Variants I 08

8. 

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Spitz nevus-like variant. In these accommodations, it would not be necessary to then assume that such a lesion, in a variant category, has the same bioIogic potential as a common melanoma with cornparable physical dimensions. Prognostic evaluations and therapeutlc recommendations could be altered and modified to accommodate variants.

Variant nevi: Variants of nevi are well-defined. They provide the basis for a definition of variant dysplaslas (the atypical nevi), and of variant melanomas. 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 minimal deviation melanoma, but are also known to be representative of particular benign 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 significant features of either lesion.

Those pathologists who often include a category of “uncommon” melanomas in their stores of virtual images are faced with the problem of providing - along with their diagnoses of these "uncommon" melanomas - meaningful guidelines for treatment. The current trends for the local therapy of common rnelanomas are toward conservatism (i.e., 1 cm margins even for thick lesions). Regional node dissection remains an option for lesions greater than 1.5 cm in vertical dimensions, and for some thinner lesions showing level IV invasion.

Atyplcal nevi and their relationship to certain variant (minimal deviation) melanomas: Combinations, in which patterns of a typical nevus and those of a premalignant melanocytic dysplasia (as commonly manifested in lesions of the dysplastic nevus syndrome) are admixed, identify the respective lesions as "atypical nevi." An extension of this definition has application in the recognition of atypical halo nevus, atypical Spitz nevus, atypical combined nevus, and atypical pigmented spindle cell nevus. Atypical nevus of the dermal type, and atypical cellular blue rievus are exceptions; representations of the epidermal patterns of premalignant melanocytic dysplasia are not a requisite.

Atypical halo nevi: Atypical halo nevi show the basic patterns of typical halo nevi but, in addition, are characterized by features of prernalignant melanocytic dysplasias in lentiginous and junctional patterns in the epidermis away from dermal components. They manifest the qualities of both haIo rnevus, and atypical nevus of the dysplastic nevus syndrome. Just as there are atypical halo nevi, in which the patterns of premalignant melanocytic dysplasia are combined with those of typicaI halo nevus, there are examples of spindle cell nevus of the Spitz type in which patterns of premalignant melanocytlc dysplasia also are represented. Some examples of atypical spindle cell “nevus” of Spitz type are mostly lentiglnous and junctional with minlmal or no dermal components. The concept of "junctional nevus” of the Spitz type carries with it the implication that, if left undisturbed, such a lesion would evolve into classic Spitz nevus. In addition, there is the implication that if all Spitz nevi could be examined at the proper moment, the pattern would be that of ”junctional" Spitz nevus. With close attention to patterns, “junctional nevus” of Spitz type usually is an atypical nevus. Such lesions usually show nuclear atypia; upward migratlon of indivldual tumor cells into the epidermis; and markers for host imrnune response (lymphoid.infiltrates and dermal fibrosis, often in lamellar patterns). In these variations, there may, or may not, be a lesion centrally with the features of either classic Spitz nevus, or MDM of the Spitz type. The designation, atypical Spitz nevus, carries with it the implication that the lymphoid infiltrates, and the patterns of lamellar fibrosis have the same significance as similar findings in common premalignant melanocytic dysplasias. In addition, there is an implication that; if left undisturbed, an atypical spindle cell nevus of Spltz type (atypical Spitz nevus) might evolve into a MDM of Spitz type, or a Spitz nevus-like melanoma.

Variant melanomas (as defined on the basis of features shared with common nevi, including unique cytologic features, stromal relationships, and host immune response): Many of the variant lesions, as anticipated in the preceding section, are poorly documented. For poorly defined variants whose biologic potential is poorly understood, our only current options have been an assignment to either a benign or premalignant category, or to the common (typical) melanoma categories. These compromises relate to a willingness on the part of most observers, in the assignment of unusual lesions to specific categories, to restrict their options to the major categories, and to use these limited categories as defaults. For some examples, or for other observers, if some of the cytologic features of a problematic lesion overlap with those of some of the variant nevi, there is a hesitancy to then assign these "nevus-like" lesions to the category of melanoma; in this compromise, a melanoma may be assigned to a benign category.

In the recognition of variant nevi and related dysplasias, the evocation of relevant virtual images from an examination of their real images are routine endeavors in the daily practice of pathology. The real images evoke virtual images which are commonly associated with a benign process. The evoked virtual images may mask other features indicative of melanoma. The significance of a vertical growth component in the recognition of a melanoma is generally accepted (the dissenters are mostly engaged in linguistic masquerades: they see the patterns but mask them with problematic linguistic symbols). An appreciation of the interrelationships of radial and vertical growth should provoke virtual images of a precursor transforming into melanoma.

Minimal deviation melanoma: The concept of MDM is a compilation of conceptual tools for the manipulation of patterns in radial and vertical growth components (patterns I & II and patterns III & IV, respectively). In the concept of MDM, close attention to patterns in vertical growth has application to definitions of variants of melanoma. In large part, the concept of MDM placed great emphasis on a vertical growth component, and defined the minimal requisites for the recognition of early vertical growth. It accepted any associated patterns, that do not satisfy the criteria for recognition of vertical growth, as being no more than a marker for a remnant of a precursor lesion. In it, an attempt was made to define criteria for the recognition of the role of variant nevi, or variant dysplasias, in the evolution of variant melanomas with emphasis on three dimensional, vertical growth components as the sine qua non for the assignment of a problematic lesion to the melanoma category.

All the variant melanoma-like lesions, with some features which overlap with those of variant nevi but with other deviant features that are melanoma-like, have been included as special variants of "melanoma" in the category of MDM. The latter concept has the utility of providing separate categories for deviant lesions and, in addition, for providing guidelines for the management of lesions with poorly defined biologic potentials (melanoma-like lesions of uncertain, or unknown, biologic potential) .

In the characterization of typical melanomas, emphasis is placed on the patterns in radial growth, or on the absence of a radial growth component. If, instead, attention is given to the vertical growth components, the classification of melanoma is greatly expanded. In this alternate approach, there are as many variants of melanoma as variants of nevi. In addition, for most variants of nevus, there is an atypical counterpart in which the epidermal features overlap with those - as seen in the epidermis - of the common premalignant melanocytic dysplasias. In this approach, variants of MDM are given recognition, but the baggage associated with the designation is avoided. The variant melanomas have identity mainly as the counterparts of the variant nevi (e.g., Spitz nevus, combined nevus, blue nevus,  etc.): they also qualify as variant minimal deviation melanomas. Some of these lesions deserve recognition as variants of melanoma on the basis of distinctive patterns of variant vertical growth. The concept of melanocytic neoplasia of indeterminate malignant potential also has application for variant melanomas. Poorly defined biologic potentials would justify the inclusion of these variant lesions in separate categories of borderline melanocytic neoplasia of indeterminate malignant potential.

Some melanomas have been dismissed as entities because collected series have not included an example. For instance, it has been stated that there are no "true melanomas" of giant congenital nevi in infancy; the respective reviewers who promote this caveat, having not personally encountered examples that were associated with metastasis and death, simply have dismissed the possibility.

Many lesions, that have been assigned to the category of nodular melanoma (a wastebasket or default category), are distinctive cytologically. Other lesions, of a similar or different, nature, have been assigned to a "nevoid" category of melanoma. The latter option has become fashionable. Many lesions, that currently are being assigned to the "nevoid" category, show features which overlap with some lesions in the category of MDM (e.g., pigmented spindle cell melanoma of the minimal deviation type). Other examples of nevoid melanoma are bland and organoid (truly nevus-like). Cytologically, some of these organoid lesions (with nevus-like patterns) are biologically high grade.

If attention is given to variance in vertical growth, and if some melanomas are designated as deviant from type on the basis of size, patterns, and cytologic features, the lesions so designated must also be viewed with caution, if therapeutic recommendations are to be based on Breslow's criteria. These concerns were addressed in the concept of MDM. Many of the lesions, which might also qualify as variant melanomas of nevus­like type, were originally defined in the concept of MDM.

Of those lesions with features of both a variant nevus and a melanoma, some examples may also share features of premalignant melanocytic dysplasias, but the most important shared attribute is the presence of a vertical growth component. With the limited clinico-pathologic correlations that are currently available, only MDM of the halo nevus type would be properly evaluated by Breslow's criteria. This approach is valid because MDM of halo nevus type, almost by definition, falls in the good prognosis category. In addition, most of its features are merely modifications of features seen in other thin common melanomas. Other variants, if thin, also present few problems in regard to management. By virtue of their vertical dimensions, they would fall in the borderline category. For all other variants that are not thin, it would be hazardous 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. For uncommon melanomas, measuring greater than 1 mm in vertical dimensions, caution should be advised in regard to the need for prophylactic node dissections even though some uncommon melanomas with features of variant nevi do metastasize.

Conceptually, some dysplasias may evolve into halo nevus­like melanoma in association with a precursor lesion that would qualify as classic halo nevus. In MDM of both halo nevus type and Spitz type, patterns with the attributes of a dermal remnant of a benign nevus often are preserved adjacent to the nodule of atypical cells (i.e., vertical growth component). If cytologic comparisons are made of the features of cells in the remnant with those in the nodules, the features of the two will prove to be disparate, with atypia being a more significant feature of the cells in the nodules. These variants qualify as transformed halo nevi or “transformed Spitz nevi.”

In an alternate category, the attributes of these two MDMs may even include lentiginous and junctional pattterns of a dysplasia (i.e., radial growth component), a nodule of cytologically atypical cells (i.e., vertical growth component), and markers for host immune response. In these examples, the attributes of the radial component in the epidermis qualifies as a remnant of an atypical nevus of corresponding type. Many examples of MDM of the Spitz type are associated with markers for a remnant of an atypical nevus of Spitz type with the implication that these MDM have had their origin in “atypical Spitz nevus.” Similarly, many examples of MDM of halo nevus type are associated with markers for a dysplastic precursor. Atypical halo nevus-like MDM, and atypical Spitz nevus-like MDM would appear to evolutionary changes in corresponding atypical nevi. With MDM of both atypical halo nevus type, and atypical Spitz nevus type as models, it is tempting to propose that other variant atypical nevi have a relationship to variant melanomas that is comparable to the relationship between common atypical nevi and melanomas of the types.

Some Spitz nevus-like lesions, and some MDM of the halo nevus-like type have a vertical growth component, but not all such examples are associated with remnants of a preexisting Spitz, or halo, nevus, or with radial spread in the epidermis in patterns that might be characterized as a remnant of a atypical spindle cell nevus of Spitz type, or atypical halo nevus (i.e., lentiginous and junctional spread in the epidermis away from both the vertical growth component and any remnant of the dermal component of a preexisting halo “nevus” or Spitz “nevus”); they would thus qualify as de novo variants.

In all examples of variant melanomas, the basic patterns of a benign variant nevus, or an atypical variant nevus may be preserved, but focally, or relatively uniformly, the respective cells are atypical and show mitotic activity. In some variants, such as MDM of the dermal type, halo nevus type, and even some nevoid variants, the cytologic atypia is moderate to moderately severe, and the cells are relatively uniform in regard to nuclear characteristics. The nuclei tend to be intermediate in size with an increased prominence of nucleoli. Epithelioid features (a cytologic characterization of cells with abundant cytoplasm and often, but not invariably, with rounded outlines) are common in the dermal, halo nevus-like, and Spitz nevus-like variants of MDM, and may be a source of confusion in the sub-typing of MDM.

In at least one example of MDM (i.e., Spitz variant), nuclear atypia and cytologic pleomorphism are often prominent features. The features may be sufficiently developed to qualify as large cell anaplasia. In contrast to the bland nuclear qualities commonly manifested in MDM arising in the setting of the dysplastic nevus syndrome, the nuclear grade of MDM of the Spitz type usually is high. Often the neoplastic cells in the dermal components of such lesions show distinct lavender or basophilic cytoplasm, but in other examples, the cytoplasm of the tumor cells, in common with cells of ordinary “nevi” of the Spitz type, is palely acidophilic.

Clearly, there is room for morphologic distinctions in the classification of melanocytic neoplasia.

The variants of nevi and malignant or borderline counterparts include:

             1. typical (common) nevus  1a. atypical (dysplastic) nevus

                          1b. thin malignant melanoma (most                                    often expressed as a common final                                    pathway in vertical growth (i.e.,                                     superficial spreading melanoma)

                           1c. malignant melanoma measuring                                     greater than 1 mm in height

       2. genital nevus

                           2a. atypical genital nevus

                           2b. melanoma of genital nevus type 

        3. halo nevus

                          3a. atypical halo nevus

                          3b. MDM of halo nevus type

      4. Spitz nevus

                4a. Atypical nevus of Spitz nevus-like type

                4b. MDM of Spitz type including examples arising in Spitz nevus, examples in atypical Spitz nevus, examples that might otherwise be classified as combined nevus of Spitz type, and de novo examples

                4c. melanoma with Spitz nevus-like features

      5. combined nevus of common type (including deep penetrating

         nevus)

                5a. atypical combined nevus

                5b. MDM of the combined type

      6. pigmented spindle cell nevus

                6a. atypical pigmented spindle cell nevus

                6b. MDM of pigmented spindle cell type

      7. blue nevus (including nevus of Ota and Ito)

                7a. pigmented spindle cell melanoma

                7b. combined nevus of blue nevus type

       8. cellular blue nevus

                 8a. atypical cellular blue nevus

                 8b. melanoma arising in cellular blue nevus

                 8c. melanoma arising in deep               neurocristic melanocytic               hamartoma (generally a               process affecting an area              corresponding to the                distribution of the                   trigeminal nerve)

9. giant congenital nevus (and some small variants)

                              9a. borderline melanocytic dysplasias                                           of infancy and childhood

                               9b. MDM of dermal type

                               9c. MDM arising in atypical                                           congenital nevus

                                9d. melanoblastoma of infancy

10. acral nevus                     10 a. atypical acral nevus

                                10 b. acral lentiginous melanoma 

11. nevus in sun-damaged skin

                                 11 a. lentigo maligna

                                 11 b..lentigo maligna melanoma

Variant Melanomas: (A collection of neoplastic spectra, each comprised of segments having a relationship to variant nevi, and all presented in a roughly alphabetized order)

Balloon cell nevus: In some melanocytic lesions, an alteration of cytoplasmic organelles results in cells - some of which are in clusters -with more abundant, vacuolated cytoplasm. This alteration is common as an inconspicuous alteration in the dermal component of the common nevi. In balloon cell nevi, the organoid patterns of a typical nevus are preserved. In lesions with balloon cell components, some of the affected cells contain widely spaced melanin granules in the cytoplasm; perhaps balloon cell transformation is a process related to demelanization of cytoplasm.

Balloon cell transformation is also common as a focal alteration in the setting of premalignant melanocytic dysplasias; it becomes a conspicuous alteration, if prominent in the lentiginous and junctional components.

Balloon cell melanoma: In balloon cell melanomas, the presence of balloon cells complicates the interpretation of patterns, and tends to cloud the distinctions between a nevus cell variant and a melanoma. Organoid patterns, which are characteristic of balloon cell nevi, are not preserved in balloon cell melanomas. The nuclei of the balloon cells of a melanoma tend to be plump with open chromatin patterns and a prominent central nucleolus. Mitoses are also a feature of balloon cell.........

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