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Combined “nevus:”
Combined “nevus” (and its monomorphic variant, the deep penetrating “nevus”), is a recent addition. In it, two types of “nevus” cells 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 spindle cell component is interspersed among, and often extend beyond, a component of common nevus cells into the deeper portions of the dermis. In some examples, the spindle cell component is isolated in a specific stroma to form an expansile nodule. Some examples 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 variants of atypical combined “nevus.” They should be qualified as melanocytic neoplasia of indeterminate malignant potential.
Rarely, lesions of combined “nevus” type are associated with metastases of the spindle cell component to regional lymph nodes. 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 atypical patterns in the primary site. In such lesions, the cells in the primary site show an alteration in nuclear / cytoplasmic ratio with crowding of nuclei. Open chromatin patterns with central nucleoli and mitoses are also features. The fascicles of cells are broad and closely spaced to form a nodule (a pattern that also qualifies as a typical vertical growth-like pattern). The eventual course of these metastasizing lesions may be comparable to some examples of MDM of the Spitz type, and may have little potential for disseminated spread. Additional studies and follow-up are required before these lesions are definitively characterized. Provisionally, such lesions are also melanocytic neoplasias of indeterminate malignant potential (MDM of the combined “nevus” type, nuclear grade II or greater).
Deep penetrating “nevus” shares the basic features of the common combined “nevus” but is not associated with a component of common nevus cells. To clearly exclude a combined pattern, step sections of the block would be required. Other variants of combined “nevus” include the blue nevus type, the cellular blue nevus type, and perhaps a Spitz variant.
Cellular blue nevus is a well documented lesion and presumably 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:
1) fibrosis and melanogenic spindle and dendritic cells
2) fascicular patterns and melanogenic spindle and dendritic cells
3) fascicular patterns in which fascicles are closely spaced and cells are pale, amelanotic, and spindle shaped.
The fibrosing patterns of type I are prominent in the peripheral superficial portions. The cellular, close fascicular patterns are often central in the deep portions. The more loosely arranged pigmented spindle cell patterns are found at the periphery of the cellular, close fascicular patterns. Cellularity is also a feature of the perifollicular components. The perifollicular cellular components commonly bulge into the subcutis. Mitoses are uncommon. 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).
Regressive changes are prominent in some examples of cellular blue nevi. Focal lysis of groups of tumor cells result in zones of relatively acellular, watery fibrous tissue. 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 (similar vascular changes commonly are present in schwannomas). Cellular and nuclear pleomorphism is often a feature of the tumor bordering zones of regression. The changes are similar to those of “ancient change” in schwannomas. Changes of these types in a cellular blue nevi have been characterized as ancient change. As originally proposed, and in reference to melanocytic lesions, the designation, ancient change, did not discriminate between regressive changes in cellular blue nevus and neoplastic progressions in MDM of the dermal type. With follow-up, the “regressive” changes of MDM of the dermal type seem to be more in the nature of neoplastic transformations; to characterize the cellular changes of MDM of the dermal type as regressive is inappropriate.
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 which 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, which, on occasion, arise in these lesions, qualify as variant melanomas; they often are minimal deviation in character; they share features with atypical cellular blue nevus (MDM of the cellular blue nevus type).
In contrast to 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 cell “nevus” of dermal type). The diagnosis of atypical cellular blue “nevus” is best reserved for lesions in which a remnant of a pre-existing benign component is preserved. Atypical cellular blue nevus is characterized by a nodule of atypical cells with cytologic disparity when comparisons are made between the cells of the nodule and neighboring remnants of the pre-existing cellular blue nevus; the atypia is moderate and nuclear changes are uniform in the nodule. Nuclei of cells forming the nodule are plump and hyperchromatic. Nuclear pleomorphism is not a requisite feature. Mitotic activity is a feature. Such lesions might also be characterized as MDM of the cellular blue nevus-like type. Metastases from atypical cellular blue “nevus” are parenchymal in regional lymph nodes, but seem to be rarely associated with progressive disease. They are not simply capsular inclusions as seen in association with some giant congenital nevi. Some atypical pigmented lesions in the clinical setting of cellular blue nevus (but without an associated 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. Some examples of LMM in vertical growth may show patterns which might be mistaken for a portion of a common, but atypical, 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 lesion that is sometimes 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; they tend to be dendritic in outline. Heavily pigmented examples are difficult to interpret on H&E stained sections, and might be interpreted as melanoma. Some “spindle cell” melanomas, as encountered in the setting of ALM or LMM, are composed of atypical, heavily pigmented, dendritic cells.
Minimal deviation pigmented spindle cell melanoma of the dermal type is an uncommon variant. Pigmentation is variable and, perhaps, this variant might be better characterized as spindle cell MDM of non-Spitz type. It shares features with malignant cellular blue nevus, and might be considered a de novo variant of the latter (it is distinguished by no recognizable remnant of a pre-existing cellular blue nevus). Its tumor 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 fascicles which are closely aggregated, or 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 with a columnar component that extends into the deeper portion of the dermis (keyhole configuration). If this column extends into the subcutis, it usually has a bulbous extremity (this configuration is common in the spindle cell category and is a common feature in the setting of classic Spitz “nevus”). 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 are 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 variants of atypical cellular blue “nevus.” In practice, the metastases from some examples of MDM of pigmented spindle cell type may be widespread. On this basis, minimal deviation pigmented spindle cell melanoma 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 classic sites which are 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 of dermal type does not appear to be sequentially related to pigmented spindle cell nevus of Reed.
There is a poorly defined group of pigmented spindle cell lesions of the skin which are borderline in cytologic features, and mostly confined to the reticular dermis. Lentiginous 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 demis 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 neurotropic 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 the affected patients. Adequate local excisions and careful follow-up are appropriate recommendations. This category received emphasis in the contribution on MDM by , et al.
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