Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.     

Glycogen content in the liver and skeletal muscles in certain types of experimental nanism

The presence of various types of birthmarks was determined in 1,058 newborn infants under 72 hours of age. Of these, 79.5% were white, 6.2% were black, 11.2% were ladinos, and 2.6% were Asiatic. Mongol spots were present in 9.6% of the white babies, 95.5% of the black babies, 81% of the Asiatic babies, and 70.1% of ladino infants. Pigmented lesions were present in 42 (4%) of the infants. Biopsies obtained in 34 (3.2%) revealed that only one-third (11) of these were melanocytic nevi. Salmon patches were present in 40.3% of the infants, recognizable early strawberry marks in 2.6%, and port-wine strains in 0.3%. In addition to birthmarks, it was determined that 30.3% of the 508 babies examined at one of the two hospitals had toxic erythema of the newborn.     

The active site specificity of the Yersinia protein-tyrosine phosphatase

Previous studies have shown that B700, an albumin-like murine melanoma antigen, has a human homologue termed H700. Polyclonal antibodies to B700 also bind to all cultured human, swine and hamster melanoma cells, suggesting that B700 is a "pan-melanoma" antigen. The objects of this investigation were: (a) to determine if 2-3-3, a monoclonal antibody to B700, can be used to identify human melanomas in formalin-fixed, paraffin-embedded tissues, and (b) to determine the specificity and potential diagnostic value of 2-3-3. Forty-eight of the 49 human melanomas, including spindle melanoma cells, stained positively, as did five of the eight pigmented naevi including cellular spindle naevi. Twenty-six of the 32 human non-melanomatous lesions were negative for 2-3-3 staining (weakly positive on one breast carcinoma and positive on five neural tumours). These results indicate that 2-3-3, a monoclonal antibody to the mouse melanoma antigen B700, can be used to identify H700 in archival specimens. 2-3-3 may have an advantage over HMB45, which is the most commonly used antibody for melanoma diagnosis, because of its immunoreactivity with spindle melanocytic lesions. Antibodies to B700 may prove to be a useful adjunct in the diagnosis of human melanoma and related lesions.     

Ultraviolet exposure and the development of banal and atypical naevi--a cross-sectional study on Cura?ao and in The Netherlands

The atypical naevus is both a risk factor for and a precursor lesion of melanoma. Sunlight is known to be an important aetiological factor for melanoma. Whether solar exposure is also involved in the initiation of (atypical) naevi is an issue of current interest. We performed a cross-sectional study among 270 inhabitants in the cloudy Netherlands and 282 white Dutch immigrants of the tropical island Cura?ao to investigate whether solar exposure plays a role in the development of atypical naevi. All participants were interviewed and underwent total skin examination; banal melanocytic naevi and atypical naevi were counted. There was no significant difference in the mean number of melanocytic naevi > or = 2 mm or > or = 5 mm between Cura?ao and the Netherlands. Furthermore, there was no significant difference in the mean crude and age standardized prevalence of atypical naevi between the Netherlands and Cura?ao. In both groups individuals with atypical naevi had significantly more total naevi. Concerning the role of sun exposure in the development of naevi in the Netherlands, we found that the total naevus count had a significant association with cumulative sun exposure before the age of 12 as well as with two or more painful sunburns before the age of 12. In Cura?ao these relationships were not observed. In contrast, however, on Cura?ao the presence of atypical naevi showed an association (odds ratio = 2.6, 95% confidence interval 1.1-6.0) with the highest level of cumulative sun exposure and with painful sunburns before the age of 12 (odds ratio = 2.6, 95% confidence interval 1.2-5.5). In the Dutch group these associations were not significant. We hypothesize that in the development of banal naevi there is an association between the total number of naevi and sun exposure only at low exposure levels; however, after overstepping a critical threshold a further association between melanocytic naevi and sun exposure is lacking. Sunlight exposure before the age of 12 plays a complex role: only very high exposure levels seem to contribute to the development of atypical naevi.     

Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens

There is debate about the margin of normal tissue that should be included with excisions of melanocytic lesions of the skin, and about which lesions should be referred for specialist care. We describe the determinants of the margins of excised melanocytic skin lesions and of referral patterns from primary care. Copies of the pathology reports of melanocytic skin lesions excised from two cities in tropical Queensland were obtained; questionnaires about each lesion were administered to the excising doctor. Data about 3275 lesions (2914 naevi, 130 lentigos, 151 melanomas, 51 dysplastic naevi, 21 Hutchinson's melanotic freckles and eight other melanocytic lesions) were analysed. Twenty-one per cent of the treatment sessions involved the excision of more than one lesion; 5% involved three lesions or more. Most lesions were managed by one doctor. The overall mean margin of excision was 2.8 mm. It was greater for longer qualified doctors, surgeons and college-affiliated general practitioners, for lesions excised to address malignancy (3.0 mm) rather than cosmetic appearance (2.4 mm), for Hutchinson's melanotic freckles (5.9 mm) and melanomas (5.1 mm) compared with benign lesions (2.7 mm) (P < 0.001) and for older patients (2.6 mm for those < or = 15, 3.5 mm for those > 40 years) (P = 0.001). Wider excisions of skin melanocytic lesions are performed by older and more experienced doctors, on older patients, and for lesions in which malignancy is being addressed.     

"Blue" variant of naevus spilus

We report on a 29-year-old female patient with an unusual pigmented lesion of the face. Clinically the lesion looked like a pigment patch of the naevus spilus type, while histological examination revealed the presence of dermal melanocytosis and multiple common blue naevi with a discrete lentiginous component in addition. The melanocytic nature of the infiltrate was ascertained by immunohistochemistry analysis using S 100 protein and HMB 45 antibodies. We interpret this lesion as agminated blue naevi in association with lentigo simplex, an unusual variant of speckled lentiginous naevus.     

Cytomorphology of adenocarcinoma of lung presenting as submandibular salivary gland mass: report of a case diagnosed by fine-needle aspiration biopsy

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.     

Atypical melanosis of the foot

We present a case of a seemingly malignant pigmented lesion on the foot, arising in a Japanese female. Clinically, the lesion was characterized by irregular borders and variegated pigmentation closely mimicking those of acral lentiginous melanoma in situ. However, the histologic findings revealed only focal, slight, melanocytic hyperplasia with minimal cytologic atypia along the basal layer. Despite the malignant clinical features, thorough histologic examination failed to disclose any area with significant melanocytic atypia or evidence of malignancy. To the best of our knowledge, no similar lesions with the clinical appearance of melanoma in situ and completely lacking histologic evidence of malignancy have been reported. We, therefore, prefer to designate this lesion as atypical melanosis of the foot, to highlight the clinically atypical findings and to distinguish this from malignant melanoma in situ of the foot (1).     

Effects of outcome expectancies and disinhibition on ad lib alcohol consumption

CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target cells. It has recently been reported that melanoma cells in vivo express a significant amount of CD95L, thereby being immediately able to kill CD95-bearing immunocompetent cells specific for cancer antigens, which infiltrate the lesions. In this study, we employed immunohistochemistry using an antibody directed against CD95L to investigate at which stage the melanoma CD95L expression is turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These included benign and dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph node metastases. CD95L was expressed in all of the advance-phase melanomas as well as lymph node metastases of cutaneous origin, whereas neither melanoma in situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To investigate a link between positivity and tumour size, the data were analysed on the basis of Breslow thickness, and indicated that expression was observed only when tumours were thicker than 0.75 mm. We next compared expression of CD95L and HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage I, whereas HMB-45 was not only expressed in melanoma cells but also in benign pigmented naevi. This indicated the advantage of CD95L staining to diagnose melanoma. The present study indicates the significant correlation between tumorigenicity and expression of CD95L, and thereby raises the possibility that CD95L may be a useful diagnostic marker for malignant melanomas.     

One single erythemagenic UV irradiation is more effective in increasing the proliferative activity of melanocytes in melanocytic naevi compared with fractionally applied high doses

The effect of a single irradiation with UV light on the expression of Ki67 antigen, topoisomerase II alpha, proliferating cell nuclear antigen (PCNA), the melanocyte activation marker HMB-45 and protein p53 in melanocytic naevi was investigated 1 week after application of a single erythemagenic UV dose and after daily exposures with suberythemagenic doses over 4-6 weeks. To assess the effect of UV irradiation, one half of each naevus was shielded with black tape during the UV exposure, and the irradiated part and the non-irradiated parts were evaluated separately. Except for HMB-45, a double staining procedure was performed to distinguish between labelled melanocytes and keratinocytes. After semiquantitative assessment of the staining signal the irradiated part was compared with the non-irradiated part of the same naevus. Morphological changes and an enhanced proliferative/ reparative activity in melanocytes were much more frequent in the naevi irradiated with a single erythemagenic UV dose than in those given repeated suberythemagenic doses. In addition, the keratinocytes showed an increased labelling for PCNA and p53 after the single irradiation. These data may support the importance of intermittent UV exposure and sunburns in the development of both benign and malignant melanocytic lesions.     

Computer use by dentists and dental team members

Melanocytic naevi on the face and neck of 110 Brisbane secondary school students aged 16-17 years were mapped according to specified regions to investigate the dose-response relationship between ultraviolet (UV) radiation and melanocytic naevi. Highest naevus density occurred in regions receiving a mean UV dose of 0.2-0.4 relative to the vertex while densities were low in minimally and maximally exposed regions. This pattern of naevus distribution was unaffected by sex or phenotypic features such as skin colour or degree of freckling. These findings suggest that there is a narrow dose range over which UV radiation can effectively promote the proliferation of melanocytes. A comparison of the regional distribution of naevi on the face and neck with that of solar keratoses appearing over 1 year on the heads of residents of a neighbouring town has shown them to differ significantly. This study may shed some light on the unknown, yet expectedly complex, relation of UV radiation to melanocytic naevi.     

Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts

We studied 722 reexcision scars of benign and malignant lesions (except melanocytic lesions) excised over a 24-month period. The formalin-fixed, paraffin-embedded tissue sections were examined histologically and immunohistochemically. The histological features of melanocytic hyperplasia were present in 59 cases (8%), 56 from the sun-exposed skin of the face and neck and three from the trunk [p < 0.00001]. The most common sites were the nose and lower eyelids, but the forehead was also frequently involved. Of the 59 patients, 41 were women (p < 0.0001). Basal cell carcinoma was the most frequent original lesion in both sexes (80%). No melanocytic hyperplasia was found in 663 cases (298 on the trunk and extremities and 365 on the head and neck). We have seen this reaction pattern following reexcision of melanocytic lesions as well. Thus, interpreting reexcision margins when lentigo maligna or similar lesions are reexcised may be fraught with difficulty. It is important for pathologists and dermatopathologists to recognize this phenomenon because histologically the presence of increased numbers of large melanocytes could be misinterpreted as melanoma in situ.     

Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection

Females with Turner syndrome (TS) are alleged to have increased numbers of melanocytic naevi. Although a high count of acquired melanocytic naevi (AMN) is one of the major risk factors for melanoma, this malignancy has been reported only rarely in patients with TS. The purpose of this study was to explore the effects of environmental and genetic factors on AMN count and density in TS. AMN count and density in 24 patients with TS treated with growth hormone (GH). 24 GH-treated females with GH deficiency (GHD) and 24 normal females were compared in a cross-sectional study. The average AMN density in TS was 50 naevi/m2 as compared with 18 naevi/m2 in the GHD group and 24 naevi/m2 in normal controls (P = 0.001 and P = 0.004, respectively). Duration of GH therapy did not correlate with AMN count (P = 0.44) or AMN density (P = 0.81). The pattern of distribution of naevi between constantly exposed, intermittently exposed and unexposed skin was similar in all groups. Sun exposure was the major factor that affected the regional AMN densities in the control groups, but not in the TS group. The findings of our study indicate that the effects of environmental factors on AMN count and density may vary among genetically different populations. A review of the literature suggested that melanoma is no more prevalent in TS than in the general population.     

Depolarization-induced tyrosine phosphorylation of p130(cas)

OBJECTIVE: To determine whether there were immediate adverse effects of an umbilical artery pH < or = 7.0 in term and near-term infants. STUDY DESIGN: All infants triaged to the newborn nursery with an umbilical artery pH < or = 7.0 from May 1993 through April 1994 (n = 37) were prospectively identified; 35 of the 37 infants were enrolled and matched with nonacidemic control infants (n = 35). Organ system dysfunction (neurologic, renal, hepatic, gastrointestinal) was evaluated either clinically or biochemically with selected blood and urine parameters. RESULTS: Acidemic and control groups were similar for pregnancy complications before labor, but acidemic infants were more often delivered by cesarean section (20/35 vs 6/35, p = 0.001). No differences existed between acidemic and control infants in gestational age, birth weight, neurologic evaluations, hearing deficits, feeding tolerance, and hepatic function. The acidemic group had a higher mean serum creatinine than control infants on day 2 of life (0.90 +/- 0.34 vs 0.71 +/- 0.12 mg/dl, p = 0.005) and a greater number of infants with a urine Chemstrip positive for heme (14/35 vs 3/35, p = 0.005). No differences existed between groups in time to first void, urine specific gravity, and number of infants with microscopic hematuria. CONCLUSION: Term and near-term infants born with an umbilical artery pH < or = 7.0 and triaged to the newborn nursery on the basis of a stable appearance in the delivery room do not have clinical manifestations of hypoxia-ischemia in the 48 hours after birth. The higher mean serum creatinine for acidemic compared with control groups is presumably prerenal in origin and results from processes responsible for profound fetal acidemia. Infants with an umbilical artery pH < or = 7.0 and assessed to be clinically well can be treated similar to nonacidemic infants.     

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.     

Lymphocyte markers in newborn infants

Purified peripheral blood lymphocytes from 20 newborn infants and 12 adults have been studied for the presence of surface markers. Adults and infants did not differ in the percentage of sheep RBC-binding cells (means 58-65%) or in Ig-bearing cells measured by the mixed antiglobulin reaction (means 7.2-11.6%). However, newborn infants had a significantly lower percentage of lymphocytes binding Fc of IgG (mean 10.4%) as compared to adults (mean 17.2%). No overall correlation between plasma Ig levels and Ig-bearing lymphocytes was found but a single infant with increased plasma IgA also showed the highest level of Ig-bearing lymphocytes among all infants.     

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.     

Results of electroacupuncture

A series of 37 patients with Gorlin's syndrome is described; 23 had the typical naevi, 19 had jaw cysts and only 10 had both. A wide range of associated deformities was noted. The need for early identification of patients at risk is stressed; follow-up is essential for 2 reasons: The naevi although indistinguishable histologically from basal cell carcinomas only rarely require radical removal. The jaw cysts are locally invasive and should be radically removed when small. In 8 patients examined there was a low level of alpha-globulins in the plasma. Spontaneous involution of the naevi may occur in un-irradiated skin.     

Human acquired naevi are clonal

Naevi are nearly universal in humans, yet their cellular origin remains obscure. Understanding the cellular and molecular mechanisms involved in naevus development may be important in understanding the pathogenesis of malignant melanoma. This study aimed to discover whether human acquired naevi are premalignant by examining whether they are clonal. To determine clonality naevi were removed and separated into epithelial and naevus cell fractions and the DNA prepared and digested by a methylase-sensitive restriction enzyme. The highly polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by a polymerase chain reaction and examined by gel electrophoresis and autoradiography. In polyclonal cell populations both alleles are usually seen as two distinct bands, whilst clonal populations yield a single band. Using these techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from 40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal, while all of the epithelial cell controls were polyclonal. These data are novel and have great importance for understanding the development of human acquired naevi and cutaneous malignant melanoma. Because monoclonality is a marker of neoplasia, or preneoplasia, our data support the hypothesis that common acquired naevi should be considered to be premalignant lesions, similar to colonic polyps. Such lesions may have undergone the first molecular step(s) in the development of cutaneous malignant melanoma. Understanding the events involved may lead to new methods of prevention and treatment.     

Activation of epidermal melanocytes is independent of epithelial proliferation and vascularization. Immunohistologic study using HMB-45 antibody with review of the literature

Antibodies against HMB-45 antigen are widely used in the immunohistochemical investigation of melanocytic tumours as a marker of activation. While malignant transformation is one explanation for HMB-45 expression, we searched for other factors by investigating 252 biopsies of non-melanocytic skin lesions with 21 different diagnoses for the presence of HMB-45, using both single and double staining techniques. Epidermal melanocytes in lesions with an increased epithelial proliferation-either neoplastic or reactive-and lesions with a prominent vasculature showed an enhanced expression of HMB-45. The results indicate that the presence of HMB-45 is not only influenced by primary melanocytic changes but also may be dependent on epithelial proliferation and vascular factors. These mechanisms should be considered when interpreting HMB-45 staining of melanocytic lesions.