mart-1-antigen and Dysplastic-Nevus-Syndrome

Dysplastic nevi may occasionally display alarming histological features. One of these features is the presence of upward spread of melanocytes (pagetoid melanocytosis), identified either on routine histologic sections or after immunohistochemistry using one of the melanocytic markers. Forty-three cases of dysplastic nevi with mild to moderate atypia were selected and retrieved, and Melan-A staining was performed. Melan-A-positive cells with pagetoid architecture were present in 27 cases (63%). Of these, only 5 cases demonstrated pagetoid architecture on routine staining. It is concluded that Melan-A staining should be used only with caution as an adjunct to routine histology in the evaluation of dysplastic nevi with mild to moderate atypia because the identification of pagetoid melanocytosis using this technique has the potential to lead to an erroneous diagnosis of melanoma.

Topics: Adolescent; Adult; Aged; Biomarkers; Biopsy; Diagnosis, Differential; Diagnostic Errors; Dysplastic Nevus Syndrome; Female; Humans; Male; MART-1 Antigen; Melanocytes; Middle Aged; Retrospective Studies; Severity of Illness Index; Skin; Young Adult

There is a relationship between sunlight and the development of melanocytic neoplasms. Because the incidence and excision of melanocytic neoplasms varies according to season, we sought to determine if dysplasia and/or intraepidermal melanocytic expression differed in a cohort of dysplastic naevi (DN) removed in January compared with a similar cohort removed in August. The DN were graded based on the degree of dysplasia, and the number of intraepidermal melanocytes were counted after immunohistochemical staining with HMB-45 and Melan-A. There was no seasonal difference in the grading of the dysplastic naevi in either season (P = 0.08). Comparing 85 cases from August and 86 from January, there was a larger number of Melan-A-positive melanocytes in the August samples (P < 0.02), and a larger number of HMB-45-positive melanocytes in January (P < 0.01). This difference may be related to seasonal variations such as exposure to ultraviolet light exposure; however, there was no difference between the two groups in the degree of atypia seen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Child, Preschool; Cohort Studies; Dysplastic Nevus Syndrome; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Middle Aged; Multivariate Analysis; Seasons; Ultraviolet Rays; Young Adult

Regressing nevi are considered an example of an efficient early antitumoral response preventing the development of neoplasia. The underlying mechanism has not been elucidated, although an immune-based destruction of melanocytes is supposed. The aim of this study was to provide evidence of an effective immunosurveillance of pigment lesions in a patient at high risk of melanoma.. A patient with the dysplastic nevus syndrome and a history of melanoma was included in this study. Since 2003, a marked regression of almost all nevi was observed. Immunohistochemistry was performed and the antigen specificity of T-cells was analyzed on T-cells isolated from a regressing nevus by flow cytometry using HLA-A2-peptide tetramers containing Mart-1(26-35), gp100(280-288), gp100(209-217) and tyrosinase(369-377). Immunohistochemistry of the regressing nevi showed a strong infiltrate of CD4 + and CD8 + T-cells. Flow cytometric analyses demonstrated the presence of a CD8 + T-cell response against gp100(280-288) and Mart-1(26-35) both in peripheral blood and in a regressing nevus.. These findings indicate that an immune reaction against melanocyte differentiation antigens can target specifically nevi without signs of vitiligo and suggests that boosting the anti-melanocyte immune response in patients at high risk for melanoma may prevent tumor development at an early stage.

Topics: Blotting, Western; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dysplastic Nevus Syndrome; Flow Cytometry; gp100 Melanoma Antigen; HLA-A2 Antigen; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanocytes; Melanoma; Middle Aged; Monophenol Monooxygenase; Skin Neoplasms; T-Lymphocytes, Cytotoxic; Vitiligo

Recent studies indicate that WT1 and Bcl2 protein are detected in melanocytic lesions of the skin. We examined, for the first time, WT1 and Bcl2 expression in a variety of conjunctival melanocytic lesions to evaluate their diagnostic utility compared with other melanocytic markers.. Protein expression and localization of WT1 and Bcl2 were studied by means of immunolabeling and semiquantification in 123 conjunctival melanocytic lesions (71 benign nevi, 21 atypical nevi, 11 primary acquired melanosis, and 20 malignant melanomas). Ancillary immunohistochemical studies were performed with Bcl2, S100, HMB45, and Melan A antibodies.. WT1 showed a graded increase in expression in lesions with increasing atypia. Higher mean numbers of WT1-positive cells correlated with increasing atypia in melanocytes. In all cases, Bcl2 expression was positive and more robust than was S100, HMB45, or Melan A expression. WT1 and HMB45 frequently showed diffuse and strong staining in atypical nevi, primary acquired melanosis with atypia, and malignant melanomas compared with benign lesions.. Bcl2 is a highly sensitive immunohistochemical marker for melanocytic tumors of the conjunctiva; HMB45 and WT1 staining distinguishes benign from malignant lesions.. Our results show that HMB45 and WT1 immunolabeling is helpful in the evaluation of conjunctival melanocytic lesions. Accordingly, we recommend the development of an immunohistochemical panel to classify these lesions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Child, Preschool; Conjunctival Diseases; Conjunctival Neoplasms; Dysplastic Nevus Syndrome; Female; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Melanosis; Middle Aged; Neoplasm Proteins; Nevus, Pigmented; Proto-Oncogene Proteins c-bcl-2; S100 Proteins; WT1 Proteins; Young Adult

We present two cases of melanoma arising in a dysplastic nevus that contained intradermal sebocyte-like melanocytes characterized by a scalloped dark-staining nucleus surrounded by the pale multivacuolated cytoplasm imitating sebaceous differentiation. Both patients were women, aged 49 and 55 years. Location included the back and temporal area. Microscopically, both cases had the following features in common: the melanoma in situ, which was of the superficially spreading type, was associated with a dysplastic compound nevus, in which the sebocyte-like cells were identified in the intradermal nevus part of the lesion. The sebocyte-like cells comprised a minor component but were immediately recognizable and appeared as cells with multivacuolated neoplasm and scalloped nuclei arranged in nests. Some contained melanin in the cytoplasm. They stained positively for S-100 protein and melan A but were EMA and HMB-45 negative. The conventional part of the nevi demonstrated the same phenotype, with the exception of the melanocytic nests located at the dermoepidermal junction that were HMB-45 positive. The cases are discussed in the context of the pertinent literature.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Dysplastic Nevus Syndrome; Female; Humans; MART-1 Antigen; Melanocytes; Melanoma; Middle Aged; Neoplasm Proteins; Neoplasms, Multiple Primary; S100 Proteins; Sebum; Skin Neoplasms