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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histologic presence of benign dermal nevus cells in contiguity with primary cutaneous melanoma, as a distinct population separate from malignant melanocytes, was evaluated in a large referral data base. The melanomas were limited to superficial spreading melanoma (SSM) and nodular melanoma (NM). Overall, dermal melanocytic nevi were found associated with 1126 of 1954 primary SSM/NM (57.6%). When the melanomas were stratified by tumor thickness, an inverse relationship between the presence of benign nevus cells and tumor thickness was found: 64.9% of tumors less than 0.76 mm and 64.5% of those between 0.76 and 1.69 mm were associated with dermal nevi, whereas in the thickness range 1.70-3.60 mm, there were 45.6% associated nevi, and in melanomas greater than 3.60 mm, there were only 32.0% noted to have nevus cells. When melanomas were separated by nevus type, it was found that 41% were associated with an acquired pattern nevus, 38% with congenital pattern nevus, and 21% with dysplastic nevus. It may be concluded that 1) the histologic presence of nevus cells is a common event in SSM/NM; 2) the association of melanocytic nevus and melanoma is more easily demonstrated in thinner tumors; and 3) acquired pattern nevi, congenital pattern nevi, and dysplastic nevi are all potential precursors of melanoma.
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PMID:Melanocytic nevi in histologic association with primary cutaneous melanoma of superficial spreading and nodular types: effect of tumor thickness. 844 Sep 14

The term ocular melanoma refers to a heterogeneous group of cancers of melanocytic origin. The precursor of most cases of conjunctival melanoma is known to ophthalmologists as primary acquired melanosis. This condition passes through well-defined stages of tumor progression. Although tumor progression is not obligatory, as a conjunctival melanocytic lesion acquires new biologic properties it is more likely to progress further. Although junctional nevi are seldom encountered beyond childhood and primary acquired melanosis usually develops in middle-aged individuals, these two conditions may be histologically indistinguishable. Most junctional nevi eventually show evidence of differentiation, whereas nearly half of the cases of primary acquired melanosis with atypia progress to melanoma. Therefore, it is possible that aging may modulate the capability of certain clonal proliferations to differentiate. Uveal melanocytes normally reside in mesenchyme, so that the traditional histologic criterion for establishing the diagnosis of most melanomas--breach of an epithelial basement membrane--does not apply. Because uveal melanomas are not easily accessible to incisional biopsy (without disruption of vision), only two points in the spectrum of tumor progression are defined clinically: nevus and melanoma. Experimental evidence suggests that a spectrum of atypical melanocytic proliferations separates benign nevi from melanomas capable of generating metastases. Unlike conjunctival melanomas that spread first to regional lymph nodes, choroidal and ciliary body melanomas preferentially spread first to the liver and are examples of organ-specific metastases.
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PMID:Tumor progression in ocular melanomas. 844 Sep 16

p53 Protein immunohistochemical expression is a wide-spread feature of the malignant phenotype; most melanomas are reported as p53 positive, while nevi are reported as p53 negative. We investigate a series of 75 benign nevi and 47 melanomas (40 primary and seven metastatic) to evaluate their pattern of p53 immunoreactivity with a panel of specific antibodies (PAb1801, PAb240, DO7, and CM1) in view of a possible diagnostic role of p53 immunostaining. Our results demonstrate that 15% of nevi show p53 immunoreactive nuclei (usually in less than 1% of the cells) and that 30% of melanomas show p53 immunoreactive nuclei (one case with 20% immunoreactive cells, six cases with 1% to 5% positive cells, and four cases with less than 1% positive nuclei). p53 Positivity was seen also in basal and suprabasal keratinocytes. p53 Positivity in nevi is at variance with literature data supporting that nevi are p53 negative. p53 Positivity in nevi and in epidermis may be related to mechanisms of DNA repair, apoptosis, or to a specific phase of the cell cycle. In our series, p53 expression in melanomas is not as frequent as reported in the literature. Population-based differences or differences in case selection and sample handling may account for the above discrepancies. The demonstration of p53 positivity in benign skin lesions greatly hinders the possibility of a diagnostic use of p53 immunostaining in dermatopathology.
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PMID:p53 Protein expression in nevi and melanomas. 751 47

We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma.
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PMID:Melanoma mimicking dermal and Spitz's nevus ("nevoid" melanoma). 851 1

To determine whether loss or inactivation of the putative tumor-suppressor gene, p16, represents an initiating or a secondary event in the progression of human melanoma, we evaluated the status of this gene in early and advanced-stage melanomas of sporadic origin. The results of this analysis revealed p16 deletions in 4/6 primary and 6/14 metastatic melanoma cell lines but not in 3/3 metastatic melanoma specimens. Surprisingly, p16 deletions were also detected in 8/8 benign compound nevi and in 1/3 normal human melanocyte isolates. To investigate whether these deletions in benign and malignant stages of the human melanocytic system were specific for p16, we analysed the same specimens and cell lines for expression of p21, another cyclin-dependent kinase inhibitor and potential tumor suppressor. In contrast to p16, expression of p21 was detected in 3/3 melanocytes, in 3/3 benign nevi, and in greater than 50% of malignant melanoma cell lines and specimens. Finally, because of the recently documented inverse relationship between expression of p16 and pRb protein in a variety of tumor cell lines, we analysed some of the p16-positive and negative melanoma cell lines for the presence of pRb protein. The results demonstrated pRb protein in each of these cell lines. Taken together, although this study revealed deletions of the p16 gene in a significant number of sporadic primary and metastatic melanoma cell lines, they were also detected in benign nevus specimens and in some normal human melanocyte isolates. Thus, these findings cast some doubt on the role of this gene as being causal to the onset and progression of human melanoma, in particular, sporadic melanoma.
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PMID:Differential expression of the cyclin-dependent kinase inhibitors p16 and p21 in the human melanocytic system. 864 98

Integrin alpha 2 beta 1 is a transmembrane protein receptor for collagen and laminin previously reported as a melanoma tumor progression antigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta 1-integrin chain of alpha 2 beta 1. In vitro, both alpha 2 beta 1 and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line motility (measured as mean migration rates), correlates with metastasis. To determine the in situ distribution of these proteins, we used monoclonal antibodies directed against the alpha 2-integrin subunit of alpha 2 beta 1 and alpha-actinin on frozen sections of 33 melanocytic proliferations, which included dermal nevi, primary melanomas, and metastatic melanomas. We found that the superficial portion of all of the melanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of staining for alpha-actinin in the cells in the deep reticular dermis. In contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha 2 beta 1; the expression of this protein correlated with the later stages of melanoma progression. Our findings suggest that alpha-actinin protein levels initially decrease and then increase during melanocytic tumor progression, whereas the alpha 2 subunit protein appears in the later stages of melanoma progression. The variable distribution of these proteins is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations.
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PMID:In situ distribution of integrin alpha 2 beta 1 and alpha-actinin in melanocytic proliferations. 887 27

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.
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PMID:CD40 is a prognostic marker in primary cutaneous malignant melanoma. 895 30

CD44 is an integral membrane glycoprotein that is a principal receptor for hyaluronan and plays a role in cell-extracellular matrix interactions. Recent studies of melanomas in mouse models have suggested that increased CD44 expression by these tumors may relate to metastatic potential. Immunohistochemical expression of CD44 (standard [s] and variant [v6]) in benign and malignant nevomelanocytic lesions was assessed in formalin-fixed, paraffin-embedded tissue and was correlated with histological parameters and prognostic factors. Cases included benign nevi (three junctional, four compound, five intradermal, five blue, six Spitz, one deep penetrating), architecturally disordered (dysplastic) nevi (three, and primary (22) and metastatic melanomas (eight). All of the benign lesions showed diffuse and essentially uniform membrane staining of CD44s in nevomelanocytic cells, regardless of lesion size, depth, or extent of dermal involvement. In contrast, semiquantitative analysis (0 to 3+) of the primary melanomas showed heterogeneous and decreased staining of CD44s, which inversely correlated with lesion size (-0.569) and depth of invasion (-0.622 and -0.617 for Breslow's depth and Clark's level, respectively). These results were significant at P < .05. CD44s expression in metastases paralleled that of their respective primaries. None of the benign nevomelanocytic lesions showed CD44v6 staining. In contrast, all of the malignant nevomelanocytic lesions showed cytoplasmic staining of the tumor cells. Pretreatment with chondroitinase did not alter CD44s staining. CD44s expression by immunohistochemical determination is uniform in benign nevomelanocytic lesions. Malignant melanomas show decreased, heterogeneous staining that inversely correlates with increasing size, depth, and level of invasion. CD44 expression may be a prognostic indicator in malignant melanomas. Tumor staining with anti-chondroitin sulfate monoclonal antibodies suggests that CD44s may be expressed as a chondroitin sulfate proteoglycan in primary melanomas.
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PMID:CD44 expression in benign and malignant nevomelanocytic lesions. 895

Atypical (dysplastic) nevi are melanocytic lesions, which are precursors of melanoma as well as markers of increased melanoma risk. Although these lesions exhibit distinct clinical and histological features, their molecular features are largely unknown. To determine whether atypical, compared to benign nevi, from patients with a clinical history of malignant melanoma reveal molecular changes, we analyzed these lesions for the expression of two growth factors (basic fibroblast growth factor and transforming growth factor alpha), their receptors (fibroblast growth factor receptor-1 and epidermal growth factor receptor), and two cell adhesion molecules (MUC18 and alpha v beta 3 integrin), all of which are expressed in primary and metastatic melanomas. The results demonstrated a statistically significant correlation (P = 0.02) between increasing degrees of histological atypia and expression of epidermal growth factor receptor in the epidermal keratinocytes of atypical melanocytic lesions. Furthermore, both atypical and benign nevi revealed considerably high levels of overall gene activity in their dermal melanocytic and epidermal keratinocytic compartments. In contrast, the epidermal-dermal junction wherein melanoma evolves showed little gene activity, suggesting that molecular events occurring adjacent to this junction may be important for melanocytic transformation.
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PMID:Molecular analysis of melanoma precursor lesions. 895 42

The diagnosis of malignant melanoma requires clinical recognition of suspect lesions, biopsy, and histologic examination. Histological features which serve to distinguish malignant melanoma from their benign counterparts can be found in both the epidermis and dermis. The intraepidermal component of a common acquired nevus usually consists of more or less uniform theques of melanocytes located at or near the tips of rete ridges. Most melanomas are characterized by less orderly intraepidermal growth with areas in which melanocytes lose their nesting characteristics and are distributed more diffusely, sometimes replacing the basal keratinocytes by confluent growth and sometimes by invading upwards either as single cells or small nests into the upper reaches of the epidermis. Nested melanocytes can be found along the basal layer in malignant melanoma, but these nests are usually quite variable in size and location with respect to the tips of the rete ridges, and they are often irregularly distributed along the breadth of the lesion. The dermal component of malignant melanoma usually shows little tendency towards maturation, unlike that of benign nevi. Mitotic figures are unusual to find in the dermal component of common acquired nevi. When they are present, the possibility of melanoma should be considered. Other cytological features can also be useful in the diagnosis of malignant melanoma, particularly when there is marked cytological atypia; however, in some lesions, the cytological changes are not so pronounced and correct diagnosis depends on evaluation of growth pattern. While distinguishing between melanoma and atypical moles can be difficult, problems also arise in distinguishing melanoma from other neoplastic processes. The most common differential diagnosis includes melanoma, paget's disease, and pagetoid Bowen's disease. Desmoplastic melanoma is frequently difficult to distinguish from spindle cell squamous cell carcinoma and atypical fibroxanthoma. Histochemical and immunocytochemical stains are useful in resolving these problems. The pathology report of a melanoma should include the diagnosis, the maximum thickness of the tumor, the adequacy of the surgical margins (if the lesion has been excised), the presence or absence of ulceration, tumor regression, angiolymphatic invasion, and satellitosis. The inclusion of patients in treatment protocols may require additional information such as the host response of tumor-infiltrating lymphocytes, mitotic index, and Clark's level of invasion.
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PMID:Melanoma: criteria for histological diagnosis and its reporting. 897 May 88


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