Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions. Comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis

OBJECTIVE: To compare the reliability of a new 7-point checklist based on simplified epiluminescence microscopy (ELM) pattern analysis with the ABCD rule of dermatoscopy and standard pattern analysis for the diagnosis of clinically doubtful melanocytic skin lesions. DESIGN: In a blind study, ELM images of 342 histologically proven melanocytic skin lesions were evaluated for the presence of 7 standard criteria that we called the "ELM 7-point checklist." For each lesion, "overall" and "ABCD scored" diagnoses were recorded. From a training set of 57 melanomas and 139 atypical nonmelanomas, odds ratios were calculated to create a simple diagnostic model based on identification of major and minor criteria for the "7-point scored" diagnosis. A test set of 60 melanomas and 86 atypical nonmelanomas was used for model validation and was then presented to 2 less experienced ELM observers, who recorded the ABCD and 7-point scored diagnoses. SETTINGS: University medical centers. PATIENTS: A sample of patients with excised melanocytic lesions. MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the models for diagnosing melanoma. RESULTS: From the total combined sets, the 7-point checklist gave a sensitivity of 95% and a sepcificity of 75% compared with 85% sensitivity and 66% specificity using the ABCD rule and 91% sensitivity and 90% specificity using standard pattern analysis (overall ELM diagnosis). Compared with the ABCD rule, the 7-point method allowed less experienced observers to obtain higher diagnostic accuracy values. CONCLUSIONS: The ELM 7-point checklist provides a simplification of standard pattern analysis because of the low number of features to identify and the scoring diagnostic system. As with the ABCD rule, it can be easily learned and easily applied and has proven to be reliable in diagnosing melanoma.     

Quantification of vascularity in nodular melanoma and Spitz's nevus

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity. The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi. In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europaeus agglutinin I-stained sections by computer-assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD +/-5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD +/-3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85x10-4mm2, SD +/-10.32; nodular melanomas: 7.88x10-4mm2, SD +/-5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling). Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas. Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.     

Melanocytic nevi and risk of cutaneous malignant melanoma in southern Spain

The main objective of this study was to assess whether cutaneous malignant melanoma (CMM) shows a stronger relation with the melanocytic nevi count at the site where CMM was diagnosed than with the melanocytic nevi count at other sites, stratifying by histologic CMM type, in a southern Mediterranean population. Cases and controls were selected from a population in southern Spain in 1988-1993. The study population included 116 incident cases with non-familial CMM (International Classification of Diseases 9th Revision (ICD-9) code 172), and 116 controls matched 1:1 for sex and age (+/- 4 years). Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface by clinical skin examination performed by a dermatologist. Crude and multiple risk factor-adjusted odds ratios and 95% confidence intervals were computed by conditional logistic regression analysis. After adjustment by skin type, unexposed skin color, and sun exposure, CMM was found to occur significantly more frequently in individuals with a high number of melanocytic nevi at the same site where CMM originated (odds ratio (OR) for >8 nevi = 12.0, 95% confidence interval (CI) 1.3-108.2). The ability to predict the number of melanocytic nevi on different anatomic sites on CMM, but excluding the CMM cases on each corresponding site, was also examined. A significant trend with the number of nevi on the anterior surface of thighs was found (OR for >4 nevi = 4.5, 95% CI 1.4-14.9). Melanocytic nevi count on the melanoma site was the variable most closely related to superficial spreading melanoma subtype (SSM) (OR for >8 nevi = 82.19, 95% CI 2.72-2,454). On the other hand, the number of melanocytic nevi on the melanoma site was unrelated to risk of CMM subtypes other than SSM. These results support the hypothesis that nevi are an important risk factor for melanoma, especially SSM, in populations with a darker ethnic background.     

Effect of Pichia anomala killer toxin on Candida albicans

BACKGROUND: An acral lentiginous melanoma in situ on the sole is often difficult to differentiate with the naked eye from an acquired plantar melanocytic nevus. Recent technical advances in epiluminescence microscopy have contributed to the differentiation of these two pigmented skin lesions. OBJECTIVE: In this study, the correlation between dermatoscopic and histopathologic findings of acral lentiginous melanoma in situ on the sole are compared to those of acquired plantar melanocytic nevi. METHODS: Three acral lentiginous melanomas in situ on the sole, and two cases of acral lentiginous melanoma were compared with 50 acquired plantar melanocytic nevi by means of dermatoscopy and histopathology. Results: The dermatoscopic surface profiles of acquired melanocytic nevi were composed of linear pigmentation accentuated mainly on the sulcus superficialis. Histologically, some areas of the sulcus superficialis corresponded to rete ridges of the epidermis, and nests of nevus cells were also often located there. In contrast, the acral lentiginous melanomas in situ showed diffuse, irregularly shaped pigmentation distributed in a disorderly fashion over the entire surface. Histologically, isolated areas of proliferation and small nest formations of atypical melanocytes were irregularly distributed in the epidermis. CONCLUSION: A distinctive dermatoscopic feature of acral lentiginous melanoma in situ is diffuse and irregular pigmentation over the entire surface of the lesion. This feature is helpful for differentiating acral lentiginous melanoma in situ from acquired plantar melanocytic nevi.     

Associated factors in the prevalence of more than 50 common melanocytic nevi, atypical melanocytic nevi, and actinic lentigines: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society

Several case-control studies identified common and atypical melanocytic nevi as major risk indicators for the development of cutaneous melanoma. The present investigation was planned to detect factors associated with the prevalence of these melanoma risk markers. Whole-body examination findings and interview data of 513 melanoma patients and 498 age- and sex-matched control subjects were analyzed. Existence of more than 50 common melanocytic nevi and the presence of atypical melanocytic nevi were significantly related to age and gender, with significantly elevated relative risk for their prevalence before the age of 60 and in males. Additionally, sunburns before the age of 20 were significantly associated with both more than 50 common melanocytic nevi (relative risk = 1.7) and the presence of atypical melanocytic nevi (relative risk = 1.5). Actinic lentigines were found more frequently with increasing age, and the presence of actinic lentigines was significantly related to a tendency of freckling in adolescence (relative risk = 2.0) and to two or more sunburns after the age of 20 (relative risk = 1.6). In conclusion, sunburns before the age of 20 contribute to the development of multiple melanocytic nevi and atypical melanocytic nevi. In adulthood, this type of sun exposure is associated with the development of actinic lentigines. The relative risk of developing cutaneous melanoma increases in association with the development of these benign melanocytic lesions.     

Increase of melanocytic nevus counts in children during 5 years of follow-up and analysis of associated factors

OBJECTIVES: To investigate nevus development in childhood and to examine causative related factors such as pigment phenotype and the role of sun exposure in the development of melanocytic nevi. DESIGN AND PARTICIPANTS: Nevus counts were performed in kindergarteners (n = 866) before the age of 7 years and again 5 years later (n = 377). Eligible for analysis were 357 children who were examined twice. Possible related factors were searched for by standardized interviews with parents. RESULTS: The mean number of nevi measuring 1 mm or more was 9 in the first examination and the number measuring 2 mm or more, 4. Five years later, the mean number of nevi measuring 1 mm or more was 40 and the number measuring 2 mm or more was 16. Children with poor sun tolerance had statistically significant more nevi (relative risk, 3.7;95% confidence interval, 1.9-7.2). The presence of freckles was a strong predictor for a high increase of melanocytic nevi (relative risk, 2.1; 95% confidence interval, 1.3-3.3). The number of days per year with intensive solar exposure was an independent prognostic factor. The relative risk for the development of melanocytic nevi was increased by a factor of 1.6 in children who had more than 21 days of intensive sun exposure per year (95% confidence interval, 1.0-2.5). CONCLUSION: The development of melanocytic nevi in childhood is strongly related to characteristics of pigmentation associated with poor sun tolerance. In addition, we found evidence for the influence of UV radiation on the number of acquired melanocytic nevi in childhood.     

Survival and histopathologic characteristics of human melanocytic nevi transplanted to athymic (nude) mice

Melanocytic nevi (n = 406) covering a range of sizes and gross morphologic features were excised from human donors, sampled for histologic diagnosis, and transplanted to athymic (nude) mice. Ninety percent of these xenografts survived transplantation, of which a subset was irradiated daily with ultraviolet light to promote neoplastic transformation. Over 16 weeks of observation, nearly all grafts histologically showed focal inflammatory cell infiltration and fibrosis, progressing in approximately 30% of grafts to complete regression at final observation. During the inflammatory phase, the nevi often had junctional intraepidermal melanocytic hyperplasia in a lentiginous pattern, with cytologic hypertrophy, dendritic morphology, and hypermelaninization. These changes were evident in approximately 20-30% of nevi where they were absent before transplantation, suggesting that host factors, such as those related to the immune response, had stimulated growth. Graft survival was independent of nevus size and initial histologic diagnosis. No melanomas developed in any of the grafts, either spontaneously or with ultraviolet irradiation. These results indicate that successful transplantation can be achieved in a high proportion of human nevus xenografts and that the majority survive for a period of time that would be sufficient for experimental studies. The host response, however, has effects on intraepidermal melanocytic growth that lead to progressive fibrous replacement of the nevus, introducing significant artifacts that compromise the model. Furthermore, malignant transformation of engrafted melanocytes seems to be a rare event, which would limit studies of neoplastic progression in the transplanted melanocytes. Nonetheless, the intraepidermal melanocytic pattern described here evidently constitutes one pattern of melanocyte growth that could be exploited experimentally for studies of growth and differentiation control in melanocytes.     

Adhesion molecule expression in normal skin and melanocytic lesions. Role of UV-irradiation and architectural characteristics in nevi

Cell adhesion between surfaces of cells and to extracellular matrices represents a fundamental mechanism in tissue organization and influences the biological behaviour and the architecture of tumors. We investigated the expression of various adhesion molecules in normal skin (n=5), nevi (n=29), and malignant melanoma (n=10) by immunohistochemistry. Special attention was paid to the correlation between adhesion molecule expression and the respective architectural features, e.g. UV-induced morphological changes, and the arrangement of melanocytes in congenital nevi. In nevi, a single erythemagenic dose of UV-light did not influence the integrin expression of melanocytes, but results in an upregulation of alpha3 beta1- and alpha6 beta1-integrin within the suprabasal layers of the epidermis. This suprabasal labelling was associated with an increased number of suprabasal melanocytes in UV-irradiated nevi which were detected with HMB-45 antibody. Nine of 10 congenital nevi demonstrated a labelling of alpha4 beta1-integrin only in melanocytes of the deeper dermis. This integrin previously has been associated with high tumor thickness and the clinical outcome in melanomas. The integrin profile observed in melanomas differed in part from that seen in nevi with expression of beta2- and beta3-integrins in some cases. The results may indicate a correlation between adhesion molecule expression and histopathological findings in melanocytic lesions.     

Interobserver concordance in discriminating clinical atypia of melanocytic nevi, and correlations with histologic atypia

BACKGROUND: The clinical features attributed to atypical (formerly ?dysplastic") nevi and to the atypical multiple mole melanoma syndrome have been used in clinical practice, as well as experimentally, to assign melanoma risk. Little information is available, however, on the interobserver reliability in assessing those features. OBJECTIVE: Our purposes were to quantify interobserver and intraobserver concordances in recognizing certain atypical characteristics of nevi and to correlate the clinical assessments with the histologic characteristics. METHODS: Three observers evaluated clinical photographs of 100 pigmented lesions (predominantly melanocytic nevi, with some lentigines and seborrheic keratoses) from 95 subjects, of whom 85 were family members of four multiple melanoma kindreds and 10 were spouses. Each lesion was rated for border irregularity, color variegation, surface contour irregularity, pigment diffusion, and macularity versus papularity. Predictions were made as to the histologic diagnoses and presence of melanocytic atypia for those lesions judged to be nevi. RESULTS: The pair-wise concordances before agreement on specific criteria were quantified by kappa statistics, which indicated slight to fair agreement in judging the atypical clinical characteristics; concordances increased to moderate levels after consensus development of criteria for color variegation and assessment of macularity, but agreement on the other features remained limited. Whereas macularity and color variegation did correlate somewhat with higher grades of histologic atypia, correlations were generally low between the clinical and histologic diagnoses. CONCLUSION: There is limited interobserver reliability in the clinical assessment of nevus atypia, although correlations do exist between some atypical characteristics and grades of histologic atypia. Because of the low concordances, the clinical discrimination of the melanoma-associated atypical nevus phenotype should rely more on quantitative aspects of the trait, such as total numbers or maximal sizes of nevi, rather than on the subjective determinations of atypia.     

Pluripotential melanoblastoma, a unifying concept on malignancies arising in congenital melanocytic nevi: report of two cases

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.     

Nucleolar organizer regions in conjunctival nevi and melanomata

The objective of this study was to compare the argyrophil nucleolar organizer region (Ag-NOR) counts of conjunctival nevi and melanomata and to compare the efficacy of this method in their differential diagnosis. Nine histologically diagnosed conjunctival nevi and three conjunctival malignant melanomas were studied. Representative sections were stained using the AgNOR technique. Fifty cells of each melanocytic lesion were randomly selected without knowing their histologic diagnosis. The AgNORs were visualized at a magnification of x1000. They consisted of clusters >1 micron in diameter and of satellites <1 micron in diameter, which were counted and recorded for each cell separately. The mean AgNOR count for the nevi was 1.12 clusters and 1.72 satellites per cell, while the count for the melanomas was 1.6 clusters and 6.8 satellites per cell. These results are statistically significant. There was no overlap between the number of AgNOR clusters and satellites in conjunctival nevi and melanomas, indicating that the AgNOR count might be a useful tool in distinguishing benign from malignant conjunctival melanocytic lesions.     

The augmentation of melanocytic nevi in guinea pigs by solar-simulated light: an animal model for human melanocytic nevi

Strong epidemiological evidence confirms the role of sunlight in human melanoma induction. Furthermore, the frequency of melanocytic nevi is a good indicator of future development of melanoma and a short-term marker of adverse reactions to melanoma-inducing sun exposure in humans. Thus, the aim of this study was to develop and define an animal model for sunlight-induced nevi that can be used as a surrogate model for sunlight-induced melanoma. Five treatment groups of 30-40 Hartley albino guinea pigs/group were treated with topical 7,12-dimethylbenzanthracene at a dose range of 6-240 mg on the dorsum of the skin. At week 20, half of the animals in each group were given a 12-month regimen of minimal erythemal solar-simulated light, 3 times/week, increased weekly to maintain erythema. These regimes induced epidermally derived pigmented melanocytic nevi clinically and histologically similar to human nevi (junctional, compound, and dermal). S100 and HMB45 staining was also consistent with the patterns seen in human nevi. In contrast to the high-dose 7,12-dimethylbenzanthracene-treated animals (60 and 240 mg), where solar-simulated light had no effect on nevi multiplicity, those groups treated with low doses (24, 12, and 6 mg) had a significant increase in nevi multiplicity after 12 months of solar-simulated light treatment (24 mg, 0.5 nevi/animal unirradiated versus 1.4 nevi/animal irradiated, P = 0.03; 12 mg, 0.2 unirradiated versus 1.2 irradiated, P = 0.02; 6 mg, 0 unirradiated versus 1.9 irradiated, P = 0.008). UVB-induced minimal erythemal dose was unaltered after exposure to photoreactivating light, consistent with the observation of others that placental mammals lack the DNA photolyase responsible for strong photoreactivation seen in nonplacental mammals and lower metazoans. Thus, our guinea pig model has some of the essential elements required to be a robust animal model for human nevi and a surrogate model for melanoma. These nevi are augmented by solar-simulated light, are histologically similar, occupy the same level within the skin, have the same natural history as human nevi, and are produced in an animal lacking strong photoreactivation. These features are not found in any previously described small laboratory animal model.     

Prognostic significance of allelic losses in primary melanoma

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each significantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041).     

Dynamics of cell-associated viremia and antibody response during the early phase of lentivirus infection in sheep

OBJECTIVE: To investigate the characteristic epiluminescent microscopic features of early lesions of malignant melanoma affecting glabrous skin, which is the most prevalent site of the neoplasm in nonwhite populations. DESIGN: The epiluminescent microscopic features of various kinds of melanocytic lesions affecting glabrous skin were investigated using a videomicroscope. All the diagnoses were determined clinically and histopathologically using the standard criteria. SETTING: A dermatology clinic at a university hospital. PATIENTS: The following 130 melanocytic lesions consecutively diagnosed at our department were examined: 16 lesions of acral lentiginous melanoma, 6 lesions of malignant melanoma in situ, and 108 lesions of benign melanocytic nevus (acquired or congenital). MAIN OUTCOME MEASURE: The incidence of each characteristic epiluminescent feature was compared among disease categories. RESULTS: On epiluminescent microscopy, malignant melanoma in situ and the macular portions of invasive malignant melanoma showed accentuated pigmentation on the ridges of the skin markings, which are arranged in parallel patterns on glabrous skin. This "parallel ridge pattern" was found in 5 (83%) of 6 lesions of malignant melanoma in situ and in 15 (94%) of 16 lesions of malignant melanoma. The parallel ridge pattern was rarely found in the lesions of benign melanocytic nevus. Most benign melanocytic nevi showed 1 of the following 3 typical epiluminescent patterns: (1) a parallel furrow pattern exhibiting pigmentation on the parallel sulci of [he skin markings (54%), (2) a latticelike pattern (21%), and (3) a fibrillar pattern showing filamentous or meshlike pigmentation (15%). The remaining 11 benign nevi (10%) showed a nontypical pattern. CONCLUSION: Because epiluminescent microscopic features of early malignant melanoma on glabrous skin are characteristic, we can effectively detect early lesions using this noninvasive method.     

Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions

In recent years, it has become evident that T cells can recognize peptides of melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor cell surface and can subsequently destroy these cells. It is thus feasible to develop immunotherapeutic approaches based on the melanocytic marker profiles of melanoma cells. One of the predictors of the success rate of such a treatment is the extent of positive (target) tumor cells within the lesions of the patient. First, we investigated the presence of these three proteins in 18 human melanoma cell lines using RT-PCR and immunohistochemistry. In 11 cell lines, mRNA and protein of all three markers could be detected; in one cell line, only two markers were present, and six melanoma cell lines showed no evidence for these markers. Secondly, we stained frozen sections of 105 human melanocytic lesions, 13 common nevocellular nevi, 13 atypical nevi, 13 early primary melanomas (Breslow < 1.5 mm), 25 advanced primary melanomas (aPM; Breslow > or =1.5 mm), and 41 melanoma metastases (MM) with antibodies against glycoprotein 100, melanoma antigen recognized by T cells, and tyrosinase. In addition, we used the 3,4-dihydroxy-L-phenylalanine reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results in a subset of the lesions. In the benign lesions, glycoprotein 100 was more prominently expressed in epidermal melanocytes, whereas melanoma antigen recognized by T cells was encountered in all or nearly all dermal melanocytes in all nevocellular nevi and atypical nevus lesions. Tyrosinase was found in a lower percentage of melanocytes, both in the epidermis and in the dermis within these lesions. With regard to heterogeneity of staining within the malignant lesions, we found that 54% (early primary melanomas), 48% (aPMs), and 56% (MM) of the lesions stained within the same staining category for all three proteins studied. Approximately 17% of the aPM and MM lesions did not show positive tumor cells for any of the three proteins. We conclude that a subgroup of patients with high expression should be selected for immunotherapeutic treatment approaches based on the presence of these proteins.     

Focal segmental glomerulosclerosis in children with acute lymphocytic leukemia: case reports and review of literature

In a randomised double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicilic acid daily (ASA, CAS 50-78-2) has been evaluated in the presence of placebo (n = 8), 40 mg pantoprazole (CAS 102625-70-7) daily (8 a.m.) (n = 16) and 300 mg ranitidine (CAS 66357-35-5) daily (8 a.m.) (n = 16) in healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days, endoscopic controls were performed at entry and repeated at day 14. At entry, the mean endoscopic score averaged 1.0 +/- 0.0 (+/- SEM) in the ASA/placebo, in the ASA/pantoprazole and the ASA/ranitidine group. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (lesion score of 6.8 +/- 1.4 (+/- SEM). Concomitant administration of 40 mg pantoprazole daily offered significant protection against 300 mg ASS daily on day 14 (2.1 +/- 0.6) (+/- SEM) (p < 0.05) vs ASA/placebo. 300 mg ASA plus 300 mg ranitidine daily reduced the damaging score to 4.9 +/- 1.2 (+/- SEM) (n.s. vs ASA/ placebo). Our data suggest that coadministration of 40 mg pantoprazole daily reduces significantly gastroduodenal lesions evoked by 300 mg ASA daily.     

Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression

The c-kit gene encodes a transmembrane receptor that has tyrosine kinase activity. c-kit plays a role in hematopoiesis, gametogenesis, and melanogenesis. c-kit is found in melanocytes, and there is evidence that expression is lost in melanoma. We studied 85 melanocytic lesions for c-kit by immunohistochemical techniques using a monoclonal antibody. The lesions included banal nevi, junctional and compound nevi with melanocytic dysplasia, nontumorigenic radial growth phase melanoma, tumorigenic vertical growth phase melanoma, and metastatic melanoma. We found intense membrane staining in normal melanocytes and mast cells. Staining in compound nevi was strongest in junctional and superficial dermal components, whereas dermal nevi showed weak reactivity. Dysplastic nevi stained strongly, particularly in junctional cells. In melanoma, strong reactivity was most prominent in radial growth phase disease, but there was little or no staining in vertical growth phase and metastatic melanomas. In summary, c-kit protein is expressed in normal melanocytes, benign nevi, dysplastic nevi and nontumorigenic melanoma, but expression is lost in tumorigenic primary melanomas and metastases. The role of c-kit loss in advanced melanoma requires additional investigation.     

Vitamin D prophylaxis in children with a single dose of 150000 IU of vitamin D

INTRODUCTION: Blue nevi are small acquired melanocytic tumors. Two clinical forms are described, a fibrous form and a cellular form. Giant nevi are exceptional. CASE REPORT: We describe a patient with a giant blue nevus of the scalp. In addition to this congenital, noninvasive tumor the patient presented numerous cutaneous melanocytic nevi. The main lesion was removed by surgical exeresis followed later with reconstruction plasty. The histological examination of the surgical specimen showed an infiltrating blue cell nevi. After a 4-year follow-up, there has been no recurrence and no metastasis. DISCUSSION: There have been 11 cases of giant blue nevi reported in the literature. All were congenital lesions with polymorphous clinical and histological aspects. Fibrous forms are noninvasive and cellular forms have a potential for local invasion, whether shortly after birth or later with invasion of muscles, bone and meninges without intracerebral extension. Congenital blue nevi require early surgical exeresis.     

Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience

PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.