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remarkable symmetry. If, focally, the fascicles extend into the papillary dermis, they focally cluster to form a solid plaque or nodule; the solid portion pushes into the dermis. The nodule, when represented, tends to be central; lentiginous and junctional components will be symmetrically distributed on both sides of it. This lesion may be confined to the papillary dermis but, for some examples, thin fascicles and individual cells may infiltrate the reticular dermis among the collagen bundles (a Spitz nevus-like quality). Patterns of “maturation” (“differentiation?”) in which cells and their nuclei are smaller in the deeper portions of the lesion are a prominent feature of some examples. Lymphoid infiltrates at the interface between the nodule and the dermis generally are not a prominent feature.

Pigmented spindle cell nevus of Reed is not a marker for the dysplastic nevus syndrome. The spotty, irregular patterns of premalignant dysplasias in the setting of the dysplastic nevus syndrome contrast sharply with the uniform patterns and symmetry of PSCN.

It has been argued that pigmented spindle cell “nevus” is nothing more than a pigmented variant of spindle cell nevus of Spitz type. The two differ cytologically, in aggregate patterns, and in clinical settings. The differential diagnosis of PSCN is unlikely to include angioma (a common clinical characteristic of Spitz nevi), but is likely to include premalignant dysplasia, and melanoma. The proponents of such a compromise admit that they recognize the patterns of PSCN; they identify its features among those of Spitz nevus-like type. They could just as easily classify all Spitz nevus-like lesions with alternating patterns of PSCN as variants of the latter. If an assignment is required for these mixed patterns, they should be to the category of combined nevus. To include the PSCN in the category of Spitz nevus would require an expansion of the definition of pigmented, but otherwise classic, Spitz nevus. It would enlarge the general Spitz nevus category, and require modifications in the accepted criteria. In short order, the addition would be recognized as an intruder. Once recognized as such, it would be reassigned as a separate entity to its former category. From a review of pictorial documentation in early reports, it is likely that some examples of PSCN have been included in the Spitz category. Contrarily, some examples of pigmented spindle cell nevus of the Spitz type probably have been included in reports of PSCN. Invariably, in the definition of new disorders, the initial efforts are too broad and the respective category will prove to be too heterogeneous.

In atypical pigmented spindle cell “nevus, the basic patterns are preserved, but the cells at the dermal-epidermal interface have plump, elongated nuclei with delicate chromatin, irregular nuclear outlines, and prominent central nucleoli. Markers for host immune response, including lymphoid infiltrates and papillary dermal fibrosis, are variable features; they are more common in examples exhibiting nuclear grade II. Mitoses are more common in the atypical variants. For atypical variants in which the dermal component forms an expansile nodule, a decision to classify respective lesions as either atypical spindle cell “nevus,” or MDM of the pigmented spindle cell type becomes arbitrary; in turn, any arbitrary choice will prove to be difficult to defend.

If pigmented spindle cell nevus of Reed has an atypical counterpart and if the atypical counterpart is accepted as a marker for neoplastic progressions, we should anticipate that some examples will progress to become deceptively bland pigmented spindle cell melanomas (a variant of MDM). Some MDM of the pigmented spindle cell type (lesions that have lost distinguishing features of pigmented spindle cell nevus, and have metastasized) may be transformed pigmented spindle nevi.

For atypical spindle cell nevus of Reed in which cytologic atypia and overall bulk of tumor raises the question of a diagnosis of MDM, an alternate designation might be "borderline melanocytic neoplasia of indeterminate malignant potential (PSCN type) (note: nuclear grade II).

Combined nevi: In part, the characterization of variants of nevi is based upon distinctive cytologic features of the cells in each variant. In examples in which two or more cell types are represented in a single lesion, the patterns of the respective nevi are combined (i.e., the combined nevi). In most examples of combined nevi, components of typical nevus cells are admixed with those of some other type of nevus such as deep penetrating nevus (common type), blue nevus, cellular blue nevus, or Spitz nevus. The common combined nevus (and its monomorphic variant, the deep penetrating nevus) is a recent addition. In it, two types of nevus cells, each in different patterns, are combined. In the common variant, typical nevus cells in nevus cell patterns are combined with distinctive, plump, pigmented spindle cells in fascicular patterns. The fasciculated, spindle cell component is interspersed among, and often extends beyond, a component of common nevus cells into the deeper dermis.

Some examples of combined nevus are associated with patterns of premalignant dysplasia at the dermal-epidermal interface; such examples qualify as atypical combined nevus. In some examples, atypia is manifested mostly in the dermal component and is associated with a higher mitotic rate than usually encountered in typical combined nevi. Such lesions qualify as dermal variant of atypical combined nevi.

In one variation of the common form of combined nevus (deep penetrating nevus- like), fascicles of pigmented spindle cells are loosely and regularly spaced in a condensed fibrous matrix to form an expansile nodule with remnants of a typical nevus (a population of typical nevus cells) outside the confines of the nodule. The nodule might be mistaken for the vertical growth of a melanoma, but the cytologic features, and the fasciculated patterns are no different from examples of combined nevus in which the fasicles of pigmented spindle cells are interspersed among nests of common nevus cells, or collagen bundles of the reticular dermis.

Deep penetrating nevus shares the basic features of the common combined nevus, but is not associated with a component of common nevus cells. Step sections would be required to clearly exclude a combined pattern in such a lesion. Other variants of combined nevus include the blue nevus type, the cellular blue nevus type, and perhaps a Spitz variant.

Although a category of minimal deviation melanoma of combined nevus type has not been adequately documented, there are rare lesions of the combined nevus-like type that are associated with metastases of the spindle cell component to regional lymph nodes. Such lesions qualify as minimal deviation melamoma of combined nevus-like type: they may be comparable to atypical cellular blue nevus (i.e., MDM of blue nevus-like type) in which nodal metastases are not harbingers of disseminated disease. The metastases are parenchymal rather than capsular in type, and the metastatic cells are cytologically atypical. These findings in the metastatic sites are associated with variant patterns in the primary site. The cells in the primary site show an alteration in nuclear/cytoplasmic ratio with crowding of nuclei. Open chromatin patterns, central nucleoli, and mitoses are also features. The fascicles of cells are broad and closely spaced to form a nodule (a vertical growth component). The eventual course of the metastasizing lesions in this category is unknown. Such lesions might also be compared to some examples of MDM of the Spitz type that metastasize to regional but appear to have little potential for disseminated disease. Additional studies and follow-up are required before these metastasizing lesions of limited potential are definitively characterized. A characterization of such lesions as "borderline melanocytic neoplasias of indeterminate malignant potential” (e.g., MDM of the combined nevus type, cellular blue nevus type, and Spitz type) would be appropriate (note: nuclear grade I-II) .

The blue nevi: Cellular blue nevus, a well documented lesion, presumably is of origin from "dermal melanocytes." It has a predilection for the scalp, the buttocks, and the dorsa of the hands and feet. Histologically, zonal variations in both patterns and cytologic features are characteristic of the classic variant. The variations include 3 patterns: 1) fibrosis and melanogenic spindle and dendritic cells; 2) fascicular patterns and melanogenic spindle and dendritic cells; and 3) fascicular patterns in which fascicles are closely spaced and cells are pale, amelanotic and spindle shaped. The fibrosing patterns (pattern I) are prominent in the peripheral superficial portions. The cellular, crowded fascicular patterns are often central in the deep portions. The looser, pigmented spindle cell patterns are found at the periphery of the areas in which amelanotic cells are arranged in closely grouped fascicles (cellular patterns). Cellular, closely spaced fascicles are also a feature of perifollicular components. The perifollicular components commonly extend along the involved follicles and form nodules which bulge into the subcutis. Mitoses are uncommon in all three patterns. Some examples are monomorphic. The monomorphic variations include:

1) uniform sclerosis and melanogenesis (fibrosing variant);

2) sclerosing and fasciculated patterns with melanogenesis (melanocytic variant);

3) fasciculated and neuroid patterns, generally amelanotic (schwannian variant) There are rare, amelanotic, sclerosing variants.

Regressive changes are prominent in some examples of cellular blue nevi. Zones of relatively acellular, watery fibrous tissue mark areas in which groups of tumor cells have undergone lysis. In these zones, extravasated red blood cells and hemosiderin deposits may be a prominent feature. Vascular changes include ectasia, fibrinoid degeneration and fibrosis of vessel walls, and subendothelial collections of foamy histiocytes. Cellular and nuclear pleomorphism is often a feature of tumor cells bordering zones of regression. The changes are similar to those of "ancient change" in schwannomas. It would be inappropriate to dismiss these lesions as "ancient nevi." These lesions are cellular blue nevi with regressive ("ancient") changes and the regressive changes have apoptotic qualities. The designation, "ancient nevus," has been proposed as a generic designation that has application to cytologic atypia in a variety of “nevi.” As currently defined, the designation fails to discriminate between regressive changes as seen in some examples of cellular blue nevus, and neoplastic progressions in MDM of the dermal type.

Deep mesenchymal melanocytic hamartomas are composed of melanogenic spindle cells in the deep soft tissue. The favored site of involvement is the soft tissue of the face in a distribution which corresponds to that of one of the branches of the trigeminal nerve. These deep hamartomas share features with cellular blue nevus but do not show the prominent zonal variations in patterns that characterize many cellular blue nevi. They often show the regressive changes seen in some examples of cellular blue nevus. Some examples are associated with patterns of cellular blue nevus in an overlying dermal component. Spindle cell neoplasms (variant melanomas) may arise in these lesions. Often these melanomas are minimal deviation in character; they share features with atypical cellular blue nevus (MDM of the cellular blue nevus type) .

In contrast to epidermal patterns in atypical halo and atypical Spitz nevi, atypical cells in lentiginous and junctional patterns at the dermal-epidermal interface are not a requisite for the diagnosis of atypical cellular blue nevus (or atypical pigmented spindle cell nevus of dermal type). Atypical cellular blue nevus is characterized by a nodule of atypical cells with cytologic disparity when comparisons are made between the cells in the nodule and neighboring remnants of cellular blue nevus: the atypia is moderate, and nuclear changes are uniform in the nodule. Nuclei of cells forming the nodule are round, or oval, and hyperchromatic. Nuclear pleomorphism, by definition, is not a requisite feature. Mitotic activity is a feature. From the perspective of the concept of MDM, atypical cellular blue nevus is MDM of the cellular blue nevus type. The metastases from atypical cellular blue nevus generally are parenchymal in regional lymph nodes (as are the metastases that sometimes are associated with some examples of MDM of the Spitz type; metastases that are unlikely to be associated with progressive disease (i.e., a feature in common with many of the "metastasizing Spitz nevi" and, perhaps, in common with MDM of the combined nevus type). They are not simply capsular inclusions as seen in some giant congenital nevi.

The diagnosis of atypical cellular blue nevus is best reserved for lesions in which a remnant of a preexisting benign component is preserved. Some atypical pigmented lesions in the clinical setting of cellular blue nevus, but without histologic representation of a remnant of cellular blue nevus, are acceptable as de novo atypical cellular blue nevus.

There is little evidence of a significant potential for malignant transformation of the common blue nevus.

The dermal melanocytoses (nevus of Ota and Ito) have a documented potential for malignant transformation, but the potential is low. Such lesions are unlikely to show a "primary configuration." They are likely to be pigmented and spindle cell in type.

The recently described epithelioid blue nevus (a component of the Carney syndrome) might be a source of error in regard to interpretation. In this variant, plump tumor cells have plump, round nuclei with marginated chromatin. Heavily pigmented examples are difficult to interpret on H&E stained sections and might be misinterpreted as melanoma. Blue nevus of "animal" type (i.e., multifocal and perifollicular) may be related to epithelioid blue nevus.

Minimal deviation pigmented spindle cell melanoma of the dermal type is an uncommon variant. Its cells are variably pigmented, spindle shaped, and fairly uniform in nuclear characteristics. Often, the nuclear chromatin is heavily marginated, and nucleoli are central and acidophilic. Mitoses may be few in number and widely scattered. The cells form closely aggregated fascicles, or they are interspersed among collagen bundles of the reticular dermis. MDM of the pigmented spindle cell type is often oval or rounded in outline in the upper portion of the dermis; commonly a column of closely aggregated fascicle of cells extends from the superficial portion into the deeper portion of the dermis (keyhole configuration). If this column extends into the subcutis, it usually has a bulbous extremity. At the margins of the tumor, the fascicles extend into the neighboring dermis among collagen bundles. Collagen bundles are also entrapped in the tumor among the closely aggregated fascicles. Lesions of this type appear to have been included in reports of "metastasizing Spitz nevus."

Many of the features, commonly represented in minimal deviation pigmented spindle cell melanoma of the dermal type, are also common in cellular blue nevi, particularly the overall configuration of both lesions. It might be argued that these lesions are merely monomorphic variants of atypical cellular blue nevus. In practice, the metastases from some examples of minimal deviation melanomas of pigmented spindle cell type may be widespread. On this basis, minimal deviation pigmented spindle cell melanomas should not be equated with, and simply dismissed as, atypical cellular blue nevus. In addition, minimal deviation pigmented spindle cell melanoma is less likely to involve the classic sites affected by cellular blue nevi (e.g., the scalp, the buttocks, or the dorsa of the hands and feet.). Minimal deviation pigmented spindle cell melanoma is not regularly and sequentially related to pigmented spindle cell nevus of Reed.

There is a poorly defined group of pigmented spindle cell lesions of the skin that are borderline in cytologic features and mostly confined to the reticular dermis. Lentinginous and junctional components are variable, and often are inconspicuous; if represented, they often appear to be incidental, and do not appear to have made a significant contribution to the dermal component. In such examples, the papillary dermis is neither significantly involved, nor widened. Mitotic activity is a feature but mitotic rates are usually low. In the concept of MDM, such lesions were included in the category of MDM of the pigmented spindle cell type. Some examples are associated with minimal deviation neutotropic components. Some examples might qualify as "nevoid" melanoma. Some lesions of this type probably have been included in reports of cellular blue nevus. Lesions in this poorly defined category are treacherous in regard to prognostications. These lesions, when evaluated by Breslow's criteria, are not as predictable as the typical (common) variants of melanoma. To provide therapeutic recommendations by modified Clark's and Breslow's criteria might result in unnecessary surgery for most of these patients. Adequate local excisions and careful follow-up are appropriate recommendations. This category received emphasis in the contribution on MDM by Mihm, et al. Some fasciculated and spindle cell lesions are amelanotic but, in all other respects, resemble pigmented spindle cell MDM. Such lesions might be characterized as MDM of indeterminate spindle cell type; they are composed of plump spindle cells with pale or clear cytoplasm, and oval or round nuclei with marginated chromatin. The component cells cannot be characterized as either Spitz nevus-like, or pigmented spindle cell nevus-like.

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