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The presence of lymphoid cells resembling those found in areas of lymphocytoma
in the lumen of blood vessels was taken to represent involvement of the blood
stream. In some instances actual erosion of a vessel wall located within a mass
of tumor was found and obviously such an erosion would permit a mechanical
washing of tumor cells into the circulation. It was necessary to exercise consid-
erable care in some cases to distinguish between a leukocytosis of heterophils
or lymphocytes and abnormal numbers of tumor cells in the blood.

There were only slight differences in the degree of involvement of the different
forms of lymphocytoma (Table 8). Grade 4 involvement was noted more fre-
quently in cases of nodular lymphocytoma and least often in the combined diffuse



NEOPLASTIC DISEASES IN CHICKENS 13

Table 8 — Degree of Involvement in 213 Cases of Lymphocytoma
Figures represent percent of affected organs or tissues having the respective

degree of involvement. Cases are grouped twice: according to form of tumor

and on the basis of nerve involvement.

Number of Degree of Involvement**

Organs and

Tissues Grade 1 Grade 2 Grade 3 Grade 4

Involved*

Form of Tumor

Diffuse 387 12.9 16.5 26 9 43 7

Nodular 66 18.2 19,7 15. i 47

Diffuse and Nodular.. . 369 16.8 21.7 29.8 31.7

Nerve Involvement

No nerves involved. .. , 517 15.2 17.4 27.8 39.6

Nerves involved 305 15.1 22.0 26.2 36.7



Total 822 15.1 19.1 27.2 38.6

♦Affected nerves and blood not included.

**Graded from 1 to 4, with Grade 1 representing a small amount of tumor and Grade 4 heavy
infiltration.

Table 9. — Weight of Organs Affected with Lymphocytoma,

Mean weights expressed as percent of body weight, with standard error of the
mean. Figures in parentheses indicate number of observations in group.

Mean Weight as Percent of Body Weight

Liver Spleen Kidney Ovary

Form of Tumor

Diffuse 12.46± .92 .71±.06 1.19+14 1.48+.40

(27) (21) (43) (17)

Nodular 10.61± .94 .65±.23 .85 + . 12 .70 + .1S

(11) (7) (10) (4)
Diff use and Nodular. . 9.75 + 1.20 .89+29 .79+06 .94+. 27

(27) (21) (36) (8)
Nerve Involvement

No nerves involved 11.82+ .68 .83 + .15 .93+09 .97+28

(53) (41) (60) (19)

Nerves involved 7.68 + 1.22 .51+12 1.12 + .22 1.69 + .45

(12) (8) (29) (10)

Total 11.02+64 .78+13 .99 + .08 1.22+25

(65) (49) (89) (29)

Organs not affected with

Lvmphocvtoma 3.80+ .40 .30 + .05 .35 + . 01 .46 + . 21

(9) (11) (5) (4)



14 MASS. EXPERIMENT STATION BULLETIN 391

and nodular form of the disease. Practically no difference was noted in the
various grades of involvement between the group of lymphocytomas in which
nerve tissue was affected and the group in which the nerves were free of tumor.

The organs of some of the cases of lymphocytoma w'ere weighed at the time
of necropsy. The weights of the organs most commonly found affected with
lymphocytoma are listed in Table 9. They are expressed as percentage of carcass
weight so that comparisons ma\- be made between the different groups. No
attempt was made to distinguish between the weight of organs with different
degrees of involvement, although those with Grade 4 infiltration were usually
heavier than those with less infiltration. The relative number of different grades
included in the various groups is approximately comparable. In a few instances
weights were obtained on unaffected organs of birds with lymphocytoma. These
are indicated in Table 9 and serve for comparison with weights of affected organs.
The standard error of the mean was calculated for each group. The mean values
for the liver, kidney, and ovary when affected with diffuse lymphocytoma were
larger than when they were affected with either of the ether two forms of lym-
phocytoma. In the case of the spleen, the differences were not significant. A
comparison of the group with nerves affected and the group with nerves not
affected indicates a smaller liver and spleen and a larger kidney and ovary in
cases in which the nerves were also involved, but only in the case of the liver was
the difference statistically significant.

Egg Production. — Data on the egg production of chickens that developed
lymphocytoma were available for only 15 cases (Table 10). These data are
meager yet they suggest certain features on which more information is needed.
All of these cases came from one flock on which careful records were kept. The
productive life, that is, the interval between the first and last egg produced,
varied from 3 to 333 days (average, 104' days). During this time the birds laid
from 2 to 176 eggs (average, 60 eggs). The productive index as used is an arbi-
trary value obtained by dividing the number of eggs laid by the productive life
in days. This factor varied from 0.074 to 0.863 and averaged 0.584. A similar
production index was calculated from the records of the flock in which these
cases were found. Inasmuch as the average productive life of the diseased birds
was the first 108 da>s of production, a comparable set of figures was obtained
from the flock records. The production of the flock during the first 150 days
of the laying period averaged 80 eggs per hen, which provides a production index
of 0.534 that may be compared with the findings in the cases of lymphocytoma.
Ten of the hens with Ij-mphocytoma had laid 25 or more eggs before developing
the disease; and of these, eight had a production index higher and two a produc-
tion index lower than the average for the flock. These results, compared with the
slightly higher average production index for the group that developed lympho-
cytoma suggest that those hens which developed the disease were average to good
producers.

Another point of interest in connection with egg production was the interval
between cessation of egg laying and necropsy. It seems obvious that the presence
of a disease condition such as lymphocytoma would have an effect on egg pro-
duction. It is generally recognized that many acute diseases of chickens, such as
respiratory infections, will cause a sudden decrease or cessation of egg production.
The interval between the last egg laid and necropsy of a case of lymphocytoma
may give some indication of the duration of the disease. In the cases reported,
this period was relatively short, averaging 38 days and ranging from 4 to 73 days
(in eight of the cases the interval was from 30 to 40 days). The extremely short
interval of 4 days noted in Case T 1743 may have been due to the fact that the
tumc of the bursa of Fabricius caused sufficient obstruction to preclude laying



NEOPLASTIC DISEASES IN CHICKENS



15



of an egg, as a misshapen egg was found in the oviduct. The period between the
last egg laid and necropsy did not seem to be affected either by the type or by the
extent of the disease.



Table 10. — Dal-^ on Egg Production of Chickens with Lymphocytoma.

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 da vs.



Case


Age at


Pro-


Number


Pro-


Interval


No.


Necropsy


ductive


of Eggs


duction


from Last Organs Affected and Degree




(Days;


Life

(Days)


Laid


Index


Egg to of Involvement
Necropsy
(Days)



T 2104



T 13 75

T 124



T 43
T 168



Form of Tumor — Diffuse



T 35


*K


314


47


T 66


D


480


210


T 169


D


316


3


T 246


K


550


^ii


T 3 743


D


409


204


T 117


K


315


108



K 306



D 379



D 354
K 253



K 345
D 338



K 268



28
116
2
173
176



63



.596
.552
.667
.520
.863
.074



39

73
44
44
4
13



Liver 4, intestine 4

Peritoneurn 4

Ovary 3, heart 3. marrow 3

Skin and subcutis 4

Bursa of Fabricius 4

Ovary 4, liver 2, kidney 2,
lung 3, adrenal 2, periton-
eum 1, nerve in 4 sites

Ovary 4, peritoneum 4, ad-
renal 4, pancreas 3, intes-
tine 2, nerve in 2 sites



108



Form of Tumor—

67 .62C



Nodular

40



Liver 4, spleen 4, kidney 2,
marrow 1



Form of Tumor — Diffuse and Nodular



122
34



79
129



89
16



52
43



.730
.470



.659
.333



.678



21



47
35



T 155


K 299


28


19


.679


T 164


D 313


45


26


.578



30



Liver 1, kidney 1, peritoneum
1, Bursa of Fabricius 4

Liver 3, kidney 4, marrow 2,
adrenal 1

Liver 4, spleen 3. kidney 3

Ovary 4, kidney 4, adrenal 4,
musculature 3, heart 3,
lung 2, spleen 1

Ovary 3, skin and subcutis 4,
thymus 4, adrenals 2, peri-
toneum 2, lung 3, proven-
triculus 2, intestine 4.
spleen 1, kidney 1, one
nerve

Liver 3, peritoneum 4, one
nerve

Liver 3, lungs 3, peritoneum
4, adrenal 2, proventricu-
lus 1, one nerve



Average



38 Four organs per case



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



Discussion

Deposits of neoplastic lymphoid tissue in nerves of chickens are the subject
of controversy as to whether they represent foci of lymphocytoma or are a part
of the disease known as fowl paralysis. A consideration of this controversy
naturally leads to the question of whether or not a distinction should be drawn
between fowl paralysis and lymphocytoma. In other words, should each of these
conditions be considered as a separate entity? During the last fifteen years this
subject has been argued pro and con. The results of attempts at experiniental
transmission of the conditions have not led to a conclusive answer. The results
and conclusions as set forth in the excellent monograph on fowl paralysis by
Pappenheimer, Dunn, and Cone (24) pilblished in 1926 are most modern and are



16 MASS. EXPERIMENT STATION BULLETIN 391

comparable with more recent results obtained by experiments indicating a trans-
missible character for fowl paralysis and a possible etiological relation with lym-
phocytoma. Opposed to the results indicating experimental transmission of
fowl paralysis are experiments of other investigators who obtained negative
results.

The present study, being confined to observations on pathological anatomy of
lymphocytoma, does not permit conclusions on questions concerning etiology.
Deductions, therefore, must be considered in this light without regard to the
results of transmission experiments.

The pathology of the nerve lesions seen in fowl paralysis has been described
as both inflammatory and neoplastic in character. The inflammatory lesions
consist of an infiltration with polyblasts (lymphocytes, histiocytes, and plasma
cells), oftentimes associated with a proliferation of Schwann sheath cells and de-
generation of neurons in the ganglia. The infiltration may be mild and con-
fined to perivascular areas or diffuse; or dense and diffusely scattered in the nerves.
The inflammatory lesions are usually confined by the nerve sheath, although in
some instances a similar perineural infiltration may be observed. The neo-
plastic lesions difTer from the inflammatory in that the infiltrating lymphoid cells
have a neoplastic character, are actively multiplying, and m,ay be so aggressive
as to almost entirely replace the nerve elements within the nerve sheath. Such
neoplastic areas may readily encroach upon and penetrate the nerve sheath with
infiltration of the adjacent tissue. It would be a simple matter to separate cases
of fowl paraKsis into a group with inflammatory lesions and a group with neo-
plastic lesions if it were not for those cases in which one type of process seems to
merge into the other. Such a separation would, therefore, have to be made on a
purely arbitrary basis.

The primary purpose was the study of a group of lymphocytomas and not of
fowl paralysis, which meant that it was necessary to establish certain criteria
for the cases to be included. Such a plan is based on the premise that lympho-
cytoma and fowl paralysis are different disease processes. In view of the tact
that lymphocytoma may be found in almost any tissue of the body, it did not
seem reasonable that nerve tissue would be immune or resistant to such a tumor.
The plan developed and followed for this study, therefore, was to include all
cases in which any organ or tissue, including nerve, was suspected of being in-
volved with neoplasia. Those cases of fowl paralysis in which gross examination
made it reasonably certain that the lesions were confined by the nerve sheath,
leaving the visceral organs free of neoplasia, were not included. The plan would
thereby exclude many cases of fowl paralysis in which the nerves were infiltrated
with neoplastic lymphoid cells, for these cannot be distinguished on gross exam-
ination from the cases in which the lesions are inflammatory in character (Plate
III, Figures 5 and 6).

Among the 213 cases of lymphocytoma were 83 in which nerves were involved
(Table 2). Of this number (83), there were 23 cases in which the nerve lesion
or lesions were confined to an area in which the adjacent e.xtra-neural tissue was
likewise infiltrated with lymphocytoma. The question arises of whether or not
such cases represent an extension of the process from within the nerve to without
or the reverse. As judged from this material, it would seem that both would
occur. There were 19 cases in which nerve lesions were confined to either the
nerve of Remak* or the anterior mesenteric plexus and immediate nerve radical,
and lymphocytoma was found in the adjacent tissue of the gonad, peritoneum,
or adrenal. In the majority of these the pathology suggested that the tumor



The main trunk nerve of the mesentery arising from both the anterior and posterior mesenteric
plexuses of the autonomic nervous system.



NEOPLASTIC DISEASES IX CHICKENS 17

invaded the nerve from without, for the nerve was the more lightly infiltrated
(Plate III, Figure 2). In 3 cases, lymphocytoma was confined to the soft tissue
surrounding nerves in the regions of either the brachial or lumbosacral plexuses
and immediate radicals.

An interesting finding in this collection of lymphocytomas was the relatively
small number of cases of the nodular type in which nerves were involved (Table 2).
A ratio of about 2 to 3 existed between the cases with and without nerve involve-
ment when lymphocytoma was either diffuse or diffuse and nodular in type.
This ratio changed to 1 to 9 in nodular lymphocytoma. Actually only two cases
of nodular lymphocytoma were observed in which nerves were involved. One
of these was an extension of lymphocytoma of the adrenal and ovary into an
anterior mesenteric nerve ganglion and might easily have been overlooked.
The significance of this finding is obscure. The number of cases is small, and it is
possible that the observation may be due to chance.

The explanation of the group of 60 cases with nerve involvement at a site re-
moved from lymphocytoma of other tissue is subject to a difference of opinion.
A number of conceptions are possible. They may represent instances of metas-
tasis of the tumor to a nerve from a primary focus situated in a visceral organ.
They maN' have developed in the nerve in response to a hypothetical causative
agent of lymphocytoma. They may be lesions of fowl paralysis existing ccinci-
dentally with lymphocytoma, assuming that there are separate agents respon-
sible for each disease. Or a single agent may be responsible for both lymphocytoma
and fowl paralysis and the response in nerve or other tissue depend upon factors
as yet unknown. These questions cannot be answered from the data, and a satis-
factory explanation must await settlement of the problem of etiology of the
diseases.

No satisfactory explanation has been advanced for the existence of different
types of lymphocytoma. Nodular and diffuse lymphocytoma have been rec-
ognized and described by Feldman (7) and Mathews and Walkey (19), as well
as others; and another manifestation — combined diffuse and nodular lympho-
cytoma — has appeared in this study. A possible explanation for these different
types has developed as a result of this study, based on the theory that the host
exerts a variable degree of resistance against growth of the tumor. Thus, diffuse
lymphocytoma is a disease in which little resistance is offered on the part of
the host, and the nodular form develops when considerable resistance to growth
is offered. The diffuse and nodular form results when the resistance is moderate
in degree. The data do not provide conclusive evidence for such a theory, but
do offer some support. On the basis of such a contention, one would expect that
the type of disease in which most resistance was offered by the host would be
the least widespread, and this was the finding in the case of nodular lympho-
cytoma (Table 6). One might also expect that the degree of individual organ
involvement would be least in the nodular form, and it was found that 37.9
percent of the affected organs were Grade 1 or 2 in cases of nodular lympho-
cytoma as compared to 29.4 percent Grade 1 or 2 in cases of diffuse lymphocytoma
(Table 8). Although data with respect to organ weights indicated no statistically
significant difference between the three forms of lymphocytoma (except in the
case of the kidney), the suggestion remains that the relative weights are greater
in diffuse lymphoc\toma. A larger series of cases in which the organs have com-
parable grades of involvement should be examined to settle this point. The
histology of the different types also lends itself to support of the theory of re-
sistance on the part of the host. A nodular, circumscribed focus of lympho-
cytoma surrounded by a connective tissue wall of variable thickness suggests an
attempt on the part of the host to localize and wall off the tumor from the rest
of the body (Plate III, Figure 4). Reactions of this type have been noted in



18 MASS. EXPERIMENT STATION BULLETIN 391

the later stages of regression of implants of a transplantable hmphoid tumor
of the chicken (Olson 22).

The results of the study seem to indicate that lymphocytoma is a systemic
disease affecting the widely distributed lymphoid cell system. The histogenesis
of lymphocytoma, therefore, does not conform with the commonly accepted
theory of histogenesis of neoplasia in which it is believed that tumors arise as the
result of a single cell or localized focus of cells assuming a state of neoplasia. In
spite of this feature, the invasiveness and apparently purposeless progressive
growth of lymphocytoma seem sufficient to characterize the disease as a neo-
plasm. Lymphoid tissue capable of becoming transformed into the malignant
cells of a lymphocytoma probably exists in nearly every part of the body, yet
certain organs were more often affected with the disease than others. These
organs are not necessarily those rich in lymphoid tissue, for the bone marrow,
thymus, and bursa of Fabricius in which such tissue is abundant were not found
affected as often as other organs relatively deficient in this respect. It is reason-
able to believe that the lymphoid tissue of such organs as the liver, spleen, kidney,
and gonad, in which lymphocytoma was more commonly found, is more sus-
ceptible to the action of the hypothetical causative factor or factors of lympho-
cytoma. This susceptibility may be due to some particular functional state of
the lymphoid tissue in those organs in which the disease occurs.

Myelocytoma

PentimaUi (25) described two cases of this disease and applied to it the term
"myelocytoma." Mathews (17) later gave an excellent description of the gross
and microscopic characteristics of 37 spontaneous cases to which he applied the
term "leukochloroma," adopted from a similar tumor of man which often has a
green color that is lacking in myelocytoma of the chicken. This fact together
with the prior application of the term "myelocytoma" would seem to be ample
justification for the use of the latter term. Twenty cases of myelocytoma were
encountered in this collection of neoplastic disease of the chicken. These cases
fit into the descriptions given by Mathews and, therefore, only a dursor\- resume
is necessary.

The average age at necrops}- of 8 birds that died was 35.2 weeks, with the
oldest 55 weeks and the youngest 16 weeks. The average age of 12 birds that
were killed for examination was 32.7 weeks, with a maximum of 56 and a minimum
of 5 weeks. The age of birds with myelocytoma was more nearly like that of
birds with lymphocytoma than that of birds with leukosis (Tables 3, 11, 13).
The sex distribution was 15 females and 5 males, or a ratio of 3 to 1. Two cases
of myelocytoma were found to be associated with leukosis and are discussed in
the section dealing with leukosis. One case was found to be associated with
embryonal nephroma, and one with fowl paralysis.

The liver was involved with the tumor in 16 instances. The amount of in-
filtration varied considerably but in general was moderate and usually confined
to the periportal areas. In two cases there was a rather marked hyperplasia
of lymphoid elements in the periporta' areas in addition to infiltration with neo-
plastic myelocytes. Since myeloid metaplasia may, occur in the periportal areas
of the liver in chickens without myelocytoma, it becomes necessary to establish
an arbitrary standard for the diagnosis of myelocytoma in the liver. The stand-
ard set in this work was that the myelocytes of a myelocytoma were to be at the
same stage of development; that is, there should be no evidence of transitional
forms from the lymphoid elements of the periportal areas to mature granulocytes.
When such a condition was found, the process was regarded as myeloid meta-
plasia and not myelocytoma. Myeloid metaplasia may be noted frequently



NEOPLASTIC DISEASES IN CHICKENS 19

in the liv^er of the chicken and was a secondar\' finding in the livers of two cases
of myelocytoma. The livers affected with m\elocytoma were usually not so large
as those affected with lymphocytoma (Plate IV). The average weight of eight
affected livers was 5.65 percent of the body weight, with extremes of 14.6 and
3.2 percent (Table 11). The figure for average size is slightly high, for the value
in six of the eight cases was less than 5.65 percent.

Table 11. — Summary of Data on Twenty Cases of Myelocytoma.
Figures in parentheses indicate number in group.

Age at Necropsy Weight of Organs Expressed

(Weeks) as Percent of Body Weight



Died Killed Liver Spleen Kidney

(8) (12) (8) (8) (4)



Maximum 55 56 14.6 .86 .80

Minimum 16 5 3.2 .37 .39

Average 35.2 32.7 5.65 .55 .622

Additional Notes: 2 cases were associated witli granuloblastic leukosis.
1 case was associated with embryonal nephroma.
1 case was associated with fowl paralysis.

The spleen was involved in 12 of the 20 cases. The average size was 0.55
percent of the body weight in eight instances. Diffuse infiltration of the pulp
with neoplastic myelocytes was the characteristic finding.

In eight instances the kidneys were affected. The degree of involvement varied
from a slight intertubular infiltration to almost complete replacement of paren-
chyma with solid masses of myeloc\tes. The average weight of four affected
kidneys was 0.622 percent of the body weight. This figure is not a fair example,
for it represents the findings on only two cases.

Other organs and the number of times they were found affected are as follows:
gonad 13, parathyroid 8, thymus 6, lung 5, thyroid 5, adrenal 4, pancreas 3, and
heart 2. Histological examination was made of the lung and thymus in only
6 cases. The nerve ganglia of the anterior mesenteric plexus were infiltrated by
extension from the adrenal in 4 cases (Plate V, Figure 1). In 12 cases, there
were either sheetlike or nodular masses adjacent to the visceral or parietal peri-
toneum. A common finding was the arrangement of soft white nodular tumor
tissue near the ribs, concentrated at the costochondral junctions or on the sternum
(Plate IV). In one instance the tumor was spread along the spinal column of
the trunk, tending to infiltrate the bodies of the vertebrae, as in two cases de-
scribed by Mathews. The bones of the skull were affected with myelocytoma
in two instances (Plate V, Figures 3 and 4). In one, the process was confined to
the region of the nasal sinus; and in the other, the disease affected the dorsal aspect
of the cranium and was also found on the ventral aspect of vertebral column in
the region of the testis.

A variable number of m,>eloc>'tes was noted in the lumens of the blood vessels
of tissues at the time of microscopic examination. Smears of the blood obtained
before death were available for study in only four cases. In several cases imprint
preparations of tumor nodules were prepared by staining with May-Grunwald



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