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Biased manipulation of real images:
If, following the histologic examination of a problematic lesion, no melanoma cells are extant or, even if only a few widely spaced nests of atypical cells are represented , a diagnosis of melanoma, that is based solely on the real images, may be difficult to defend. On the other hand, a weak or biased expert may interpret the melanophages in such a site as evidence of residual melanoma cells, and may even be able to successfully defend such an erroneous position in a “court of law”(if this is a proper characterization of some of the courts in some of the states). All the troublesome patterns of a regressed primary lesion tend to become moot in the face of a documented metastasis. A subsequent review of earlier, less diagnostic material, is then likely to seem less troublesome than during the initial evaluations. To impose, in retrospect, the virtual images of a metastasizing melanoma on the real images of the regressed lesion, as seen in the initial histologic material, is presumptuous; this presumption leads to expressions of confidence that may not have been forthcoming, if the roles of respective pathologists, and the sequence of events could be reversed. Unbiased manipulations of real and virtual images, that are of a different order, would be required to put the original images in proper perspective. In the sequence, in which metastases are identified prior to the identification of a site of regression in the skin, the metastases would have occurred prior to, or during, the regression of a vertical growth component.
That a metastasis may flourish, and the primary source of the metastasis may simultaneously regress is a biologic paradox. The explanation probably is related to peculiarities of anatomic sites, to dedicated systems of immunity in the respective sites, and to an interplay of tumor cells, and distinctive stromas. The process of regression in the site of a primary melanoma may adversely alter relationships between neoplastic cells and stroma. These alterations may favor the dissemination of neoplastic cells. With dissemination to new sites, the cells may find that only certain new sites are immunologically favorable.
In one collection of fanciful virtual images, the growth of latent metastatic melanoma in a lymph node may be adversely influenced by “humors” originating in a site of regression in the skin. The metastases would have been occult, but would become overt during the process of regression in the primary site.
Conservative prognostic evaluation:
Prognostic evaluations are primarily based on size (Breslow’s criteria) with other parameters being of lesser significance; this is prime evidence of the importance of a vertical growth component.
Many surgical specimens from melanocytic lesions are the product of a punch or shave biopsy, and some of the specimens are not even from the most worrisome clinical site within the lesion. Commonly, the worrisome patterns on a histologic specimen extend to margins of the sections. The available patterns on such specimens, even though incomplete, should be evaluated by modified Clark’s, and by Breslow”s criteria to provide some indication of what the lesion may represent. Often, when the entire lesion becomes available, no identifiable residua of the melanocytic lesion will be found; the provisional guidelines then become the final guidelines.
When providing therapeutic guideline from material that is obviously incompletely sampled, the interpretation should be qualified as a “conservative evaluation.” It should be noted in the report that the prognostic evaluations, and therapeutic guidelines must be considerd conservative, and that, when the entire specimen becomes available, the evaluations and prognostications may need to be modified. For example, a biopsy of a lesion showing the pattern of either a high grade dysplasia, or a vertical growth component may also show one or both margins to be involved by one or the other. In the face of a compromised specimen in which margins are involved, the lesion should be characterized on the basis of the most significant component. If a portion of a vertical growth component is represented, the evaluation should include a measurement of the height of the represented portion of vertical growth. The diagnosis should also be qualified as being “conservative,” and subject to change when the entire lesion becomes available for examination. The re-excised specimen may not contain residual tumor, and the conservative evaluation must then be utilized as the definitive evaluation.
In the presence of regression, a qualifier, promoting the caution, that the evaluation may prove to be conservative, is required. Regression in a melanocytic lesion generally is manifested by local interruption of patterns. In the interrupted areas, both the epidermis and the papillary dermis tend to be free of atypical cells. In addition, the papillary dermis tends to be widened, and often is delicately fibrotic. It contains an increased number of dilated, thin wall vessels, and variable infiltrates of lymphoid cells. In some examples, clusters of melanophages may be prominent. If these patterns are represented in a lesion that otherwise qualifies as a dysplasia, and if the patterns of regression extend to a lateral margin, it is advisable to recommend a wider excision of the area, even if the atypical cells themselves are not represented at the margin. The conservative prognostic evaluation is a caution to the clinician for either a wider excision, or for the need to not underestimate the potential of a common melanoma, or dysplasia on the basis of what may be incomplete representation of important components, or parameters.
Uncommon melanomas:
If a category of “uncommon” melanomas is included in stores of virtual images, the respective pathologists will be faced with the problem of providing, along with their diagnoses of these “uncommon” melanomas, meaningful guidelines for treatment. The category of “uncommon” melanomas might include some, or all, of the following:
1. MDM of halo nevus-like type
2. MDM of Spitz type
3. MDM of the pigmented spindle cell type
4. MDM of the dermal type (including lumpy-bumpy lesions of giant congenital nevi; atypical nodular hyperplasias)
5. MDM of the combined type
6. MDM of the cellular blue nevus-type (atypical cellular blue nevus)
With the limited clinicopathologic correlations which are currently available, only MDM of the halo nevus-like type (dysplasia-like variant) would be properly evaluated by Breslow’s criteria. The criteria probably do not have application for MDM of the halo nevus-like type (dermal variant). Most example of MDM of the halo nevus-like type (dysplasia-like variant) are thin, and would fall in the good prognosis category. In addition, most of the features of this variant of MDM are merely modifications of features seen in common thin melanomas with the exception of the marker for a dermal component resembling halo nevus. Some other lesions in these variant categories present few problems in regard to management; they are thin, and would thus fall in the borderline category. For all the others, it would be presumptuous to provide guides to therapy that are based on Breslow’s criteria. With few exceptions, such lesions should be conservatively re-excised, and the patient followed.
The current trends for the local treatment of common melanomas are toward conservatism (e.g., 1 cm margins for thick lesions). In the past, regional node dissection has been a favored option for lesions greater than 1.5 mm in vertical dimensions, and for some thinner lesions showing level IV invasion. Sentinel node biopsy has become a currently popular option. Currently, the trend is away from prophylactic node dissection with, instead, emphasis on sentinel node biopsy. A positive sentinel node is then an indication for node dissection. For uncommon melanomas, caution should be advised in regard to the need for prophylactic node dissection, even though some uncommon melanomas with features of variant nevi do metastasize. With sentinel node biopsies, there is increasing evidence of the capacity for some of these variant lesions, particularly in the Spitz category, to metastasize or recur locally (c20t3P1-8, c25t3P1-6, & c26t3P1-6). The evidence of nodal metastasis in this group has not been a great aid in defining prognostic features that would be of use when faced with the next, problematic primary lesion.
Documentation of uncertainties:
If, by histologic criteria, the nature of a melanocytic lesion is uncertain, the uncertainties should be documented along with cautions against overly aggressive treatment. In these conundrums, a consultation (in writing, and from someone actively engaged in consultation work) may lessen the hazards for patients and physicians. Concern for the manner in which both histologic criteria,and implied clinical behavior may influence the care, and well-being of a patient are important in formulating a diagnosis. Unfortunately, such concerns may also color the interpretative process, and modify the manner in which virtual images, having once been imposed upon real images, will impact upon the significance of the real images.
If, in the examination of real images of a histologic section, a recall of relevant virtual images is weak and deficient, the respective observer must be sensitive to his inadequacies. If, in this quandry, melanoma is a tentative consideration, then, before committing the patient to the impact of extensive surgery, or other forms of aggressive therapy, consultations may put the confounding virtual images in a better perspective.
In the evocation of virtual images for the interpretation of melanomas, the character of the virtual images are influenced by individual prejudices. A rather common prejudice, leading to the evocation of fanciful virtual images, holds that cutaneous melanomas first metastasize to regional lymph nodes, and that any subsequent disseminations occur only from the nodal site. Support for this prejudice has not been documented, and clinical observations commonly contradict it. For a lesion with demonstrated capacity for metastasis, the initial metastatic site is not predictably limited. Bloodborne and lymphatic metastases may be synchronous, and are a possible eventuality from any primary melanoma which has entered vertical growth. The factors controlling the selection, and expression of metastatic sites are natural for the individual neoplasm; they include genetic alterations, immune responses, stromal peculiarities, and the accidents encountered in the growth of tumors (e.g., vascular or nerve sheath invasion). To ignore all these factors, and simply cite delay in treatment as the determinant of a poor result, is to claim an understanding of all the many biologic attributes. Such an assertion is a contradiction of nature’s way, but an assumed privilege of representatives of the legal industry.
Irrelevance of prognostic parameters:
Prognostic parameters, such as Breslow’s criteria, are based upon statistical data, and primarily are of value in the formulation of therapeutic guidelines (8). In practice, the potential of a particular melanoma cannot be reliably defined by the utilization of prognostic parameters. Only in retrospect does the biologic potential of both thin, and thick melanomas become obvious. Only those melanomas which have fulfilled their potential and metastasized are truly manipulable in statistical analyses. Unfortunately, the legal profession habitually abuses these cautions; its members assume that the behavior of any given example of a newly diagnosed melanoma can be anticipated by the evaluation of prognostic parameters. In practice, these parameters have little relevance to the inherent potential of newly diagnosed melanomas, particularly thin variants.
Speculations, that a given lesion in the borderland of melanocytic neoplasia (e.g., thin lesions in the common dysplasia-melanoma sequence) had metastasized prior to a local excision of the primary lesion, if mostly based on findings from a histologic examination of the excised specimen, will be incorrect more often than not. In this borderland, lesions on both sides of the border might be characterized as borderline melanocytic neoplasia of indeterminate malignant potential. Some lesions of the borderland have the patterns of a dysplasia (patterns I & II), and some have the patterns of melanoma (thin patterns III & IV). For some examples of vertical growth components, consisting of only 5 or 6 regularly spaced nests of cells in at least two strata, the patterns themselves become borderline in regard to making a precise separation between dysplasia patterns, and melanoma patterns.
A definition of borderline melanocytic neoplasia in the premalignant dysplasia-melanoma sequence greatly lessens the threat that our terminology will lend itself to manipulation by the legal industry.
Evidence of progressive malignant disease, having subsequently been documented for a lesion which had not been controlled in the primary site, but had been observed, and histologically documented at an earlier stage, does not, in retrospect, qualify the primary lesion at the time of the initial observation as a fully evolved malignancy. Significant alterations in the nature, and potential of the neoplastic cells may have occurred in the interval between the two encounters. This position would not be defensible in the concept of “one melanoma, biologically and histologically.”
Margins of excision:
On histologic sections of biopsy specimens, the margins of excision of premalignant melanocytic dysplasias commonly are involved. A shave is the common technique for the initial biopsy procedure. For low grade (mild to moderate) dysplasias, if the margins are involved histologically, a re-excision of the area is not required, if , by an evaluation of clinical criteria (a clinical inspection of the biopsy site shows no evidence of residual lesion), the lesion can be considered to have been completely excised (caveat: If the atypia of a lesion is sufficient clinically to initially provide an indication for biopsy, if a residual portion of the lesion is evident clinically after biopsy, and if the histologic report documents both a dysplasia, regardless of the degree of atypia, and involved margins of excision, the original indications remain valid; the lesion should be excised [with an additional shave biopsy being adequate for the low grade lesions]). For moderately severe to marked dysplasia, if the margins are histologically involved, then a conservative re-excision of the site with margins sufficient to encompass any clinically evident, residual disease is recommended.
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