Intraepidermal distribution patterns of melanocytes in the melanocytic lesions on the sole: proposed criteria for histopathologic diagnosis of plantar malignant melanoma in situ

Eighty-eight melanocytic lesions on the soles of Japanese were histologically investigated. Increased numbers of solitary melanocytes above the basal layer of the epidermis were often found in the benign melanocytic nevi on the sole: in 5 lesions of 9 congenital melanocytic nevi, 22 of 65 acquired melanocytic nevi, and 1 of 5 dysplastic nevi. In addition, a moderate degree of nuclear atypia of proliferating melanocytes was frequently observed in the benign melanocytic nevi on the sole: in 3 lesions of 9 congenital melanocytic nevi, 17 of 65 acquired melanocytic nevi, and 2 of 5 dysplastic nevi. Therefore it cannot be said that increased numbers of solitary atypical melanocytes above the basal layer is a characteristic histologic feature of early malignant melanoma in situ. Combining the intraepidermal distribution patterns of melanocytes and maximum diameter of the lesion, we propose criteria for histopathologic diagnosis of plantar malignant melanoma in situ.     

Relation of maximum diameters of plantar malignant melanoma to various prognostic factors and prognosis of patients

The following factors were investigated in 43 cases of plantar malignant melanoma: maximum diameters of primary lesions, Clark's subtypes, clinical stages, UICC's stages, Clark's levels of invasion, Breslow's tumor thickness, and prognosis of patients. Relation of maximum diameter of primary lesions to various prognostic factors and prognosis of the patients was analysed. It was revealed that there were no statistically significant relationships between maximum diameters and other various factors. In our series, however, all patients with plantar malignant melanoma less than 14 mm in diameter are alive without metastasis. Judging from our previous and present studies, the following two points are the most important for improving the prognosis of patients with plantar malignant melanoma: 1) Catching all pigmented lesions on the sole that are more than 7 mm in diameter and examining them histologically, if they have no possibility of being congenital melanocytic nevus or black heel. 2) Treating plantar malignant melanomas adequately before they become 14 mm in maximum diameter.     

The differential diagnosis of intraepidermal malignant lesions using immunohistochemistry

The malignant intraepithelial proliferations--malignant melanoma level I, bowenoid epithelial dysplasia, and mammary as well as extramammary Paget's disease--may cause differential diagnostic difficulties. We have examined 12 cases of malignant melanoma level I, nine cases of bowenoid epithelial dysplasia, 17 cases of extramammary and five cases of mammary Paget's disease for S100 protein, carcinoembryonic antigen (CEA), cytokeratin, and keratin to evaluate the sensitivity and specificity of these reactions with regard to their differential diagnostic value. Antibodies against S100 reacted specifically with the tumor cells in intraepithelial malignant melanomas; antibodies against CEA reacted specifically with the tumor cells in Paget's disease; and cytokeratin and keratin antibodies reacted with the epithelial tumor cells in Paget's disease as well as in bowenoid epithelial dysplasia. However, only antibodies to CEA and keratin showed 100% sensitivity. We conclude that the investigated antibodies may be of differential diagnostic value in cases of intraepidermal neoplasias, but that a negative reaction does not exclude diagnosis of these diseases.     

Reliability of the histopathologic diagnosis of malignant melanoma in childhood

OBJECTIVE: To assess interrater reliability in the diagnosis of malignant melanoma in children. DESIGN, SETTING, AND PARTICIPANTS: We collected 85 slides of melanomas diagnosed in patients younger than 17 years through a network of dermatopathologists and dermatologists. The slides were classified into 3 categories: (1) slides from children with metastatic melanoma; (2) slides from disease-free children with a follow-up of less than 5 years; (3) slides from disease-free children with a follow-up of 5 years or longer. Category 1 was considered the gold standard. Four pairs of expert dermatopathologists reviewed the slides and classified them into melanoma, nevus (including Spitz nevus), or ambiguous tumors. INTERVENTION: None. MAIN OUTCOME MEASURE: Concordance between pairs of experts. RESULTS: For category 1 slides (n = 20), the concordance was weak to moderate. For category 2 slides (n = 47), the concordance was weak. For category 3 slides (n = 18), the concordance was poor to moderate. CONCLUSION: This study demonstrates that the reliability of diagnosis of melanoma in childhood is poor, even when submitted to experts.     

Clinical guidelines for the early detection of plantar malignant melanoma

Of 144 pigmented lesions excised from the soles of Japanese patients, 140 were melanocytic. Apart from congenital melanocytic nevi, only a few benign acquired melanocytic nevi on the sole were more than 7 mm in maximum diameter and none exceeded 9 mm. In contrast, all plantar malignant melanomas, including malignant melanoma in situ, were 9 mm or more in maximum diameter. In addition, the majority of plantar melanocytic lesions excised from patients who were older than 50 years of age were malignant melanoma. On the basis of these data, we propose clinical guidelines for the early detection of plantar malignant melanoma.     

Pigmented breast carcinoma. A clinical and histopathologic simulator of malignant melanoma

A case of infiltrating breast carcinoma presenting as a pigmented lesion of the areola and nipple is described. The pigmentation was found to be primarily due to interspersed melanocytes and melanophages within the tumor. The histologic criteria and the differential immunohistochemical staining characteristics of melanoma and breast carcinoma are presented. Also emphasized is the difficulty in differentiating pagetoid malignant melanoma and epidermotrophic breast carcinoma.     

Angiotensin-induced hypertension and chemotherapy for multiple lesions of malignant melanoma

By continuous infusion of angiotensin II, a marked increase in blood flow can be induced in tumour tissues, with no increase in normal tissues. This functional characteristic of tumour blood vessels, i.e., lack of autoregulation, has been utilized as an aid to chemotherapy by selectively enhancing drug delivery to tumour tissues. We describe our results in seven patients with malignant melanoma.     

The seven features for melanoma: a new dermoscopic algorithm for the diagnosis of malignant melanoma.

The clinical diagnosis of melanoma has a mean sensitivity of 67%, dermoscopy or dermatoscopy is a non invasive technique which improves this sensitivity. Our purpose was to create a simple dermoscopic method for the diagnosis of melanoma useful in daily office practice. For this reason a training set of 218 cutaneous pigmented lesions was used and scored for 16 dermoscopic features: for each feature sensitivity, specificity and statistical significance were evaluated. The results were used to create a simple dermoscopic diagnostic method of only seven dermoscopic features (7FFM). The method was used to evaluate a test set of 713 pigmented skin lesions consecutively observed. The diagnostic dermoscopic method developed gave a sensitivity of 94.6%, a specificity of 85.5% and an efficiency of 87.6%. Our method improves the sensitivity in the diagnosis of melanoma and can be used for the screening of pigmented skin lesions.     

Role of zyxin in differential cell spreading and proliferation of melanoma cells and melanocytes

Cell spreading, proliferation, and survival are modulated by focal adhesions linking extracellular matrix proteins, integrins, and the cytoskeleton. Zyxin is a focal-adhesion-associated phosphoprotein with one domain involved in the control of actin assembly and three protein-protein adapter domains implicated in the regulation of cell growth and differentiation. We characterized zyxin expression in normal human melanocytes and six melanoma cell lines in relation to cell spreading, growth, and differentiation using Western immunoblotting techniques, image analysis, flow cytometry, and confocal microscopy. We found that zyxin, focal adhesion kinase, and paxillin were significantly upregulated in melanoma cells compared to melanocytes. Zyxin expression directly related to cell spreading and proliferation and inversely related to differentiation, whereas focal adhesion kinase correlated only to cell spreading and paxillin did not significantly correlate with any of the parameters. Treatment of melanoma cells with 12-O-tetradecanoylphorbol-13-acetate downregulated zyxin expression, inhibited cell spreading and proliferation, and promoted differentiation. In contrast, 12-O-tetradecanoylphorbol-13-acetate, a mitogen for melanocytes, induced upregulation of zyxin expression in melanocytes. These findings are consistent with a role of zyxin in modulation of cell spreading, proliferation, and differentiation. Therapies directed at the downregulation of this focal adhesion phosphoprotein in melanoma cells implicate a new approach for controlling melanoma cell growth.     

"Compound blue nevus": a reappraisal of "superficial blue nevus with prominent intraepidermal dendritic melanocytes" with emphasis on dermoscopic and histopathologic features.

We describe 5 cases of "compound blue nevus" (CBN) ("superficial blue nevus with prominent intraepidermal dendritic melanocytes," "Kamino nevus"). Dermoscopically in 2 of 4 cases the bluish pigmentation characteristic of blue nevi was centrally replaced by a black lamella, with black dots and brown globules also observed in one case, thus revealing a structural asymmetry suggestive of melanoma. Histopathologically, pigmented parakeratosis was the underlying histopathologic finding of black lamella and dots/globules. Immunohistochemistry highlighted the unique histopathologic feature of CBN, namely, single dendritic melanocytes at the dermoepidermal junction with striking intraepidermal prolongations. Our findings confirm that CBN is a distinctive variant of blue nevus that may mimic cutaneous melanoma both clinically and dermoscopically.     

Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance

Forty-eight malignant melanomas of the extremities, 1 mm or less in maximal thickness, were studied to better define microscopic criteria of regression in thin melanomas. Eleven tumors (23%) exhibited definite regression in the form of one or more segmental areas (defects) where the invasive component was replaced by mononuclear cell infiltrate and fibrosis. Thirteen other tumors (27%) had diffuse, nonsegmental changes classified as probable regression. Nineteen lesions (40%) lacked regression, although 14 of these contained focal evidence of host response. Five melanomas (17% of lesions less than 0.75 mm thick) were equivocal for regression. There were no recurrences or metastases. The histologic diagnosis of regression in thin melanomas requires subjective judgments, but segmental defects represent a potentially reproducible criterion. Their width can be measured, and the proportion of the melanoma that has undergone regression can be estimated. The preponderance of data from the literature, supported by this study, indicates that regression has no prognostic importance in the vast majority of thin melanomas. There are observations, however, to suggest that in rare cases, regression may negate the prognostic value of microstaging of a thin melanoma. To date, the type and extent of such regressive changes have not been adequately defined.     

Six cases of metastatic malignant melanoma with apparently occult primary lesions.

We report here six cases of malignant melanoma in which metastatic lesions were detected first. Of these, two cases showed some peculiar features: one exhibited widespread subcutaneous bleeding, probably due to venous rupture, and the other case had a rare primary lesion on the penis. In the Japanese literature, there have been 46 cases of malignant melanoma in which metastatic lesions were detected prior to the initial ones. The preferential site for metastasis was the lymph node (32 cases). The primary lesion was unknown in 35 patients. The outcomes were available for 36 of the 46 patients; 23 died, including 18 who died within two years.