|
Prognostic categories:
The prime prognostic categories have relevance to qualities that are discernible in evaluations of the vertical growth component. They are based primarily on a measurement of the distance the deepest nest of atypical melanocytes is from the granular layer of the epidermis ( a measurement that generally is perpendicular to the surface of the lesion; an irregular skin surface requires some creativity in selecting the site for measurment; a tangential section may seriously compromise efforts at an evaluation of “thickness”). The commonly emphasized categories include: 1) lesions up to 0.75 mm in vertical dimensions, 2) lesions in the range of 0.76 to 1.50 mm in vertical dimensions, and 3) lesions greater than 1.50 mm in vertical dimensions. In giving credence to the value of these parameters, an observer will likely come to presume that his measurements, and prognostications have relevance in regard to the biologic potential of any selected individual lesion, a presumption played upon by plaintiff’s attorneys.
In defining a borderland of melanocytic neoplasia, the dimensions of the commonly emphasized categories have been modified:
Category I lesions are thin lesions measuring less than 1 mm in vertical dimensions; included in this category are high grade dysplasias (patterns I & II), and thin melanomas (patterns III & IV). Lesions in category I are unlikely to metastasize. With rare exceptions, such lesions are biologically innocent. To characterize all these thin lesions as unqualified melanomas unfairly stigmatizes a large group of patients. In practice, these thin, level II or III lesions, in the categories of high grade dysplasias, melanomas-in-situ, SSM, LMM, ALM, and melanomas arising in atypical nevi (i.e., evolving from common premalignant dysplasias but not manifesting the features of the common final pathway), rarely metastasize, even if the limits for the definition of category I are extended to 1 mm. Such thin lesions are best characterized as borderline melanocytic neoplasias of indeterminate malignant potential, and qualified as either dysplasia, or melanoma variants.
In the modified range of 1 mm to 1.5 mm, only lesions in vertical growth (i.e., patterns III or IV) have real relevance to the diagnosis of melanoma. Melanomas in this range are only slightly more predictable than those less than 1 mm in vertical dimensions; the likelihood of predicting metastases from any individual lesion in this category is sufficiently remote to justify the characterization of category II lesions as unpredictable, thin melanomas, or as intermediate melanomas of indeterminate malignant potential.
Lesions in category III (beyond 1.5 mm in vertical dimensions) qualify as “real” melanomas; the prognostic parameters begin to take on a semblance of predictability.
In the above scheme in which segmentation of a neoplastic continuum is based on both patterns in the dermis, and the vertical dimensions of any vertical growth components, there is a borderline category, an intermediate category, and a category of “real” malignant melanoma. The categories of melanoma are defined on the basis of vertical dimensions, and the expected prevalence of metastases in relationship to the vertical dimensions (Table I).
The three categories, as developed in the preceding section, are a compromise in which physical attributes are related to prognosis. The arbitrariness, as to the significance of the designation, “melanoma,”for category I lesions, is documented by an inability to identify those rare members of the category with a capacity for metastasis.
The character and pleomorphism of melanoma in vertical growth components is generally ignored in the assignment of respective lesions to a common category. For example, a vertical growth component may be composed of small, rather bland amelanotic cells in closely spaced nests of relatively uniform size ( Thin Melanoma (c19t3)). These cells may be difficult to distinguish from common nevus cells, if a remnant of a nevus is available for comparison. If, in such a lesion, the patterns at the dermal-epidermal interface are those of the common final pathway (as manifested in the radial growth component of a fully evolved SSM) then the minimal deviation character of the vertical growth component will likely be ignored and, in turn, the lesion will likely be assigned to the category of SSM. On the other hand, in providing prognostications for such a lesion, the vertical growth component, with no attention to the character of its small, bland cells, will be the prime determinant. It is paradoxical to place emphasis on a population of cells (i.e., the radial growth component) which is mostly a new growth of limited expanse at the dermal-epidermal interface, and to ignore the character of the vertical growth component in characterizing most melanomas.
Estimates of nuclear (tumor) grade in the vertical growth component may have utility in the classification of melanoma. In this approach, most lentigo maligna melanomas would be low or intermediated grade (minimal deviation), and all superficial spreading melanomas (i.e., lesions with a high degree of atypia in the vertical growth component [pattern of common final pathway]) would be high grade melanomas. A pleomorphic lesion with the pattern of the common final pathway at the dermal-epidermal interface, but with a preponderance of bland (minimal deviation) nuclear features in the vertical growth component would be evaluated by the nuclear grade of the latter component, and be characterized as low or intermediate grade. If such an exercise were to become common practice, designations such as lentigo maligna melanoma, acral lentiginous melanoma, and superficial spreading melanoma might become anachronisms.
In practice, a certain elegance and utility, that is lacking in cold evaluations of nuclear grade, reside in our “archaic” designations. In practice, a combination of the two options would appear to be the best compromise.
Analysis of neoplasms (comparisons with cryptanalysis and transmission analysis):
In the practice of histopathology, patterns are analyzed for the purpose of rendering a diagnosis, and to provide therapeutic guidelines. Real images, having been observed, must be compared with evoked virtual images (as they relate to a variety of processes); then, all the images must be amalgamated. In these endeavors, the intention is to find matching pairs among the real and virtual images, and to structure from them a scenario.
In the analysis of a histologic section of a neoplasm, the biologic potential of the neoplasm is anticipated in predictions rather than assurances. In an observer’s interplay of images, virtual images, once imposed on real images, may modify, or alter, the appreciation of the real images in a detrimental manner. In such an event, a diagnosis (with its dependency on the relevancy of imposed virtual images) may prove to be inappropriate.
In one portion of the spectrum of melanocytic neoplasia, the nature of respective neoplasms cannot be sharply defined by manipulations of real and virtual images. Designations, such as severe junctional or compound dysplasia, “melanoma-in-situ,” and thin “melanoma” at level II are assigned relevance in the interpretation of certain stages of neoplasia, but are merely arbitrary segments along a neoplastic continuum. They are not mutually independent segments; there are conceptual overlaps. To defend one of these segments to the exclusion of the others promotes controversies, a technique much used by some authorities. Simple manipulations of the virtual or real images in this limited portion of the neoplastic continuum cannot resolve, and manipulations of the related linguistic symbols can only worsen, the controversies.
Molecular “pathologists” would have us believe that some controversies can be resolved by appropriate marker studies. If cell markers, as demonstrated with labelled monoclonal antibodies, prove to be inadequate, some technologists, having failed with one technique, will then direct us to more sophisticated techniques, such as polymerase chain reactions, etc.
The problems in the molecular approach to the analysis of neoplasms are comparable to those of crytographers in wartime. It is the role of crytographers to anticipate the plans, and intentions of the enemy. Their efforts may be of great assistance, if coded messages are intercepted, and decoded. In this endeavor, the process is characterized as cryptanalysis. If successful, intentions and ambitions will be exposed, and can be thwarted by effective countermeasure.
If the code has not been, or cannot be, broken, or, if broken but subsequently changed, then monitoring messages, without attention to their actual meaning, and correlating the messages to other known parameters, such as frequency of transmissions as they might relate to the increased activities of destroyers in anticipation of battle, or the identification of the location of aircraft carriers which, although under radio silence, are known to be part of a fleet in common with the destroyers, will often provide useful information. This technique is characterized as transmission analysis.
Molecular pathologists would have us believe, that by a modification of cryptanalysis, they have access to, or will decode, messages from borderline lesions. They then will be able to clearly resolve the conflict of whether a lesion is a precursor, or a fully evolved malignancy. Their success would then make an analysis of histologic patterns in the borderland a moot endeavor. In fact, most of what the molecular pathologists accomplish is transmission analysis. The borderline neoplasm is by nature ambiguous, and its genetic messages will prove to be equally ambiguous. A fully evolved malignancy will transmit messages which are decipherable but, in such examples, histologic patterns are equally informative.
Surgical pathologists, in their attempts to grade neoplasms, and to provide prognostic and therapeutic guidelines, must also deal primarily with transmission analysis. The associations between grades of neoplasia, mitotic rate, and degrees of differentiation on the one hand, and clinical behavior on the other are only hinted at in histologic evaluations. Time is the final arbiter in the evaluation of the potential of a neoplasm.
A pathologist, who, with the aid of a historical perspective, has offered an interpretation which is in conflict with some earlier report by a different pathologist, has placed himselt in a compromised position. It would be a conceit for him to offer an evaluation of the performance of pathologists who have earlier reviewed the identical material without the luxury of historical perspective, if he then were to characterize his offering as unbiased. The following scenario is an example of the evocation, and manipulation of fanciful virtual images:
A thin melanocytic lesion has been excised with histologically free margins. With subsequent follow-up, regional lymph node metastases, but no local recurrences, are discovered. In the evaluations of this sequence, virtual images of a lesion which had metastasized prior to the excision of the primary lesion most often are (or should be) evoked. Histologically, the primary lesion may have been diagnosed originally as a nevus, melanocytic dysplasia, or melanoma. The exposed clinical sequence, independent of any regard for the histologic patterns, or the vertical dimensions of the primary lesion, evokes virtual images of a primary lesion that had evolved into a melanoma (a lesion with vertical growth). With subsequent reviews, the real images of the histologic sections of the “primary” lesion are certain to be conditioned by the imposition of the evoked virtual images, images which have relevance to the knowledge that there has subsequently been a local metastasis. In this sequence, with any markers for a dysplastic nevus in the “primary” site, it becomes tempting, in retrospect, to assign the “primary” lesion to the melanoma category. It may even be possible to list “features” (i.e., real images) of the “primary” lesion in confirmation of this diagnosis. A special liberty, available mainly to those who subscribe to the concept of “melanoma-in-situ,” and “SSM” at level II, blurs the distinctions between dysplasia and melanoma. Such subscribers, in the face of documented metastases, are especially prone to assign a problematic lesion to the category of “melanoma.” The manner in which virtual images may have modified the interpretation of a suspected “primary” lesion seldom is formally acknowledged. If the thin “primary” lesion had been originally interpreted as a benign process, the capabilities of the original pathologist, who may have struggled in his interpretation of deceptive cytologic features of a thin problematic lesion, then become suspect. That the original pathologist, in his initial interpretation of the “primary” lesion, may have been betrayed by inadequacies in his store of virtual images then will be a likely presumption. In fact, both the expert and the original pathologist would have been “done in” by nature’s ability to mask the potentials of a thin, recently evolved lesion, or by a “thicker” lesion in the MDM category.
|
