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PubMed1992

Application of morphometric methods to the cytologic study of intradermal nevi.

Twenty-one intradermal nevi were studied by morphometric methods in an attempt to morphologically characterize the two types of nevus cell--epithelioids, type A, and fusiforms, type C--and to quantify the differences between them. Morphometric parameters of the intradermal nevi were compared with similar parameters of melanocytes and melanoma cells so that the maturation rates of the nevi cells could be established and to see if the parameters might indicate the degree of malignancy. Superficial nevus cells were differentiated from deep cells by their larger size and larger nuclear area. Nuclear area appeared to have potential for differentiating benign from malignant tumors. Decrease in cellular area appeared to indicate maturation rather than atrophy. Melanoma cells were differentiated by their larger size. Cell nuclear perimeter appeared to have confirmatory value, while cell perimeter was inconclusive.

Biopsy↗
PubMed1989

HMB-45 staining of dysplastic nevi. Support for a spectrum of progression toward melanoma.

Dysplastic nevi are melanocytic tumors that occupy intermediate positions in the spectrum of melanocytic proliferations. Although they are invariably cured if completely excised, their biologic potential if left untreated is unknown. We examined a series of such lesions with HMB-45, a melanocyte-specific antibody, in order to explore protein expression within these borderline lesions. HMB-45 has previously been shown to label intraepidermal melanocytes within melanomas and within all nevi. Intradermal melanoma cells also label with HMB-45, but dermal nevus cells within common melanocytic nevi do not normally stain. In contrast, we found mild to moderate staining of nevus cells within the papillary dermis of dysplastic nevi and within residual nevus cells adjacent to malignant melanomas. In the same lesions, we demonstrated strong staining of intraepidermal melanocytes. Thus, dermal nevus cells within dysplastic nevi and within residual nevus cells adjacent to malignant melanomas are expressing low-level amounts of a protein expressed by melanoma cells, but not by dermal nevus cells within wholly benign melanocytic tumors. This lends support to the concept of these lesions as precursor lesions with undetermined biologic potential.

Antibodies, Neoplasm↗
PubMed1990

[Histological and immunohistochemical studies on nevocellular nevi in the dermis. With special reference to the histogenesis of nevus cells].

The author has performed study on the histogenesis of the nevus cells in the nevocellular nevi. In the study, specimens of the intradermal nevi in 124 cases were evaluated histologically and immunohistochemically and the following results were obtained: 1) Findings of hematoxylin eosin staining It was observed that three types of cells, including type A cells (epidermoid type cells), type B cells (lymphoid type cells), type C cells (neuroid type cells) were found to run through an intermediate stage from the upper part to the lower part of the nevocellular structure, although they disclosed different histological structures. In 39 (31.5%) of the 124 cases, Meissner's corpuscle-like cells were confirmed. 2) Findings of immunohistochemical staining i. Of the type A, type B and type C cells, the S-100 alpha protein stain was essentially negative. Meissner's corpuscle-like cells were selectively positive by this stain. ii. Although no particular difference was noted in the staining of S-100 protein between the type A and type B cells, a somewhat greater proportion of positive cells was noted in type C cells. In the Meissner's corpuscle-like cells, a notably higher positive conversion of cells was observed as compared to those of the three other types of cells. iii. Type A, type B and type C cells compared more or less similarly for the positive ratio of neuron-specific enolase but the ratio was unusually high in the Meissner's corpuscle-like cells. 3) Findings from routine electron microscopic staining i. Similar to the light microscopic findings, the nevus cells were found to change in shape uninterruptedly from the upper layer to the lower layer of the dermis. Unusually marked changes were noted both in the number and shape of the melanosome and premelanosome in the cytoplasm. ii. In the Meissner's corpuscle-like cells both melanosomes and premelanosomes were missing but a finding suggestive of a neuroid structure was affirmed. As noted above, the results of the histological, immunohistological and electron microscopic studies were in support of the general findings suggestive of a gradual shift of the nevus cells from the upper layer to the lower layer in the dermis, which prompted the author to support the so-called "neural crest origin hypothesis".

Adolescent↗
PubMed1990

A hypothesis incorporating the histologic characteristics of dysplastic nevi into the normal biological development of melanocytic nevi.

A lentiginous pattern of intraepidermal melanocytic hyperplasia, with mild to moderate, random cytologic atypia, forms the conventional basis for the histologic definition of a dysplastic nevus. It is proposed here that these changes actually represent the histologic pattern of a nevus in an active phase of radial growth. The lesser degrees of atypia considered by others to be required for the diagnosis are suggested to overlap changes commonly seen in banal nevi and lentigines. This hypothesis allows the parsimonious concept that a nevus, originating as a lentigo, can at the later sequential junctional, compound, or intradermal stages expand peripherally by a resumption or persistence of the lentiginous pattern of proliferation. The random atypia that is seen in such lesions is suggested to be incidental to the proliferative process rather than indicative of dysplasia as conventionally defined. A familial melanoma-associated phenotype could be accommodated in this model by postulating a heritable defect in mechanisms that control the number or sizes of these hyperplastic lesions.

Dysplastic Nevus Syndrome↗
PubMed1982

Use of monoclonal antibodies in detection of melanoma-associated antigens in intact human tumors.

The use of antimelanoma monoclonal antibodies on tissue sections using a two-step indirect immunoperoxidase technique is reported. Antibodies 691-13-17 and 691-I5-Nu4B reacted with dysplastic nevus cells and all melanomas tested, but not with normal skin melanocytes, intradermal nevi, or lentigines. Antibody 691-13-17, directed against DR antigen, reacted also with Langerhan's cells, macrophages, and a subpopulation of lymphocytes. Antibody 691-I5-Nu4B reacted only with melanomas. The technique allows analysis of the expression of antigens by tumor cells in situ.

Adult↗
PubMed1997

Immunohistochemical markers for distinguishing Spitz nevi from malignant melanomas.

In this study, we demonstrate that immunostaining with MIB-1 and anti-bcl-2 is a useful tool to distinguish compound Spitz nevi from malignant melanomas. Forty-six cases of Spitz nevi and 50 cases of vertical growth-phase melanomas (Clark III-V) were compared for the immunoreactivity of MIB-1 and bcl-2 in the intradermal component of the lesions. As many as 76% of the Spitz nevus cases showed a low percentage (0-2%) of MIB-1 immunoreactivity. In the malignant melanomas, such a low MIB-1 index was shown in only 2% of the cases. The average MIB-1 index in malignant melanomas and Spitz nevi was 29.7 and 4.0%, respectively. bcl-2 was negative in only 4% of the melanoma cases, whereas the corresponding value was 72% in Spitz nevi. Statistical analyses using Students t test showed that the differences were highly significant (P < 0.001). By considering the immunoreactivity for MIB-1 and bcl-2 in the individual cases, we found that as many as 96% of the melanomas both expressed a bcl-2 positivity and exhibited a MIB-1 index exceeding 2% in the dermal component. The corresponding value was as low as 6% in the Spitz nevi.

Antigens, Nuclear↗
PubMed1990

Characterization of the role of melanoma growth stimulatory activity (MGSA) in the growth of normal melanocytes, nevocytes, and malignant melanocytes.

Melanoma growth stimulatory activity (MGSA) was originally described as an endogenous growth factor for human melanoma cells. To test the hypothesis that an MGSA autocrine loop is responsible for the partial freedom from growth control observed in nevocytes and melanoma cells, MGSA growth response and MGSA mRNA/protein levels were examined in these cells compared with normal melanocytes. As a single agent, or in combination with other factors, MGSA stimulated the growth of normal human epidermal melanocytes as well as other growth promoters for melanocytes. Nevocytes were not as responsive to exogenous MGSA as melanocytes. MGSA mRNA was minimal or not detected in cultured normal melanocytes, although the protein was present when the cells were cultured in the presence of serum/growth factors and absent when serum/growth factors were omitted. In contrast, MGSA mRNA was constitutively expressed in the absence of exogenous growth factors in cultures established from benign intradermal and dysplastic nevi and melanoma lesions in different stages of tumor progression. Nevus cultures contained immunoreactive MGSA protein in the presence of serum but were negative or only faintly positive in the absence of serum. Melanoma cell lines were positive for MGSA protein in both the presence and the absence of serum. Thus, continued expression of both MGSA mRNA and MGSA protein in the absence of exogenous hormones or serum factors may correlate with partial freedom from growth control exhibited by malignant melanocytes.

Blotting, Northern↗
PubMed1991

Nucleolar organizer regions in malignant melanoma and melanocytic nevi. Comparison of two counting methods.

Using a silver staining technique, we studied nucleolar organizer regions (AgNOR) in paraffin sections of junctional nevi, compound nevi, intradermal nevi, blue nevi, dysplastic nevi, Spitz nevi, lentigo maligna, malignant melanomas in nevus, superficial spreading melanomas, and nodular melanomas. Two methods of counting black dots within nuclei were employed. One method was to count the discrete black dots within the nuclei, including the tiny black dots seen within the nucleolus; the second method did not take into account the subsidiary cluster of tiny black dots seen within the nucleolus, instead treating these dots as a single structure. Whichever method we used, a significant difference was found between the pooled mean AgNOR numbers for benign and malignant lesions. We found an overlap, however, between benign, in particular Spitz and dysplastic nevi, and malignant lesions when considering individual counts of AgNOR using both methods. We conclude that studying AgNOR does not seem to be a useful technique to differentiate Spitz and dysplastic nevi from malignant melanomas.

Diagnosis, Differential↗
PubMed1999

Balloon cell change in cellular blue nevus.

Balloon cells are altered melanocytes with clear vacuolated cytoplasm caused by a defect in the process of melanogenesis. Although rare, balloon cell change has been observed in a variety of melanocytic proliferations, particularly intradermal melanocytic nevi and melanoma. When present, such features may lead to difficulties in diagnosis, particularly with other clear cell neoplasms. We report an unusual case of the development of balloon cell change in a cellular blue nevus, a phenomenon that has not been extensively addressed in the literature. The importance of recognizing this change in cellular blue nevus to avoid misinterpreting the lesion as malignant is discussed.

Cell Transformation, Neoplastic↗
PubMed2003

PNL2, a new monoclonal antibody directed against a fixative-resistant melanocyte antigen.

We report the production of a new monoclonal antibody, PNL2, directed against a fixative resistant melanocyte antigen. The analysis of PNL2 immunostaining on a broad range of normal or malignant human tissues and on various melanocytic lesions revealed its high specificity. PNL2 gave a strong cytoplasmic staining of skin and oral mucosae melanocytes, and staining of granulocytes when used at high concentration. PNL2 stained all intra-epidermal nevi irrespective of their histologic type, but common intradermal nevi and the dermal component of compound nevi were largely non-reactive as only scattered nevus cells in the papillary dermis were labeled. PNL2 labeled more than 70% of the neoplastic cells in all primary melanomas irrespective of their histologic type. However, PNL2 did not label desmoplastic melanomas. All metastatic melanomas were also stained but the percentage of labeled cells was occasionally lower than the primary tumor. PNL2, as anti-Melan A and HMB-45 antibodies, stained most of the clear cell sarcoma cells, and a few cells in angiomyolipomas and lymphangioleiomyomatosis. None of the other non-melanocytic lesions tested were labeled. Proteomic approaches showed that the immunoaffinity purified PNL2-binding complexes isolated from melanoma cell lines comprise at least TAP1, Clathrin 17 and prealbumin proteins, but not the gp100 recognized by HMB-45. In conclusion, this new monoclonal antibody, PNL2, is directed against a new fixative resistant melanocyte associated antigen. This antigen is chemically resistant and thus allows immunostaining after melanin bleaching or decalcification. We also demonstrate that it is different from Melan A and from gp100, even if PNL2 and HMB-45 staining patterns are sometimes similar.

Animals↗
PubMed1982

Electron microscopy of a nevus cell aggregate associated with an axillary lymph node.

The cellular composition of the so-called nevus cell aggregate (NCA) or inclusion has been the subject of controversy. Although the predominant opinion is that these cells are neval, some investigators suggest that they are related to glomus cells. In order to investigate this further, an NCA in the capsule of a nontumorous axillary lymph node obtained from a patient with breast cancer was removed from a paraffin block and processed for electron microscopic study. Ultrastructurally, uniform, round nevus cells with indented nuclei, dispersed chromatin, randomly oriented cytoplasmic fibrils, and a few mature melanosomes were identified. These cells closely resembled cutaneous intradermal neval cells and appeared unrelated to glomus cells. It is postulated that these NCA could be a noncutaneous anatomic source of some malignant melanomas.

Aged↗
PubMed1978

The relation of nervous elements to intradermal nevi. As electron microscopic study.

Intratumoral nerves of dermal nevi were investigated by electron microscopy in order to elucidate the role of neural elements in the development of these tumors. The following results were obtained: 1. Intratumoral nerves exhibit an increased cellularity, but the number of myelinated fibers is reduced. 2. Nevus cells type B and C are frequently present within nerve fascicles. 3. Unmyelinated axons were found in close relationship to nevus cells. 4. Schwann cells may show proliferations similar to early stages of neurofibroma and can be differentiated from unpigmented tumor cells by their relation to axons only. These findings indicate that identical cell populations are present within the intratumoral nerves and the tumor itself. Therefore, the theory of a neural component in the histogenesis of intradermal nevi is supported.

Adult↗