Epithelioma of the mouth

Preface

The following monograph is the out growth of a series of investigations, entered into in the course of professional study, for the purpose of elucidating to the author, some obscure points in the pathology, ethiology, and treatment of epithelioma of the mouth. Originally designed for personal use only, the notes made, early assumed the character of a study of the subject, which, in accordance with urgent requests, is now presented to the profession.

H. I. OSTEOM.

CHAPTER II. Epithelioma of the Mouth

CHAPTER I.

The Epithelium of the Mouth.

For our present purpose it is convenient to study the epithelium of the mouth.

This will be found to include the lining of the buccal cavity, the covering of the tongue, and the essential part of all the glands that pour their secretions in front of the pharynx.

Before the fourth week in the life of the human embryo, there is developed at the lower part of the face a broad, transverse cleft. This is the primitive mouth, (stromodocum), and while the initial step in its development is a growth inwards of that part of the face which corresponds to the embryonic depression, the future enlargement of the buccal cavity depends more upon the growth outwards of the fronto nasal process in the middle, the superior maxillary processes on the sides, and the mandibular plates, which are continuous with the maxillary processes, than upon the extension inwards, the deepening of the primitive cleft.

Developed as it is from the face, and carrying with, it the covering of the face, the investing membrane of the mouth is derived from the epiblastic layer of the blastoderm. This depression of the epiblast, the future mouth, forms a sac, that is at first closed posteriorly, having only an anterior opening between the processes above mentioned. Not until the eighth or ninth week is a communication established between the mouth and the pharynx — the latter is of mesoblastic origin — by breaking down the anterior wall of one cavity, and the posterior wall of the other.

It is thus seen, that the mouth and the pharynx are in the embryo, two separate non- connecting cavities, the first having its origin in the epiblastic layer, the second in the hypoblastic layer, and visural mesoblast.

This embryonic differentiation suggests the possibility of a corresponding distinction being made between the future functions, of these two divisions of the alimentary canal ; but also, and especially because of its bearing upon the etiology of the diseases of the mouth, of establishing a relation between the blastodermic layer represented, and the form of disease that it develops. It must be confessed, however, that this anticipation has thus far been only partially realized ; for while the differentiation of the embryo into layers, and the development of these layers into organs and parts with an unchanging regularity and exactness, has been demonstrated, it cannot at present be shown that, for example, the glands of the mouth, and the glands of the pharynx, may not develop exactly similar diseases, and present indistinguishable histological conditions.

The usual method of the development of glands — by a prolongation inwards of the epithelial layer upon which the secreting organ is to open, — renders it probable that the mouth, whatever may be its mature conformation, when viewed in its simplest form, presents a continuous layer of tissue, without depressions or elevations ; and that the variously formed recesses that constitute the salivary and mucous glands, are a later development, to meet the requirements of the growing organism.

This anatomical distinction, which marks the functionally active mouth, forms two convenient divisions for studying the buccal epithelium, — the non-glandular, and the glandular tissue ; but let it be emphasized that they have the same genesis, and that their histological distinctions are the result of functional requirements.

The features by which epithelial tissue is recognized, are few, but well marked. The cells though variously shaped are nucleated, and everywhere in close apposition, or are held together by a cohesive substance that is not always apparent. They are arranged on a base of connective tissue — the membrana propria, or in the case of glands, the stroma — in the form of one or more layers, in which there is no vascular system, but in which the supply of nerves is sometimes quite abundant. These layers of epithelial cells constantly cover the surface of the body, and those canals and cavities that communicate with the surface. They may, therefore, be looked upon as defining the body, as constituting a natural boundary to the organism, and as everywhere presenting a surface upon which contact with external objects is effected.

The definiteness with which epithelial tissue, as distinguished from the bodies that enter into its construction, is recognized, is not found to be equally true of the individual epithelial cells, for these, when isolated, are not always clearly characteristic ; and especially when young and immature, before they have assumed either the form or function of a special variety, are not distinguishable from other cells while in a transition state, or from other varieties of epiblastic derivatives. A reason for this exists in the fact that epithelial cells are not permanent bodies. With peculiar rapidity, they pass through their different stages of evolution, and do not accomplish their physiological perfection until immediately before they are destroyed, or thrown off. Hence, it is apparent that as one variety of epitkeliuni can pass into any other variety, if the conditions and requirements are favorable for such a metamorphosis, it is impossible to predict the form that the young cell may assume.

Functionally active epithelial cells are not provided with a cell wall, but are composed of protoplasm in the form of a fine riticulum, in the meshes of which is found the peculiar cell contents. The nucleus and nuceoli are also composed of a riticulum, that is apparently continuous with that of the cell body, but the nucleus is constantly surrounded by a double contoured limiting membrane. Such naked bodies are young cells, of which the outer zone of protoplasm has not hardened into "formed material," to give a protective envelope.

The contents of epithelial cells will be found to vary with their function, and the period of functional activity at which they are examined, for all epithelial cells a.re secreting bodies, the nucleus probably possessing an elective power over the substance secreted and elaborated.

The non-glandular, or investing epithelium of the mouth, which is directly continuous with the epithalial covering of the face, belongs to the stratified pavement variety. It is composed of several layers of differently shaped cells, the deeper or attached layer being generally columnar, while the superficial layer presents flattened scales, that slightly overlap each other,and are not always provided with nuclei. Between these layers may be distinguished an intermediate layer of polygonal cells, having blunt angles.

The regeneration of epithelium, a regeneration made necessary by the constant desquamation of the cells of the superficial layer, always takes place from the deeper layer, the cells of which do not lie in immediate contact with each other, but are united by means of spines and ridges — probably the continuation of the reticulum of the cell body — which, projecting from the surface of one cell, are received in corresponding depressions, or upon similar spines of other cells, by which means are formed intercellular channels.

These tubes probably constitute a vascular system, that of necessity changes with the multiplication of the cells, and have no other walls than the limitations of the epithelial cells. It is not unlikely that nerves also occupy these channels.

Below the columnar epithelial cells, and resting upon a layer of loose connective tissue that serves to unite the buccal mucous membrane to the underlying parts, is the corium, a structure made up of connective tissue fasciculi and elastic fibres, which give rise to papillae, the whole of especial interest in the present study, as being the tissue that contains and supports the numerous mucous glands found in this region.

The epithelial covering of the tongue and soft palate differs somewhat from the stratified epithelium found on the cheeks, lips and hard palate. It accurately invests the papillae of the tongue, and the taste buds, dipping down between these ; and over the circumvallate papillae at the base of the organ becomes very thick, entirely concealing the minute secondary papillae, that are developed from the apex of some of the conical papillae.

The epithelial covering of the secondary papillae is characteristic. Over these elevations the epithelium is arranged as a separate horny layer, prolonged into processes that extend far beyond the papillae that it covers. From this circumstance these papillae have been called filiform.

The epithelial cells of the filiform papillae are usually more or less hard, containing only a small proportion of protoplasm, and frequently no nucleus. As with other epithelial cells, they are constantly being thrown off, and their place supplied from the deeper layers.

The larger portion of the soft palate is covered with scaly and stratified epithelium, that presents no marked differences from the investment of other parts of the mouth ; but at the upper portion the epithelium is ciliated, and in places columnar. .

In common with other mucous membranes, that which lines the cavity of the mouth is constantly bathed with mucous. This secretion is accomplished either by the investing epithelial cells, which elaborate murine within their protoplasm, and discharge it, probably at the same time, and with the cell body either intact or destroyed ; or by minute glands situated within the sub-mucosa.

In reference to the first method, it is to be noted that the columnar cells are especially concerned with the formation of mucous. These cells often become so much distended with mucigen that they lose their columnar shape and assume the chalice or goblet form, by bulging near the free border. At the same time the nucleus is found pressed against the inner and attached part of the cell. From the distended part of the cell, when this does not burst, a drop of mucous may frequently be seen to exude, which increases the peculiar form of the cell. The

EPITHELIUM OE THE MOUTH 21

scaly or stratified cells do not, to any extent, secrete mucous ; and these occupying the most superficial layer of the membrane, it is probable that the deeper epithelium of the mouth, though columnar, is more especially for the purpose of regenerating the outermost layer of cells, and of less service in secreting mucous ; it is not, however, denied that, under certain circumstances, they may perform this office.

It thus appears that the buccal mucous is almost exclusively of glandular manufacture, and is to a limited degree only, elaborated by the investing epithelium.

A description of the epithelium of the buccal mucous glands would, in a great measure, be a repetition of what has been already said concerning the epithelial investment of the mouth. For, as we have seen, to a certain but varying degree, all mucous epithelium is glandular, that is to say, it performs the function of secretion.

The mucous glands of the mouth are minute, compound acinous organs — similar to the salivary glands — that are formed by a prolongation of the investing epithelium, into the sub-mucosa. They are lined with columnar cells, which when active, assume the chalice shape referred to.

The glands are situated on the inner side of the lips, principally the lower, on the cheeks, on the hard and soft palate, beneath the lymph follicles at the base of the tongue, and behind the lingual V near the papillae vallata and foramen caecum. On the inferior surface of the tip of the tongue, the glands form two elongated patches — the glands of Blandin and Nuhn — the ducts of which open on each side of the fraenum linguce.

The ducts of the buccal mucous glands are usually very short, and are lined with columnar epithelium ; the gland itself is filled, rather than lined, with the same variety of cells.

The other glands of the mouth, in the function and construction of which epithelial cells bear a principal part, are the salivary glands. These are arranged in three pairs. only two pairs of which are situated in the mouth, but the parotid glands are included among the buccal glands, because their function does not differ essentially from the other salivary glands, and, also, because their secretion is poured into the month, together with that from the sub-maxiliary and lingual glands.

The salivary glands belong to the group of acinous glands, and in every instance consist of a variously branched tube, lined with epithelium. The alveoli or terminal branches, are lined with large tessellated epithelium, and the other part of the tube with columnar epithelium. These salivary tubes pass in different directions within the interior of the gland, and perform an important part of the process of secretion. The} 7 are not to be confounded with the excretory duct of the gland, the office of which is probably largely mechanical in assisting the flow of the saliva from the gland. The salivary tubes are not possessed of muscular fibres.

In the alveoli of the sub- maxillary and sub-lingual glands are found two species of epithelial cells. Mucous cells, which are large and pyramidal, with their apex towards the centre of the alveolus, and their nucleus almost in contact with the basement membrane ; and small, granular, irregular cells, united in groups, in the form of crescents, that are usually situated at the base of the alveolus, when their convexity is against the basement membrane, and their concavity is occupied by the mucous cells ; sometimes these crescents are found in the centre of the alveolus, between two mucous cells.

These cells contain a serous albuminous fluid, which, mingling with the murine of the mucous cells, constitutes saliva. The paroted gland contains only serous albuminoid cells, the mucous cells being conspicuously absent from this salivary organ.

The essential elements in the secretion of saliva are, as in all glands, the epithelial cells; but from the fact that healthy saliva contains no morphological elements, it may be asserted that neither the mucous nor the serous cells of the salivary glands contribute more than their contents to the formation of saliva. It is not probable that physiologically the cells of these glands are destroyed in the process of secreting saliva, but rather, that they elaborate their peculiar contents, and then enter into a state that favors the discharge of this elaboration, without the disintegration of the cell body.

The regeneration of salivary glandular epithelium is a less active process, than the regeneration of the epithelial cells that form a part of the secretion of other glands, is known to be. In health, therefore, the morphology of the salivary cells is more accurately described as a multiplication than as a regeneration, the latter term conveying an impression of cellular loss that does not belongto the secretion of saliva. This fact has an important bearing upon the etiology of epithelioma, aud will be discussed in its appropriate place.

The multiplication of salivary cells probably takes place through almost the entire length of the salivary tubes, and the alveoli of the acinous gland. The process is believed to be associated with the varicose fibrils of the columnar cells that lie in contact with the membrana propria, into which they project, and form alveolar like groups. At least in some instances, the proliferation of salivary epithelium, is accomplished independently of the nucleus of the columnar cells, for the nucleus that appears in the new cell seems to originate in the cell itself, by a process of free cell formation, and not by a division of the nucleus of the previously existing morx3hological element.

Passing in review this brief description of epithelium, and of epithelium of the mouth, we find that epithelial cells, especially those that invest the mucous membranes, perform the function of secretion, and that the arrangement of these cells into alveoli, is not. for the purpose of changing their function, but to facilitate and increase their powers of functional activity.

It has further been observed that the life cycle of epithelial cells is quickly completed, and ends with the casting off of the cell from the surface upon which it is developed ; that in many instances, though probably not forming an essential part of secretion, the cell, either as a broken down body, or with its unity undisturbed, is a constant element in the secreted fluid ; its presence, however, is frequently indicative of a pathological state.

It has also been observed that the epithelial cells of the salivary glands are capable of undergoing a process of free cell formation ; that the nucleus, which is generally credited with a controlling influence over cell division, is in this instance, powerless to impart to the progeny of the columnar cell, the physiological function, for which it, the cell, exists ; and that, therefore, though the cells so formed may follow a perfectly normal course, their genesis renders it possible for them to do otherwise.

CHAPTER II.

Epithelioma of the Mouth.

It is characteristic of epithelial neoplasms wherever developed, that they resemble in the arrangement of their component parts — connective tissue and epithelial cells — to a greater or less degree, glandular tissue. This likeness may in some instances, for example in adenoma, be so striking as to give the impression of a duplicate gland ; and in other instances, for example in carcinoma, so remote as to present, only in isolated parts, the general features of secreting tissue — a vascular basement membrane of connection tissue, upon which is spread an investment of non- vascular epithelial tissue.

To epithelial neoplasms, and by this is understood epithelial tissue that is abnormal in genesis, arrangement and function, may be attributed a clinical history of the most marked malignancy ; a malignancy that seems to be in inverse ratio to the resemblance that the new growth bears to glandular tissue.

In seeking the cause of this incompat ibility with the life of an organism, it is not satisfactory to attribute the entire sum of malignancy to the simple multiplication of epithelial cells, either as a primary growth, or as a secondary deposit ; neither can so much virulence be made to depend upon the dissemination through the system of a hypothetical poison that is manufactured in a particular cell area — the epithelial neoplasm. But if to this variety of the tumor disease, we apply the principles of rational pathology ; of a pathology that has its genesis in physiology, and that finds in normal operations, the prototype of abnormal operations, though still having much to explain, we establish our investigations upon ascertained laws, and will learn that as all vital phenomena are related, and because in every instance health must proceed disease, life antedate death, the malignancy that accompanies a particular histogenesis, is the result, either of an increase or a decrease of the function of the part or tissue effected, and not dependent upon a superadded vital process.

An examination of the function of epithelial cells, furnishes an insight into at least one of the causes of their marked malignancy when their function is perverted. Thus, the office of epithelial cells, especially the columnar investing epithelium of the mucous membrane, and of the secreting glands, is to extract from the blood a peculiar pabulum.

In certain proportions this pabulum is physiological in the blood, but if it falls below, or rises above the limits of a normal quantity, it is evident that we have to deal with a more or less pernicious alteration of the nutrient fluid. Now if by the numerical increase of epithelial cells — a constant condition of the growth of epithelioma — the functional activity of that particular cell area is augmented, either the blood is deprived of some of its constituents, or some manufacturing organ is called upon to maintain its normal standard. Is there not in this found an explanation of the cachexy that follows the development of epithelioma; of the malnutrition, and wasting of tissues that do not appear until the epithelial cells, the gland cells, have multiplied beyond their normal number ; until the function of secondarily effected glands, as when the lymphatics become implicated, is so altered as to convert the lymphatic gland into one that resembles the organ primarily diseased.

But this is not the only effect of the multiplication of epithelial cells, for it becomes evident that these cells, while they appropriate more pabulum than should be removed from the blood, are also capable, by virtue of their glandular endowment, of originating an entirely new and abnormal secreting function, the performance of which not only represents a process of removing from the blood elements that form a part of its normal composition, but also a manufacturing process, by which the elements secreted by the abnormal glands cells, are by them elaborated and returned to the system in a condition, harmful, if not poisonous. In this sense a neoplasm may be said to owe its malignancy to a peculiar poison, but the possibility of such a poison is one of the closing features of a series of phenomena, that if they are not sufficient to cause the distraction of the organism, certainly reduce vitality to such a degree, as to render the system unable to resist even slightly adverse conditions.

Epithelioma of the month has its origin in the epithelial cells, either of the mucous membrane, the mucous glands, or the salivary glands.

Two distinct initial processes are observed in the development of epithelioma of the oral mucous membrane. The more highly malignant form, first appears in the substance of the investing membrane, as a nodule of epithelial cells. From the centre of this nodule the ulceration proceeds outwards, the more superficial layers of tissue being gradually involved in the process of destruction. The extension of the nodular variety of epithelioma is not confined to the superficial tissues, but is essentially an infiltrating growth that involves contiguous structures.

From the primary nodule, processes composed of the same epithelial .cells, project into the sub-mucosa, until finally this structure is occupied in every direction by the same carcinomatous mass. The neoplasm is further enlarged by separate nodules uniting. These deeper parts may join in the ulceration process, and then give rise to excavations in the centre of the epithelioma, from which may sometimes be pressed a yellowish, cheesy mass, composed of broken down epithelial cells, and cells that have passed into a state of fatty degeneration.

All of the carcinomatous tissue is not included in the destructive process of ulceration, but there constantly exists a shell of >epitnelial cells, hard and closely packed, more or less supported ux^on a stroma of connective tissue, which forms the indurated base so characteristic of epithelioma. The stroma upon which the outer zone of carcinoma cells rests, and that supports the collections of epithelial cells that occupy the parenchyma of the neoplasm, is sometimes embryonic, partaking of a sarcomatous character. Such a mixed histology marks a superlative degree of malignancy.

The ulceration of an epithelioma shows no disposition to develop cicatricial tissue, even though a temporary scab is formed. Neither is there observed the contraction that constitutes a feature of other ulcerations, the entire process is one of the destruction of existing tissues, without reconstruction ; of the substitution of erratic for normal morphology.

The other and more benign variety of epithelioma of the mucous membrane of the mouth, begins on the surface of the epithelial layer, as a crack, or at first, as a simple abrasion, that later ulcerates, the ulceration extending superficially and never involving the deeper structures. Sometimes a small soft wart, is the first lesion observed ; but probably that condition is generally, if not always, preceded by a slight fissure, the irritation of which is sufficient to cause such a proliferation of epithelial cells, as would form a condyloma.

The initial lesion, from its apparent insignificance, is easily overlooked by both patient and surgeon.

Excepting for the depth of tissue involved, the two varieties of mucous epithelioma of the mouth are with difficulty distinguished, after ulceration has become well developed. There is the same zone of induration surrounding both processes ; the same spreading ulcer ; the same healthy tissue beyond the sharply defined, hardened border, and the same enlargement of the lymphatic and salivary glands. The diagnosis will rest principally on the early history of the case, and on the degree of rapidity with which it reaches a fatal termination.

Any of the minute tubular glands of the mucous membrane of the mouth may be the seat of epithelioma, and it seems probable, that occasionally the nodular variety of mucous epithelioma arises in these structures.

By a process of proliferation, the secreting cells soon occupy the interior of the gland and its excretory duct, converting the organ into a solid mass of epithelial cells. The morbid process being communicated to the superficial epithelium by means of the opening of the gland, or a ''catalytic action" taking place, ulceration follows as in the nodular variet}^ of mucous epithelioma. Epithelioma of the mucous glands possesses marked malignancy ; and it is apparent that the situation of the invaded organ, in the loose connective tissue, offers peculiar advantages for the infiltration of contiguous structures.

Epithelioma of the salivary glands begins as a proliferation of the columnar epithelium of an isolated nodule. Other parts of the gland are soon involved, and the process spreading outwards, both deep and superficial ulceration supervenes. The rjrocess of destruction, however, generally belongs to the later stages of the disease.

The tumor is at no time well defined from the connective tissue in which the salivary gland lies ; and the stroma of the neoplasm becomes either embryonic, or, from inflammation excited by the epithelial cells, entirely disappears, as the neoplastic process progresses.

It is, therefore, not unusual for epithelioma of the salivary glands to present a mixed histology. The connective tissue stroma may be replaced by sarcomatous tissue, which becomes incorporated into the tumor, forming a net- work between the groups of epithelial cells. As with the epithelioma of the mucous glands that show this mixed minute anatomy, the salivary epitheliomata are highly malignant.

It is also observed, agreeable to the two sets of cells found in the salivary glands, that mucoid elements may be mingled with the characteristic epithelial cells of the neoplasm. This arrangement has not been seen in epithelioma of the parotid gland, because of the absence of mucoid cells from that organ.

The minute anatomy of epithelioma of the mouth, shows in every direction, the distinguishing features of pavement epithelioma generally.

To the naked eye the tumor presents a grey or rose tinted appearance. On section, the mass is found to be of unequal consistence, and to be made up of dense collections of epithelial cells, arranged in concentric layers that resemble the leavf s of an onion. Between these bird-nest bodies a less dense connective tissue stroma lies, that may exhibit in different parts almost any degree of development. In this stroma, the arteries, veins and capillaries pass, but are never continued into the epithelial tissue.

It will thus be seen that there is little in the individual cells of epithelioma when isolated, to determine the nature of their genesis. Normal epithelial cells, when functionally active, or when subjected to pressure, assume various shapes : it is, therefore, the arrangement of these elements that must be looked upon as bearing a principal part in the neoplasm ; and their relation to the connective tissue, that anatomically distinguishes epithelial, from connective tissue neoplasms.

If the section of the abnormally proliferating epithelium is made to extend through the matrix of the growth, it will be found that there is no absolute dividing line between the tissues, save in their arrangement, and that this peculiar arrangement of epithelial and connective tissue, becomes less marked towards the periphery of the mass, passing by imperceptible gradation, into healthy tissue.

The absence of a limiting membrane to epithelial neoplasms, is the chief cause of their invasion of neighboring structures, and of the infection of lymphatic glands.

Though, as we have seen, any part of the epithelial lining of the mouth may become the starting point of epithelioma, this neoplastic disease shows a preference for certain locations, to the almost entire exclusion of others.

As a primary disease, epithelioma of the mouth is rarely developed in other locations than the lips, the gums, the salivary glands, the tongue, and the palate. The tonsil? the cheeks, and the floor of the mouth, are generally attacked secondarily, or by direct continuity of tissue.

The reasons for the immunity enjoyed by some parts of the mouth, and the susceptibility shown by others, is not always discoverable. If we receive mechanical or chemical injuries as etiological factors, and we certainly are not justified in excluding either, there is found a class of exciting causes of epithelioma of the lips, gums, and anterior part of the tongue ; but the entire mouth is subject to much the same kind and degree of trauma, with the different results named ; there must, therefore, be other etiological factors, that either alone or in conjunction with traumatic causes, are powerful to excite a local neoplastic process. I am inclined to believe that the principal factor in the etiology of epithelioma of the mouth, will be found to relate to the peculiar kind and degree of functional activity of the minute mucous glands situated in the region affected. The theory that epithelioma owes its origin to a perverted glandular function — not necessarily of a secreting organ, but generally so, because there the glandular function is intensified — has elsewhere been referred to, and there is no reason for excluding the present variety of epithelioma from that hypothesis.