Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi.

INTRODUCTION: The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma. OBJECTIVES: In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN. METHODS: A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination. RESULTS: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%). CONCLUSIONS: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.

Annular Lichenoid Dermatitis (of Youth).

About 20 years after its first description, Annular Lichenoid Dermatitis of Youth (ALDY) is recognized as a distinctive lichenoid dermatosis with specific clinical and histological features. The disease occurs mostly in young persons all over the world, runs a chronic course, and has an obscure etiopathogenesis. Clinically, lesions consist of persistent, asymptomatic erythematous macules and round-oval annular patches with a red-violaceous non-scaling border and central hypopigmentation, mostly localized on the groin and flanks. Histology shows a peculiar lichenoid dermatitis characterized by irregular epidermal hyperplasia with an alternation of thinned and quadrangular rete ridges and a dense band-like lichenoid infiltrate of lymphocytes in the papillary dermis. Typically, there is infiltration of lymphocytes into the lower epidermal layers with massive necrosis/apoptosis of keratinocytes, which is limited to the tips of rete ridges. Dermal lymphocytes are usually CD3+, CD4+, while most of the intraepidermal T cells are CD8+. Analysis of TCR-γ-chain gene rearrangement displayed polyclonality in all cases examined. Differential diagnosis mainly includes morphea, mycosis fungoides, annular erythemas and inflammatory lesions of vitiligo. Topical corticosteroids and topical tacrolimus represent the most effective drugs for ALDY treatment.

Correlation between digital epiluminescence microscopy parameters and histopathological changes in lentigo maligna and solar lentigo: A dermoscopic index for the diagnosis of lentigo maligna.

BACKGROUND: The clinical and dermoscopic differentiation between lentigo maligna (LM) and solar lentigo (SL)/initial seborrheic keratosis (SK) may be difficult. OBJECTIVE: Our aim was to identify digital epiluminescence microscopy (DELM)-specific criteria that can be helpful in distinguishing LM from SL/SK and to propose a new model of LM dermoscopic progression based on a study of DELM-histopathological correlation. METHODS: A total of 167 consecutive doubtful pigmented lesions of the head (105 LM and 62 SL/SK) were studied. DELM assessment was based on the presence or absence of 15 DELM parameters that were subsequently examined histologically. Statistical analysis was performed to determine which DELM parameters were most strongly associated with LM. RESULTS: The finding of at least 1 of 4 parameters (ie, brown globules, a "necklace" pigment network, an atypical pigment network, and dark-brown/blue-gray ribbonlike structures) showed to be an extremely sensitive (99%) and specific (83.9%) DELM criterion to discriminate between LM and SL/SK. LIMITATIONS: Our findings were obtained by examining medium-high magnification DELM images. CONCLUSIONS: The finding of 1 or more among the 4 above-mentioned DELM parameters allows for the correct identification of 99.0% of the LM lesions, and - when the score is 0 - the correct classification as non-LM, of 83.9% of the SL/SK lesions.

Eruptive disseminated Spitz nevi.

BACKGROUND: The solitary form of Spitz nevus is a common clinical entity in children, typically occurring on the face and extremities. However, less frequent variants of Spitz nevi, such as agminated forms and eruptive disseminated Spitz nevi (EDSN), have been described. The agminated form is characterised by localised clusters or segmental distribution of Spitz nevi on the face, back, or extremities. First described as "eruptive juvenile melanomata", EDSN is the rarest clinical variant, consisting of a widespread eruption of Spitz nevi, most frequently involving the trunk, buttocks, and proximal limbs, and usually occurs in the second to third decade of life. OBJECTIVES: To describe a case of EDSN and review the literature. MATERIALS & METHODS: Twenty-seven cases of EDSN, including a 12-year-old female patient with EDSN presented here, were reviewed. RESULTS: EDSN generally exhibits an abrupt, eruptive onset (developing over few months), followed by a slow progressive course of new lesions that continue to appear over a long period, resulting in hundreds of papules and nodules. In all reported cases, the EDSN lesions involved the trunk, often affecting the legs and arms, and sometimes the scalp. A number of possible precipitating factors were reported. CONCLUSION: A periodic self-examination, total body photography, a dermoscopic 3-6-month follow-up during the eruptive phase (extending to 9-12 months during the stable phase), and prompt surgical excision of lesions that may be malignant is recommended, however, to date, no malignant transformation of EDSN has been reported.

Prior knowledge of the clinical picture does not introduce bias in the histopathologic diagnosis of melanocytic skin lesions.

A common debate among dermatopathologists is that prior knowledge of the clinical picture of melanocytic skin neoplasms may introduce a potential bias in the histopathologic examination. Histologic slides from 99 melanocytic skin neoplasms were circulated among 10 clinical dermatologists, all of them formally trained and board-certified dermatopathologists: 5 dermatopathologists had clinical images available after a 'blind' examination (Group 1); the other 5 had clinical images available before microscopic examination (Group 2). Data from the two groups were compared regarding 'consensus' (a diagnosis in agreement by ≥4 dermatopathologists/group), chance-corrected interobserver agreement (Fleiss' k) and level of diagnostic confidence (LDC: a 1-5 arbitrary scale indicating 'increasing reliability' of any given diagnosis). Compared with Group 1 dermatopathologists, Group 2 achieved a lower number of consensus (84 vs. 90) but a higher k value (0.74 vs. 0.69) and a greater mean LDC value (4.57 vs. 4.32). The same consensus was achieved by the two groups in 81/99 cases. Spitzoid neoplasms were most frequently controversial for both groups. The histopathologic interpretation of melanocytic neoplasms seems to be not biased by the knowledge of the clinical picture before histopathologic examination.

Tumor-infiltrating lymphocytes predict cutaneous melanoma survival.

Understanding differences in survival across distinct subgroups of melanoma patients may help with the choice of types of therapy. Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the role of TILs in melanoma mortality is controversial. The aim of this study was to investigate independent prognostic factors for melanoma mortality. We carried out a 10-year cohort study on 4133 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 1998 and December 2008. The probability of survival was estimated using Kaplan-Meier methods and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). The 10-year survival rate for melanoma decreased with increasing Breslow thickness (Pfor trend<0.0001) and with age (Pfor trend<0.0001) whereas survival increased with increasing levels of TILs (Pfor trend=0.0001). The 10-year survival rate for melanoma divided into TILs intensity as scanty, moderate, and marked was 88.0, 92.2, and 97.0%, respectively. In the multivariate Cox model, the presence of high levels of TILs in primary invasive melanomas was associated with a lower risk of melanoma death (hazard ratio 0.32; 95% confidence interval 0.13-0.82) after controlling for sex, age, Breslow thickness, histological type, mitotic rate, and ulceration. After including lymph node status in the multivariate analysis, the protective effect of marked TILs on melanoma mortality remained (hazard ratio 0.37; 95% confidence interval 0.15-0.94). The results of this study suggest that the immune microenvironment affects melanoma survival.

Spiky follicular mycosis fungoides: a clinicopathologic study of 8 cases.

BACKGROUND: The early stages of follicular mycosis fungoides (FMF) have not been described previously in the literature. OBJECTIVE: Our goal was to better categorize the clinicopathologic features of early stages of FMF. METHODS: The clinical notes of patients with a diagnosis of FMF seen during the previous 5 years were reviewed to identify any cases that at presentation had only hyperkeratotic follicular lesions. RESULTS: Eight patients (five male, three female) with a mean age of 55.4 years were enrolled. Noteworthy, FMF was not a clinical consideration in any of these patients initially. Patients presented with disseminated, slightly erythematous, hyperkeratotic, spiky follicular papules which, histopathologically, showed hyperkeratotic columns protruding from follicular plugging in concert with selective infiltration of the infundibular epithelium by atypical, mostly CD4+, lymphocytes. T-cell clonality was demonstrated in four of eight cases. The mean duration of the lesions before diagnosis was 17.1 months. The course was indolent in most of the cases (median follow up: 18 months), whilst progression to overt FMF was noted in two patients. LIMITATIONS: The number of cases is small and follow up relatively short. CONCLUSIONS: Spiky FMF is a deceptive clinicopathologic presentation of FMF that has been poorly described and that can mimic numerous follicular disorders.

Systematized organoid epidermal nevus with eccrine differentiation, multiple facial and oral congenital scars, gingival synechiae, and blepharophimosis: a novel epidermal nevus syndrome.

Epidermal nevus syndrome is a clinically variable and genetically heterogeneous group of mosaic conditions characterized by the concurrence of extensive epidermal nevus with additional cutaneous and extracutaneous manifestations. This term groups together well-characterized clinical entities, as well as dozens of apparently unique associations, which need further delineation. We report on a 23-year-old woman presenting the previously undescribed combination of widespread eccrine proliferation, multiple facial and oral pox-like lesions, gingival synechiae, blepharophimosis, body asymmetry, and mental retardation. The patient has a healthy monozygotic twin. The eccrine proliferation is intermingled with areas of unaffected skin with a linear/segmental distribution on the limbs. The clinical presentation of such a complex phenotype fits well with the genetic mosaicism theory. The histologic findings, consisting of proliferation of immature to well-formed eccrine duct-like structures located in the deep dermis and interspersed with an abundant fibrous stroma constituted of horizontally oriented collagen fibers, seem a possible hallmark of this condition.

CDKN2A and MC1R analysis in amelanotic and pigmented melanoma.

Amelanotic melanoma (AM) is a rare subtype of melanoma with little or no clinically visible pigment; it is more difficult to diagnose than pigmented melanoma (PM), and has a worse prognosis. In the attempt to find a genetic explanation for the distinction between AM and PM, we conducted a case-case study, matching AM and PM patients, and testing them for germline mutations in high- (p16INK4A, p14ARF, CDK4) and low-penetrance (MC1R) melanoma susceptibility genes. Similar CDKN2A mutations were found in both sets of melanomas. A p14ARF splice germline mutation was detected for the first time in an Italian family with AM. This rare mutation, which has been described only once previously, may be involved in predisposition to the amelanotic phenotype in combination with germline MC1R variants and coordinate somatic expression of pigmentation genes and their regulators.

Schöpf-Schulz-Passarge syndrome: further delineation of the phenotype and genetic considerations.

Schöpf-Schulz-Passarge syndrome is a rare ectodermal dysplasia, characterized chiefly by multiple eyelid apocrine hidrocystomas, palmo-plantar keratoderma, hypodontia, hypotrichosis and nail dystrophy. The clinical spectrum and the most likely inheritance pattern(s) have not yet been completely defined. We report here on two, unrelated patients presenting with additional, previously unreported features, including hypoplastic nipples and optic atrophy. Both individuals were born to consanguineous parents, and one also has affected siblings. A literature review identified 23 additional cases. Multiple eyelid apocrine hidrocystomas, described in all of the cases, are the hallmark of this condition, although they usually appear in adulthood. The concomitant presence of eccrine syringofibroadenoma in most patients and of other adnexal skin tumours in 44% of affected subjects indicates that Schöpf-Schulz-Passarge is a genodermatosis with skin appendage neoplasms. However, the risk of skin and visceral malignancies is not increased. Pedigree study demonstrates that 9 of the 13 published familial cases may be explained by an autosomal recessive mutation, while the remaining pedigrees show apparent vertical transmission compatible with genetic heterogeneity. The benign disease course and advanced age at diagnosis could also suggest locus homogeneity for a recessive mutation with instances of pseudodominant inheritance.

Sensitivity, specificity, and diagnostic accuracy of three dermoscopic algorithmic methods in the diagnosis of doubtful melanocytic lesions: the importance of light brown structureless areas in differentiating atypical melanocytic nevi from thin melanomas.

BACKGROUND: Over the past decade numerous epiluminescence microscopy (ELM) criteria and algorithmic methods have been developed to improve the diagnosis of cutaneous melanocytic lesions. OBJECTIVE: Our purpose was to compare the sensitivity, specificity, and diagnostic accuracy of 3 algorithmic methods (pattern analysis, ABCD rule of dermoscopy, and the 7-point checklist) on a series of highly atypical melanocytic lesions. We also determined the diagnostic value of distinct ELM structures by evaluating their frequency in these lesions. METHODS: A total of 198 consecutive atypical macular melanocytic lesions were studied. ELM assessment was based on the presence or absence of 23 dermoscopic features. Two ELM-experienced dermatologists classified each lesion as benign or malignant using the pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist method. After surgical excision, 102 lesions were histologically diagnosed as Clark's nevi and 96 as thin melanomas (TMs) (mean tumor thickness, 0.3 mm). ELM and histologic diagnoses were then compared to assess the sensitivity, specificity, and diagnostic accuracy as well as positive and negative predictive values (PPV and NPV, respectively) for TMs of the 3 algorithmic methods. Univariate and multivariate analyses were performed to determine which ELM criteria were most strongly associated with TM. RESULTS: Of the melanocytic lesions studied, 82.3% were correctly diagnosed by using pattern analysis (85.4% sensitivity, 79.4% specificity, 79.6% PPV, and 70.8% diagnostic accuracy), compared with correct diagnosis of 79.3% (84.4% sensitivity, 74.5% specificity, 75.7% PPV, and 67.8% diagnostic accuracy) and 71.2% (78.1% sensitivity, 64.7% specificity, 67.6% PPV, and 57.7% diagnostic accuracy) with the ABCD and the 7-point checklist methods, respectively. The 7-point checklist yielded the highest number of false-negative results (21.8%) with respect to the ABCD rule (15.6%) and pattern analysis (14.6%). Univariate analysis showed that an atypical pigment network, a pigment network with sharp margins, irregular nonuniform brown globules, a nonuniform pigment distribution, homogeneous areas, and light brown structureless areas were the most sensitive and specific ELM features for TM. A backward stepwise logistic regression analysis revealed that the criterion with the strongest TM association was light brown structureless areas (odds ratio = 27.9; 95% confidence interval, 8.6-90.9). LIMITATIONS: The presence and value of light brown structureless areas should also be investigated in clinically nonatypical macular melanocytic lesions. CONCLUSION: The pattern analysis method showed the highest sensitivity, specificity, and diagnostic accuracy for TM. Light brown structureless areas were both a statistically significant discriminator and the most reliable predictor of TM (PPV = 93.8%, positive likelihood ratio = 16). Therefore the use of this previously underestimated ELM criterion may not only improve diagnostic performance of equivocal macular melanocytic lesions but also significantly decrease the rate of false-negative results obtained with the 7-point checklist method.