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If nuclear grade is a valid parameter, it may have relevance with the capacity for a melanoma to enter the desmoplasia-neurotropism sequence. The type of melanoma which enters vertical growth showing intermediate nuclear grades in the dermal component, and prominent lenitiginous qualities in any associated epidermal component, seems to have a propensity for desmoplastic, and neurotropic transformations.
Neurotropism may be manifested in spindle cell nevi, such as Spitz nevus, combined nevus, or cellular blue nevus. Neurotropism may also be encountered in the setting of giant congenital nevus.
VI. Nodular melanoma:
The category of nodular melanoma commonly is manipulated as if it were biologically and histologically homogeneous. Some nodular melanomas in the clinical setting of lentigo maligna melanoma (actinically damaged skin of an elderly, fair-skinned patient) are composed of remarkably bland, pigmented spindle cells in fascicular patterns. Such lesions are better characterized as de novo lentigo maligna melanoma, or as de novo minimal deviation pigmented spindle cells melanomas. In a similar vein, some forms of “nodular” melanoma are “de novo” counterparts of SSM, or acral lentiginous melanoma. The list is not exhausted with these examples; there are overlaps between the nodular and “nevoid” categories. In characterizing nodular melanomas as de novo variants, the observer is admitting an inability to identify a remnant of a precursor; no judgements regarding the nature of the lesion at an earlier stage of evolution is implied. Nodular melanomas are manipulable by attention to depth of invasion and “thickness;” to degrees of cytologic atypia; to cell type; and to clinical setting. The category of nodular melanoma is accessible for subclassifications; many of its components might be better assigned to some other category. The designation might be best restricted to lesions whose patterns in vertical growth are indistinguishable from those of the vertical growth component of fully evolved SSM (i.e., high nuclear grade, and large cells, often with pleomorphism). Other lesions might be better assigned to other categories, and additionally characterized as de novo variants of other neoplasms, such as LMM, ALM, MDM, “nevoid” melanoma, etc.
A Borderland of Neoplasia (melanocytic system)
The clinical presentation of lesions in the melanocytic system is varied; it ranges from thin, flat lesions to large, polypoid lesions; some examples are ulcerated. Clinicopathologic correlations have established that certain histologic patterns are predictive of, and that other histologic patterns are unlikely to be associated with, progressive disease. These varied presentations, and patterns are manipulable. Herein, segments of neoplastic continua, comprised of both precursors, and fully evolved melanomas, are defined in virtual images.
In the conceptualization of common melanocytic neoplasia, it is necessary to segment neoplastic continua, and to provide labels for the segments. The manner in which a neoplastic continuum is segmented impacts upon the structuring of virtual images and, in turn, upon the significance of the histologic diagnosis of melanoma. Herein, two major segments include the dysplasias, and the melanomas. In toto, the spectrum to be segmented extends from mild dysplasias to high grade melanomas (including lesions with significant bulk). The major segments are also divisible, but the definitions of the smaller segments are by no means uniform. Having once segmented the continua, and labeled the segments, the manipulations of the patterns are subject to individual biases, and to a quality that lends arbitrariness to the selected segments, namely the fluidity of neoplastic processes.
It is the role of the pathologist to define, and label segments. In turn, he, and others, must manipulate the segments and their patterns to provide correlations with clinical observations. Finally, these real and virtual images, in combination with clinical data, are to be manipulated to provide therapeutic guidelines. In these perambulations, the manner in which the continua have been segmented is influential.
Deeply imbued virtual images of the common melanomas have become second-nature for all but a few of us. The few actually are compelled by nature to have, and use them, even if they do not acknowledge them. The manipulations, by rote, which are involved in diagnosis, and prognostications of common melanoma, such as SSM, have been hardly questioned.
In an examination of the full expression of a spectrum of changes in the common melanocytic neoplastic continua, including those of a temporal nature, there are portions of the neoplastic continua, corresponding to particular periods in the evolution and life history of melanomas, in which the histologic patterns fail to sharply discriminate between precursor, and melanoma. For most examples, the troublesome and arbitrary portions (defined segments) of these neoplastic continua are representative of examples of melanocytic neoplasia that are thin in vertical dimensions, with most examples measuring less than 1 mm in height (thickness).
A store of relevant virtual images is a requisite for the interpretation of a borderland of melanocytic neoplasia. High grade dysplasias, and incipient (thin) melanomas are included in the borderland. Degrees of cytologic atypia, host immune response, nodular or plaque-like patterns, levels of invasion (modified Clark’s criteria), and depth of invasion must be given an accounting in the categorization of lesions of any defined segments in this borderland of melanocytic neoplasia.
Sets of criteria have been designed and strongly promoted to aid in the partitioning of melanocytic neoplastic continua, but for each offering in the category of thin melanocytic neoplasia, different morphologic features have been emphasized. The differences are a reflection of the individuality of the virtual images of each of us. They also are a reflection of the imprecision of virtual images in the segmentation of neoplastic continua, of the limitations of language for the characterization of neoplastic phenomena as related to segmentations, and of the susceptibility of practicing pathologists to public babble and bombast. Public babble and bombast are part and parcel of the tendency of some observers to function in the realm of controversies.
Offerings of defined segments in the defined borderland have been defended by their proponents as if the differences also impact on a patient’s well-being. In defining differences between dysplasias and melanomas, the borderland is particularly troublesome. Similar problems with borderlline neoplasia have been encountered in other organ systems.
The borderland (a different perspective):
In most categories of epithelial neoplasia in a variety of organ systems, the borderland of neoplasia is defined simply on the basis of the limited distribution of nests of neoplastic cells in the stroma. The definition depends on the relationships between nests of cells and their stroma (the identification of features which characterize invasive nests is a requisite), and the manner in which the relationships impact on prognosis.
With squamous cell neoplasia of the uterine cervix as an example, the designations, keratinocytic dysplasias and carcinoma-in-situ, have been largely supplanted by a graded system of “intraepithelial neoplasia.” The segment, carcinoma-in-situ, if selected, is likely to be defended as if it is the sole precursor of invasive carcinoma (i.e., as if it is the only optional segment leading to invasive carcinoma). In fact, invasive patterns are common in the immediate vicinity of precursors showing: 1) lesser degrees of atypia than those of classic carcinoma-in-situ, and 2) architectural derangements. The obvious step (i.e., qualifying microinvasive carcinoma as keratinocytic neoplasia of indeterminate malignant potential) has not been made.
For some examples in some organ systems, even large neoplasms may qualify as borderline. A borderland of neoplasia has been defined for large ovarian neoplasms. For the borderland of ovarian epithelial neoplasia, the lesions may be considerable in size, even to the point of compromising attempts to adequately sample a given example. Bordeline lesions share some of the histologic characteristics of fully evolved malignant ovarian neoplasms, but are basically distinguishable by an absence of foci in which there is recognizable stromal invasion (again, definitions of stromal invasion are required); large bulky lesions with significant atypia are qualified as atypical, if foci of stromal invasion are not identified on multiple sections. These lesions with characteristics of “atypical cystadenomas,” even though large, are characterized as borderline ovarian neoplasia of low, or uncertain malignant potential. They are borderline ovarian epithelial neoplasias of indeterminate malignant potential. Recently, relationships between isolated nests and stroma have been assigned great significance, but the identification of even a few scattered foci of “invasion” may not greatly alter the factual “borderline” nature of these lesions.
Three additional areas badly in need of a definition of a borderland of neoplasia are represented by encapsulated neoplasms of the thyroid, well differentiated cartilaginous neoplasms of bone, and prostatic neoplasia as encountered on needle biopsy specimens.
In the segment, “melanoma-in-situ,” neoplastic cells are confined to their native site (epithelium) and, as their most distinctive characteristic, migrate individually among keratinocytes. Melanoma-in-situ is manifested in single cells patterns; clearly, cellular phenomena are basic to its definition. Paradoxically, proponents of the utility of this segment have offered the corollary that there are “no melanoma cells, only melanomas.” In other shemes, the designation, melanoma, has application only for those segments in which neoplastic cells have migrated out of their native domain, and have joined other similar cells to share in the economy and the utility of a community (vertical growth at level III), or have become active migrants in the reticular dermis (diffuse vertical growth at level IV).
The borderland of common melanocytic neoplasia includes high grade dysplasias; it reaches beyond the limits of the dysplasia patterns into the domain of patterns which identify “melanomas” with a potential for metastasis. In this borderland, the major discriminator for the recognition of the “melanoma” pattern, as distinguished from the “dysplasia” pattern, is a vertical growth component (3,6,7). In vertical growth patterns, the pertinent virtual images depict the emergence of a clone of neoplastic melanocytes with the capacity to survive and multiply in the immunologically hostile environment of the papillary dermis. Such a clone would either be dermal in location, and independent of the phenomena at the dermal-epidermal interface, or would have an epidermal component from which nests of neoplastic cells are delivered into the dermis at a rate exceeding the capabilities of the host immune responsne. In addition, the capacity to induce a stroma and a blood supply for the neoplastic cells would be embodied in the images.
The segment of the neoplastic continuum which encompasses thin melanocytic neoplasms (i.e., less than 1 mm in vertical dimensions) in the common premalignant dysplasia-melanoma sequences (a specification embracing common variants, actinic variants, or acral variants) is a borderland; the troublesome patterns are found at the transition from level II to level III. Included are high grade “dysplasias” and “thin melanomas” measuring less than 1 mm in vertical dimensions. All such lesions are borderline melanocytic neoplasias, a category that is divisible into “two” dimensional lesions (dysplasia types), and “three” dimensional lesions (melanoma types).
In the final analysis, all the options in regard to the segmentation of melanocytic neoplastic continua have utility. In part, the final decision, as to the appropriate segmentation of the neoplastic continua, may have relevancy to the manner in which each segment lends itself to distortions by the legal profession; any scheme which becomes more or less universal in acceptance places an onus on practicing dermatopathologists to conform in a general manner. This approach is hardly scientific; if promoted solely as a guard, it is prostitution of the art of pathology.
Borderline dysplasia:
Currently, virtual images in a borderland of melanocytic neoplastic phenomena must be molded to accommodate a variety of designations. Without regard for cytologic atypia, real images in this borderland provide no clear distinctions between some grades of dysplasia, as promoted in some schemes, and lesions that in other schemes have been characterized as “melanoma” at level I or II. The designation, “melanoma,” if selected for the characterization of patterns in this limited portion of a neoplastic spectrum (the borderland of the dysplasias), easily influences the character of respective virtual images; the aggregate patterns of what in some schemes is a dysplasia then, under the influence of our virtual images, can come to be thought of as having melanoma-like potentials.Practically, prognostications, in this borderland of neoplasia, are meaningless; metastases, if they occur, are too infrequent to lead credence to our common prognostic parameters. A metastasis from a “level I or II dysplasia,” or a “level I or II melanoma” would suggest that a vertical growth component has spontaneously regressed, or that it remains in a paraffin block, or a formalin bottle.
Borderline melanoma:
Herein, in the dysplasia-melanoma sequence, thin melanomas (i.e., at least pattern III) measuring less than 1 mm in vertical dimensions are representatives of a borderland of melanocytic neoplasia (they are prototypic of minimal deviation [incipient] melanomas in this neoplastic system). For lesions in this limited physical range, the usefulness of prognostic parameters is only slightly improved over that for lesions in the borderline dysplasia category (i.e., pattern II lesions). In the diagnosis of thin borderline melanomas (lesions with an indeterminate capacity for metastasis), only in retrospect, and in rare instances, will the distinctions between lesions showing patterns I or II, and thin lesions showing patterns III or IV be validated as having provided a distinction between melanoma precursors and melanomas. If a lesion in the borderland of neoplasia (i.e., thin, typical melanoma: a pattern III or IV lesion) has demonstrated a capacity for metastasis, the phenomena might, in retrospect, be characterized as a validation of the concept of MDM as related to the segment, “thin melanoma.
The particular segment, thin melanoma, might be better characterized as borderline neoplasia (melanoma variant) rather than common, thin melanoma.” This accommodation finds justification in the observation that all segments of the common melanocytic neoplastic continua that are thin, and either pattern II or III, are prognostically unpredictable, if the object of the prognostication is to identify specific lesions which have metastasized at the time of initial histologic diagnosis of melanoma.
Exceptions to the validity of usual prognostic parameters are implicit in the definition of minimal deviation variant melanomas (i.e., the “malignant” counterparts of variant nevi). In some variant nevi, patterns may be encountered which in part satisfy many of the requisites for the diagnosis of a variant of MDM, but are known to be representative of lesions with no risk for metastasis. Both deep penetrating nevus, and the related combined nevus may on occasion show patterns which partly satisfy the criteria for recognition of a variant vertical growth component, but the respective lesions have mostly proved to be benign. Significantly, markers for host immune response (lymphoid infiltrates) usually are not features of either lesion.
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