WHITHERS, Part 3
THE NATURE OF SEEDS, ANATOMIC BOUNDARIES,
AND TAKING ROOT
THE EXERCISES OF HISTOPATHOLOGISTS
By Richard J. Reed, M.D.
Histopathologic interpretations are the product of exercises, each measured in increments. Even at the base level, each change in magnification is a step to a new dimension; such steps, in whatever sequence, take on the aspects of dimen- sionalities. Although the basic procedure of microscopy is a series of steps, mechanics have little to do with the actual interpretation of histopathological real images; virtual images have all to do with it. Virtual images, to be used in the interpretative process, are the accumulated residua from prior encounters with histologic patterns. They exist in post-retinal stores and have significance only as relativities to which real images are to be compared.
In post-retinal stores, virtual images are diffused; they are not far removed in their substance from the stuff of dreams. They whiff about and are not equally accessible at all times. In-transit virtual images are those which have been mobilized from out of the stores. For virtual images to be utilized in response to a set of new real images, appropriate ones must be selected from among those of the in-transit group. In- transit virtual images are too ephemeral to be accommodated by the pure physicalities of simply manipulating a microscope. These virtualities, of considerably less substance than the real images which can be manipulated by the simple expedient of changing magnifications, are ours to mold during the course of the interpretative process. Only in the practical application of this dreamy stuff can some degree of structure be imposed. Once central or post-retinal virtual images have been mobilized (i.e., in-transit) and, from among the transients, relevant virtual images selected, structured, and imposed on real images, the problems then become nosological, requiring the assignment of designations. In the latter process, designations become so imbued with implications as to qualify as “intensions.” “Intensions”, in the form of the words which we choose and which are then to be transmitted in our reports, hopefully will be assimilated to aid in the formulation of plans by clinicians.
NUMERATIONS AND THE ART
In the practice of surgical pathology, morphologic findings (real images) come to be imbued not only with the relativities of our morphology-engendered virtual images but also with therapeutic implications. The two parameters merge first in the act of imposing in-transit virtual images on real images. They become one in the structuring of intensions (i.e., the selection of words). The intangibles which are to be packed into the real images are divisible into two general categories: 1) the whiffs of virtual images which are readily manipulable, and 2) relatively fixed dimensionalities of a numeric nature. The former, if not easily accommodated in, and among, the real images, will have been stuffed in place. In the process, some, or a lot, of molding may have been required in the formulation of interpretations. As a consequence, the fit is not always perfect but generally conforms to guidelines in the adage professing that everything should be in its place, with the assumption that there will be a place for everything.
For a specific disease, each new structuring of relevant, in-transit virtual images, each new molding of intensions, eventually will have an impact on the character of stores of post-retinal virtual images; the stores will expand and be enriched. With repetitive molding of in-transit virtual images, some degree of precision is likely to be added to the post-retinal milieu.
Numerations are something else. Numeric exercises are rewarded only with a more detailed acquaintance with a menu of available reactions. Some, such as the physical limits to be observed in the definition of a category of intraductal epithelial neoplasias (i.e., atypical hyperplasias) of the breast, are impractical and beyond the point of utility.
PATHOLOGISTS, NUMERATIONS, AND ONCOLOGY
Pathologists accommodate the whims of oncologists; they do so by providing a plethora of numerations. Numerations (laboratory studies and special stains, such as immunoreactions) currently are equated with evaluations of the severity of biologic threats posed by general categories (not individual examples) of cancer) They have come to dominate our literature, so much so that it is becoming increasingly difficult to be sure if an author even has a solid base in the morphology of disease.
THE INDIVIDUALISTIC NATURE OF SURGICAL PATHOLOGY,
PATIENTS AND DISEASE,
PERVERSIONS OF HISTOLOGIC INTERPRETATIONS,
AND THE GENERAL NATURE OF ONCOLOGIC THERAPEUTIC REGIMENS
Pathologists are individuals; their interpretations are equally individualistic. Patients are individuals; for them, their diseases are at least as individualistic as are the respective interpretations by pathologists. A pathologist recognizes the individuality of a patient's disease but generally is unaware of the impulses which, in themselves, give the patient his identity. To be too closely aware of such impulses would jeopardize the objectivity of histologic interpretations. As a primary agent for patients, pathologists often take the position that their interpretations have validity even though some, or many, of them may be far removed from accuracy and, in turn, may fail to provide appropriate guidelines to treatment. The individuality of pathologists is manifested in this general attitude. This treasured individuality becomes evident when the opinions of a primary pathologist are challenged, either by a consultant or in a medico-legal claim. It is evident in the common plea of defendants: "I couldn't call it." Both the individualistic nature of pathologists' practices and the restricted arena in which they practice are evident in such a plea; the smallness of the conceptual world of pathologists is revealed. The self- righteousness of this plea is taken by the emoting pathologist as a statement of absolution; a plaintiff's attorney is likely to take a different tack.
In treating cancer, oncologists base their regimens on data derived from studies of groups. Measurements (dimensionalities and numerations, including stages and grades), all collected from studies of groups, comprise the data to be analyzed in the selection of regimens. In practice, oncologists place patients (individuals) in analyzed groups. They then treat the individuals as if each is ideally representative of the assigned group (one becomes the other); oncology has no individuality and its practitioners are impatient with that manifested in the common practice of pathology. In group protocols, patients frankly have no identity.
POLITICAL AND SOCIAL INFLUENCES AND THEIR THERAPEUTIC IMPLICATIONS
The treatment of cancer has been influenced by politics. Oncologists, masquerading as pathologists (they have adopted the lingo), have catered to whims of the public (i.e., groups with special interests); as social instruments, oncologists are sensitive to the interests of particular groups. With such influences, it is possible to place aesthetics above common sense (i.e., mastectomies are to be avoided).
The stored virtual images of pathologists are a flux; they must be continually modified to accommodate political and social influences. The modifications, once having become a part of post-retinal stores, greatly influence how morphology-based images appear on recall. Modifications and accommodations notwithstanding, the common endeavors of pathologists remain most individualistic; histologic interpretations, with unavoidable finality, are invariably stamped with the imperfections of their source.
The in-transit virtual images of pathologists, including the numerations with all their social implications, must be structured during the act of being imposed; individuality and structuring of virtual and real images are part and parcel. Once relevant virtual images have been imposed and with them, real images stuffed, the interpretations (i.e., manipulated virtual images from which intensions have been generated) can be used to influence the selection of a group treatment regimen and, in turn, to unpredictably affect the clinical course of afflicted individuals. With the supply of numerations by pathologists and with the manipulation of the data by oncologists, patients, as individuals, come to be lost in the scatter among statistical boundaries (Fig. 1 & 2); their identity is restored in either therapeutic success or failure. The unpredictableness of oncologic endeavors is the attribute which will restore the individuality of patients; in acknowledging this attribute, the relativity of oncologic treatment regimens is revealed.
The social imbuements of the diagnosis of melanoma are such as to turn oncologists, and to lead desperate patients, to heroic resorts. Threads of the barest type are likely to be grasped. Witness the recent interferon fad.
There is great utility in divorcing certain histologic patterns of melanocytic neoplasia from their social imbuements. If a borderland of melanocytic neoplasia (or, for that matter, of any neoplastic system) is to be defined and manipulated, patterns, which currently are intrinsic in the assignment of a problematic thin lesion to the category of melanoma, can be utilized with equal facility in the assignment of the same lesions to a borderland. Such patterns and parameters can be used as a measure of neoplastic progression without burdening the respective patients with the stigma associated with the diagnosis of melanoma. The parameters, which would be of use in characterizing borderline melanocytic lesions, include vertical dimensions, types of vertical growth patterns, and patterns (levels) of invasion. They all can be incorporated as ancillary data in formulating the diagnosis of borderline melanocytic neoplasia of indeterminant malignant potential. In the act, restraints will have been imposed. They serve to protect these same patients from the exploits of aggressive oncologists.
THE DIAGNOSIS OF MELANOMA: ITS RELATIVITIES
The virtual images of the melanocytic system can be structured (Figs. 1 & 2). There are options (Figs. 3,4,5,6,7, & 8). In oncological practice, boundaries along the axis of the neoplastic system will have therapeutic implications. In such structures, the manner in which we define the neoplasm, melanoma, greatly influences the assignment of the locations of boundaries beyond which oncologists are willing to do harmful things to patients (Figs. 3,4,5,6,7, & 8). If we too willingly accommodate the ambitions of oncologists, we become their agents. If we enable them, there is a potential for the boundaries along the axis of neoplastic systems to become impermanent; boundaries then can be shifted by whim to accommodate the vicariousness of questionably effective treatment regimens (e.g., interferon).
THE IMPERSONALITY OF PATHOLOGISTS' VIRTUAL IMAGES
Ideally, a pathologist is impersonal. In fact, objectivity in the histologic interpretation of real images depends upon the isolation and independence of the observer. Virtual images that are imbued too greatly with emotion are unreliable. The stored virtual images of pathologists, although only whiffs, can, and have, become complexities derived from a variety of sources; they are no longer entirely ours alone. It is difficult for them to remain individual when so much of them is borrowed and imposed. If too pliable in our response to outside influences, we might become an instrument of "evidence-based medicine" (what a revolting thought). In such responses to a variety of extraneous influences, sameness takes over; evidence-based medicine is the politicians' and "CEOs'" avenue leading us to a sameness.
PATTERN ANALYSIS, KEYWORDS, AND PERSPECTIVES
(IN TRANSIT VIRTUAL IMAGES)
Pattern analysis is based on a correlation between real images of histologic sections as observed at low magnifications, and parcels of virtual images, particularly those which have become embodied in keywords. Once a pattern (set of real images) evokes a keyword, a cascade of virtual images (in-transit virtual images) ensues. To give in to such transients is tempting, particularly near the end of a long day when many demands may have already been made on an observer. The temptation should be resisted; other reinforcing clues should be sought and identified. Clues which might easily restore objectivity to such a histologic exercise can be easily overlooked in the rush to complete the task. Urgency leads to the imposition of virtual images, but also compromises evaluations of the appropriateness of the imposed images. For example, a teacher often has the opportunity to observe the influence of in-transit virtual images on the workings of the interpretative process. A student of pathology (i.e., a dermatology resident), who is engaged in the interpretation of a histologic section as a teaching exercise, often searches for key-items. Something as undistinguished as the discovery of an eosinophil may trigger a critical response and direct the interpretative process to a proper category. In observing a section of a masto- cytoma, a student may, at low magnification, evoke from his stores the virtual images of a "grenz" zone with the implication that he should then look for features of granuloma faciale at higher magnification. Having made such a determination, he might well "find" such features even if they are not embodied in the real images; he can impose them even though some, or all, are extraneities. If the teacher abuses him from pursuing the implications of a grenz zone, he may, at higher magnification, describe "Indian- file" patterns with the implications that an infiltrate of mononuclear cells in the reticular dermis represents metastatic lobular carcinoma of the breast (the age of the patient would not have been provided as a prelude to the interpretation). If left to his own devices, he might well conclude that a population of monomorphic cells in the dermis is representative of a metastasis from a breast carcinoma, and impose the relevant virtual images on the real images of the section; he will "see" the pattern of metastatic breast carcinoma. If the teacher cautions him and points out that "Indian-files" are not diagnostic of metastatic carcinoma, the student may then return to observations rather than keywords until he hits upon a locus containing eosinophils; "eosinophils" then becomes a keyword which leads him to an appropriate set of virtual images; it evokes new sets. The diagnosis of mastocytosis becomes obvious and then his "grenz zone" is converted into the virtual images of papillary dermal edema. The extraneities of a "grenz zone" and "Indian-files" then would be discarded, and the primality of an infiltrate of distinctive mononuclear (mast) cells would be substituted for the discards. In this sequence, the pitfalls of pattern analysis and related keywords are exposed. More importantly, both our susceptibility to inappropriate in-transit virtual images and our ability to manipulate and impose those same images, independent of reality, is revealed. Along such avenues, lies the vulnerability of practitioners of histopathology.
DEFINITIONS OF NEOPLASTIC PROGRESSIONS
(CAPRICE, WHIMSY, AND FANCY)
Melanoma in situ, if translated into the images of our garden, is nothing more than a bin full of seeds, all of which are variably ripe for sowing. In the case of melanoma in situ and its taxonomic correspondent, moderately severe or marked premalignant melanocytic dysplasia, the bin is full; add another seed to the container (the epidermis) and the contents of the bin will likely spill over (Fig. 9); a few seeds will, in this manner, find their way into the soil. For the lesser degrees of premalignant melanocytic dysplasia, the bin is less than full; there may, however, be cracks in the container, and some seeds may spill into the soil (the papillary dermis). Clark's level II melanoma would translate into a garden in which some seeds have been spilled out of the bin, or sown, but having reached the soil, have failed to germinate (i.e., at level II, local growth is limited and at a practical level, dissemination is not a threat). In the concept of MDM, fullness of the bin is a direct measure of a progression in the "hybridization" of the seeds; the more the seeds deviate from the original, the greater the degree of dysplasia and the greater is the likelihood that the bin is near to being full (Fig. 9); a spill beyond the limits of the container is likely.
In high grade dysplasias, room in the bin is compromised and some of the seeds are unable to sit upon its floor. In the concept of MDM, the upward migration of atypical melanocytic cells in the epidermis, in association with markers for a melanocytic dysplasia (Fig. 9), would be features strongly favoring a characterization of the related process as a moderately severe or marked dysplasia. Along the common path of melanocytic neoplasia (Figs. 1 & 2), the neoplasm, melanoma, as promoted in the concept of MDM, was something farther along the axis of the neoplastic system than a mere intraepithelial process (Figs.1&2, 3,4,5,6,7,8, & 9).
DESIGNATIONS AS OBSTACLES TO CONCEPTUALIZATIONS
In a process as subject to whims and impressions as are the interpretative processes of pathologists, a firm opinion and clear definition of what is a melanoma would seem to be more of a conceit (there is an amazing array of conceited pathologists) than a statement of fact. It is advantageous to provisionally set the word aside and, in the clearing, to structure images without regard for biologic implications. New intensions then might be molded.
Perspective impacts on the nature and appropriateness of our virtual images. In a willful reversal of the self-centered human approach, the well-being of our seeds and plants (i.e., tumor cells and tumors, and not the host) might become the object of our attention. What, of particular histologic patterns, provides insights into the nature of a tumor and its microscopic stage?
Certain designations have become imbued with biologic implications. In the concept of MDM, vertical growth was equated with a stage of neoplasia for which the designation, melanoma, was deemed appropriate. Even more to the point, evaluations of the vertical dimensions of melanocytic neoplasms (i.e., Breslow's criteria) have been shown to be so closely correlated with predictions of a likelihood for metastasis that they have been appropriately cited as prime prognostic parameters. In view of its considerable negative relativity (as being of value in providing insights into a true biologic potential for metastasis in certain early stages along the axis of neoplastic progressions (Figs. 1&2 & 6)), the designation, melanoma, should be reserved for those stages, along the axis of the neoplastic system, which more predictably relate to a potential for metastasis. In this approach, thin lesions measuring less than 1.5 mm in vertical dimensions might be appropriately characterized as something other than outright melanoma.
There are advantages in utilizing vertical growth patterns, as well as measurements of vertical dimensions, to characterize melanocytic neoplasia without a necessity to also require that the findings have pertinence only in the evaluation of melanomas. There is a borderland of neoplasia in which parameters such as patterns of vertical growth, vertical dimensions, levels of invasion, etc., have utility without becoming, in the process, stigmata for "melanoma." It is possible to identify and record these relevant features without restricting their use to lesions which have been unequivocally labeled "melanoma." It is possible to speak of borderline and intermediate melanocytic neoplasia and, in so doing, to describe patterns, dimensions or other unusual histologic features which are currently thought of as peculiar to "melanomas." With current, common intent, the peculiar features might otherwise cause respective lesions to be assigned to the category of "melanoma." The field of pathology is broad and ample. The manipulation of virtual images and the imbuement of intent by a pathologist are permissive acts; some of the practitioners of pathology are intolerant of permissiveness.
A GARDEN NEEDING ATTENTION
Our garden has been meagerly tended up to this point (see Parts 1 & 2). We have examined the soil and looked at devices for evaluating how our garden grows. We have begun to remove weeds (extraneities), and paid attention to the sowing of seeds and the effects of altered soil on the sown seeds. To fully nurture the plant, we need to expose the factors which lead first to germination of the seeds, and then to "taking root." The nature of the seeds also needs attention. "Hybrids" (genetic deviants) are the seeds of "progressions." They may be more, or less, demanding than their natural counterparts. The lymphoid infiltrates of melanocytic neoplasia can be compared to infestations of insects (Fig. 10). It might then be proposed that their purpose is generally not beneficial to existing populations of neoplastic cells (seeds) but that, in response to the effects of such infestations, mutations of the seeds may lead to strains which are less susceptible to the harmful effects of the insects. The blood supply of the papillary dermis has relevance to the content of both moisture and nutrients in the soil. Finally, there is an aspect of our selected neoplasm which defies a comparison with the phenomena of growing plants in a garden; the dissemination of tumor cells is too destructive to be compared with the delicate gift of life in the process of pollination.
INTERVAL OF SUSCEPTIBILITY
With the stromal changes of the mild to moderate dysplasias, nests of atypical cells in the dermis tend to be isolated from the cytolytic effects of the host immune response. In the transition to higher grades of neoplasia, the character of the stroma is altered; it becomes loose and myxoid. Either the neoplastic melanocytes induce collagenolytic changes in the stroma, exposing portions of some of the nests of the neoplastic cells, or the lymphoid infiltrates focally erode the condensed stroma to expose portions of nests of neoplastic cells. In either case in the transition phase, the neoplastic cells in their progressions come to be exposed. The lymphoid infiltrates may focally eradicate portions of the population of neoplastic cells. On the other hand in the interplay between lymphocytes and neoplastic melanocytes, clones with greater aggressiveness and less susceptibility to the immune response may evolve. Peculiarly, zones of regression are often encountered adjacent to vertical growth components - the effects of one regressive process seems to promote the progression of a counter-process. Perhaps it is in this interval that some MDM have their origin (Fig.3).
The seeds of a pathologist's garden are not a plant and yet the genetic instruments, which are a requisite for the transition from independent seeds to the proliferating communal cells of a plant, are inherent in each. In the act of becoming melanoma, the fluidity, looseness, and accommodativeness of the soil must be favorably altered. The transition from seed to plant is heralded by the appearance of that stage in which seeds are converted into proliferating colonies of cells in the soil (stroma). A colony must acquire a degree of organization to be characterized as a plant. In like manner, neoplasia has intermediate stages and it is harmful to too soon characterize a colony of neoplastic cells as a melanoma. The transition is not an instantaneous event but is incremental with each new cellular event evoking new events in the soil. In toto, the finality of all these events is as difficult to define as is that of life for groups who are concerned with abortions.
Conditions must be right for germination to occur. In the process of germination, the needs of the proliferating cells must be met by an increase in nutrients, fluid, and even kinins. If we search for that stage which most properly defines the transition from precursor to melanoma, we find a zone of relativity and this nebulous zone forms a domain between precursor and "real" melanoma (Figs. 1 & 2).
With common seeds (mild to moderate atypia) and early on (mild to moderate dysplasias), stroma tends to be compacted around sown seeds in the soil of the papillary dermis (Fig. 10). The seeds sit in isolation in the altered papillary dermis. Insect infestations (lymphoid infiltrates) tend to be confined to the dermis beneath the zone of compacted stromaASIDE. In part, they might be characterized as inimical for the germination of seeds; the compacted soil (altered stroma of an inflamed, widened, and fibrotic papillary dermis) is not conducive to germination. On the other hand, the alteration may have two sides. It may also, or even singularly, represent a determination by the seeds that at their stage of "hybridization," their interests would be best served by an alteration in the soil which denies insects (lymphocytes and histiocytes) access to the cells. From this viewpoint, the condensed stoma of a fibrotic papillary dermis takes on the qualities of a defensive shell. Occasionally, patterns, in which the lymphoid infiltrates irregularly erode the condensed stroma to gain access to the melanocytic cells, are encountered. In these regions, the effects of an encounter between insects and seeds may promote alterations in the seeds which will alter the nature of relationships and promote the survival and proliferation of seeds in the soil. On the other hand, the interplay may lead to eradication of the seeds (i.e., regression)ASIDE.
INCREASES IN NUMBER OF CELLS PER UNIT AREA
IN THE ABSENCE OF GERMINATION
In evaluating melanocytic neoplasias, dimensionalities currently provide the prime prognostic parameters. For fully evolved melanomas, a measure of a single dimension is the most significant guide to both local and regional therapy. For our garden, it is appropriate to ask: What is the physicality of seeds in a bin, or seeds which have been sown but have not germinated? If the bin is sufficient, it will accommodate the seeds in a single layer along its floor. When viewed in a cross-section (i.e., a plane which is perpendicular to the floor of the bin), the patterns are basically as one dimensional as are the patterns of a histologic section of " melanoma in situ". If seeds have been sown into the papillary dermis (soil), but are randomly and loosely scattered, then the physicality of the resultant pattern should be evaluated without regard to any component left in the bin (the epidermis); with the given stipulations, such patterns would also be one dimensional. On the other hand, sow the seeds at intervals, allowing sufficient time between sowings for the seeds of earlier sowing to sink into the soil, and the patterns produced on a cross section will have dimensionality in stratified patterns. If we further complicate the conditions by using different hybrids for each of the sequential sowings, then not only will there be stratification in number of layers but also in genetic types. If we additionally require that, with each new sowing, we will sow a "hybrid" more progressive than its predecessor, we will have produced conditions comparable to those commonly encountered in the study of early, progressive melanocytic neoplasia of common type (i.e., lesions of the type encountered in the dysplastic nevus syndrome). In evolving premalignant melanocytic dysplasias, if nests of neoplastic cells are stratified and loosely, but regularly, spaced in the papillary dermis, then the most advanced (highest grade) neoplastic cells will be found at, or near, the dermal-epidermal interface. The least advanced and most nevus cell-like component will be in the deep portions of a widened papillary dermis; it will be representative of the oldest, but also the first, generation.
The nature of the seeds may influence the condition of the soil. Peculiarly, the higher the grade of atypia (dysplasia), the looser the stromal response. Nests of cells showing moderate atypia may be outlined on the dermal side by several layers of fibrous lamellae. On the other hand, nests of cells in junctional patterns showing a high grade of atypia are likely to be confronted by a loose edematous, vascularized stroma.
The distribution of seeds which have been sown into soil relates directly to the condition of the soil. Unbroken soil is inimical. Broken soil allows the seeds to stratify and some will likely germinate. In the early evolution of a melanocytic dysplasia, the soil (stroma) condenses around the newly sown seeds in the papillary dermis; it is condensed and its fibers are either randomly and diffusely arranged, or they are arranged in laminated patterns. In either case, a condensed stroma is inimical to the process of germination; delicate or mucinous stroma is favorable for germination.
In our socialized and politicized schemes for relating histologic patterns to treatment, the emphasis is primarily on dimensions. We feel compelled to measure something and the results of such measurements are assumed to be guides to therapy. We do these things notwithstanding the fact that malignancy is, for individual lesions, a phenomenality rather than a dimensionality. The phenomenality of a malignancy is a measure of retrospect; it has the qualities of a finality; something bad did, or did not, happen; social implications from this perspective become inconsequential. The dimensionality of a neoplasm is a measure of prospect; it correlates with age of neoplasia and, in regard to biologic potential, up until the emergence of the requisite phenomenality, has only social relevance.
SEEDS AND SOIL
Having been spilled or sown out of the bins, there are no assurances that the seeds in the soil will germinate. Several factors impact on the relationships between seeds and soil. A few seeds randomly and widely spaced in a widened papillary dermis are of little importance as a predictor of progressive growth (Fig. 9). The greater the number of seeds in the soil the greater the likelihood that some of the seeds will germinate.
If the soil is not prepared, the seeds may become entrapped in the soil; germination then is unlikely (Fig. 11b).
Prior to germination, seeds are loosely but irregularly spaced in a loose, inflamed soil. In the search for evidence of germination, the number of nests of seeds (i.e., greater than five) and the number of strata of such nests (2 or greater) might be sufficient to suggest the possibility of early germination of seeds, but some of the features of the soil are also important in the evaluations. Some of the patterns are related to the number of seeds delivered to the soil during the sowing (a physical rather than a vital phenomenon) (Fig. 11a & b). Loose soil (stroma) favors germination. Condensed soil is inimical to germination (Figs. 12 & 13). The soil may be diffusely condensed (Fig. 12, 13, & 14) or concentrically laminated about the seeds. The pests (lymphoid cells) tend to be confined to a zone beyond that of the condensed soil. An impasse can be created (Fig. 10).
Infestations of insects (lymphoid cells) are variable in association with the seeds in the soil (Figs. 14 & 15a & b). For examples with low hybridization (atypia) of the seeds, the infestations are likely to be minimal; the native seeds are more resistant. With arrested growth, the infestations are often confined outside the zone of condensed stroma (Fig. 13). With higher degrees of hybridization (atypia), the infiltrates are more uniformly distributed and often the pests intermingle among seeds in nests (Fig.15a). They may even attack cells in the bin (i.e., epidermis) (Fig. 15a).
Seeds which have germinated form closely spaced clusters in the soil (Fig. 16 & 17). They have become independent of any subsequent sowing of seeds.
Finally, the root system, in its independence, may invade beyond the prepared bed (Fig. 18).
OUT OF THE REED PATCH
(........OUT OF THE SHADE AND INTO THE HEAT)
In this examination of a special garden, overgrown with the weeds of neglect, alterations in members of a special segment of the garden, the melanocytic system, have been correlated with changes in the character of the stroma. In progressions affecting this system, the characterizations of certain stages as being representative of a community of cells, and of the interactions among the cells as having the defining qualities of such a community establish the attributes of the respective cells as relativities. The members of this community have the potential to forsake all communal concerns and to disseminate without regard for native soil or natural boundaries; they become migrants with little respect for native boundaries and with little need for a prepared soil (stroma).
There are other gardens (i.e., neoplastic systems) with many other gardeners in attendance. In them are different communities and varying peculiarities of the soil. The other communities have their own relationships to soil and have their own aggressiveness. It is increasingly apparent that in most, if not all, of these other gardens, phenomena and stages are basically comparable to those in the Reed Patch; with the proper imposition of virtual images, borderlands can be defined. In addition, the other gardeners surely face comparable difficulties in the interpretation of the significance of early stages of "germination". Until the borderlands of all the gardens are properly defined, pathologists will continue to speak of atypical hyperplasia as if each individual pathologist, when using the designation to describe certain stages of neoplasia in whatever garden he is tending, is stuffing the same intensions into the same relevant real images as will all the other gardeners when faced with similar encounters. Atypical hyperplasia is an inappropriate designation for certain neoplastic stages in a setting such as mammary neoplasia, if its application is equal for both intraepithelial lesions and for invasive, but early, small lesions. The distinctions between patterns of growth should be given recognition even for lesions of the borderlands.
We have wandered in the PATCH as if what we do there has universal application. The produce to be sent out of the PATCH is of a special type. It is linguistic; reports are structured of words; communication is the aim. Even using words which seem to have universal acceptance, it is remarkable how uncommunicative communication can be. Clearly, the melanoma of one patch may be nothing more than a sowing in another patch. The imposition of an authoritarian air on the nature of the produce of one patch does not necessarily mean that the produce of another patch is unacceptable. The lack of correspondence between the actual intent of a pathologist in structuring his report, and what the recipient might take to have been the intent of the pathologist can lead to problems. Obviously, there is sufficient overlay of virtual images in a report to disguise the intent of a pathologist. A report is not simply a recitation of morphologic findings. There are subtle and hidden meanings that unfortunately often remain subtle and hidden. In structuring a report, a pathologist has an obligation to not unwittingly impose restrictions on therapeutic options. The numerations of pathologists are mostly left unqualified; they appear as oblique attempts at communication. The translation of the numbers beyond basic correlations with therapeutic guidelines are the responsibility of the clinician. A vague histologic pattern on an inadequate biopsy can be translated into a specific diagnosis as a guide to treatment, but such a molding of images should be qualified as an incomplete or provisional interpretation.
Some gardeners look at their patch and see a remarkable variety of plants. Some, having a remarkably similar field of view, see a single type, with variations only in size and age of the plants.
THE "EYES" AND "I'S" OF PATHOLOGY
"Eyes" are basic to the discipline and the practice of pathology. Of all the medical specialties, the practitioners of histopathology are perhaps most dependent on visual stimuli and their abilities to manipulate related images. The practice of histopathology is a visual art; it is a discipline in which images are translated into words. We stuff the words that we select with virtual images. Some degree of individuality is also imposed. There are no assurances that the implications hidden in our “stuffings” will be carefully dissected from each package and properly digested during the consumption of the product. It is common for guidelines or cautions to be lost or ignored during the translation of an histopathological report. This is not evidence of a careless act. It is an intrinsic flaw in human communication.
The "I's" of pathology are another matter. The introduction and free utilization of this pronoun in scientific dialogue transforms intensions into possessions. Intensions are too universal to be claimed as priorities and, then, identified as the property of an individual. The editorial "we" is less offensive but, with the intensions imposed when creating a report, and, in the travails of someone else having to read and interpret such a report, what may appear to be the editorial "we" can easily become an imperial "we" in masquerade. Packages of virtual images that remain too closely identified with an individual have either been too blatantly touted by their proponent, too blatantly denounced by an opponent (often the same individual is the culprit for both abuses), or too poorly documented to receive general acceptance. The "I's' of pathology should be appreciated as an intrusion of extraneities of a personal type into the modus of histopathological interpretations. In such ventures, who the intruding pathologist thinks he is becomes one additional intension to be stuffed into our packaged intensions. An "I" is an authoritarian intrusion which contradicts the need of pathologists to express their impersonality. It is a statement that an interpretation is overriding simply by the authority of an assumed papal-like infallibility. Certainly, not all interpretations are equal but it is not the weight of an imposed ego which determines the value of a report. It is instead the correspondence of an interpretation with the subsequent course of disease in a respective patient. In any case, reliance in histopathological interpretations should be on the "eyes" and not the "I's".
Dr. Reed would appreciate comments directed to him at: firstname.lastname@example.org
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