Benign dermoscopic network patterns in dysplastic melanocytic nevi

Background/aims: Epiluminescence microscopy (ELM) is a non-invasive clinical technique, which by employing the optical phenomenon of oil immersion makes surface structures of the skin accessible for in vivo examination and provides additional criteria for the diagnosis of pigment skin lesions (PSLs). Many ELM criteria have been described. One of the most important ELM criteria is the pigment network (PN).
Objective: The aim of this study is to identify benign ELM (dermoscopic) network patterns of dysplastic melanocytic nevi (DMN).
Methods: This study included 907 dysplastic melanocytic nevi in 178 patients. Prior to biopsy, each lesion was photographed with oil immersion, and the images were viewed on a high-resolution compact slide projector. For each PSL, the ELM Network Features and ABCD-score were evaluated.
Results and discussion: The benign dermoscopic network features in DMN are the presents of a regular PN with delicate lines and margins, which predominantly thins out at the border of the lesion. For DMN, with these features, the mean ABCD score is smaller than ABCD-score for DMNs with irregular, prominent PN and network patches, ending abruptly at the periphery. In DMN with a network predominantly thinning out at the border of the lesion several uniform network patterns were found—diffuse network pattern, patchy network pattern, structureless center pattern, globular center pattern, and pigmented-blotch center pattern.
Conclusions: Benign features of pigment network are regularity, delicacy and thinning out at the border of the lesion. Benign dermoscopic network patterns are diffuse network pattern, patchy network pattern, structureless center pattern, globular center pattern, and pigmented-blotch center pattern. They can be found in DMN with a network predominantly thinning out at the border of the lesion.     

Common acquired melanocytic nevi, dysplastic melanocytic nevi and malignant melanomas: an image analysis cytometric study

We used computerized image analysis cytometry in analyze 10 melanocytic lesions from each of the following categories: common acquired nevi, melanocytic nevi with architectural features of dysplasia, dysplastic melanocytic nevi (DMN) with slight atypia, DMN with moderate atypia, DMN with severe atypia, and superficial spreading melanomas. The nuclei of at least 50 consecutive nevomelanocytes in the most atypical zones were digitized at ×1000 under oil immersion, without knowledge of diagnosis by one observer. Grading of atypia was based on current practices as described in the literature. The results showed significant differences ( p < 0.05) in nuclear area and standard deviation of nuclear area between melanoma and DMN with severe atypia, and between DMN with severe atypia and all other categories of nevi. There were no differences among any lesions with respect to nuclear shape. No differences in nuclear area were found among DMN with moderate, or slight atypia, nevi with features of dysplasia, and typical nevi. These results show for the first time objective distinction of low-grade (slight-moderate atypia), and high-grade or severe atypia in pre-malignant nevomelanocytic lesions of the skin.     

Agminated acquired melanocytic nevi of the common and dysplastic type

We previously reported a single case of agminated acquired melanocytic nevi, consisting of a localized clustering of banal and atypical moles. We now report 4 more cases, confirming that the initial case was not an isolated finding. We examined the lesions clinically, with a dermoscope, with a Wood's light, and in 3 cases with UV photography so as to exclude nevus spilus from the differential diagnosis. The presence of an underlying dysplastic nevus syndrome phenotype in 4 of the 5 cases raises the possibility that agminated nevi arise as a consequence of postzygotic loss of heterozygosity and, thus, may represent a type 2 segmental manifestation of the atypical mole syndrome phenotype. Further studies of similar cases using microdissection techniques for analysis of loss of heterozygosity pattern are warranted.     

Clinical features of dysplastic nevi

The clinical features of 100 dysplastic nevi were tabulated. Although certain characteristics were present in most or all of these melanocytic nevi, there was a marked heterogeneity of other clinical features. The preponderant type of large (greater than or equal to 8 mm) melanocytic nevus in patients with classic dysplastic nevi is a papule or plaque with the following characteristics: multicoloration (various shades of tans, browns, reds, or black); slightly raised height for its broad diameter; mamillated surface; and lack of hypertrichosis. An atlas illustrates some of the clinical varieties of melanocytic nevi in this syndrome.     

A hypothesis incorporating the histologic characteristics of dysplastic nevi into the normal biological development of melanocytic nevi

A lentiginous pattern of intraepidermal melanocytic hyperplasia, with mild to moderate, random cytologic atypia, forms the conventional basis for the histologic definition of a dysplastic nevus. It is proposed here that these changes actually represent the histologic pattern of a nevus in an active phase of radial growth. The lesser degrees of atypia considered by others to be required for the diagnosis are suggested to overlap changes commonly seen in banal nevi and lentigines. This hypothesis allows the parsimonious concept that a nevus, originating as a lentigo, can at the later sequential junctional, compound, or intradermal stages expand peripherally by a resumption or persistence of the lentiginous pattern of proliferation. The random atypia that is seen in such lesions is suggested to be incidental to the proliferative process rather than indicative of dysplasia as conventionally defined. A familial melanoma-associated phenotype could be accommodated in this model by postulating a heritable defect in mechanisms that control the number or sizes of these hyperplastic lesions.     

Alterations of mismatch repair protein expression in benign melanocytic nevi, melanocytic dysplastic nevi, and cutaneous malignant melanomas

Immunoperoxidase-staining methods were used to examine the expression of hMLH1, hMSH2, and hMSH6 mismatch repair (MMR) proteins in 50 melanocytic lesions. Microsatellite instability (MSI), screened previously in these lesions by polymerase chain reaction-based microsatellite assay, showed low-level microsatellite instability (MSI-L) in 11 of 22 melanocytic dysplastic nevi (MDN) and two of nine primary cutaneous malignant melanomas (CMMs) but not in the benign melanocytic nevi (BN). Mismatch repair proteins were widely expressed in the epidermis and adnexal structures. All lesions showed positive immunoreactivity with a gradual decrease in the MMR staining values during the progression from BN to MDN to CMMs. The average percentage of positively (PP) stained cells for hMLH1, hMSH2, and hMSH6 in BN was 85.50 +/- 1.95, 77.90 +/- 4.50, and 87.11 +/- 1.85, respectively. The PP cell values in CMMs were significantly reduced as compared with BN (75.22 +/- 3.57, p= 0.01; 56.11 +/- 8.73, p= 0.02; 65.22 +/- 6.47, p = 0.0002 for hMLH1, hMSH2, and hMSH6, respectively). No comparable significant difference was found between microsatellite stable and MSI-L lesions (p = 0.173, p = 0.458, and p = 0.385), suggesting a lack of correlation between MMR expression and MMR function. There was a direct correlation between PP cell values of hMSH2 and hMSH6 (R = 0.39, p = 0.008), implying that their expression could be regulated by a common mechanism. Thus, an important finding of these studies was the reduction of MMR protein levels in CMMs; whether this reflects underlying genetic or epigenetic mechanisms is still to be determined.     

Increased intraepidermal melanocyte frequency and size in dysplastic melanocytic nevi and cutaneous melanoma. A comparative quantitative study of dysplastic melanocytic nevi, superficial spreading melanoma, nevocellular nevi, and solar lentigines

Dysplastic melanocytic nevi (DMN) are distinguished histologically by a hyperplasia of variably atypical intraepidermal melanocytes in a lentiginous epidermal pattern. In order to further characterize the intraepidermal melanocytes of DMN, 4 representative specimens each of DMN, acquired nevocellular nevi (NCN), solar lentigines (SL), and superficial spreading melanoma (SSM) were selected on the basis of predetermined criteria, confirmed in a blind histologic assessment, and compared in a quantitative morphologic study using 6 micron-thick hematoxylin and eosin stained sections of L-dihydroxyphenylalanine (dopa) preincubated vertical tissue slices of lesion and adjacent normal skin. The average melanocyte frequency, expressed as the percent of dopa-reactive perikarya among 600 consecutive basal unit cells, was significantly greater in DMN (60 +/- 23%) than in NCN (18 +/- 3%), SL (25 +/- 7%), and adjacent skin (14 +/- 3%), but similar to that in SSM (71 +/- 11%). The average mean diameter of 200 consecutive epidermal basal unit melanocytes was significantly larger in DMN (11 +/- 2 microns) than in NCN (7 +/- 0.4 microns), SL (6 +/- 0.1 microns), and adjacent skin (6 +/- 0.4 microns), but significantly smaller than in SSM (16 +/- 3 microns). The observed similarities of intraepidermal melanocytes in selected DMN and SSM, as well as distinct differences from melanocytes in selected NCN and SL, support the hypothesis that some varieties of DMN may represent potential precursors of cutaneous melanoma.     

Immunohistochemical expression patterns of the microRNA-processing enzyme Dicer in cutaneous malignant melanomas, benign melanocytic nevi and dysplastic melanocytic nevi

Dicer is an essential cytosolic enzyme necessary for processing pre-microRNAs into mature microRNAs (miRNAs). Although a variety of malignancies have been attributed to perturbations in the miRNA machinery, there has been little research conducted on the role of miRNAs in cutaneous malignant melanoma and its premalignant lesions. In this small pilot study, we therefore investigated the distribution of Dicer by immunohistochemistry in cutaneous malignant melanomas, as well as in benign and dysplastic melanocytic nevi. Dicer was assessed in ten cutaneous malignant melanomas (CMM), benign melanocytic nevi (BMN), and dysplastic melanocytic nevi (DMN), by standard immunohistochemical staining. Semiquantitative analyses determined expression indices (EIs), which associate the conventional area fraction of labeled cells with immunostaining intensity scores, based on visual qualitative examination by two independent observers. Mean EI scores were significantly higher in the CMM group compared to those in the BMN group (p??0.05). For CMM we observed a significant correlation of Breslow tumor thickness and Dicer EI (r = 0.84, p = 0.022). For all three groups investigated, Dicer-positive staining was primarily located in the epidermis, specifically in melanocytes. By immunohistochemistry, Dicer staining was significantly higher in melanoma cells than in benign melanocytes. This preliminary study indicates that alterations in the miRNA machinery could exist and should be subject of further investigation.     

HMB-45 staining of dysplastic melanocytic nevi in melanoma risk groups

To evaluate the hypothesis that reactivity of the intradermal component of melanocytic nevi to the monoclonal antibody HMB-45 correlates with melanoma risk, dysplastic compound melanocytic nevi were examined for expression of the HMB-45 epitope in three subject groups differing in epidemiological risk for melanoma. The study groups consisted of 10 subjects with dysplastic nevi and a personal history of melanoma, 25 subjects with dysplastic nevi and a history of melanoma in one or more first degree relatives, and 15 population control subjects with sporadic dysplastic nevi. For each case, sections from one lesion, immunohistochemically processed for HMB-45 binding, were evaluated by two pathologists without knowledge of the clinical data. Of all dysplastic nevi, 98% showed diffusely positive cytoplasmic staining of the junctional nevomelanocytes and 90% had such positive staining of those cells within the superficial dermis. Nevus cells within the deeper dermis did not stain positively in any case. Furthermore, the data showed no differences in frequency, pattern, or intensity of HMB-45 reactivity between the subject groups. These observations indicate that evaluation of dysplastic nevi with the monoclonal antibody HMB-45, an apparent marker of proliferative or otherwise stimulated melanocytes, has no discriminating value for identifying subjects at increased historical risk for melanoma. The data, however, support the concept that so-called dysplasia within nevi, as defined by histologic criteria, actually represents the active or proliferative phase of melanocytic nevi.     

Clinical and dermoscopic features of congenital melanocytic nevi

BackgroundCongenital melanocytic nevi (CMN) are nevomelanocytic nevi which are present at birth. In this study, we set out to determine the clinical and dermoscopic properties of CMN.MethodsA total of 239 lesions were diagnosed as CMN. Dermoscopic properties were noted. Age, sex, nevus location and nevus size of the patients were also collected from the patient records.ResultsA total of 239 lesions were diagnosed as CMN in 239 patients (age ranged from 1 month to 63 years (20.79 ± 13.76 yr); 114 [47.7%] males and 125 [52.3%] females). Most of the lesions were medium-sized CMN, followed by small and large ones. The most common localization was upper extremities (23.8%), followed by head and neck, back, and lower extremities respectively. Dark brown was the most common colour seen in dermoscopy (115 patients, 48.1%), followed by light brown (69 patients, 28.9%) and black (55 patients, 23%) respectively. The most common dermoscopic findings of CMN was hair follicles followed by dots (70%) and perifollicular hypopigmentation (51%).ConclusionsOur study describes the normal clinical and dermoscopic features of CMN. It should be kept in mind that, CMNs are quite common lesions, and melanomas can arise from them. Knowing and being familiar with the normal properties of these common nevi will help us determine whether a nevus is suspicious or not.     

Focal melanocytic atypia in dysplastic nevus cell nevi. Results of a serial section study

Dysplastic nevi were diagnosed according to the ABCDE rule for recognition of early melanomas in 11 patients with familial dysplastic nevus syndrome (DNS) and in 39 patients with the sporadic variant of DNS. All these 50 patients exhibited multiple dysplastic nevi. On routine histological examination melanocytic atypia confirming the histological diagnosis of dysplastic nevus was found only in 12/50 cases. However, when cut consecutively dysplastic nevi with melanocytic atypia were diagnosed in 17 further cases (34%). In most cases (72.4%) only a mild degree of atypia (grade I) was found. Dysplastic nevi with severe melanocytic atypia (grades II-III) were found in all groups of sporadic and familial variants of DNS (with and without melanoma). To improve the prognostic value of the histological examination in dysplastic nevi significantly it must be of interest to add the degree of melanocytic atypia. With increasing degree of melanocytic atypia also the typical histological feature of dysplastic nevi become more significant. Since such atypia in dysplastic nevi is not necessarily sited in the centre of the lesion and since in most cases melanocytic atypia occurs focally, we believe that histological examination of dysplastic nevi must be undertaken by step section. Lesions suspected of being dysplastic nevi must be excised with margins of at least 2-5 mm for a correct histological diagnosis.     

Treatment of melanocytic nevi

Pigmented nevi are a heterogeneous group of lesions that range from uniquely curable with laser treatment, to partially responsive, to unresponsive or dangerous. This article presents laser and IPL treatment strategies from a clinical perspective for nevi organized by their typical responsiveness. A rationale for surgical excision, laser, and/or medical therapy in individual patients is also presented. Despite significant recent progress, it is clear that much understanding are still lacking about optimal laser treatment for pigmented lesions.     

Epiluminescent microscopy score for differential diagnosis of dysplastic nevi]

Specific epiluminescent microscopical criteria of histopathologically defined dysplastic nevi are yet unknown. The diagnostic evaluation of dysplasia and atypia is especially based on microscopic assessment of combined morphologic and coloured details of melanocytic lesions. Differences, skin microscopically analysed, between a group of 55 dysplastic nevi and a comparative group of 130 junctional and compound nevocellular nevi were statistically significant for 12 characteristics. Thus a score could be established for surface microscopic differential diagnosis of dysplastic nevi.