Immunohistochemical characterization of Spitz's nevus: differentiation from common melanocytic nevus, dysplastic melanocytic nevus and malignant melanoma

Recently it has been reported that Spitz's nevus possesses a deranged melanogenesis with formation of the spherical melanosomes also seen in superficial spreading melanoma (SSM) and dysplastic melanocytic nevus (DMN). To characterize the nature of Spitz's nevus, immunohistochemical studies were carried out in 9 cases of this condition using monoclonal antibodies (MoAbs) which identify (a) human melanosome-associated antigen (HMSA-1 and HMSA-2), (b) S-100 protein (α and β subunits), (c) Leu-7 (HNK-1), (d) β2 microglobulin (B2MG), and (e) neuron specific enolase (NSE). In contrast to SSM and DMN, none of the 9 cases showed any significant reactivity with MoAbs HMSA-1 and HMSA-2. Similar to cutaneous malignant melanoma (CMM) and DMN, and unlike common melanocytic nevus (CMN), anti-S-100 protein α subunit MoAb reacted from moderately to intensely with Spitz's nevus, and anti-S-100 protein β subunit MoAb reacted weakly. Anti-B2MG MoAb was reactive with 8 of 9 cases. Only one case showed cytoplasmic reactivity to anti-Leu-7 MoAb. Polyclonal NSE was found in 7 cases at varying intensities. Our immunohistochemical study indicates the distinct, benign neoplastic nature of Spitz's nevus which has immunoreactivities differing from those of CMM, DMN and CMN.     

"Atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus: a critique in historical perspective of three concepts flawed fatally

Our purpose in undertaking this Arbeit was to review all articles published about "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus, to criticize them in a fashion that illuminates, and to come to conclusions compellingly about those subjects. We found that an overwhelming majority of neoplasms that claimed to be "atypical Spitz's nevus," "metastasizing Spitz's nevus," and "malignant Spitz's nevus" were, in fact, melanomas ( Table 1). Moreover, in our estimation, those designations, and variants of them, like "atypical Spitz's lesion," "atypical dermal melanocytic lesion with features of Spitz's nevus," "atypical Spitzoid melanocytic neoplasm," and "problematic Spitzoid melanocytic lesion," are mere evasions from a diagnosis, straightforwardly, of either Spitz's nevus or melanoma. Diagnoses in pathology equally bogus are "minimal deviation melanoma," "borderline melanoma," "nevoid melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic lesion of uncertain biologic potential." Rather than admit uncertainty forthrightly, those who employ circumlocutions like those just mentioned resort to linguistic maneuvers that, at first blush, seem to be "academic" and constructed in such a way as to appear to convey confidence, rather than tentativeness, on the part of a histopathologist. On further scrutiny, however, each of those cliches is revealed to be devoid of content. For example, "malignant" Spitz's nevus and "metastasizing" Spitz's nevus not only are contradictions in terms, but they are outrageous violations of fundamental principles of classic Virchowian pathology, and "atypical" Spitz's nevus not only is a redundancy because the neoplasm was so atypical to Spitz, herself, she insisted (from the time she spawned the idea in 194 through 1951 it was a "malignant melanoma," but is abject intellectually, those who invoke it never setting forth, in clear-cut fashion, criteria for what constitutes a "typical" Spitz's nevus in contradistinction to an "atypical" one.     

'Tubular' epithelioid cell nevus: a new variant of Spitz's nevus

The term Spitz's nevus refers to a large spectrum of nevi composed of spindle and/or epithelioid cells. We report on a hitherto undescribed tubular variant of a dermal epithelioid nevus, characterized by aggregates composed exclusively of cuboidal cells with the prominent feature of tubular or microcystic structures, Immunohistochemically, the epithelioid cells expressed melanocytic markers (S-100, NKI/C3) lacking markers for cytokeratin or carcinoembryonic antigen. The three-dimensional analysis of the lesions by confocal laser scanning microscopy revealed the structural configuration of tubular or microcystic empty spaces bordered by cuboidal nevus cells. This rare variant of epithelioid nevus is another example for the remarkable diversity of Spitz's nevi.     

A comparative study of Spitz nevus and nodular malignant melanoma using image analysis cytometry

Image analysis cytometry can be used to estimate both nuclear DNA content and area in tissue sections. Since nodular malignant melanoma and Spitz nevus can show a remarkably similar light microscopic appearance, but may differ in behavior, we studied typical examples of these neoplasms to determine whether cytometric differences existed. Analysis of relative DNA content alone could not discriminate between these 2 entities in the 13 cases that we examined. However, Spitz nevi and nodular melanoma clearly differed in terms of maturation, which we defined as the difference between the mean nuclear size or mean nuclear DNA content of the uppermost and deepest melanocytes in each lesion. Maturation as defined by a decrease in mean nuclear DNA content proved highly significant (p less than 0.005). Only Spitz nevi showed a lesser DNA content in the deepest dermal cells as compared with upper dermal cells, suggesting that some Spitz nevi have an admixture of diploid and hyperdiploid cells in their upper portions, but mostly diploid cells in their deep portions. Only nodular melanoma showed higher mean DNA content in deep dermal cells as opposed to superficial dermal cells, suggesting that some nodular melanomas may either have clones of cells in their deep portions that have higher levels of ploidy, or more cells in the deep portion of melanomas may be in active phases of the cell cycle. Our study suggests that important cytometric differences exist between Spitz nevi and nodular melanoma, and that these could be exploited to develop cytometry into an adjunctive clinical technique.     

Nevus of large spindle and/or epithelioid cells (Spitz's nevus).

By now it is well recognized that there is a benign melanocytic nevus, common in the young and common enough in adults, that has histological features that are confusable with those of malignant melanoma. The anomaly is usually referred to as benign juvenile melanoma, sometimes as Spitz's nevus, and, by some histopathologists, as spindle and epithelioid cell nevus. All the histological subtleties and variations of the condition are still not fully appreciated and some of them are still being misinterpreted as those of malignant melanoma. We herewith present a study designed to clarify the issue and offer firm criteria for histological differentiation of the nevus in point from malignant melanoma. We also suggest a new name for it and supporting arguments therefor.     

Identification of basement membrane components in eosinophilic globules in a case of Spitz's nevus.

A case of Spitz's nevus with eosinophilic globules was examined using antibodies for several components of the basement membrane. Aggregated tumor cells revealed the same characteristics as normal nevocytic nevi, that is, they were surrounded by laminin and type-IV collagen, whereas type-VII collagen was absent. All of these components of basement membranes, including type-VII collagen, were also found in eosinophilic globules, which were densely stained by these antibodies. It is assumed that these eosinophilic globules are essentially composed of basement membrane components, which are probably synthesized by epidermal and possibly also by melanocytic tumor cells.     

Becker's nevus and malignant melanoma

We describe 9 patients who presented Becker's nevus (BN) together with a malignant melanoma (MM). Eight patients were male. In 5 patients the MM was on the same body site as the BN. The melanoma was of the superficial-spreading type in 7 cases and in 1 patient was within the BN. Twice a dysplastic-nevus syndrome was diagnosed and in 2 patients a familial melanoma. To the best of our knowledge this is the first report of the co-occurrence of BN and MM.     

Key points in the dermoscopic diagnosis of hypomelanotic melanoma and nodular melanoma

Nodular melanoma (NM) and amelanotic/hypomelanotic melanoma (AHM) often present a challenge to the diagnosing clinician. A significant proportion of AHM are nodular in nature. Such tumors may lack features of asymmetry and altered peripheral pigmentation routinely observed in other melanoma subtypes. This lack of distinguishing clinical features can potentially result in delayed diagnosis or inappropriate treatment. This review highlights the key points in evaluating the range of lesions where AHM or NM are considered in the differential diagnosis and summarizes current evidence in relation to pigmented and vascular dermoscopic diagnostic criteria for both.     

Malignant melanoma arising in a nevus spilus

Malignant melanoma arising within a nevus spilus is rare. Nevus spilus is characterized by darkly pigmented macules and papules with background hyperpigmention. We report a 65-year-old woman who presented with a melanoma arising in a nevus spilus that had been present since birth.     

Malignant melanoma arising in a nevus of Nanta

Papillomatous fleshy facial nevi have a low risk of malignant transformation. In addition, they may undergo ossification in their depths; a nevus with bone is known as a nevus of Nanta. Such a nevus in a 60-year-old female gave rise to a malignant melanoma.     

Congenital Spitz nevus clinically mimicking melanoma

The differentiation between atypical variants of Spitz nevus and melanoma is often difficult given the many clinical and histopathologic similarities between the two. We report a case of an infant with a congenital scalp lesion exhibiting clinical features of melanoma, including variegation and regression of pigmentation and a rapidly changing appearance. Histologic examination of the excised lesion revealed a benign congenital Spitz nevus. This case emphasizes the need for clinical and histologic correlation in determining the benign or malignant nature of atypical pigmented lesions in infants.