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In the preceding scenario (i.e., end of c11t3), but with the knowledge of subsequent clinical findings, and under the influence of the imposition of relevant virtual images, the real images of an excised, primary lesions will have been reappraised, and histologically reinterpreted as a “melanoma.” The reappriasal eventually may prove to have provided an inaccurate depiction of events. In fact, there may have been a real melanoma which was the source of the metastasis, but had been removed (and may even have been misdiagnosed). As an alternative, the actual primary melanoma may have spontaneously regressed; the patient may have no recall of such events. In this approach to problematic cases, the fallibility of virtual images must be in the forefront of deliberations.
Some examples of “SSM” at level II with purported metastases may be representative of the distortions produced by fanciful virtual images. It behooves the pathologist to investigate the clinical setting, and to inquire regarding other possible primary sites when faced with the prospect of a metastasizing “SSM” at level II (i.e., “metastasizing level II lesion”). With few exceptions, a true metastasizing melanoma, initially interpreted as showing only level II invasion, will, on additional sections, show an area of acceptable vertical growth, or an area of regression.
In general, prognostications are based on the identification of features which relate to the grade of neoplasia. In common with the grading of most malignant neoplasms, features of melanomas, such as nuclear and nucleolar size, distribution and content of nuclear chromatin, nuclear-cytoplasmic ratio, cohesiveness of cells, and mitotic rate, are to be evaluated in arriving at the diagnosis, even if these parameters are not given great significance in routine prognostications.
Melanomas and histologic grade:
The (hopefully) relevant virtual images, and the respective taxonomic selections of a responsible pathologist are interdependent. In the concept of melanoma, virtual images and a designation, whose relativity to the concept of malignancy (another term imbued with relativity) is dependent on both the whims of the respective observers, and the nature of selected virtual images, are amalgamated. In the final analysis, the validation of melanoma, as a true malignancy, is relative to the subsequent clinical course, after the primary lesion has been excised and controlled.
In many melanomas, histologic “grade” and size (“age”) seem to be correlated. With physical size as the chief criterion, and as a measure of the “age” of a neoplasm, few “malignancies” are as unpredictable, and as prone to metastasis at an “early age” as melanoma. Many thin melanomas are low, or intermediate in regard to histologic grade (e.g., nuclear grade). Such lesions are given recognition in the concept of MDM. Most large (thick) melanomas are high grade; they not only tend to be high grade lesions but, commonly, are pleomorphic in vertical growth (they are old enough to have experienced many intra-lesional transformations).
Minimal deviation and nuclear grade:
Generally, it is convenient to utilize three nuclear grades but, on occasion, the degree of atypia in melanocytic neoplasia is extreme. Such lesions have an anaplastic quality, and might be characterized as grade IV. In some anaplastic lesions, polymorphism is also a feature (e.g., melanoma may even masquerade in the generic category of atypical fibroxanthoma). For the common dysplasia-melanoma syndromes (including those in the setting of the dysplastic nevus-melanoma syndrome, the LM-LMM category, and the acral lentiginous dysplasia-melanoma category), small, thin lesions are less likely to show a high nuclear grade than are thick lesions. In part, deviations in degree of atypia in thin melanomas of the common (typical) categories are given recognition in the concept of minimal deviation melanoma. In addition, variant vertical growth is commonly a feature of thin typical melanomas; it is an attribute which might be cited as an expression of the deviations encountered in the minimal deviation categories of the common dysplasia-melanoma complex. Finally, the very fact that these examples of low grade lesions are thin (less than 1 mm in height) provide an indication for appending qualifications to, or in place of, the diagnosis, “melanoma” (e.g., borderline melanocytic neoplasia of indeterminate malignant potential).
The quality of low to intermediate nuclear grade (grade I & II), as often manifested in thin, common melanomas, is not a regular attribute of some of the less common variants of minimal deviation melanoma (e.g., the Spitz variant).
In practice, size, as evaluated by a measurement of the dimension of a lesion along an axis that is perpendicular to the epithelial surface, and that overlies the greatest expanse of tumor, is the prime prognostic parameter. In consultation practice in the evaluation of a specific lesion, conflicts relate to the interpretation of variable patterns, particularly the interpretation of the significance of a population of nevus-like cells at the deep margin of the lesion. In general, the mild atypia often displayed in remnants of a nevus at the margin of a melanoma should be ignored; this nevus cell-like population should not be included in the prognostications. It is often more difficult in these prognostications to ignore the small cell population at the deep margin of many nevus-like (nevoid) MDM.
In defining vertical growth (i.e., patterns III & IV), as the sine qua non for the diagnosis of melanoma, the criteria for the recognition of early vertical growth are based on extrapolations from the patterns of a fully evolved vertical growth component of “real” (i.e., category III) melanoma (e.g., a lesion measuring 2.5 mm in vertical dimensions). Neophytes, or the uninformed (e.g., surgeons) will often assume that there are predictable correlations between Clark’s criteria and Breslow’s criteria. They will assume that there will be a precise cut-off in vertical dimensions at the transition from level II to level III, and from level III to level IV. In practice, the correlations are imprecise with significant overlaps. A level IV lesion may be as thin as the thinest level III lesion, and some level II lesions may be “thicker” than a level III or IV lesion. Some thin melanomas, with a minimal representation of the requisite number of nests for the recognition of vertical growth, may be as thin as 0.3 mm in vertical dimensions.
Generally, in the evaluation of melanomas, depth of invasion (Breslow) is likely to be considered a correlate of bulk; with such a perspective, a tumor at level V would be expected to be a bulky lesion. Actually, invasion to level V, and significant tumor bulk at the same level are not always correlated. Some melanomas may enter vertical growth in a superficial site, and then extend “in situ” along, and within, skin appendages. Subsequently, a second vertical growth component, near or at level V, may issue from the adnexal component without having attained significant overall bulk (i.e., secondary loci of vertical growth arising from neoplastic melanocytes affecting the skin appendages). Such lesions may behave as would a bulky, solid level V lesion; level V may be a significant measure of prognosis without attention to bulk, if the component at this level also shows migrant (diffuse) patterns of interstitial vertical growth (as it often does).
Lentigo maligna melanoma is an example of a melanoma that may enter vertical growth from components involving hair follicles, or the sweat gland apparatuses. The deep portions of the respective lesions at level V may be relatively small in cross-sectional diameter, but may show diffuse vertical growth with infiltration of neoplastic cells among collagen bundles of the reticular dermis. Some examples of SSM may enter vertical growth deep in the dermis or subcutis from components involving sweat apparatus and, at level V, the vertical growth components of such lesions may have small cross-sectional diameters. Such lesions usually enter vertical growth at this level in patterns of diffuse infiltration (diffuse or migrant vertical growth). These qualities, in combination with a rich vascular plexus, may provide an explanation for the aggressive behavior of some of these lesions.
In the investigation and prosecution of malpractice claims, lawyers fuss over the dimensions of a melanoma; how the dimensions relate to prognosis is their concern. Another point of contention is “standard of care” which, in part, requires a judgement regarding how other pathologists would have performed, if confronted with the material in contention. In particular, the question posed is “would other pathologists have been more ‘likely than not’ (i.e., 51%) to render a ‘correct’ diagnosis (one that would be congruous with the subsequent clinical course), or to commit the same ‘error’ as the defendant?” If this approach is put in perspective, then we should also define at what histologic stage (Breslow) would 51% of patients, all with a similar lesion, be committed to a fatal course. For purposes of discussion, a figure such as 2.5 mm might be offered as an arbitrary cutoff point. In other words, the likelihood of a fatal course above the cutoff point would become “legally” significant. Only beyond this point would statistics become “valid” (using the biased parlance of lawyers) as the basis for a claim of malpractice. Below that point, the assumptions that the patient is committed to a fatal course is mostly a guess, with accuracy dependent on the vagaries of nature; not the prescience of a pathologist, or the “self-righteousness” of attorneys.
Documentation of real and virtual images:
A report without a microscopic description is certainly acceptable by current standards, but does not provide evidence that the pathologist’s observations , and his evoked virtual images are relevant to the real images, or that the final diagnosis will be guide to either clinical behavior, or to treatment. It may come to pass that such a report will be cited as a deviation from a “standard of care,” but such an assessment would not automatically identify the related performance of a pathologist as negligent. On the other hand, careful evaluations of histologic, and cytologic features, and documentation of the evaluations in a report go a long way in resolving problems of culpability.
Ulceration:
Ulceration is common over the vertical growth components of melanomas. Its prevalence is directly proportional to the “thickness” of the respective vertical growth components. Having been often cited as a significant prognostic parameter, efforts have been extended to provide a definition of what constitutes significant ulceration. Objectively, ulceration is nothing more than a covariate of “thickness” (i.e., size of vertical growth component). The significance of either typical, or variant vertical growth components as related to the frequency of ulceration has not been examined.
Density and distribution of lymphoid infiltrates have often been emphasized in prognostic evaluations. Tumor infiltrating lymphocytes have been cited as prognostically important. It is difficult to make a sharp separation between tumor infiltrating lymphocytes and halo nevus-like phenomena.
Although mostly denigrated, level IV invasion has utility, particularly in the evaluation of thin lesions. If, in developing therapeutic options, emphasis is placed on scant infiltrates of lymphocytes, the pathologist should also record whether those examples, which are relatively free of lymphoid infiltrates, are also at level IV. The two features are correlated. They also are often correlated with fascicular, spindle cell patterns.
Regression:
An appreciation of areas of regression requires the manipulation of virtual images. In the process, virtual images, which give recognition to the implications of a cellular immune reaction, are to be integrated with the real images of markers left behind after a population of neoplastic melanocytes have undergone lysis. Regression is common in the setting of both halo nevus, and as a focal alteration in the dysplasias. In these processes, the end-result could be histologically indistinguishable from an area in which the vertical growth component of a melanoma has undergone complete regression (c24t3P1-4). (Note: I wonder if the reader appreciates how much impact the concept of “melanoma-in-situ” has on a concept which identifies regression of a vertical growth component as a significant event in the life history of a common melanoma?)
Melanoma may metastasize, and then regress only in its primary site. In this sequence, a careful examination of the patient, and a history of a lesion that has spontaneously regressed, or has “fallen off” may provide important clues for the identification of the site from which the metastases originated. In remnants of such lesions, markers for halo nevus-like phenomena may be represented; lesions showing such patterns may represent examples of regressing MDM of halo nevus-like type.
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