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of cases and their classification will finally
clear up.

Somewhat generally speaking, there seems
to be no doubt that a tendency to cancer ex- 1
ists in some families; and if this be true, as
we believe it to be, we may also recall the
physiological suggestion referred to in other
chapters, that a toxin may pass from the pla- )
centa to the foetal circulation, predisposing
the foetus to a malignant formation at the in-
tervention of the secondary cause. It appears,
to us that, if cancer is inherited, the geo-
graphical history of cancer should have some
bearing on the subject, and to some extent we
have carried on investigations of our own in-



28 CANCER

this direction, although not enough to have
derived from them alone positive conclusions.
Investigations as to the character of disease
on an island (Pitcairns Island), which is so
remote from civilization that mixture of for-
eign blood has practically never been intro-
duced, shows that cancer has never been seen.
This is on the authority of Miss McCoy, a
trained nurse, a resident of the island, who
recently visited this country.

On some other small islands, not far from
each other, in the West Indies, but not so
much isolated, there is a large mortality from
malignant growth, while in the neighboring
island it is very small.

The above data, while not conclusive, and
not definite enough to be of much scientific
value, strengthen our views as to the part
played by heredity in cancer. This, combined
with what we have been able to find out about
the animal transmission as mentioned above,
with the knowledge we have of the transmis-
sion of other diseases resembling cancer,
backed up with our clinical experience —
while the exact method, the exact proportion,
or the exact laws governing such transmissions
in human beings is still a subject to be defi-
nitely settled in the future — have given us a



HEREDITY



29



very positive belief that there exists a hered-
itary tendency to cancer transmission; but
with the exact physiological and anatomical
laws governing these we are not as yet fa-
miliar.



PART II
NATURE OF CANCER

CHAPTER I

Nature of Cancer

We wish to make it clear that, in this chap-
ter as well as the preceding ones, we have no
desire to overload this little volume with ma-
terial which can easily be obtained by those
particularly interested in the subject, more
fully from many of the more recent works,
written by men more familiar than ourselves
with the pathological and histological tech-
nique; but it has seemed wise to call atten-
tion to the conclusions most generally accepted
at the present time, hoping that by such means
this book may be more of an aid to those in-
terested in the diagnosis of cancer who may
not have the opportunity to obtain this infor-
mation or are not already conversant with it.
At the same time it helps to make clear any
theories of our own we have desired to pub-
lish and enables us to present the results of

30



NATURE 31

any original work which we have done in a
somewhat more suitable setting.

Cancerous growths partake of the nature
of tumors, and hence a discussion of the
characteristics of tumors from a pathological
standpoint will be essential before we can
consider the minute structure of cancerous
growths. Powell White has defined a tumor
as a mass of cells, tissues, or organs, resem-
bling those normally present in the body, but
arranged atypically, which grow at the ex-
pense of the organism, without at the same
time subserving any useful purpose in the
host. This definition most satisfactorily ful-
fills all the conditions noted by pathologists
or surgeons in connection with tumors in gen-
eral. All tumors are derived from pre-
existent cells of the body, which they re-
semble more or less closely. However, in
certain conditions the characteristics of the
cells may revert to a primitive form so that
they no longer resemble the cells of the tis-
sues from which they were derived. Hence
their origin is defined. Tumors whose cells
preserve the characteristics of the original
tissue or organ are called typical growths,
but where the original characteristics of the
parent tissue or organ are lost the growth is



32 CANCER

spoken of as atypical. All tumors are com-
posed of two structures, a matrix or stroma,
and the parenchyma or the tumor cell proper.
It is the nature of the parenchyma that gives
the tumor its distinctive features. In various
tumors a wide variation in the relation of the
parenchyma to the stroma will be noted. The
general statement may be made that benign
tumors are typical. In malignant tumors, on
the other hand, the cells differ considerably
from the parent cells. There is noted a re-
version to the embryonic or vegetative form
of cell, and this reversion is spoken of as ana-
plasia. There exists a close relationship be-
tween the histological structure of the cell
and its pathology. That is to say, in innocent
tumors the cells which still preserve the
morphology of the parent may continue to
perform the functions of the organ or tissue
from which they were derived; but, on the
contrary, in malignant tumors where a varia-
tion from the prototype occurs, all functions
are lost except that of growth. In the nucleus
of the parenchymatous cells some new changes
will be observed in typical growths. The
nuclei are normal, but in atypical growths
wide variations occur in the size or shape of
the nucleus, or in multiplication, or in de-



NATURE 33

generative changes. The most common form
of variation occurs in the character of cell
division; that is, in rapidly growing tumors
instead of indirect cell division or mitosis
we shall note particularly around the margin
of the growth evidences of direct cell division
or karyokinesis.

The supporting network of the tumor or
its matrix is an outgrowth of the stroma from
the parent tissue. It carries the vascular and
lymph supply to the tumor. In the benign
type the blood vessels are well developed, but
in the malignant type they are capillaries, and
very often consist merely of a lining of endo-
thelial cells. The lymph supply is principally
through lymph spaces. No nerves have been
found in tumor stroma. Occasionally around
the periphery one may find nerve tissue that
has become incorporated in the tumor by the
invasion of neighboring tissue. A sponta-
neous disappearance of a tumor or a check
in its growth may occur, owing to a prolif-
eration of the connective tissue which chokes
the neoplastic elements. However, under
other conditions the stroma may assume ma-
lignant characteristics and proliferate in pro-
portion to the parenchyma. Or, on the other
hand, it may undergo calcareous degenera-



34 CANCER

tion. In innocent tumors no variation in the
character of the connective tissue will be
found and the parenchyma and stroma occur
side by side.

The method by which tumors proliferate
has been a subject of dispute among patholo-
gists. Some authorities have claimed that
the tumor cells cause a degeneration in the
cells of neighboring tissue, and that this de-
generation is a reversion to the type of cell
in the parenchyma of the tumor. These de-
generative, changes have been reported prin-
cipally around the periphery of the tumor, but
it has been impossible to substantiate such a
claim, because what may appear to be a sin-
gle tumor, on careful examination will ap-
pear to be a multiple tumor. However, the
more logical view entertained by the majority
of pathologists is that tumors are unicentric,
that is, they propagate by expansion and in-
filtration. When a tumor occurs by expan-
sion the increase in the tumor substance is
uniform throughout. This type of growth is
the rule in typical tumors. Malignant tumors
prefer to grow by infiltration, that is, by
peripheral extension, with little or no growth
in the center of the tumor, in fact the central
portion, deprived of its blood supply, may



NATURE 35

undergo a degenerative change or a necro-
biosis. From the point of view ot the sur-
geon and the clinician the most pertinent
classification of tumors is into groups, the
innocent and the malignant. The clinician's
conception of malignancy is radically differ-
ent from that of the pathologist. To the clini-
cian the growth which eventually entails a
fatal termination of the host is considered
malignant. The pathologist, on the con-
trary, classifies as malignant those tumors
whose cells possess definite characteristics,
and the tumor as a whole manifests properties
which experience has shown to necessitate a
fatal prognosis to the host. In other words,
to the clinician the criterion of malignancy is
the prognosis, but to the pathologist it is the
properties of the gross structure and its his-
tological characteristics. Those properties
which have been found by experience to be
invariably associated with pathologically ma-
lignant tumors are, first, rapidity of growth;
second, the vegetative or embryonic nature of
the cells; third, infiltration; fourth, the for-
mation of metastases leading to a local recur-
rence; fifth, ulceration; sixth, a tendency to
degenerative changes; and, seventh, the pro-
duction of cachexia and subsequent anemia.



36 CANCER

The rate of growth is not an invariable in-
dication of the nature of the tumor. The
general statement that malignant neoplasms
manifest a rapidity of growth, while benign
tumors are slow growing, admits of many ex-
ceptions. A slow-growing tumor is not nec-
essarily innocent. Sarcomata, however, are
almost invariably rapid in growth. Micro-
scopically, this rapidity of growth is indicated
by a peripheral invasion of adjacent struc-
tures and in the peripheral cells there will be
noted numerous points of mitosis. The
growth of the malignant tumor is independent
of the physical condition of the host.

Character of the Cell. — It was noted above
that cells of malignant neoplasms manifest a
tendency to a reversion to the primitive type,
and this reversion has been called by Hause-
mann "anaplasia." For mature cells, posses-
sion of two functions is necessary: (i) of
growth, and (2) the performance of some
specific work, e. g.^ secretion, contraction, and
so on. When such a cell undergoes a process
of anaplasia its specific function is lost, and
all the energy within the cell is expended in
unrestrained growth. Microscopical exami-
nation of cells will show evidence of the per-
formance of their specific work, as, for in-



NATURE 37

Stance, the cells of mucous membranes will
be observed to contain mucin, and this mucin
occurs in the cytoplasm, and frequently gives
the cell a goblet appearance. When anaplasia
takes place, the cytoplasm vs^ill be seen to have
diminished. The goblet appearance of the
cells is no longer noted and the nuclei are
relatively larger than under normal condi-
tions. It must be borne in mind, however,
that a diagnosis cannot be made upon changes
in one cancer cell, but an examination of the
tumor as a whole must be made, and if ana-
plasia is noted to be the rule throughout the
tumor, then it may safely be classified as ma-
lignant.

Metastasis. — The characteristic of neo-
plasms of the malignant type, which renders
their removal by surgical means a practical
impossibility, is the ability to form secondary
growths of a similar character at a distance
from the original tumor, and this character-
istic is called metastasis. But metastasis must
be distinguished carefully from a local re-
currence. The latter is the reappearance of
the malignant process in the immediate neigh-
borhood of the original neoplasm. The for-
mation of metastasis has been shown to be due
to the spreading of intact cancer cells from



38 CANCER

the primary focus to a distant site by a
combination of three processes: first, by the
lymphatic system; second, by the venous sys-
tem; and third, by the arterial system. In a
dissemination of cancerous cells the lymphatic
system plays the most important part. Such,
however, is not true of sarcomata, and most
probably this is due to the fact that the char-
acteristic cells of sarcoma, which are larger
than those of carcinoma, cannot pass through
the lymph walls, and consequently they are
passed on to the vascular system. The car-
cinomata cells, however, filter out through
the lymph walls before they reach the vas-
cular system. Cells from primary cancerous
growths may escape into the lymph system,
where they will be transported until they be-
come fixed, and at such point of fixation they
proliferate and produce a secondary growth.
Cancer cells from the primary growth may
escape into the lymphatic system. An accu-
mulation of such cells and their fixation, with
consequent proliferation along the lymphat-
ics, may cause the formation of a series of
nodules, thus producing what is known as
lymphangitis carcinomatosis. On the other
hand, the cells may not become fixed until
they reach the first lymph glands. The pro-



NATURE 39

liferation of the malignant cells here will
give rise to growths very similar to the orig-
inal tumor. In the draining of the lymph
through the lymph glands we would expect
the first series of glands to be involved, /. e.,
to manifest evidences of metastatic growths.
This is a very important diagnostic and prog-
nostic sign. Almost invariably, in cases of
malignant neoplasms, secondary tumors will
be found in the lymph glands that are the
first to receive the lymph from the neighbor-
hood of the original tumor. When, however,
the invasion has extended beyond the first to
the second series of glands, then the case must
be considered inoperable. Thus, in a case of
malignancy of the forearm, the first glands
to show metastatic growths will be the glands
of the antecubital fossa. However, if the
glands of the axilla also are involved, we
must consider the dissemination of metastases
too widespread to be relieved by surgical in-
tervention. The primary function of a lymph
gland is to check the spread of infection by
draining infecting agents from the lymph
stream, thus preventing them from entering
the vascular system. The lymphatics can
check cancer only for a time, and when the
cells have passed the first series of glands and



40 CANCER

have reached the second, this means that the
first barriers have been passed and most prob-
ably the invading cells have entered the blood
stream.

An invasion of the venous branch of the
vascular system may take place in two ways,
by the passage of the cancer cells from the
lymph system into the veins, or by the direct
invasion of the wall of the vein. In the first
case numerous metastases will be formed
throughout the lymphatic system and else-
where. In the second case, when the malig-
nant cells have found their way into the in-
tima and have eroded this, an extension of
the growth into the vein follows. If the vein
involved is of any considerable size, a fatal
hemorrhage is the issue. Whether the vein
be invaded in one way or the other, metastatic
growth will develop promptly in the lungs.
It may be said that a growth manifesting
hemorrhages has already involved the blood
vessels, and therefore the blood stream has
been burdened with intact cells that will pro-
duce metastatic growths.

An extension of cancer cells into the ar-
terial system is less common than the inva-
sion of the venous system. The arterial walls
ofifer greater resistance to the invasion of the



NATURE 41

growth. Cancer cells that primarily entered
the lymphatic system are removed from the
blood before it reaches the arteries. Cancer
cells entering the arteries would be carried
to the periphery, where they would be
blocked by the capillaries, producing periph-
eral metastatic growths. Veins, however,
carry the cells centrally. Secondary growths
even from primary peripheral tumors are
more frequently located centrally than in the
extremities.

In the peritoneal and thoracic cavities,
metastases may occur, independent of the
lymph or blood supply. Thus, a cancer of
the stomach may produce a secondary growth
in the ovaries or rectum. Such secondary
growths are due to the fact that cells become
dislodged from the original growth through
the movements of the viscera, or by surgical
manipulation, or palpation. Such cells may
be carried to a distant part of the cavity by
the peritoneal or pleural fluid, and wherever
they become fixed produce secondary tumors.

Our advice to the clinicians, then, is to
avoid all unnecessary manipulation of tumors
suspected of possessing malignant character-
istics or a tendency thereto.

Recurrence. — From the point of view of



42 CANCER

clinical medicine the salient feature of ma-
lignant tumors is their tendency to local re-
currence, that is, to appear, after their re-
moval, in the vicinity of the original growth.
The fact that tumor excisions have been
ineffectual in promoting permanent cures
must be attributed to this property, charac-
teristic of malignancies. Obviously it is of
little value as a diagnostic sign; however, a
knowledge of the means by which recurrence
takes place is of inestimable practical value
to the surgeon and should form the basis of
his technique.

We know that a malignant neoplasm does
not develop anew, but that cancer cells in a
number of possible ways have been left intact
in the organism and that these cells serve as
a nucleus for a second tumor. The cancer
cells migrating from the original tumor may
have become fixed at some distance from the
parent cell, and the new tumor due to these
cells may be separated from the original
w^ound by a margin of healthy tissue. As has
been previously pointed out, cancer cells
migrate principally through the lymphatic
and venous systems.

Elsewhere it has been shown that cancer
cells disseminate throughout the organism



NATURE 43

primarily by the lymphatic system. A dif-
ferent growth of the primary tumor may ex-
tend into the lymphatic ducts and proliferate
there, checking the flow of the lymph. In
the removal of all the tissues that microscop-
ically appears to be diseased, the cells that
have permeated the lymph system may be left
intact and a recurrence will follow through
these remaining cells. Particular attention,
therefore, must be given in surgical technique
not alone to the removal of the tissue that
has the gross appearance of a cancer growth,
but as well as to the excision of all tissue in the
neighborhood that is known to be prone to
the dissemination of cancer cells, and this
tissue should be removed as widely as the
anatomical relations to other parts will per-
mit. This fact must especially be borne in
mind in the surgical treatment of growths in
organs or tissues that have a rich lymph sup-
ply, as, for instance, the breast. By means of
chains of lymphatic nodes the breast is inti-
mately connected with the lymphatic glands
of the axilla, the supra-clavicular glands, the
mediastinal glands, and the glands of the op-
posite breast. Malignant neoplasms of the
breast which show a metastasis to any of these
glands may be considered inoperable. If,



44 CANCER

however, the case is operable, not only the
neoplasm, but the entire breast with the fascia
and pectoral muscles must be excised to pre-
vent a recurrence due to disseminated intact
cells. Cancer cells spread likewise to the
venous system. If a growth manifests evi-
dence of hemorrhage, in all probability the
growth has eroded the walls of the vein. The
destruction of the venous wall entails the en-
trance of malignant cells into the venous
blood, which means that metastases have taken
place and that recurrence will follow, due to
these metastases. Recurrence may be due also
to cells dislodged from the primary tumor by
mechanical manipulation, and this is particu-
larly true in recurrence within the serous
cavities, that is, within the thorax or the peri-
toneum. We cannot impress too strongly
upon the physician and the patient the risk
following undue handling of malignant tu-
mors. The therapeutic measures for the re-
lief of inflammatory processes, such as mas-
sage and rubbing, should never be employed
where the tumor is suspected of being can-
cerous, and the examinations of such growths
should be undertaken with extreme gentle-
ness and not repeated unless absolutely neces-
sary. Furthermore, the cancer cells may be



NATURE 45

disseminated by incising a growth to obtain
a piece of tissue for examination. At times
a rapid examination of the tumor by the
frozen section method may be thought ad-
visable, although positive conclusions cannot
be drawn from its results. In cases of this
kind, when practicable, a piece of tumor
should be removed by cautery, rather than by
the knife. Authorities who have had expe-
rience in handling cancer patients with and
without operations are agreed that metastases
in recurrence can be checked more rapidly in
patients where the tumors have not been ex-
cised or cut into for microscopical examina-
tion, than in cases that have been operat'
upon. It would seem, therefore, that surgical
interference — if not based upon an intimate
knowledge of the means by which cancer
cells disseminate, causing recurrence, and of
the methods of stimulating cancer cells to
proliferation — is apt to be ill-advised and
attended with unfortunate results.

Experimental work upon the transplanta-
tion of tumors in mice, from one individual
to another, have shown that a tumor may be
produced in the second host by the implan-
tation of intact cells subcutaneously. There-
fore, all that is needed to produce a second



46 CANCER

tumor is an inoculation with the living cells.
Whether cancer may be transplanted from
one human being to another in a similar man-
ner has not been proved, but statistics show
that the growth may be transferred from one
locality to another within the same individual.
As applied to the methods for treatment of
cancer, observation implies that cancer cells
coming in contact with other organs will pro-
duce secondary tumors. This is particularly
true of sloughing cancerous tumors. The
roof of the urinary bladder is very apt to
be infected from a cancer at its base. An in-
structive illustration of this point in connec-
tion with another portion of the body came
under the observation of one of the authors
recently. The patient, a man of middle age,
complained of severe penetrating pain in the
right epigastric region. The cause of the pain
was diagnosed by the surgeon as cholelithiasis.
During the operation, undertaken without a
suspicion of a malignant neoplasm, a cancer
was found in the upper right epigastric re-
gion. A piece of tissue was removed for
examination, and the wound came in contact
with the freshly incised growth. When it
w^as known that the abdominal growth was
malignant the wound was sutured and the



NATURE 47

patient was transferred to an institution de-
voted exclusively to cases of cancer. A short
time after his entrance a growth developed
along the abdominal scar and spread very
rapidly. Moreover, new vigor was appar-
ently given to the intra-abdominal growth,
which within a short time could be palpated
with ease; and at autopsy it was found to have
invaded the small intestines, and by pressure
upon the spinal cord to have produced paral-
ysis and complete anesthesia of the lower
extremities. Further, the use of a trocar in
tapping or exploring malignant tumors is in-
variably productive of the development of
secondary tumors along the line of entrance
of the instrument. The greatest number of
recurrences due to implantation of cancer
cells in healthy tissue are reported in the ex-
cision of malignant growths of the female
genito-urinary tract. Cancer of the uterus is
probably the most common form of the mal-
ady in the female sex. The removal of the
tumors of the uterus by vaginal hysterectomy
is frequently followed by the development of
the tumor in the scar in the apex of the va-
gina, or the sides of the vulva (in cases of
narrow vaginal orifice), when incisions are
made at these points to afford more space for



48 CANCER

the removal of the uterus. It is practically
impossible to keep these cut surfaces from
touching the cancerous growth and thus to
avoid an implantation of the cancer cells in
the vagina. The use of the cautery, however,
to destroy as much as possible of the growth
before its removal, although it does not ob-
viate all possibility of implantations, never-
theless may diminish the chances of infection


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