admissibly arise from pre-existing cells, it follows that the
primitive cells of a tumor are derived from those resulting from the
segmentation of the ovum or are introduced from without. Numerous
experiments have been made with a view to the inoculation of tumors,
the transplantation of living fragments of the latter to the living
tissues of a healthy individual, for the sake of producing a tumor,
but hitherto almost invariably without success. The alternative
remains that the embryonal cells are those whose derivatives are
present in, and form the essential element of, the morbid growth. All
tumors may thus be said to have an embryonal origin. As the
segmentation of the ovum eventually results in the production of
normal tissues and groups of tissues whose structure and function are
wholly different, so the possibility of the production of abnormal
groupings of tissue with corresponding irregular manifestations of
function is obvious.
The cells of the part from which a tumor arises may be regarded as
indifferent, those whose limitations of growth, like the early
embryonal cells, are only determined by the changes they undergo, or
their limits of growth may be already defined in kind, and their like
be produced in the formation of the tumor. The origin of a tumor thus
presupposes the existence of such indifferent cells, or the presence
of those whose limit of transformation has already been reached. The
leucocytes of the body, whether found as white blood-corpuscles or
lymph-corpuscles, or as the wandering cells of connective tissue, are,
as Virchow has indicated, such indifferent cells. Always present and
apparently transitory, what they are to become can only be determined
from their condition and surroundings at the time of observation.
Although their actual transformation into the various cells of a more
permanent type is merely a matter of inference in the growth of
tumors, the evidence presented by Ziegler[78] leads directly to the
conclusion that their presence is necessary to the new formation of
tissues whose growth is the result of an inflammatory process. These
tissues may occur under such restrictions as permit them to be
classified as tumors, and the granulomata, or tumors whose tissue
resembles that of the granulations upon the surface of a wound,
represent a well defined group in structure as well as method of
origin.
[Footnote 78: _Op. cit._, 150.]
{107} The production of the cells of a tumor from indifferent cells is
at present an assumption, based upon the frequent presence of the
latter within tumors and in their vicinity; and the obvious objection
arises that even if the presence of these cells is admitted as
indispensable, it by no means follows that they are directly
transformed into the more characteristic cells of the tumor. That they
may serve for the nourishment of the amoeboid cells of certain tumors
is suggested by the existence of both in morbid growths, and the
well-known property of amoeboid corpuscles to take in formed material,
even cells, from without.
The origin of tumors from cells whose limits of growth are already
defined is rendered probable from the absence, entire or in great
part, of indifferent cells from certain tumors, and the direct
continuity of the latter with a similar normal tissue of the body.
Various tumors show such an intimate relation, and there is no sharply
defined border-line between the normal tissue and that which
represents the tumor. The occasional presence of islets of well
characterized tissue at points more or less remote from the normal
position of such tissue at the time of their discovery suggests a
feasible source for an eventual tumor. Virchow long ago called
attention to isolated nodules of cartilage within bones in the
vicinity of epiphyseal cartilages, probably detached from the latter,
which might serve as the origin of a cartilaginous tumor in this
region. This inclusion of tissue is also suggested by the frequency of
certain tumors in certain regions where the developmental conditions
are favorable. Lücke[79] mentions the frequency of dermoid cysts near
the median line of the head, the vicinity of the eye, and the side of
the neck. Such regions are those where fissures exist during foetal
life, with normal involutions of the outer germinal layer; which
involutions may become irregular, and eventually included or shut in,
as the fissures become closed. A similar explanation is offered for
the frequent occurrence of cartilaginous tumors at the angle of the
jaw, it being thought probable that bits of embryonal cartilage,
during the formation of the ear, become included in the salivary
glands.
[Footnote 79: _Volkmann's Sammlung klinischer Vorträge_, xcvii. 819.]
In like manner, Cohnheim explains the frequent occurrence of certain
epithelial tumors at the orifices of the body--the cervix uteri and
the vicinity of the tracheal bifurcation--not through the exposure of
these parts to injury, but because they are regions in which embryonal
irregularities of development are likely to arise.
That congenital, local peculiarities are an important element in the
origin of tumors has already been strongly advocated by Virchow. Not
only are children born with tumors, but instances of growths
eventually arising from birth-marks, and the occurrence of certain
tumors in the same locality in successive generations of the same
family, are sufficiently familiar.
Although certain tumors are admitted to be due to congenital
peculiarities of tissue, and even to represent atypical growths from
embryonal tissue, the theory of such an embryonal origin for all
tumors seems unnecessary. The resemblance in symptoms as well as in
appearance, and even in structure, of certain tumors to inflammatory
products, and their frequent association with these, has led to the
suggestion of an irritant as an exciting cause for the tumor, even in
the absence of local peculiarities of tissue. {108} It is obvious that
were the embryonal theory of origin, as extended by Cohnheim,
universally applicable, the growth demands something more than a focus
of embryonal cells. An immediate cause for their growth after a
dormant period, extending even into old age, is required. Cohnheim
finds such in a sufficient supply of blood. He attributes the
development or rapid growth of the tumor to this feature, and supports
his view by the usual appearance of exostoses when the skeleton is at
its period of most vigorous growth, and of dermoid cysts at a time
when the formation of the beard indicates active developmental
conditions in the outer germinal layer.
The growth of ovarian cystomata at and after puberty, and of these and
mammary tumors during pregnancy, are also explained on the ground of a
more abundant supply of blood at such periods. He and others find in
physiological conditions a source for the abundant blood-supply--that
is, the efficient nutrition for the growth of a tumor. The necessity
of sufficient nutrition in the development of tumors is universally
admitted, and its source may be looked for in pathological as well as
physiological conditions.
The existence of an irritant of some sort often seems probable, and,
although its absence is more frequently determined than its presence,
it is obvious that when present it may be overlooked. Although
traumatic irritants of considerable mechanical severity exist in but a
small percentage of tumors, their occasional influence in the
production of morbid growths is not to be denied. Their action may be
explained as producing a congestion or as enfeebling the opposition of
physiological tissues to pathological growths. The importance of an
irritant as the exciting cause, however its action may take place, is
supported not only by the sequence of injuries and tumors, but also by
the frequent occurrence of tumors in parts exposed to injury and
irritation. Such exposure may result from position, structure, or
function. The orifices and prominences of the body, the retained
testis in the inguinal canal, are notoriously liable seats of tumors.
Soft, friable, and slightly resistant structures, like mucous
membranes, are not only the frequent place of origin of tumors, but
the most exposed parts of such structures are oftenest affected. The
exposure resulting from function is manifest by the relation presented
by the periods of greatest functional activity of the growth of tumors
in such organs as the mammary gland, uterus, and ovaries.
The importance of an irritant is still further suggested by the
association of tumors with inflammation. The growth of tubercles and
cancer from serous membranes is frequently accompanied by an acute
inflammation of the latter; fibrous tumors and chronic interstitial
inflammations often coexist, while elephantiasis is usually preceded
by recurrent, erysipelatous inflammation of the skin.
The recent discovery of infective organisms as an exciting cause for
many of the members of an entire group of tumors, the granulomata, has
resulted in making prominent the etiological rather than the
structural features of the tumors concerned.
Local peculiarities of tissue, whether congenital or acquired, are
thus regarded as representing the beginnings of the growth. With the
multiplication of the cells their transformation may take place or a
change in their grouping may arise. The essential condition in the
production {109} of the morbid growth is that the formation of the
cells should take place at an abnormal time or place and should
progress in a normal or abnormal manner.
The growth takes place with greater or less rapidity in one or another
direction according to the nature of the tumor and its seat. The more
closely the tumor resembles the normal structures of the body, the
slower is its growth; the more it differs in composition, the more
rapid is its progress. This difference may arise from a predominance
of cells over intercellular substance, as in the case of the sarcoma,
or it may result from an atypical combination of tissues, as seen in
the development of epithelium and connective tissue in cancer.
The seat of the tumor is of importance mainly on account of the
vascular supply of a part and the more spongy or yielding nature of
certain regions. That the more abundant the nutrition of certain
regions of the body, the more favorable the opportunities for growth,
may be admitted without question. The spongy nature of tissues implies
a predominance of cavities over solid constituents. These cavities are
lined by surfaces which represent, on the one hand, the walls of
lymph-spaces, on the other the free surfaces of the body exposed to
the air, as the mucous or cutaneous surfaces and the pulmonary
surface. The rapidity of growth in the direction of the least
resistance is amply shown in the projection of tumors above the
surface of serous membranes and the frequent presence of fungoid
excrescences in various parts of the body.
The growth of tumors extends in all directions, but a distinction has
long been drawn between the concentric or interstitial manner of
growth and the excentric or infiltrating form. This distinction is
based upon the presence of a sharply defined limitation of
pathological and normal tissues or upon the absence of such a
limitation. Such a distinction is merely of relative importance, as
certain tumors may grow in both ways. This is best observed in those
bulging superficial tumors whose base is irregularly extended into the
continuous healthy tissues.
The concentric variety of growth includes those tumors which have
commonly been described as encapsulated, and which are capable of
ready enucleation from their surroundings in virtue of a thin layer of
loose connective tissue lying between the tumor and the contiguous
tissue. Such a capsule represents the matrix, the pia mater, in which
lie the blood-vessels going to and coming from the tumor, and is often
nothing else than the distended and hyperplastic fibrous tissue
remaining after the absorption of the muscular fibres or gland-cells
from the tissues surrounding the morbid growth.
The excentric, peripheral, or infiltrating extension of the tumor
takes place when the surrounding parts are invaded by the active
elements of which the tumor is composed. The amoeboid property of the
cells of certain tumors is well known, and the possibility is
admissible that the indifferent cells of the body, so often
accumulated at the periphery of the growth, become impregnated with a
formative function by the constituents of the tumor. Such amoeboid and
wandering cells represent a means through which the growth of the
tumor may become extended in its vicinity as well as in more remote
parts of the body.
The extension in the vicinity may be continuous or the reverse, the
latter through the formation of secondary nodules, which may {110}
eventually become fused with the primary mass. The continuous growth
takes place, as has been more particularly shown by Köster, along the
lymph-channels surrounding the tumor, which may become filled,
distended, and eventually obliterated by projections from the
neoplasm. Both methods of peripheral growth, by secondary nodules and
continuous extension, represent an infection of the surrounding
tissues, especially if it be admitted that the cells through which the
increase is accomplished are direct descendants of the pre-existing
cells of the part. Not only does the extension take place through the
lymphatic vessels about the tumor, but blood-spaces as well as
lymph-spaces may be invaded. Thrombi are then found whose structure is
frequently that of the tumor, and whose connection with the same is
direct through the perforated wall of the vessel. These features in
the growth of tumors lead directly to the consideration of the means
by which multiple tumors appear in remote parts of the body after a
single tumor has appeared in a given locality, and after the removal
of such a primitive growth.
The distinction between primary and secondary tumors is now so obvious
that one is inclined to forget that the presence of numerous tumors at
various parts of the body was at one time regarded as evidence of the
constitutional or dyscrasic nature of the morbid growth. Such a
multiplicity seemed to indicate that the blood was charged with the
constituents of the tumor, which were deposited at various parts of
the body.
Although certain multiple tumors may be present in different
localities without an apparent relation between an antecedent and a
subsequent growth, such tumors are usually limited to certain systems
of the body. Multiple bony tumors are found growing from bones,
fibrous and warty tumors from the skin, and fibro-myomata from the
uterus. Cohnheim's theory of the embryonal origin of tumors may seem
applicable in such cases, but the frequent association of the
osteomata with chronic inflammatory conditions, of cutaneous warts and
fibrous tumors with local irritative processes, makes such a
hypothesis unnecessary.
Those tumors whose multiplicity is of the greatest clinical importance
are the rapidly growing forms terminating fatally. Such are those
which reappear in the scar after the removal of a cancer, or in the
adjoining chain of lymphatic glands or at remote parts of the body.
The most satisfactory explanation of their presence, and of the
generalization, recurrence, or metastasis of tumors, is derived from
what has already been stated with reference to the manner of the
growth of the latter.
It is well known from experiments on animals that various living,
normal tissues when transplanted to remote parts of the same
individual or to other individuals may continue to grow. Cohnheim
claims, as has been previously stated, that a distinction is to be
drawn in this respect between the tissues of the adult and the foetus,
where the genesis of tumors is concerned. This observer, in connection
with Maas,[80] has found that the transplanted material (periosteum),
although growing for a while, disappears at the end of five weeks, and
it is asserted that fragments of tumors, when transferred, suffer a
similar fate. Wile,[81] on the contrary, {111} who has experimented
with reference to the fate of transplanted tissues and portions of
tumors, reports that one hundred days after the transfer of periosteum
the lung was found to contain several centres of ossification. He
regards the latter as proceeding from the fragments of periosteum
introduced into the jugular vein, and his results thus widely differ
from those of Cohnheim.
[Footnote 80: _Virchow's Archiv_, 1877, lxx. 161.]
[Footnote 81: _The Pathogenesis of Secondary Tumors_, reprint from
_Philadelphia Med. Times_, July, Aug., and Sept., 1882.]
Notwithstanding the numerous experiments which have been made in
various parts of the world to excite the growth of transplanted bits
from tumors, most of them have terminated unsuccessfully. Although a
temporary growth of fragments of tumors has taken place after
transplantation, their eventual disappearance has usually occurred.
Cohnheim lays stress upon this fact in connection with his theory of
the origin of tumors. He considers that the fragments of tissue and
tumors disappear in consequence of the inability of the foreign
particles to withstand the metamorphosis of physiological tissues. If
this opposition is neutralized, the existing germs of tumors become
capable of development. Wile, however, found that eight weeks after
the introduction of a bit of cancer into the lung of an animal the
fragment had increased nearly twice in size. He also refers to the
positive experiments of Newinsky,[82] who transplanted a bit of cancer
from a dog to the subcutaneous tissue of another, young dog, and
found, after five months, not only an ulcerating cutaneous cancer at
the place of inoculation, but also a metastatic nodule of the size of
a hazel-nut in an axillary lymphatic gland.
[Footnote 82: _Allgem. medicinische Central-Zeitung_, 1876, lxxi.
875.]
For the present consideration it may be borne in mind that fragments
of normal (foetal) tissues, as shown by the experiments of Zahn and
Leopold, when introduced into the organs of animals, may become
enlarged. It is also certain that bits of tumors, after their
introduction into the tissues and organs of animals, have become
increased in size. What their eventual fate might have been does not
appear; and herein lies the weak point of the experiments with
reference to the production of secondary tumors. For such experiments
to be regarded as crucial it is necessary that a large number of
previously healthy animals, after inoculation with fragments of morbid
growths, should present in various parts of the body well
characterized tumors whose structure should be like that of the
particles introduced.
The experiments above referred to are of value in confirming the views
concerning the generalization of tumors which have been generally
admitted since Virchow's discoveries with regard to the phenomena of
embolism.
Tumors are said to become generalized when they appear not only in
various systems of the body, but in various organs and tissues. They
are found usually in considerable numbers, and with such differences
in size, shape, and appearance as to indicate different ages. Such
tumors are regarded as arising directly or indirectly from a common
source. This source is called the primitive or primary tumor, and its
derivatives the secondary tumors. The latter are usually considered as
the direct descendants of the former, although their relation may be
that of several successive generations.
The primitive tumor in its growth may extend into lymphatics and
blood-vessels, as has already been suggested. Such an extension may be
{112} so little obvious when the tumor is removed by the surgeon that
all diseased tissues are apparently separated from the body. A
recurrence of the tumor is said to take place when the growth returns
in the cicatrix, frequently in a multiple form. The explanation of
such a recurrence is based upon the probable presence, at the time of
the operation, of fragments of the tumor within the tissues forming
the base and edges of the wound. During and after the healing of the
wound their growth is supposed to continue till they become apparent
as small tumors. The progress of these recurrent tumors is at times
extremely rapid, and they may attain a considerable size in the course
of a few weeks. Such nodules are secondary in point of time, although
they were actually a part of the primary growth.
Secondary nodules in descent as well as time are those which appear at
distant parts, often after the discovery of the primary tumor. Such
nodules are regarded as resulting from the transfer of particles of
various size from the primitive growth, either through the
lymph-vessels or blood-vessels. If the invasion of the body takes
place through the former, the fragments may be floated along to the
nearest lymphatic gland, where it remains when too large to pass
through. If it retains the capacity of growth or of stimulating a like
growth, there results a more or less complete transformation of the
gland into a morbid tissue like that from which the fragments came.
Adjoining lymph-glands may become infected from the first, until
eventually an entire series becomes more or less completely
transformed into morbid growths. A like invasion of the lymphatic
glands may take place through a continuous extension along the
lymph-vessels; and it is not rare to find the sub-pleural or
sub-peritoneal lymphatics as an elevated meshwork in consequence of
the neoplastic growth within them. Such a method of extension may take
place when a cancer of the stomach or liver is associated with a
cancer of the pleura, the intervening lymphatics of the diaphragm
offering a direct and continuous communication.
With the outcropping of a tumor upon a serous surface the possibility
of the detachment of particles is at hand. These may become
transplanted to the opposed serous surface or may be transferred to
the most dependent parts, and there serve as seed for subsequent
growth.
The probability of the embolic nature of many secondary tumors was
early suggested in the history of embolism. Rapidly growing tumors
were known to be capable of perforating the walls of adjacent
blood-vessels, especially veins, and to continue growing along the
course of such vessels. The possibility of the detachment of portions
of these tumors and their transfer along the course of the circulation
was an inevitable inference from the results of experimentation with
foreign bodies. Cancerous emboli were thus recognized as a possible
variety, and their distribution was subject to the same laws as those
governing emboli otherwise constituted. Multiple nodules were
frequently found in the lungs in connection with tumors growing into
the inferior vena cava, while multiple nodules in the liver were
usually associated with tumors of the gastro-intestinal canal or other
regions whose vessels formed a part of the portal circulation. The
readiness with which portions may be detached after death from the
soft masses projecting into the interior of veins suggests the ease
with which particles may be {113} separated during life. The
experiments already referred to show that isolated fragments of tissue
serving as emboli may grow in the place of their reception, and it is
presumable that the resulting growth takes place under the same
conditions as those prevailing at the place from which the embolus
started. The question whether the secondary tumor arises from the
reproduction of elements transferred from the primitive disease, or
whether these excite a characteristic, specific growth of the cells in
the place of their retention, may still be regarded as open. The
experiments favor the former view, and they alone are capable of
satisfactorily determining the point in question.