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Halo “nevus,” continued:
Regression in the dermal component of a halo nevus is first heralded by a reduction in the density of the lymphoid infiltrates, and by the appearance of irregular, coarse, hyaline lamellae among small nests of atypical “nevus” cells, and even among individual “nevus” cells. In late stages, the papillary dermis may be widened and fibrotic; it tends to be relatively free of “nevus” cells in either the dermis or the epidermis. In some examples, lymphoid infiltrates with a high component of histiocytes fill the widened papillary dermis. A few junctional nests may be the only surviving marker of the primary process. The patterns of regression may differ little from those of a regressed melanoma. In such lesions, the nature of the original process cannot be predicted from a histologic examination of the residua of an immune mediated regression.
Halo nevus-like phenomena may be encountered in the setting of both melanomas and premalignant melanocytic dysplasias of the dysplastic “nevus” syndrome. In these diverse settings, the implications are the same as those in halo nevus; the patterns are an expression of cell mediated immunity with the target cells being neoplastic melanocytes.
Minimal deviation melanoma of the junctional halo nevus-like type shares many features with common premalignant dysplasias, and even with related thin, common melanomas. The cytologic features of the vertical growth component are not its chief characteristic. MDM of the halo nevus-like type are distinguished by the halo nevus phenomena, and usually by the thickness of its vertical growth component (height along the vertical axis of a vertical growth component); they are usually minimally deviant in regard to nuclear grades (usually low to intermediate grade), and in regard to physical dimensions (i.e., less than 1 mm in vertical dimensions). These thin examples qualify as borderline melanocytic neoplasias of indeterminate malignant potential (junctional halo nevus-like type). In this characterization, size, low to intermediate nuclear grades, and tumor infiltrating lymphocytes are all favorable prognostic findings. The vertical growth component itself often, but not invariably, is free of tumor infiltrating lymphocytes. A relative lack of tumor infiltrating lymphocytes in most vertical growth components of halo nevus-like variants of the junctional type facilitates the identification of the a small vertical growth component (i.e., one at the very limits of what might be characterized as the minimal number of clustered nests to qualify as vertical growth).
Halo nevus-like reactions are common at the deep margin of the vertical growth component of a fully evolved melanoma, but such patterns usually are ignored. On the other hand, small, poorly developed vertical growth-like components, with features which are borderline in regard to satisfying criteria for the recognition of early vertical growth, are occasionally encountered as a regional variation in what is otherwise a common halo “nevus.”
Spindle Cell Nevi and Melanomas
The category of the spindle (and dendritic) cell nevi is heterogeneous. It includes: 1) Spitz nevus, 2) blue nevus (including nevus of Ota and Ito [dermal melanocytoses]), 3) combined nevus (including blue nevus type, common [deep penetrating] type, and possibly a Spitz type), 4) cellular blue nevus, 5) pigmented spindle cell nevus of Reed, and 6) pigmented spindle cell nevus of deep penetrating (dermal) type. In this grouping, it is recognized that some Spitz nevi are melanotic, and that deep penetrating nevus is a variant of combined nevus of the common type.
Spitz variant:
Spindle cell melanocytoma (“nevus”) of Spitz type is exceptional and distinctive in comparison with most other variant “nevi.” It evolves and grows rapidly. It is usually amelanotic, and the clinical impression often is angioma. Of all the nevi, the quality of “maturation” has been most emphasized in “nevus” of the Spitz type. Pigmented spindle cell “nevus” of Reed also shows maturation. On the other hand, “maturation” is often inverted in cellular blue nevi; the deep component shows the greatest cellularity with activated nuclei. The designation, Spitz “nevus,” has proved to be an unfortunate choice. Clearly, there is a distinctive melanocytic tumor that is embraced by the designation but to characterize as a nevus introduce a unfortunate bias in attempts to conceptualize related, but more advanced, stages of neoplasia. Juvenile melanoma might be a more appropriate designation. Minimal deviation melanoma of juvenile melanoma type, step I pattern, is an alternative that should also be given consideration.
In the Spitz type of minimal deviation melanoma, virtual images, which deviate from those of both the thin common melanomas, and MDM of the halo nevus-like type, are required. These new images include worrisome cytologic atypia, and even mitotic activity of a degree that, if represented in a common melanocytic neoplasm, would strongly favor a malignant neoplasm. By custom, in current practice in which the concept of MDM is likely to be ignored, atypia in Spitz variants most often is being accommodated by simply documenting it, if it is identified in an overall setting which has Spitz-like qualities.
With the concept of MDM as a guide, a nodular component in which coarse fascicles of large atypical cells are clustered to form a nodule (in all aspects, this nodule satisfies the criteria for recognition of a typical vertical growth component) is the basic requisite for the diagnosis of MDM of the Spitz-like type. In the dermis adjacent to such a nodule, patterns of more typical Spitz “nevus” often are preserved. When Spitz nevus-like patterns are preserved at the margin of a vertical growth-like component, the combination can be cited as offering strong support for the diagnosis of MDM; the nodular component can then be viewed as a marker for neoplastic transformations leading from a pre-existing typical, or even atypical, Spitz “nevus”to MDM. Lymphoid infiltrates in some examples are marked; they provide halo nevus-like qualities (tumor infiltrating lymphocytes or halo nevus phenomena). Mitoses are fairly common in typical Spitz “nevi,” but in atypical nodular variants (MDM of Spitz-like type), even bizarre mitotic figures may be encountered. Nerve sheath and vascular invasion may also be features, but are occasional features of otherwise typical Spitz “nevi.”
Spitz nevus-like qualities:
In general, the cells of Spitz nevus-like variants are epithelioid (plump with abundant cytoplasm) at the dermal-epidermal interface, mostly amelanotic, and spindle shaped, or rounded and polygonal. Herein, as an economy, the Spitz nevus-like variants will be assigned to a spindle cell category. This approach finds justification in the many qualities shared with other spindle cell “nevi” and melanomas; the spindle cell category then is divisible into the Spitz-like group, and a non-Spitz group. Nuclear characteristics often are an aid in making the distinctions.
A wide range of cytologic features have been acceptable in the Spitz “nevus”category. At the dermal-epidermal interface of typical examples, the cells have plump, round or oval nuclei, prominent nucleoli, and delicate and marginated nuclear chromatin. Nuclear membranes are thin and sharply defined. Mitotic acivity is common near the dermal-epidermal interface.
Examples showing atypia in nests at the dermal-epidermal interface, with lentiginous and junctional beyond the dermal limits of a small, thin dermal component, and with markers for host immune response qualify as dysplastic juvenile melanomas (size and atypia are the chief parameters). Lesions of the latter type generally are associated with papillary dermal fibrosis (often in lamellar patterns), and with perivascular lymphoid infiltrates in the dermis beneath the lentiginous and junctional components. Such lesions might also be characterized as “atypical spindle cell melanocytoma of Spitz-like type.”
In other examples, centrally, at the dermal-epidermal junction, and in the dermis, if the degree of atypia is worrisome, and if the cells in these areas are arranged in broad, regularly, but loosely, spaced fascicles, the distinctions between a dysplastic variant and a thin MDM may be difficult to define . Mitotic activity, including atypical figures, may be additional features. Maturation at the deep margin may not be a feature. Such lesions, often have been relegated to the category of either malignant melanoma, but some observers, with wide limits in regard requisite criteria, will assign such lesions to the category of Spitz “nevus.” The atypia in some examples is extreme and the cytologic features often are pleomorphic. No other melanocytic lesion, with such extreme degrees of atypia, would be accepted in the category of “nevus.”
Currently in the Spitz category, a wide range of cytologic and histologic features often is being accepted as within the range of changes seen in benign lesions, or cited as the basis for characterizing the lesion as a neoplasm of uncertain, or indeterminate malignant potential. In the most typical pattern, broad fascicles of spindle (and epithelioid) cells “rain down” into the dermis from the dermal-epidermal interface. The epidermis is hyperplastic with elongated rete ridges. The papillary dermis near the dermal-epidermal interface is edematous; its vessels are ectatic. In the most characteristic patterns, spindle shaped cells with plump, round to oval nuclei form fascicles near the dermal-epidermal interface. Pale acidophilic bodies are common near the dermal-epidermal interface. Fascicles at the dermal-epidermal interface tend to separate from the epidermis with the formation of clefts. A wedge shaped configuration with the base abutting upon the epidermis, and maturation from the superficial to the deep margin are additional features. Mitoses are common; they have been observed to be more frequent in the superficial portions. Junctional and dermal variants have been described. Nerve sheath and lymphatic invasion are acceptable, if all the other features are characteristic. Fascicles of neoplastic cells tend to be more densely spaced in follicular sheaths, and in close aggregates form bulbous expansions which push into the subcutaneous fat from the confines of the perifollicular sheaths.
The concept of immunostimulation, and the significance of a locus for the elaboration of growth factors have application in an evaluation of patterns in “nevi” of the Spitz type. In the latter setting, the locus for the elaboration of growth factors would be the epidermis, and the stroma near the dermal-epidermal interface. The gradient would be depth dependent so that at a certain level away from the epidermis the cells would be remote from the locus, and would relinquish the cytologic features which distinguish a stimulated cell. From this perspective, would a Spitz “nevus” be a pigmented spindle cell nevus of Reed which has been modified by immunostimulation? There are too many dissimilar features to seriously promote such a proposition but, in practice, there are occasional examples of pigmented spindle cell “nevus” of Reed in which Spitz-like components are also recognizable (a variant of combined “nevus?”).
The concepts of variant and typical vertical growth have application in the definition of MDM of Spitz-like type. The concept of MDM of Spitz type probably should include examples with variant as well as typical vertical growth.
In my experience, most “junctional” Spitz “nevi” are asymmetrical; they are associated with markers for host immune response. At the level of the scanning lens, such lesions are most likely to be initially interpreted as a premalignant melanocytic dysplasia, or even “SSM” at level II or III. Most of these lesions appear to be distinctive variants of premalignant melanocytic dysplasias, and probably are independent of classic Spitz “nevus” (i.e., no remnants of a classic Spitz “nevus” would be represented in the adjacent dermis). In giving recognition to patterns of melanocytic dysplasia and vertical growth, the evolution from an “dysplastic or atypical Spitz melanocytoma” (“nevus”) to MDM would seem to be a valid option. From this perspective, certain minimal deviation melanomas of Spitz-like type would have evolved in the setting of a unique premalignant dysplasia, and the uniqueness would be evident in atypical cytologic features of Spitz type.
Atypical or dysplastic spindle cell “melanocytoma” of Spitz-like type is a “thin” lesion. In some of these lesions, cellular atypia may be manifested in the dermal component. By the criteria defined for the interpretation of both common minimal deviation (thin) melanomas in the setting of multiple dysplastic nevi, and minimal deviation melanomas of halo nevus-like type, it is tempting to assign the thin, atypical Spitz-like lesions with patterns of “variant vertical growth” as minimal deviation melanomas. If, however, these lesions are assigned to a category of borderline neoplasia of Spitz-like type, the need to make the arbitrary assignment of a problematic lesion to a category of either dysplasia or melanoma is avoided. If some reinforcement of this proposed assignment is required, the lesion might then be evaluated by Breslow’s criteria. If the lesion is thin, then the assignment of the lesion to the category of borderline melanocytic neoplasia will carry with it therapeutic guidelines that protect both the patient and the physicians. Perhaps, for a lesion as poorly defined as MDM of Spitz-like type, even thicker (i.e., greater vertical dimensions) lesions might be assigned to the borderline category.
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