the peculiarities of the primitive growth. If the cells of the latter
are pigmented, those of the former show the same peculiarity. If the
structure of the primitive tumor contains bone, cartilage, or squamous
epithelium, the secondary growths show like characters, though they
may be present in the heart or other organs where such tissues are not
present as normal constituents. So constant and characteristic is this
feature that the structure of the tumor is usually as well displayed
in the examination of the secondary as of the primitive nodule.
Indeed, the structural peculiarities of the growth may be more
characteristically shown in the former in those instances where the
primitive tumor has undergone degenerative changes obscuring its
histological features.
The tissues of the tumor are subject to the various changes which take
place in the normal tissues of the body. Their growth is attended with
a multiplication of cells and a formation of intercellular substance.
Tumors whose growth is the most rapid are those whose blood-vessels
are the most numerous and whose relation to the cells is most
intimate. The slower the advance of the tumor, the more permanent is
it likely to become, while the more rapid the progress, the more
transitory are its elements. The growth may continue, and yet the
actual size of the tumor may diminish through the absorption of its
degenerated parts. The cells of the neoplasm may undergo fatty
degeneration, or they may become cornified. They may undergo the
mucous metamorphosis or the amyloid and colloid degenerations. They
may take up pigment or they may produce the same. The intercellular
substance varies in its character as does that of normal tissues. It
may be slimy, homogeneous, or fibrillated. It may contain mucin,
chondrin, or gelatin, and may be infiltrated with calcareous salts.
Limited necroses with characteristic cheesy appearances are of
frequent occurrence.
Tumors may become the seat of inflammatory processes, indicated by
suppuration and fever, which may result in abscess or gangrene, or
their progress may terminate in the production of scars. Ulceration
may occur in consequence of the extension of an inflammatory process
to the surface, or it may result in the course of the degenerative
softening of a tumor. In both cases the cutaneous or mucous surface is
involved and destroyed, and the interior of the tumor being exposed
putrefactive processes, with fistulæ and sinuses, arise, the latter
favoring the retention of the product and the persistence of the
inflammatory process.
Tumors are always pathological, but the resulting disturbances vary
within wide limits and are often of a complex character. The familiar
distinction between benignant and malignant tumors is based chiefly
{114} upon this variance in the nature of the disturbances. Those are
benignant which closely resemble the normal structures of the body,
increase but slowly, and, if they attain a large size, produce mainly
mechanical disturbances. They may prove serious, even fatal, if so
seated as to interfere with the function of important parts of the
body. Very large and heavy tumors may prove burdensome solely on
account of their weight, while others of similar character, elsewhere
seated, may interfere with respiration or circulation, and eventually
with nutrition. Tumors in exposed situations may become important only
in virtue of their liability to injury, while others impede the
function of a part or an organ by pressure upon its nerves and vessels
or by obstructing its ducts.
The malignant tumors, on the contrary, differ in their structure from
the normal tissues of the body. Their growth is rapid and infiltrating
rather than slow and concentric. Such tumors usually have a
predominance of cells and thin walled blood-vessels. The former may be
little else than nuclei enveloped in an easily destructible
protoplasm, or they may be composed of multi-nucleated masses of
protoplasm, and are then known as giant-cells. The most malignant
tumors are those which tend to become generalized as well as to spread
locally. They recur locally, and appear in the nearest lymph-glands
and at remote parts of the body. The disturbances produced by the
malignant tumors depend less upon their mechanical relations than upon
their tendency to destroy tissues and disturb functions. With their
presence and progress in vital organs there is associated, from their
manner of growth, a destruction of the cells of such organs, as the
kidneys and liver, the lungs and heart. When they are seated in the
spleen and lymphatic glands, a disturbance in the blood-making process
must be associated. Their occurrence in the alimentary canal opposes
the admission, digestion, and expulsion of its contents, and produces
disturbances varying as to the seat and peculiarities of the tumor.
The progress of the malignant tumor is often associated with
ulceration, watery discharges, and hemorrhage. The frequent
coexistence of emaciation, weakness, anæmia, and a yellowish
discoloration of the skin forms a group of disturbances which,
included under the name "cachexia," have long been prominent as
significant of malignant tumors. At the present day this cachexia is
regarded rather as the result than the cause of the tumor, whereas
formerly the reverse was the case.
The modern classification of tumors is based chiefly on their
structure, in part upon their method of origin, and in part upon their
cause.
With the observation of the similarity of appearances in the flesh of
which the external and internal neoplasms are composed, the suggestion
readily presented itself to regard the external tumors and the
internal growths as similar in character. External forms, physical
characteristics, clinical peculiarities, all proved insufficient as a
means of identifying the two, and the step was a short one which led
to the minute study of the flesh of the tumor and a comparison of its
resemblances and differences. This comparison obviously included a
knowledge of the structure and peculiarities of normal tissues. As
histological studies advanced, so did the pursuit of pathological
histology, and the tumors which were once designated as encephaloid,
mastoid, pancreatoid, or nephroid, from real {115} or fancied
resemblances to certain organs of the body, became analyzed into their
microscopic rather than macroscopic characteristics.
It is unnecessary to say that the modern classification of morbid
growths owes its foundation and a large part of its superstructure to
Virchow, whose classic work, _Die Krankhaften Geschwülste_, showed the
direction which future investigators were to pursue and the nature of
the discoveries likely to result.
The tumor represents the result of the growth of a tissue or tissues
which are like or resemble those which form the normal constituents of
the body. Although a new formation is present, it is composed of
tissues lying within the possibilities of the individual. A new
formation of feathers, as Virchow suggests, is beyond the productive
powers of human tissues, though within those of feathered animals. A
goose can produce a tumor containing feathers, not one in which hairs
are found; in the human species tumors containing hairs may occur, not
those, however, in which feathers are present. Although the cells of
the tumors of man may deviate in their appearances from the cells of
normal tissues, this deviation is never so extreme that their analogue
cannot be met with in some part of the body.
As the normal tissues originate from pre-existing tissues, so the
pathological tissues of the tumor grow only from the antecedent
tissues. The matrix from which the tumor arises is a normal tissue.
There is produced from it, as a neoplasm, either a tissue which
follows the type of the maternal tissue, a homologous tumor, or one
which deviates in type from that of the matrix, a heterologous growth.
Although the latter differs in its composition from that of the
matrix, it does not vary essentially from a like tissue to be found
elsewhere in the body. It occurs where it does not belong either in
place, time, or quantity. The homologous tumor appears rather as a
hypertrophy of the tissue from which it arises, and the line between
this variety of growth and a simple hypertrophy is often purely
arbitrary.
Although tumors, in the more limited sense, are solid, fleshy masses,
the new formation of tissues may result in the presence of a tumor
within which is a cavity with various contents. Such a cavity is not a
mere hole, but has a distinct wall of connective tissue lined with
epithelium or endothelium. A distinction is thus drawn between cysts
and growths--one which is of daily importance in the practice of
medicine--and Virchow's oncology includes the consideration of the two
varieties of tumors.
Cystic tumors are subdivided according to the nature of their contents
and the method of their origin. One group is composed of clotted blood
within cavities resulting from the laceration of tissues or in
preformed spaces. If the cyst primarily is merely a rent, the wall
becomes thickened in time from a growth of the limiting tissues, and
the blood-clot, of which the tumor was chiefly composed, may remain or
become absorbed. If the latter event occurs, its place of deposit may
become obliterated by a fusion of the walls of the cyst, or may
persist from the subsequent addition of serum.
The cystic tumor whose contents are extravasated blood is the
hæmatoma, familiar instances of which are met with in the hæmatoma of
the dura mater, of muscle, of the vulva, and the polypoid hæmatoma of
{116} the uterus. The latter is the long retained and constantly
enlarging blood-clot, due to the adherence of portions of the placenta
after childbirth.
The second group of cystic tumors has for its contents a more watery
fluid, and to this the term hygroma is applied. This watery fluid
lies, for the most part, within preformed cavities, and its
accumulation is connected with a dilatation of these cavities.
Instances are met with in the tumors resulting from the accumulation
of fluid in the membranes of the brain or spinal cord, and in the
ventricles of the former or in the central canal of the latter. These
lead to the congenital cystic tumors of the cranium or spine, with
watery contents. The ganglion, the house-maid's knee, as also the
hydrocele of the tunica vaginalis, are regarded as hygromata. The
hydrocele of the neck and elsewhere in the subcutaneous or
intermuscular connective tissue is now removed from the hygromata to
the tumors which arise from lymph-vessels. A like transfer of other
hygromata might be made in accordance with the prevailing views
concerning the cavities in which the watery fluid is accumulated.
A third group of cysts contains material which represents essentially
a production from the wall, with a difference of composition dependent
upon the nature of the wall. Such cysts give rise to tumors through
the retention of their contents, and they are called retention-cysts
or retention-tumors. In the wall of the cysts is a gland-tissue, which
may line the surface or lie beneath. The glandular structures may be
cutaneous, mucous, or represent a part of the great glands of the
body, as the liver and kidneys. The atheromatous cyst of the skin, the
mucous cysts of the gastro-intestinal mucous membrane, and the ovula
Nabothi of the uterus are examples of the retention of secretion
within glands. The dropsical dilatations of the antrum, the vermiform
appendage, the uterus, the biliary and renal canals furnish instances
of tumors resulting from the retention of secretion on a large scale.
In the subsequent history of these retention-cysts the secretion may
be modified chemically and physically; the cells upon the walls may be
transformed from columnar forms into flattened and scale-like
varieties. In time, the original secretion frequently becomes a watery
fluid, resembling the contents of the hygroma previously mentioned.
This grouping of cysts in contradistinction to fleshy tumors omits the
consideration of a series of cystic tumors of enormous size, the
multilocular tumors of the ovary. This class represents a more complex
form of cystic growth--one whose tendency is toward the reproduction
of cysts, to which the term cystoma is applied. The cystoma is the
result of an active new formation of epithelium and connective tissue,
and is classified as a variety of the epithelial group of tumors.
Morbid growths, as distinguished from cysts, are divided by Virchow
into the simple and complex forms. The former consist of a single
tissue, the histoid tumors; the latter of several tissues suggesting
an organ, the organoid tumors; while still others, in which the number
and grouping of tissues is so complex as to simulate systems of the
body, even monstrosities, have received the term systematoid or
teratoid tumors.
Virchow claimed that the growth of most tumors took place from the
connective tissues, and that most of the organoid tumors, especially
cancer, arose from the formative action of the connective tissue in
the part where {117} it first made its appearance. The structure of
cancer suggested an organ, as it consisted of collections of cells
resembling epithelium, within spaces or alveoli whose walls were
formed of connective tissue. The epithelioid cells of the cancer, as
well as the connective-tissue corpuscles, were considered to arise
from pre-existing cells of connective tissue.
The first, most important, modification of Virchow's views, which has
led to a more rational appreciation of the relation of the various
tumors, especially of the epithelial group, to each other, arose in
consequence of the investigations of Thiersch and others with regard
to the origin of certain cancers. This observer[83] claimed that the
epithelioid element of cutaneous cancers arose in all instances from
pre-existing epithelium, either of the rete mucosum or cutaneous
glands. Similar views were suggested, with various degrees of
precision, by other authors concerning certain cancerous tumors
elsewhere, but were first applied to all cancers with a more exact
formulation by Waldeyer,[84] to whom the prevailing views with regard
to the histogenesis of morbid growths are due. According to him, the
essential (epithelioid) element of all primitive cancers arises from
pre-existing epithelium; consequently, no cancer-cell can arise except
in organs where epithelium is normally present.
[Footnote 83: _Der Epithelial Krebs, namentlich der Haut, etc._,
1865.]
[Footnote 84: _Virchow's Archiv_, 1867, xli. 470; 1872, lv. 67;
_Volkmann's Sammlung klinischer Vorträge_, 1871, xxxiii.]
This comprehensive statement was rendered possible by the
embryological researches of Remak at the outset, and afterward by
those of His and Waldeyer. Remak showed that after differentiation of
the cells of the ovum into the several germinal layers, those from one
layer could not serve to originate the cells belonging to another
layer. The development of normal tissues takes place within the limits
defined by this differentiation. Epithelium thus is not derived from
connective tissue, nerves, or muscles, nor was the reverse known to
occur. To His is due the exact appreciation of the superficial cells
of serous membranes, which had been previously called epithelium, and
had thus been confounded with the epithelial cells of mucous or
cutaneous membranes and of secretory glands. He showed that these
cells had a wholly different origin from epithelium, and were simply
scale-like cells of fibrous tissue, to which he applied the name
endothelium. The latter is now used as the term for the thin, squamous
cells of fibrous tissue, whether they are found lining the walls of
the great serous cavities or the smaller lymph-spaces, the
endocardium, or the inner coat of blood-vessels and lymphatics.
The importance of this distinction is obvious when the occurrence of
tumors, called cancers, is observed in parts which contain no
epithelium. Aside from the vagueness of the term cancer, as applied
clinically, tumors are sometimes met with, even in parts where
epithelium normally does not exist, whose structure resembles more or
less closely that of cancer as usually recognized. Such tumors are to
be regarded as of an endothelial rather than epithelial character, and
as such their histogenesis falls under the general laws of the
development of tissues.
Waldeyer[85] has suggested that the primitive basis for the
development of the genito-urinary tract contains cells which are
equivalent in their possibilities of ultimate development to the
epithelium of the limiting germinal layers--a suggestion which is of
importance in permitting the {118} epithelial tumors of the ovary to
be brought under the general embryological laws of development.
[Footnote 85: _Eierstock und Ei_, 1870.]
As the growth of embryonal tissues is so defined that descendants are
like their ancestors in all respects, so the development of tissues in
the adult is regarded as defined with equal precision. Eberth and
Wadsworth[86] have shown that the regeneration of corneal epithelium
takes place from pre-existing epithelium. E. Neumann and others claim
in like manner the development of muscular tissue from antecedent
muscular cells.
[Footnote 86: _Virchow's Archiv_, 1870, li. 361.]
The relation of cancer to epithelial tumors is regarded as similar to
that borne by sarcoma to tumors composed of connective tissues. The
growth of the epithelial elements into the neighboring parts is
through paths determined by pre-existing or new-formed connective
tissue. The active element of the cancer lies more especially in its
epithelioid cells, and its growth takes place in an atypical rather
than a typical manner. Of the various epithelial tumors, there are
those like the cutaneous horn or corn, the adenoma or cystoma, whose
epithelial growth takes place in accordance with normal methods of
production. The epithelioid constituent of the cancer, on the
contrary, grows often with great luxuriance and with but little
tendency to carry out the normal mutual relations of the epithelium
and connective tissue of the part from which it proceeds. The
epithelioid masses or sprouts are composed of cells whose relation to
each other resembles that of normal epithelium in the absence of an
intercellular substance, while the shapes of the cells correspond more
or less closely with that of the epithelium in the region from which
the tumor arises. The epithelioid cells of cutaneous cancers resemble
those of the surface, the rete, or the glands of the skin. Cancers of
the stomach or uterus contain epithelioid cells whose shape simulates
the varieties in the stomach and uterus. Such resemblances are carried
out in the degenerations which the cells of cancer undergo. The
horn-like, keratoid, transformation of epidermoid cells in cutaneous
cancers, the mucous degeneration of the epithelioid cells of cancers
of mucous membranes, are sufficiently familiar. Notwithstanding these
resemblances, which are also present in secondary tumors at remote
parts of the body, the epithelioid growth advances without limit and
without reproducing the normal type. Cancer is therefore defined as an
atypical, epithelial new formation.
Sarcoma, on the other hand, whose clinical features correspond so
closely with those of cancer, simulates, as shown by Virchow, the
connective tissues. It is composed of cells and intercellular
substance, both of which may be as varied as are those of the
connective tissues. The shape of the cells is as diverse and their
contents as various, while their possibilities of degeneration are
alike. The cells of the sarcoma are not simply cemented together, as
are epithelial cells, but they are separated from each other by an
intercellular substance, which corresponds in its appearance and
chemical properties with that of mucous, fibrous, cartilaginous, or
osseous tissue. The structure of the sarcoma differs from that of
these tissues in presenting a predominance of cells over intercellular
substance, while the reverse is the characteristic of most varieties
of connective tissue. In this predominant cell-formation lies its
absence of type, {119} whereas the atypical character of the cancerous
growth is manifested rather by the irregular grouping of the cellular
masses than by an abundance of cells.
As the original cancer is considered as possible only in parts where
epithelium is a normal constituent, so the primitive sarcoma is
possible only in parts where connective tissue is present. The
apparent great frequency of sarcoma in recent times is thus obviously
explained. With an agreement as to its histological characteristics,
its possible place of origin is any of the connective tissues of the
body, and their presence is universal. In the manner of its growth,
its recurrence, and generalization it is subject to the same laws
which determine similar events in the history of cancer. Its
degenerations are often the same, and its symptoms are due to the
action of like causes.
The importance of distinguishing between these atypical tumors is
real, in that it is only through the association of causes, symptoms,
and results with defined and constant characteristics that a practical
knowledge of tumors is to arise. The time-honored distinction between
malignant or semi-malignant and benignant growths is always to be
sought for, and can only be fully possessed when the natural history
of the new formations is known. With an exact appreciation of the
structure of a tumor it becomes possible to study its special
pathology. From a knowledge of the latter are to be derived those
features of importance in determining the relation of morbid growths
to other deviations from normal and physiological processes. An
immediately practical benefit arises from the Thiersch-Waldeyer
modification of Virchow's theory of the origin of tumors, in that it
permits with greater ease a more accurate clinical diagnosis.
Lücke[87] has been prominent in calling attention to the suggestions
thus presented.
[Footnote 87: _Volkmann's Sammlung klinischer Vorträge_, 1876, xcvii.]
The diagnostic value of the theory above-mentioned is rather negative
than positive. With rare exceptions, a tumor cannot be epithelial in
character if its origin is from an organ or a part in which epithelium
is absent. The possible exceptions admit theoretical explanations
which present considerable degrees of probability, and are also based
upon the existing views of the development of tissues.
A tumor whose origin from the connective tissues is determined
partakes of the characteristics of its matrix, and is a
connective-tissue tumor. Its development from fibrous tissue is more
likely to result in a fibroma; from fat tissue, a lipoma, or a myxoma;
from cartilage or bone, a chondroma or osteoma.
Tumors developing at certain periods of life in certain parts of the
body are more likely to belong to one than another of the histogenetic
groups. Tumors of the connective-tissue series are stated by Lücke as
more prevalent before the age of thirty-five years, while those of the
epithelial group are more likely to occur after this age, and cancer
of the lip is of special frequency in old age. The fibro-myoma is of
most frequent occurrence in the uterus, and rarely attains a large
size till the approach of the climacteric.