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Note: This section is dedicated to the memory of Dr. John B. O’keefe.
RIchard J. Reed, M.D.
12 Versailles Blvd.
New Orleans, LA 70125
email: rjrpjrlr@aol.com
There are special problems related to the interpretation of thin melanomas. For some of us, even the definition of thin melanoma is a problem. For those who embrace the concept of “melanoma-in-situ,” there are relatively few problems; if an intra-epithelial neoplasm is a “malignant” variant, distinguished only by its restricted growth, then certainly all such examples with, in addition, a dermal component are “melanomas.” It is as simple as that for the latter group. For the promoters of “melanomas-in-situ,” all patterns of great complexity in the dermis of these thin lesions are of little concern; the diagnosis has been established; in the words of Dr. John Dent: “Next case; steam on, son.” Certainly, a diagnosis of “melanoma-in-situ” tends to lessen the problems, if the prospects for the day includes a heavy load of surgical specimens. In thin lesions, the most consistent prognostic parameter is a vertical growth component, and the size of this component is the most consistent predictor of the likelihood for metastasis; the relationships being what they are, vertical growth and size were given primacy in the concept of Minimal Deviation Melanoma. In any attempt to define early vertical growth, attention must given to the arrangement and distribution of nests of cells in the dermis, particularly the papillary dermis (i.e., stroma). Papillary dermis basically is stroma for epidermis, including both keratinocytes, and epidermis-residing melanocytes; for neoplastic melanocytes to survive and multiply in a new domain, they must acquire the capacity to induce a specialized and vascularized stroma; this stroma may resemble a widened papillary dermis, but in typical vertical growth components, the stroma of the tumor nodule is independent of the pre-existing papillary dermis. In variant vertical growth, the stroma seems to be merely a modification of the pre-existing papillary dermis. In migrant vertical growth, the neoplastic cells have acquired the capacity to carry thin sheaths of stroma with them as the neoplastic cells migrate; these migrations probably are angiotropic.
In this section, concepts relating to a borderland of melanocytic neoplasia are discussed. The manner in which virtual images are to be related to real images in the interpretation of histologic patterns is explored. In our role as pathologists, the manner in which we approach neoplastic continua greatly impacts on our ability to define correlations between histologic patterns and stages of neoplasia. If, in the definition of neoplastic progressions, we introduce the concept of melanoma early on (i.e., by giving recognition to a stage of melanoma-in-situ), the neoplastic continuum would hardly need to be segmented; the histologic patterns beyond the stage of melanoma-in-situ would have all been embraced as “melanoma.” If we restrict the definition of “melanoma” to lesions in which patterns of vertical growth are a requisite, then there are complicated patterns which do not qualify as melanoma, but require detailed examinations and interpretations; once completed, the remaining task is an assignment of linguistic symbols. In this approach, an attempt to delineate the earliest stages of vertical growth tends to introduce arbitrariness into the interpretative process. In dealing with the arbitrariness, a definition of stages of premelanoma on the one hand, and “young” melanoma on the other provides a domain in which a morphologic borderland can be structured; by the examination of thin, metastasizing lesions, this borderland can be approached, and entered.
On the Imposition of Virtual Images and the Art of Pathology (with the melanocytic system as a model): A Philosophy recognizing the Arbitrariness of both Segmented Neoplastic Continua, and the Diagnosis of Malignancy
In all fields of art and all forms of artwork, unique imprints are expressive of the nature, and the limitations of each artist. Ambitions and aspirations, as embodied in the visions of artists, are never fully realized in their artwork. As if providing proof of the human condition, aspirations always exceed capabilities.
Although touched by technology, surgical pathology always has been, and remains, an art. Surgical pathologists, like all artists, depict in their artwork (i.e., surgical pathology reports) their interactions with nature; emotions, observations, knowledge, and reason are all integrated. The resulting artwork is a poor record of complex phenomena. Logic is an integral part of the amalgam; it cannot be avoided. Unfortunately, with the manipulation of logic, controversies flower.
The practice of surgical pathology is a most singular endeavor. In it, both images and information, all from a variety of sources, are integrated and conceptualized (by an individual). In the conceptualizations, a system of logic, requiring a distinctive language, is developed. Actually, each organ system, and many of the neoplasms of each organ system require individualized systems of logic. Perhaps, it more to the point to characterize the conceptualizations as systems of logic. The desiderata, as expressed in final written reports, include the categorization of disease, and the formulation of guidelines as to probable clinical course, and to appropriate treatment. Quality in the art of surgical pathology is measured by the degrees of concordance between the natural history of disease, and the prognostic implications (i.e., grades of neoplasia) which emanate from reports and diagnoses. Neither aesthetics nor commercialism should be considerations.
Some surgical pathologists, having been bouyed by frequent concordance between their diagnoses, and the subsequent clinical courses of the respective diseases, come to think of their diagnoses as God-like dictates to which the very nature of disease is subjected (and, in turn, responsive). Practically, for a specific case, the opinions of a surgical pathologist, and the ultimate course of a disease may be remarkably discordant; the seemingly God-like qualities of the dictates of pathologists are illusory. If a pathologist comes to assume that the God-like qualities of his dictates impact directly on natural phenomena, a self-deceit (one commonly mocked by nature) will have been promoted.
An error in the histologic diagnosis of a neoplasm will likely lead to inaccurate predictions of biologic behavior, and then to the selection of inappropriate therapeutic options. Disparities between the prognostic implications of histologic interpretations, and subsequent clinical courses, or among the opinions of different pathologists, all of whom having examined identical histological material, provide striking expositions of human frailities, once publicly exposed.
The limitations of histologic diagnosis were appreciated by Oscar N. Rambo (1): “Pathologists are physicians and human beings. They have as great a capacity for error and susceptibility to subjective distractions as other practitioners of the art of medicine. Because of certain nineteenth century dogmas and because the teaching of pathology used to be relegated primarily to the long-forgotten preclinical phase, pathologists traditionally have been regarded to be more scientific than many of their colleagues. A mystic perversion of this assumption prevails among those clinicians who believe that the pathologist, given only a piece of a patient’s tissue, has all of the other ingredients necessary to produce a statement of absolute truth at the end of his report. More dangerous to mankind is a pathologist with the same concept.”
“A first year resident or a diligent medical student should recognize common, taxonomically well behaved neoplasms with almost the accuracy of a professor; in the face of the unfamiliar, even the experienced pathologist’s observations may be no more ‘objective’ than Hamlet’s vacillations on the likenesses of cloud formations. Explanations of the inability of trained observers to decide whether they are seeing camels, weasels, or whales is offered by Hanson (2). Scientists of the purist order have long labored under the delusion that observations are equivalent to facts and that when technique is unimpeachable, failures of the scientific method must be ascribed to subjective influences on inferences from data. Hanson (2) claims that observation and inference are not truly separable and that our ability to ‘see’ is so preconditioned that it too is highly suspectible to subjective influence. The fallibility of observations and the effect of preconditioning must at least explain why a number of competent pathologists, given the same slide and clinical data, may offer an equal number of different interpretations.”
Real and Virtual Images (the Art of Pathology as manifested in the Interpretations of Histologic Sections)
The interplay of real and virtual images: The interpretation of histologic sections involves real and virtual images. Real images, the intrinsic attributes of a histologic section, are exposed by the microscopic examination of histologic sections. Virtual images, all of cerebral origin, and some in response to real images, are multifold. For each pathologist, they are accessible, in response to a variety of stimuli, and with varying degrees of accuracy and detail, from a singular repository in which (real) images become thoughts, thoughts become (virtual) images, and virtual and real images become amalgamated. To have utility, the amalgam must then be translated into language. The language is the instrument of a system of logic; it allows us to manipulate real images without the recourse of reviewing the respective histologic section. It is in the manipulation of language that individuality of each pathologist is imposed on what began as an real image, independent of the pathologist; in these individualistic impositions, personalities are introduced; once introduced, controversy follows.
In the practice of surgical pathology, real and virtual images become inseparable. Real images, relatively fixed in character, are the embodiment of the physical nature of histologic sections. Virtual images emanate from their imposer; they are subject to the vicissitudes of pathologists in their daily practices. For each pathologist, the collections of virtual images, with varying degrees of accuracy and relevancy, provide an individual perspective; we do not all see the same images.
In the evocation of virtual images, clinical details and laboratory findings often provide the initial stimuli. In turn, additional virtual images are evoked by the observation of real images during examination of histologic sections. A variety of pathogenetic and diagnostic considerations accompany both the evocation, and molding of virtual images, and the amalgamation of such images with real images.
In a common sequence, virtual images, having been mobilized following a review of clinical impressions and details, and with only tentative relevance, tend to precondition the surgical pathologist. If, during microscopy, the tentative virtual images are easily amalgamated with real images to accommodate the clinical impressions and details, they are transformed into preemptive virtual images. The interpretative process is then likely to be terminated forthwith, and the pathologist is likely to proceed to the next case with a feeling of accomplishment. This approach may become rote with the hazard that, for some cases, defects in the amalgam of virtual and real images will have been overlooked. Those virtual images, which have greater relevance to clinical data than to real images, if allowed to dominate the interpretative process, may lead to a diagnosis, consonant with clinical impressions, but more fanciful than factual. Such an amalgam is likely to be ( at least provisionally) pleasing to the clinician.
Mental facileness: The mental facileness of an observer is a significant factor influencing the quality, and accuracy of his histologic interpretations. Variable in intensity from day to day, the nadir is likely to be at the end of the workday. Pathologists, in the evocation of virtual images, generally are oblivious to compromises in their state of facileness. Under certain conditions of mental refractoriness, a pathologist may not appreciate the significance of new real images. In such a state, an observer, who has been preconditioned by responses to a variety of stimuli, may impose inappropriate virtual images and, in doing so, will have masked the nature of the real images. As a consequence, an uncommon lesion might take on the characterisitics of a more common process, or vice versa.
Inappropriate virtual images: Ideally, virtual images, having once been evoked, will have relevance for the interpretation of the nature of real images. With disturbing commonness, the results of the interplay of real and virtual images are indecisive. If clinical data are misleading, or if an impatient clinician, or another pathologist is in attendance, and is exerting undue pressure favoring a particular diagnosis, the nature of diverse, or unusual, real images may be confounded by the imposition of inappropriate virtual images. The respective observer then is at risk for betrayal by faculties which usually serve him beneficially. These distortions of the interpretative processes are common and natural. As to type, they generally are characterized as human.
Pattern analysis: Some pathologists function primarily at the level of general patterns in both the real and virtual realms. Pattern analysis at low magnifications, basically a primitive technique, is accomplished with little regard for subtle histologic details. It is the characteristic approach of neophytes, such as residents in pathology, but is the routine, initial technique in the evocation of virtual images during microscopy. Experienced practitioners may elevate the technique of pattern analysis to a high degree of sophistication. In pattern analyses of neoplasms, little leeway is provided for the interpretation of subtypes, particularly in minimal deviation, and borderline categories. False virtual images, if evoked during the examination of histologic sections at low magnifications (pattern analysis), may confound attempts to interpret problematic patterns at higher magnifications. In this situation, having imposed confounding (false) virtual images, it may be difficult to regain a proper perspective.
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