Dysplastic Naevi Research Articles

Seasonal variation in dysplastic naevi

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

Reflectance confocal microscopy accurately discriminates between benign and malignant melanocytic lesions exhibiting a ‘dermoscopic island’

The 'dermoscopic island' is a term that was recently proposed to design an area of a pigmented lesion with a uniform dermoscopic pattern different from the remainder of the lesion. The positive predictive value of this sign for the diagnosis of melanoma is about 50%. The purpose of our study was to see if reflectance confocal microscopy (RCM) permitted to accurately distinguish between nevi and melanoma in such lesions. Five lesions of five consecutive unselected patients, with a dermoscopic island but no feasible clear cut diagnosis on the basis of dermoscopy alone were examined by RCM before excision for histopathological evaluation. Two lesions corresponded to nevi, and three lesions were early melanomas arising on a benign naevus in one case, and on a dysplastic naevus in two cases. In all five cases, RCM permitted to make the correct diagnosis, with a very good correlation with conventional histopathology. Reflectance confocal microscopy appears as a promising tool not only to enhance the early diagnosis of melanoma but also to avoid unnecessary excisions of lesions with a dermoscopic island.

Pre-emptive diagnosis of a case of scabies by dermatopathology

A 39-year-old woman reported to her general practitio-ner with a new pigmented skin lesion on her right pectoral region. Dermatoscopically there were no suspicious features and the decision was made to monitor it over a three-month period. At follow-up imaging there was some minor change, possibly related to technical factors (the original camera/dermatoscope combination was not available), and after dis-cussion with the patient a decision was made to perform an excisional biopsy. The pathologist reported the lesion as a: “… dysplastic naevus of the compound type” with “… mild atypia and active lymphocytic regression.” He made the addi-tional comment: “Two apparent scabies mites are present.” This was not expected, as the patient had complained of no symptoms of scabies and no skin eruption had been observed to suggest that diagnosis.The patient returned for her routine postoperative review one week after the excision. She now complained of an intensely itchy skin eruption and wondered if she was having an allergic reaction to the local anaesthetic or antiseptic skin preparation solution used at the time of surgery. Examination

Accuracy in skin cancer diagnosis: A retrospective study of an Australian public hospital dermatology department

Accurate identification of skin lesions is vital in ensuring malignancies are not missed and that they are treated early to avoid mortality. It is also important that appropriate lesions are submitted for biopsy to decrease the costs and morbidity associated with the unnecessary removal of benign lesions. This study attempted to assess current accuracy in skin cancer diagnosis. Histology reports for all biopsies and excisions performed in an 18-month period at a public hospital dermatology department were reviewed. Dermatology registrars and consultants were involved in assessing lesions for biopsy. Calculations were made to quantify the sensitivity of melanoma diagnosis; naevi to melanoma ratio (NMR); biopsy to treatment ratio (BTR), and number needed to treat for melanoma (NNT). NNT was calculated as the number of pigmented lesions (seborrhoeic keratoses, naevi and melanoma) removed to identify one melanoma. 6546 biopsies/excisions were performed, identifying 55 melanomas. The sensitivity of melanoma diagnosis was 76% and 11% of melanomas were thought to be dysplastic naevi. The NMR was 6.4. The BTR was 1.97, indicating that one in every 1.97 biopsies was identified as a non-melanoma skin cancer. The NNT was 11.9. All dysplastic naevi and 91% of melanomas were biopsied using either shave or excision biopsy. These audits are important to ensure quality of care and could aid in identifying doctors and institutions that may benefit from further training in melanoma diagnostic algorithms. These figures can be used as a benchmark to measure the impact of new vectors in skin cancer diagnosis as they are introduced.

Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells

Cutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Additionally, melanocytes in dysplastic naevi show structural mitochondrial and melanosomal alterations and have elevated reactive oxygen species (ROS) levels. For this study we performed genome-wide expression and proteomic analysis of melanocytes from dysplastic naevus (DNMC) and adjacent normal skin (MC) from 18 patients. Whole genome expression profiles of the DNMC and MC of each individual patient subjected to GO-based comparative statistical analysis yielded significantly differentially expressed GO classes including “organellar ribosome,” “mitochondrial ribosome,” “hydrogen ion transporter activity,” and “prefoldin complex.” Validation of 5 genes from these top GO classes revealed a heterogeneous differential expression pattern. Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells.

NIR and skin impedance spectroscopic measurements for studying the effect of coffee and alcohol on skin, and dysplastic naevi

Near infrared and impedance spectroscopy can be used for clinical skin measurements and need to be evaluated for possible confounding factors; (i) are skin conditions of the patient and the subsequent skin measurements influenced by alcohol and/or coffee consumption and (ii) are measurements of dysplastic naevi (DN) reproducible over time and significantly different compared to reference skin. Near infrared and skin impedance spectroscopic data were analysed multivariately. In the first study, the skin characteristics of 15 healthy individuals were examined related to body location, gender, individual differences, and consumption of coffee or alcohol. The second study included five patients diagnosed with dysplastic naevi syndrome. Measurements were taken on DN and reference skin over time. In the first study, body location and gender had a major influence on measurement scores. Inter-individual skin characteristics and coffee or alcohol effects on skin characteristics were of minor importance. In the second study, it was shown that DN can be differentiated from reference skin and the measurements are stable over time. Moderate consumption of alcohol and coffee did not influence the results of the measurements. It is possible to follow, stable or changed, characteristics of DN over time.

Complete skin examination is essential in the assessment of dermatology patients: findings from 483 patients

Dermatological teaching has traditionally stressed that complete skin examination is essential in the assessment of patients with potential skin disease. To determine whether complete skin examination results in increased diagnoses of skin malignancies that would not have been discovered otherwise. New patients (n = 483) attending a dermatology clinic in a university teaching hospital and private dermatology practice had a complete skin examination, as is our normal practice. These patients were seen over a 9-month period (January-September 2009). All patients were examined by the same consultant dermatologist. Data were collected on patients' sex, age, presenting complaint and findings on complete skin examination. Two nodular malignant melanomas with mean Breslow thickness of 0·6 mm (0·4%) and one melanoma in situ were identified at sites distant from the patient's presenting complaint. Sixteen patients (3·3%) had a basal cell carcinoma that would not have been discovered if the presenting lesion alone had been examined. Thirty-three patients (6·8%) had actinic keratoses or squamous cell carcinoma in situ and nine (1·9%) had dysplastic naevi. A further 21 patients (4·3%) had a suspicious lesion biopsied or excised with subsequent benign histology. Seventy-three patients (15·1%) had other benign dermatological diagnoses requiring treatment or investigation. In a 9-month period, in a sample of 483 new patients, three patients (0·6%) had potentially lethal skin malignancies identified that would not have been diagnosed without a complete skin examination. Sixteen (3·3%) patients had basal cell carcinomas that would have been missed without complete skin examination. This study confirms the traditional teaching that complete skin examination has the potential to reduce morbidity and mortality from cutaneous malignancy.

The number of benign moles excised for each malignant melanoma: the number needed to treat

The ratio of benign moles excised for each malignant melanoma (MM) diagnosed, i.e. the number needed to treat (NNT), may be a useful indicator of diagnostic accuracy and the efficient use of healthcare resources, and may have personal implications for the patient. To assess the NNT for a group of consultant dermatologists serving a population of 600,000, and to compare this with similar studies from other countries. This was a retrospective analysis of data on pigmented lesions excised over a 5-year period (2005-2009). The lesions were divided into three groups: benign naevi (BN), dysplastic naevi (DN) and MM. The NNT ratio was calculated as (BN + DN + MM)/MM. In total, 4691 lesions were examined. The overall mean NNT was 6.3, with a range of 4.9-11.3 for each of nine consultant dermatologists. The mean NNT was 7.6 for female and 4.8 for male patients. There were more patients with BN (n = 3534; 75%) than with DN (n = 407; 9%) or MM (n = 750; 16%). The gender representation was similar in the DN and MM groups, but had a disproportionately female bias in the BN group (67% female, 33% male patients). Overall, there were more female patients in all three groups [2962 female patients (63%) and 1729 male patients (37%)]. The NNT of 6.3 in this study compares favourably with NNT ratios from studies of dermatologists from other countries. This study may encourage other countries and individual doctors to assess their NNT ratios, as it may be an important indicator of the efficient use of resources and the avoidance of unnecessary surgery for patients.

DERMATOLOGIC LESIONS AND RISK FOR CANCER

There are three major types of skin cancer. Basal cell carcinoma and squamous cell carcinoma are both carcinomas from epithelial cells, whereas melanoma originates from the melanocytes of the skin. Although these skin cancers can develop without precursors, there are some skin lesions which may give rise to malignancies.In chronological order, we discuss the (potential) precancerous lesions of basal cell carcinoma (sebaceous nevus), squamous cell carcinoma (chronic inflammation, actinic keratosis, kerato-acanthoma, Bowen’s disease, leukoplakia, and lichen sclerosus) and malignant melanoma (lentigo maligna and dysplastic naevi).

Anthropomorphic and hormone abnormalities in testicular cancer patients.

233 Background: Studies show a range of environmental and genetic associations with testicular cancer, specifically testicular dysgenesis, increased height, and multiple dysplastic naevi. To confirm these findings, we studied a cohort of testicular cancer patients and healthy controls. We also studied a cohort of unaffected relatives of patients to identify if any noted differences might be due to shared genetic/environmental background. Methods: We identified index cases from the hospital database. They nominated an unaffected relative and an unrelated friend. Controls were supplemented by recruitment of institutional staff. Results: 183 index cases (IC), 57 unaffected relatives (UR) and 103 unrelated controls (UC) were identified. Mean age was 47 years (25-78) IC, 44 years (18-74) in UR and 42 years (20-74) in UC. IC treated by chemotherapy (ch) had higher mean FSH than non chemotherapy patients (s)[18.98 v 13.22 (p=0.01)] and lower mean testosterone [ch:12.21, s:13.52 (p=0.04)] though mean LH [ch:7.94, s:6.05 (p=0.10)] and BMI (ch:27.38 s:26.81 (p=0.33) were not significantly different. Conclusions: In contrast to other studies, we found both testicular cancer patients and their relatives were shorter and with reduced arm length compared with controls; a sign of a possible shared genetic or environmental effect. There was no significant difference in weight, BMI, body fat %, lean body mass, and leg length. FSH and LH were significantly elevated and testosterone reduced in index cases (but not relatives) particularly in those who had chemotherapy. The lack of difference between relatives and controls suggests these are most in keeping with direct treatment effects. [Table: see text] No significant financial relationships to disclose.

Melanoma-Astrocytoma syndrome

Characterised by families with cutaneous malignant melanoma (CMM) and nervous system tumours. Initially described in a family with malignant melanoma and/or cerebral astrocytoma in eight members over three generations. Astroctytomas and cutaneous malignant melanoma have been identified in a number of well defined syndromes such as neurofibromatosis, Turcot’s, Lynch type II cancer, LiFraumeni and tuberous sclerosis. However, astrocytomas and CMM have been reported in families where the disease pattern does not fit the defined syndromes due to the absence of additional cancer types normally associated with these syndromes and mutations in genes known to predispose to these conditions (NF1, TP53, APC, MSH2 MLH1, TSC1, TSC2). In addition to astrocytoma, melanomaastrocytoma syndrome families show other tumours such as medullablastomas, glioblastoma multiforme, ependymoma, glioma, meningioma, neuroblastomas, schwannoma and acoustic neurilemmoma. All these tumours are of neural crest, mesenchymal and/or neuroepithelium origin. These families may/may not show evidence of the dysplastic naevus syndrome (DNS) common in familial melanoma. Neoplastic risk

Novice Identification of Melanoma: Not Quite as Straightforward as the ABCDs

The "ABCD" mnemonic to assist non-experts' diagnosis of melanoma is widely promoted; however, there are good reasons to be sceptical about public education strategies based on analytical, rule-based approaches--such as ABCD (i.e. Asymmetry, Border Irregularity, Colour Uniformity and Diameter). Evidence suggests that accurate diagnosis of skin lesions is achieved predominately through non-analytical pattern recognition (via training examples) and not by rule-based algorithms. If the ABCD are to function as a useful public education tool they must be used reliably by untrained novices, with low inter-observer and intra-diagnosis variation, but with maximal inter-diagnosis differences. The three subjective properties (the ABCs of the ABCD) were investigated experimentally: 33 laypersons scored 40 randomly selected lesions (10 lesions × 4 diagnoses: benign naevi, dysplastic naevi, melanomas, seborrhoeic keratoses) for the three properties on visual analogue scales. The results (n = 3,960) suggest that novices cannot use the ABCs reliably to discern benign from malignant lesions.

Diagnostic tests: Scanning for melanoma

Summary Non-invasive diagnostic tools aim at increasing accuracy of melanoma diagnosis. Clinical naked eye observation in combination with dermoscopy can be regarded as the practical reference standard to identify lesions for histopathological evaluation. Pigmented lesions need to be evaluated in the context of patient history to identify risk factors for melanoma, followed by a dermoscopically-aided entire skin examination. Patients with identified risk factors should be further examined. Total body photography is widely used in the follow-up of high-risk patients (particularly those with numerous and dysplastic naevi) and can be coupled with digital dermoscopy or videodermoscopy. New noninvasive diagnostic aids comprise multispectral image analysis, reflectance confocal microscopy and computer assisted diagnostic systems. Also, molecular profiling of lesions is an emerging technique under investigation for melanoma diagnosis.

Early melanoma with halo eczema (Meyerson's phenomenon)

We present a case of a 49-year-old man who presented with a solitary atypical pigmented lesion with a surrounding halo of dermatitis. Dermoscopy showed a pigment network at the periphery with areas of scar-like depigmentation, negative pigment network and erythema. The lesion was treated preoperatively with a potent topical corticosteroid resulting in a reduction of inflammation. Histology showed an early Clark level 1 melanoma arising within a severely dysplastic compound melanocytic naevus. There was an adjacent perivascular chronic inflammatory cell infiltrate with occasional eosinophils. Minimal, though definite spongiosis with parakeratosis was also present. The scar was subsequently re-excised achieving appropriate excision margins for melanoma in situ. Six months later, there was recurrence of dermatitis at the scar with no evidence of recurrent melanoma. To our knowledge, melanoma with Meyerson phenomenon has not been reported in the literature. This case highlights that all lesions should be evaluated on clinical and dermoscopic grounds regardless of the presence or absence of eczema. Our case adds yet another entity that may display Meyerson phenomenon and consequently a halo of eczema cannot be considered a reassuring sign when evaluating melanocytic lesions.

A support vector machine for decision support in melanoma recognition

The early diagnosis of melanoma is critical to achieving reduced mortality and increased survival. Although clinical examination is currently the method of choice for melanocytic lesion assessment, difficulties may arise in the diagnosis of atypical lesions. From both the naked eye and dermoscopic perspective, dysplastic naevi often exhibit a prominent heterogeneity of structure that renders their clinical distinction from melanoma difficult. To address these problems in diagnosis, there exists a heightened interest among researchers regarding the utility of machine learning techniques in computerised image analysis. Here we report on the utility, for dermatologists, of support vector machine (SVM) technology in melanoma diagnosis, using an archive of 199 digital dermoscopic images of excised atypical melanocytic lesions. Our best validation models achieved an average sensitivity and specificity for melanoma diagnosis of 0.86 and 0.72, respectively. Applying the best model to our test set yielded a sensitivity of 0.89, a diagnostic odds ratio of 14.09 and an area under the receiver operated characteristic curve (AUC) of 0.76. Advantages of the procedure implemented are the simplicity of feature extraction and the computationally cheap and efficient nature of SVMs. The derived model generalises well with outcomes that compare favourably with competing algorithms and expert assessment. In line with the concept of the utility of decision support systems in clinical practice, we propose that to reduce the risk of missed melanomas, both the dermatologists' assessment and the SVM diagnosis be incorporated into the clinical decision-making process.

Dysplastic naevi, again

Dysplastic naevi, again

Response to ‘Dysplastic naevi, again’

Response to ‘Dysplastic naevi, again’

Melanocytic naevi of special sites

There is a recently recognized and relatively common group of melanocytic naevi that share histopathologic features in common with dysplastic naevi and malignant melanoma. These naevi have been termed “naevi of special sites” or “naevi with site-related atypia” as distinctive features have been correlated with specific anatomic sites. The list of sites attributed with bearing such naevi is expanding and includes genitals, acral locations, flexural areas, breast, scalp, auricular regions, and conjunctiva. Despite the atypical histopathologic features, the vast majority of these lesions are benign and do not appear to have an increased risk for progression to malignancy. As authentic dysplastic naevi and melanoma may also occur at these sites, it is important for practicing diagnostic pathologists to recognize the unique features of “naevi of special sites” and avoid overdiagnosis. This group of melanocytic naevi, with emphasis on histopathologic features and distinction from dysplastic naevi and melanoma, is briefly reviewed.

Dysplastic naevi: an update

Dysplastic naevi are clinically atypical and histologically are characterized by architectural disorder and cytological atypia. Their diagnosis is reproducible if criteria and thresholds are agreed upon. They are significant only in relation to melanoma, as simulants of melanoma, as markers of individuals at increased risk of developing melanoma, and as potential and occasional actual precursors of melanoma. Morphologically and biologically, they are intermediate between common naevi and melanoma. Individuals with dysplastic naevi may have deficient DNA repair, and dysplastic naevi lesions are associated with overexpression of pheomelanin, which may lead to increased oxidative damage and increased potential for DNA damage and tumour progression.

Expression of glucose‐regulated stress protein GRP78 is related to progression of melanoma

Glucose-regulated protein 78 (GRP78) is a protein translated in response to endoplasmic reticulum (ER) stress that has been implicated in the pathogenesis and resistance to therapy of a variety of cancers. The aim of this study was to investigate its expression and role in the development and progression of human melanoma. The immunohistochemical expression of GRP78 in naevi, primary melanoma and melanoma metastases from 171 patients was correlated with clinicopathological factors and patient survival. The GRP78 immunoreactivity score (IRS) was 0.2 in compound naevi, 0.65 in dysplastic naevi, 4.65 in naevi adjacent to primary melanoma, 2.4 in melanoma in situ, 11.2 in thin (</=1.0 mm) and 18.1 in thick (>1.0 mm) primary melanoma. It was 18 and 17.3 in subcutaneous and lymph node metastases, respectively (P < 0.0001). GRP78 expression was positively correlated with increasing tumour thickness (P = 0.001) and with increasing dermal tumour mitotic index (P = 0.0004). Disease-free survival (chi(2) = 8.0703, P = 0.0045) and overall survival (chi(2) = 6.2633, P = 0.0123) in melanoma patients with IRS >25 were significantly lower than in melanoma patients with IRS <25. GRP78 expression appears to correlate with known correlates of melanoma progression and survival and requires further evaluation as a prognostic biomarker in melanoma.