New insights in naevogenesis: number, distribution and dermoscopic patterns of naevi in the elderly

Background/Objectives: It is well recognized that the number and patterns of acquired melanocytic naevi vary with age, but little is known about naevus patterns in the elderly. This is a cross‐sectional study assessing the prevalence, dermoscopic pattern and anatomical distribution of naevus subtypes in a stratified cohort aged between 60 and 89 years. Methods: Fifty‐nine patients who attended the Queensland Institute of Dermatology were recruited randomly and evenly distributed into three age groups: 60–69 years; 70–79 years; and 80–89 years. For each participant, total naevus count and morphological naevus types were recorded with respect to age, sex and anatomical location. Flat (Clark's) naevi were further subclassified according to the dermoscopic pattern as reticular, globular or structureless. Results: Using non‐parametric methods, naevus counts in the elderly decreased due to the disappearance of reticular naevi (P < 0.05). By contrast, structureless and intradermal (Unna's and Miescher's) naevi seemed to persist even into older age. Naevi on the trunk, limbs, head and neck represented 57.6%, 31.0% and 11.3%, respectively. Notably, no reticular naevi were found on the head and neck area. Conclusions: There is a progressive reduction in total naevus counts with advancing age with respect to a cohort aged greater than 60 years.     

Meyerson's naevus: a clinical and histopathological study of 11 cases

We undertook a clinical and histopathological analysis of patients presenting with Meyerson's naevi. Eleven patients with the characteristic histological features of a Meyerson's naevus were identified over a 5-year period. Diagnostic criteria included epidermal spongiosis and a dermal inflammatory infiltrate associated with a banal junctional or compound naevus. Cases were excluded if naevus cells showed moderate to severe atypia or regression. Patients were contacted by phone and interviewed regarding their lesions. The most common clinical appearance was a solitary, pruritic, erythematous eruption encircling a pre-existing pigmented naevus. The trunk and proximal upper extremities were preferentially affected. Only one clinician listed Meyerson's naevus in the clinical differential diagnosis. All cases demonstrated a pigmented junctional or compound naevus with epidermal spongiosis, parakeratosis and a perivascular lymphohistiocytic inflammatory infiltrate with scattered eosinophils. The inflammatory infiltrate consisted almost exclusively of CD3+ lymphocytes, the majority of which were CD4+. However, a substantial number were CD8+. In all patients, the lesions cleared with excision or spontaneously, without recurrence or progression to melanoma. The aetiology of this entity remains unclear and most clinicians are unlikely to be familiar with it.     

Frequency and distribution pattern of melanocytic naevi in Estonian children and the influence of atopic dermatitis

BACKGROUND: There is a strong correlation between naevus number and prospective melanoma risk. Melanoma is one of the most rapidly increasing cancers in Estonia and primary prevention programmes for melanoma that target risk behaviour in the sun have so far not been launched. METHODS: The naevus profile was examined in 549/700 9-year-old Estonian children (282 boys and 267 girls) and the presence of active atopic dermatitis (AD) was registered. RESULTS: There was a wide range of naevi (4-121) and a median total body count of 26. There was no difference in naevus count between boys and girls. No dysplastic naevi were found. Thirty-nine of 549 children (7%) had at least one lesion clinically diagnosed as a congenital naevus. Boys had more naevi on the face (median 4) and trunk (median 12) than girls (median 3 and 9, respectively, P < 0.001). Girls had more naevi on the legs compared with boys (median 4 and 3, respectively, P < 0.01). Fifty-four out of 549 (9.8%) had naevi on the palms and 18/549 (3.3%) on the soles. Children with fair skin, freckles and light hair and eye colours had significantly more naevi than those with darker colours. Thirty-one of 549 (6%) children had AD diagnosed on the examination day and they had a lower total naevus count (median 20) compared with children with no AD (median 27, n = 518, P < 0.05). CONCLUSIONS: The naevus situation in Estonian children today might constitute a starting point for evaluating the efficiency of coming preventive measures as a change of naevus number in children might serve as an early marker for a change in melanoma incidence.     

Dermatofibroma and halo dermatitis

The occurrence of a halo of dermatitis surrounding acquired naevi was initially reported by Meyerson in 1971 with histological features of focal spongiosis, parakeratosis, irregular acanthosis and a lymphocytic infiltrate in the upper dermis. When the same inflammatory reaction occurs around other lesions it is referred to as the Meyerson phenomenon or halo dermatitis. We report a rare case of the Meyerson phenomenon occurring around a dermatofibroma in a 69-year-old woman. This case highlights that the phenomenon may occur in a broad range of clinical scenarios and is not limited to acquired naevi in young adults.     

Halo congenital naevus in a middle-aged patient with vitiligo

A case of halo congenital naevus is reported on the chest of a 56-year-old Asian woman with pre-existing vitiligo. The naevus measured 3.5 cm x 2 cm and underwent depigmentation around its periphery. Dermoscopic examination showed coarse pigment in the darker centre of the naevus and depigmentation in the surrounding halo. Light microscopy showed well-formed naevus cell nests with coarse melanin granules in the papillary dermis, and surrounding fibrosis. Melanocytes extended into reticular dermis, consistent with a congenital growth pattern. There was no evidence of malignancy. The epidermis was of normal appearance. S100 staining highlighted melanocytes in the dermis. Basal melanocytes were retained at the periphery of the naevus. Based on the clinical history and histological findings, a diagnosis of halo congenital naevus was made. The naevus was not excised.     

Becker's naevus: a comparative study between erbium: YAG and Q-switched neodymium:YAG; clinical and histopathological findings

BACKGROUND: Becker's naevus (BN) may represent a distressing cosmetic handicap and a challenging issue regarding treatment. OBJECTIVES: To compare clinical and histopathological findings of patients with BN treated with two different lasers: an erbium:yttrium-aluminium-garnet (Er:YAG) system vs. a neodymium:YAG (Nd:YAG) laser. PATIENTS AND METHODS: In this prospective and comparative study we present the clinical and histopathological evolution during a 2-year follow-up of 22 patients with BN treated with only one pass of the Er:YAG laser (n = 11) or three treatment sessions with the Q-switched Nd:YAG system (n = 11). RESULTS: Clinical evaluation 2 years after treatment with the Er:YAG laser showed complete clearance (100%) in 54% of the patients (n = 6) and clearance of > 50% in 100% of the subjects. In relation to Nd:YAG laser treatments our results echo those of other authors. Numerous sessions are necessary to get an acceptable clinical clearance rate. Only one patient showed marked clearance (51-99%) after three treatment sessions. Moderate (26-50%) and mild (1-25%) clearance was observed in 45.5% (n = 5) and 27.3% (n = 3) of the patients. CONCLUSIONS: Both Er:YAG and Nd:YAG are safe tools to treat BN. However, in terms of pigment removal, one pass with Er:YAG is a superior technique to three treatment sessions with the Nd:YAG.     

Differential expression of epidermal growth factor receptor in melanocytic tumours demonstrated by immunohistochemistry and mRNA in situ hybridization

Differential expression of the epidermal growth factor receptor (EGFR) has been reported in melanocytic lesions. To evaluate these differences in EGFR expression in melanocytic tumours, formalin-fixed, paraffin embedded sections from 33 benign melanocytic neoplasms and 77 cutaneous melanomas were analysed for EGFR protein and mRNA expression using immunohistochemistry and mRNA in situ hybridization. The majority of benign and malignant lesions expressed EGFR at both protein and mRNA levels. In 7% (7/100) samples, mRNA but not protein expression was observed. Overall, a higher proportion of cells expressed EGFR protein in malignant lesions compared with benign lesions (P = 0.06), and the intensity of mRNA expression was higher in the malignant tumours (P < 0.001). No significant differences in EGFR protein or mRNA expression with tumour progression within the malignant lesions were seen. These results indicate that EGFR mRNA and protein expression is common to benign and malignant melanocytic lesions, and that an overall increase in expression is associated with malignant transformation. However, differential EGFR expression between in situ melanomas and invasive or metastatic lesions was not observed.     

Proliferative nodules of undifferentiated spindle cells arising in a large congenital melanocytic naevus

Proliferative nodules (PN) are benign lesions that arise in large congenital melanocytic naevi (LCMN). Clinically and histologically they can be difficult to differentiate from malignancies, which are also associated with LCMN. The PN in this case consisted of undifferentiated spindle cells and exhibited unusual histological features including negative stains for melanocytic markers (S100, HMB45 and MelA), negative stain for c‐Kit, high mitotic index and unusual morphology of the lesional cells. As a result, a firm histological classification could not be made, which posed a challenge for the clinical management.     

Vulval and perianal inflammatory linear verrucous epidermal naevus

Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare form of epidermal naevus. It occurs as a linear dermatitic or psoriasiform plaque, with onset usually in the first 5 years of life. Lesions are characteristically intensely itchy. We present a case of ILVEN occurring on the vulva and perianal region of a 6-year-old girl. The lesion was initially thought to be an area of lichenified dermatitis; however, treatment with even super-potent topical corticosteroids did not significantly improve the inflammation. A biopsy was performed and histopathological examination showed characteristic features. ILVEN is frequently refractory to topical treatment and surgical excision of lesions may be an option for relief of symptoms. ILVEN occasionally presents in the inguinogenital region and in this area may, like many vulval naevi, be misdiagnosed as vulvitis, psoriasis, genital warts or sexual abuse.     

Treatment of acquired junctional melanocytic naevi by Q-switched and normal mode ruby laser

BACKGROUND: Acquired junctional melanocytic naevi are harmless pigmented lesions of the epidermis, which can be of cosmetic concern. Various therapeutic approaches have been used in the treatment, but all these methods produce postoperative scarring or alterations in skin texture. Pigment laser treatment of benign pigmented lesions has shown a low potential for scarring by selectively targeting melanosomes in melanocytes and keratinocytes. OBJECTIVE: To find a fast, effective and safe treatment for the removal of acquired junctional melanocytic naevi. PATIENTS/METHODS: We first studied the effect of the Q-switched and normal mode ruby laser on 12 patients (eight women and four men) with acquired melanocytic naevi. The effect was monitored by histology and clinical photography. RESULTS: If the response to one treatment with the Q-switched laser mode was not completely effective, the lesions were subsequently treated with one or two sessions with the laser in normal mode. All flat lesions responded completely. After a follow-up period of 1 year they had not recurred. Slightly elevated lesions showed only a partial response, e.g. disappearance of the junctional part of the naevus but recurrence of the dermal part of the naevus. Red-brown junctional naevi as seen in skin types I and II did not respond well to ruby laser treatment. CONCLUSIONS: The Q-switched ruby laser was very successful in completely removing flat (non-palpable) acquired junctional melanocytic naevi, but not compound naevi, with one to three treatment sessions, without any scarring or pigmentary disturbance.     

Distribution of congenital melanocytic naevi and congenital naevus-like naevi in a survey of 3406 Italian schoolchildren

Background  Scanty information is available on the prevalence of congenital melanocytic naevi (CMN) and congenital naevus-like naevi (CNLN), particularly the small ones.
Objectives  To estimate the prevalence of CMN/CNLN in Italian schoolchildren, and to assess variations according to potential risk factors for melanoma.
Methods  We conducted a survey in 13 Italian areas on 3406 schoolchildren aged 12–17 years. Children were examined by dermatologists who assessed pigmentary traits and made a count of small (6–15 mm in diameter) and medium/large (> 15 mm) CMN/CNLN on 19 anatomical areas.
Results  Overall, 592 children (17·4%) had one or more CMN/CNLN. Prevalence of small CMN/CNLN was 16·1%, and that of medium/large CMN/CNLN was 1·8%. There was no difference between age groups and sexes. CMN/CNLN were more frequent in children with a higher number of common melanocytic naevi (multivariate odds ratio, OR = 7·1 for the highest vs. the lowest quartile), consistent in small (OR = 7·2) and medium/large CMN/CNLN (OR = 6·0). Family history of malignant melanoma (OR = 1·4) and personal history of diabetes (OR = 4·4) appeared to be directly, and sun exposure inversely associated with CMN/CNLN. No relation was evident between CMN/CNLN and pigmentary traits, anthropometric characteristics, dietary habits, freckles, sunburns, sunscreen use or history of selected diseases.
Conclusions  The association with family history of melanoma, the strong association with acquired melanocytic naevi, and the lack of association with pigmentary traits and sunburns suggest that CMN/CNLN may act as an independent risk marker for subjects at increased risk for cutaneous melanoma later in life.     

Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrhoeic keratosis): a clinical, dermoscopic and pathological case report

The association of contiguous or 'collision' tumours in the same biopsy specimen is not uncommon and is often reported in the literature. The most common association, basal cell carcinoma (BCC) and naevus, is very difficult to diagnose clinically. We describe a 38-year-old woman with a previous history of melanoma, who presented with a modified pigmented lesion of the hip that had begun to change 6 months earlier. Histologically, the lesion was a melanocytic compound naevus and a BCC with a seborrhoeic keratosis. The case was investigated clinically and by focusing on the dermoscopic features and their pathological correlates. Cutaneous collision tumours are extremely difficult to diagnose preoperatively, even with the help of dermoscopy, in particular when one of the lesions is melanocytic.     

Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice

Background Congenital melanocytic naevi (CMNs) can be associated with abnormalities of the cental nervous system (CNS) and/or with melanoma. Quoted incidences for these complications vary in the literature, as do recommendations for investigations and follow‐up. Objectives To determine the incidence of complications, and to identify phenotypic features associated with a higher risk of complications. Methods We reviewed records of 224 patients with CMNs seen in Dermatology clinic between 1991 and 2007. Patients were excluded if they had a complication at the time of referral. Magnetic resonance imaging (MRI) of the CNS was offered on the basis of CMN phenotype. Follow up was in clinic and/or by postal questionnaires. Results One hundred and twenty patients (54 boys and 66 girls) who had MRI of the CNS were included in the analysis. Mean age at MRI was 2·46 years (median 1·20). Mean follow up was 8·35 years (median 7·86). Sixty‐five per cent had naevi > 20 cm projected adult size or multiple CMNs (40% > 40 cm), and 83% had satellite lesions at birth. Outcome measures were MRI abnormality, clinical neurological abnormality, any tumour, malignant melanoma, and death. No complications were seen in the 16 patients with no satellite lesions at birth. MRI and/or clinical neurological abnormalities were found in 22 patients (18%) and were significantly associated with projected adult size of the CMN (particularly > 40 cm), and independently with male gender. Tumours occurred in five patients, two of which were malignant melanoma (1·7%). Due to small numbers there was no significant association between phenotype and occurrence of tumours. Three patients (2·5%) died (one from neuromelanosis and two from melanoma in patients with normal MRI scans). Death was significantly associated with CMN size > 40 cm. Importantly, there was no significant association between CMN distribution (including posterior axial location) and adverse outcomes. Conclusions This is the largest study of CNS imaging in patients with CMNs. We report a newly recognized association between male gender and neurological complications, dispute the previously reported association between CMN site and neurological complications, and quantify the associations between CMN size, satellite lesions and neurological complications. We make recommendations for the management of these patients.     

Histopathogenesis of inflammatory linear verrucose epidermal naevus: histochemistry,immunohistochemistry and ultrastructure

Summary Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis.     

The role of pattern analysis and the ABCD rule of dermoscopy in the detection of histological atypia in melanocytic naevi

BACKGROUND: Clinical features of melanocytic naevi correlate poorly with the presence, histopathologically, of architectural disorder and cytological atypia, making the detection of histological atypia by means of macroscopic appearance unreliable. OBJECTIVES: The aim of this study was to investigate the diagnostic effectiveness of dermoscopy in the non-invasive detection of histological atypia in naevi. METHODS: Observers blinded for histological diagnosis classified a series of 168 melanocytic naevi as common or atypical on the basis of their clinical features and on their dermoscopic profile. The diagnostic performance of both methods compared with the true (histopathological) diagnosis was assessed. RESULTS: Dermoscopy using pattern analysis showed better results than clinical examination in the non-invasive detection of naevi with architectural disorder with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A statistically significant difference in the frequency of dermoscopic parameters between atypical and common naevi was found for atypical pigment network (39% vs. 17%, P = 0.001) and dermoscopic regression structures (13% vs. 2%, P = 0.008). Dermoscopic features, which best predicted histological atypia in naevi, were regression structures (white scar-like areas or peppering), irregular vascular pattern and grey-blue areas (positive predictive values 83%, 83% and 73%, respectively). In contrast, no statistically significant difference in the mean values of the ABCD score between common and atypical naevi was found. The best diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of 4.0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis (diagnostic accuracy 30%). CONCLUSIONS: Dermoscopy by means of pattern analysis enhances the diagnostic accuracy of dermatologists in the prediction of histological atypia in melanocytic naevi as compared with clinical examination alone.     

Long‐term safety and efficacy of continuous acitretin monotherapy for three children with different severe hyperkeratotic disorders in China

Long‐term systemic treatment with acitretin for severe hyperkeratotic disorders is needed to maintain quality of life of afflicted patients, but treatment has been limited owing to its potential side‐effects including skeletal malformations, particularly for children during their growth and development. A retrospective investigation was conducted with three children afflicted with a severe hyperkeratotic disorder, namely Darier's disease, bullous ichthyosiform erythroderma or lamellar ichthyosis, who were continuously maintained on 0.2–0.3 mg/kg per day acitretin for more than 12 years after an initial period at a larger acitretin dose to bring each disease under control. The patients had good responses to acitretin treatment, which was assessed for safety, skeletal abnormalities, growth retardation and other potential side‐effects. Acitretin monotherapy was an effective treatment for these children, and maintenance doses were well tolerated with no skeletal or other observable side‐effects during the course of the study.     

RAS and RAF mutations in banal melanocytic aggregates contiguous with primary cutaneous melanoma: clues to melanomagenesis

Background  Distinguishing banal melanocytic aggregates contiguous with malignant melanoma can be a histological challenge but is essential because of the potential for a spurious Breslow measurement.
Objectives  Our aim was to ascertain whether the histological distinction between the two relates to differences in the prevalence of mutations in genes significant in melanomagenesis.
Methods  Mutations in BRAF codon 600, NRAS1 codons 12/13, NRAS2 codons 60/61 and KRAS codons 12/13 were ascertained in 18 cases of primary cutaneous malignant melanoma contiguous with banal melanocytic aggregates using laser capture microdissection.
Results  Overall, 12 of 18 cases (67%) exhibited a mutation in at least one gene. BRAF  V600E appeared to be the most commonly mutated gene in both the melanocytic aggregate (seven of 18, 39%) and the melanoma (four of 18, 22%). Both populations demonstrated a similar BRAF genomic profile in 11 of 18 cases (61%) (two BRAF  V600E, nine BRAF -WT), a similar KRAS genomic profile in 14 of 18 cases (78%) (one KRAS  G12V, 13 KRAS- WT) and a similar NRAS2 genomic profile in 14 of 18 cases (all WT). Of interest, we noted a relatively high prevalence of KRAS mutations (five of 18, 28%). The frequency of KRAS mutations in the melanocytic aggregate (five of 18, 28%) was second to BRAF  V600E, while in melanoma, the frequency was also second to BRAF  V600E but equalled that of NRAS2 (1 of 18, 6%). No NRAS1 mutations were observed. BRAF and RAS mutations appeared to be mutually exclusive with only three of 18 cases (17%) demonstrating a mutation in both genes (melanocytic aggregate only).
Conclusions  Our findings hint towards the interpretation of banal melanocytic aggregates serving as precursor lesions.