that the liver was affected in four of the five cases studied,
which suggests a predilection of the liver of the chicken for development of
hemangioma.

Lymphangioma

Only one case of lymphangioma was encountered. A descripton of the case
follows.

1. Case T 264. An 8-month-old, cross-bred female was sent to the lab-
oratory for examination. It was dead upon arri\'a), and the carcass was in poor
flesh. A considerable e.xcess of fluid was found in the peritoneal cavity, together
with fibrinous, yellow debris. Yellow debris and albuminous material were found
in the lumen of the oviduct. A tumor mass measuring 5X4X4 cm. was found
attached to the ovary by a long (5 cm.) narrow stalk. The tumor consisted of
soft, moist tissue, mottled gray and red in color. The more superficial part con-
tained many small cysts filled with clear fluid. Histologically the tumor was
composed of somewhat spindle-shaped cells with anastomosing cell processes.
In some areas they lined rather large spaces filled with faint pink staining material
(Plate XI, Figure 4). In other areas the}' exhibited a tendency to form small
capillary-like structures. The serous aspect of the tumor and some of the vis- ~
ceral organs showed changes of a chronic fibrinous peritonitis. Illness and death
of the bird were probably due to the salpingitis and peritonitis, and the tumor
Avas an incidental finding disclosed only by necropsy of the bird.

The histology of the tumor was very similar to that obser\ed in some of the
cases of hemangioma, except that no blood cells were found enclosed in spaces
formed b>- the neoplastic cells.

Leiomyoma

Thirty-four leiomyomas or tumors composed of smooth muscle cells were found.
They were firm, tough, and fibrous in consistency, and on cross section appeared
to be made up of interlacing bundles of tissue (Plate XII, Figure 5). The tumors
were usually somewhat encapsulated, were spherical or oval in shape, and varied
in size from a few millimeters to several centinieters in diameter. The largest
leiomyoma in the collection weighed 368 grams.

The smooth muscle tumors were found onh' in female chickens. The most
common site for the tumor (27 cases) was the ventral ligament of the oviduct
at approximately the mid-portion (Plate XII, Figure 2). In five cases the tumor
was in the wall of the oviduct; in one case tumor was found in both the mes-
osalpinx and the oviduct ; and in one case the location could not be determined
as the specimen consisted of a tumor mass which had been "found in the abdom-
inal cavity of a hen." In only one case was there spread or metastasis of the tumor.
In this instance the primary tumor was in the ventral ligament of the oviduct
and metastatic foci of the tumor were found in the liver and breast muscle.

Leiomyomas are classified according to the time of year they were observed,
as follows: first quarter, 6 cases; second quarter, 10 cases; third quarter, 13 cases;
and fourth quarter, 5 cases. The average age of birds with leionnoma was 61
weeks (range 26 to 107 weeks) for 15 birds that were killed for examination, and
71 weeks (range 37 to 106 weeks) for 19 birds that died.

In practically all cases, the leiomyoma was an incidental finding at the time
of necropsy. In no instance was such a tumor reponsible for specific symptoms
of the disease.

Egg production records were available on 18 of the birds affected with
leiomyoma. These data are given in Table 17 and indicate that the birds were
well above average in their ability to produce eggs. The average production



NEOPLASTIC DISEASES IX CHICKENS



35



index for the entire flock from which these chickens came was, as previously in-
dicated, 0.534 for the first 150 days of productive life. For the group with leio-
myoma, the index was 0.615, with a range from 0.418 to 0.810, and only five hens
had an index below the average of the flock. These figures become even more
significant when it is considered that the production index for the group with
leiomyoma was calculated for a period extending beyond the first 150 days of
production, which is the period of heaviest egg production. The interval between
the last egg laid and necropsy averaged only 12 days, with a range from 1 to 73
days. Such a short interval would seem to indicate that the slow-growing leio-
myoma interfered but little with egg production.

Table 17. — Data on Egg Production of Chickens with Leiomyoma.

Productive life is the interval between first and last eggs laid.
Production index is the factor obtained by dividing the number of eggs laid
by the productive life in days.



Case No.


Age at

Necropsy

(Days)


Productive
Life

(L^ays)


Number

of Eggs
Laid


Production
Index


Interval

from Last

Egg to

Necropsy

(Days)


Size of

Tumor

Average

Diameter

(mm.)


T59


*K457


270


198


.734


1


15


T 68


K479


318


133


.418


4


15


T S3


D 523


334


205


614


1


30


T 84


D 511


290


167


.576


11


35


T86


D 524


320


223


.697


22


12


T89


D534


310


138


.445


29


35


T 174


D 743


567


302


.533


3


20


T 212


D 487


291


149


.512


8


12


T258


D549


346


217


.627


1


10


**T 493


K449


264


191


.724


2


35


T854


K450


276


202


.732


4


12


***T 2207


D442


249


158


.634


3


28


T 667


D435


246


152


.618


1


30


T 1606


D 364


195


158


.810


1


10


***S 1129


D 743


472


233


.494


73


10


T283


D 606


3S3


270


.705


4


22


S 253


K 747


510


249


.488


33


20


T 95


D557


326


231


.709


12


25


Ax-erage


533


331


199


615


12


21



*K indicates that bird was killed for examination; D, that it died.
**Tumor located in both ligament of oviduct and oviduct.
***Tumor located in oviduct only.

In all other cases, tumor located in ventral ligament of oviduct.



The location of leiomyoma in the ligament of the oviduct and the heavy egg
production of chickens with this tumor lead to speculation of a causal relationship.
The report of Curtis (2) outlines well the musculature of the ligaments of the ovi-
duct, which is greater in amount in the ventral ligament than in the dorsal liga-
ment. Curtis indicated that the smooth muscle fibers of the ligaments were
directly connected with the muscle fibers of the wall of the oviduct and that
musculature in the ligaments must contribute to the physiological motility of the
oviduct. Greatest activity would occur during periods of egg production and



36 MASS. EXPERIMENT STATION BULLETIN 391

when persistent might reasonably lead to hypertrophy of the muscles. Jackson
(13) has called attention to the predisposition of smooth muscle in the ovary and
oviduct for proliferation. Sometimes this hypertrophy appears to progress
beyond functional requirements, thus leading to the development of a benign
neoplasm. Other factors must also be involved, for all hens with prolonged,
heavy egg production do not necessarily develop a leiomyoma of the mesosalpinx
and there was no direct correlation between the size of the tumor and production
index in this series.

Two birds with leiomyoma also had carcinoma of the ovary, and four others
with smooth muscle tumors had mixed tumors (carcinosarcoma) of the ovary.
The latter four cases are discussed in more detail in the section dealing with
carcinosarcoma.

Rhabdomyoma

Tumors derived from voluntar\- muscle tissue are usually considered rare,
and indeed but few cases in the chicken hav^ been described. Eber and Malke
(4) mentioned finding multiple rhabdomyoma in a poorly developed breast muscle
of a hen, and Reitsma (28) described a case in which multiple tumors were found
in the muscles of the maxilla, thorax, and abdomen. Peyron and Blier (26)
described a malignant myoma the size of an apple found in the leg of a rooster.

Two cases of neoplasia were diagnosed as rhabdomyoma in this study.

L T 303. An 8-month-old male, lame on the right leg, was killed by the
owner and submitted for examination. Isolated multiple tumors were found en-
closed within the sheaths of several muscles. These were found in the flexor
and extensor muscles in both thighs, in both pectoral muscles, and in muscles on
both sides of the thorax at the level of the second and third ribs. The largest
tumor measured 25 mm. in diameter and 35 mm. in length and was found in an
extensor muscle of the left thigh. The tumors were spindle-shaped, conform-
ing in general to the shape of the affected muscle. A striking feature was the
bilateral symmetry of location of 'the individual tumor masses. The visceral
organs and peripheral nerves were normal. The tumors were of a similar histologi-
cal composition. Malignant spindle-shaped cells replaced the muscle tissue
although bundles of degenerating muscle fibers were scattered in some areas.
The tumor cells were relatively long with tapering ends when viewed in longi-
tudinal section, and a very fine fibrillary character of the c\toplasm was noted.
On cross section, the cells were round and, when cut through the nucleus, the
latter occupied approximate!},- one-fourth the space of the cell. Longitudinal or
cross striations were not noted in sections stained with the routine hemato.xylin
and eosin combination. The nuclei of the tumor cells were elongate and some-
what vesicular. Mitotic figures were infrequently noted. The cells lay in rows
parallel to each other but did not tend to arrange themselves in compact bundles
although in some instances the cell processes seemed to anastomose with adjacent
cells. A fibroblastic stroma with well-developed collagen fibers formed a sup-
porting framework for the tumor. A Van Gieson's preparation of sections of the
tumor indicated the myogenic character of the tumor cells, as the cjtoplasm
had the staining property of muscle tissue.

2. T 141. The bird providing material for this case was a 10-month-old
pullet which had given a suspicious reaction to a test for puUorum disease and
was killed for examination. An irregular tumor mass measuring 20 X 15 X 7



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