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More than one shade of pink as a marker of early amelanotic/hypomelanotic
Abstract
Amelanotic/hypomelanotic melanoma (AHM) may be difficult to diagnose because of a lack of pigmentation. To evaluate whether dermoscopy can be useful for the diagnosis of early AHM, 133 digital dermoscopic images of lesions histopathologically diagnosed as amelanotic/hypomelanotic superficial spreading melanoma with ≤1 mm thickness (AHSSMs) ( n = 27), amelanotic/hypomelanotic non‐melanocytic lesions (AHNMLs) (e.g., seborrhoeic keratosis and basal cell carcinoma) ( n = 79), and amelanotic/hypomelanotic benign melanocytic lesions (AHBMLs) (e.g., compound and dermal nevi) ( n = 27), were dermoscopically assessed by three blinded dermatologists. Using multivariate analysis, we found a significantly increased risk of diagnosing AHSSM versus AHNML and AHBML when the lesion was characterized by the presence of more than one shade of pink (odds ratio [OR] 37.11), irregular dots/globules (OR 23.73), asymmetric pigmentation (OR 8.85), and structureless pattern (OR 7.33). In conclusion, dermoscopy may improve early AHM detection, discriminating AHSSM from AHNMLs.
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Background:
Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage.
Objectives:
To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM.
Methods:
Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria.
Results:
Overall 224 lesions in 216 patients including LM/LMM (n=55, 24.6%), AHBL (n=107, 47.8%), and AHBCC/AHSCC (n=62, 27.7%) were analyzed. Multivariable analysis showed that milky-red areas (OR=5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR=19.10; 4.45-81.96), linear irregular vessels (OR=5.44; 1.45-20.40), and asymmetric pigmented follicles (OR=14.45; 2.77-75.44) at dermoscopy, and ≥ 3 atypical cells in 5 fields (OR=10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR=10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR=7.11; 1.53-32.96), pseudonetwork around hair follicles (OR=16.69; 2.73-102.07), and annular granular structures (OR=42.36; 3.51-511.16) at dermoscopy and large dendritic (OR=6.86; 3.15-38.28) and round pagetoid cells (OR=26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM.
Conclusions:
AHLM/LMM may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion.
Background
Dermoscopy increases the sensitivity of the diagnosis of melanoma, leading to its early identification and increasing the chances of cure.
Objective
To describe the clinical and dermoscopic characteristics of superficial spreading melanomas, and to detect the differences between in situ and invasive 1-mm thick melanomas.
Methods
This was a cross-sectional study in which dermoscopic images of 58 melanomas, grouped according to their thickness, were evaluated.
Results
24 in situ melanomas were evaluated, 28 invasive melanomas with Breslow ≤ 1 mm (0.50 ± 0.22 mm) and six with Breslow > 1 mm (2.35 ± 2.02 mm). In situ melanomas were smaller than invasive melanomas. The most commonly found dermoscopic criteria were asymmetry (84.5%), three or more colors (81.0%), and atypical network (79.3%). A non-specific pattern was more common in in situ melanomas (p = 0.028) and atypical network in invasive melanomas with Breslow 1 mm presented inverted network (p = 0.018).
Study limitations
The sample was selected by convenience, since it was necessary to have a preoperative photo of the tumor, which may have led to the loss of clinically less significant lesions, as well as those highly suggestive of melanoma.
Conclusions
Melanomas in early stages showed a more frequent nonspecific pattern and atypical network, while invasive melanomas showed a multicomponent pattern, three or more colors, and an inverted network.
Background. In dermoscopic images, multiple shades of pink have been described in melanoma without specifying location of these areas within the lesion. Objective. The purpose of this study was to determine the statistics for the presence of centrally and peripherally located pink melanoma and benign melanocytic lesions. Methods. Three observers, untrained in dermoscopy, each retrospectively analyzed 1290 dermoscopic images (296 melanomas (170 in situ and 126 invasive), 994 benign melanocytic nevi) and assessed the presence of any shade of pink in the center and periphery of the lesion. Results. Pink was located in the peripheral region in 14.5% of melanomas and 6.3% of benign melanocytic lesions, yielding an odds ratio of 2.51 (95% CI: 1.7-3.8, P < 0.0001). Central pink was located in 12.8% of melanomas and 21.8% of benign lesions, yielding an odds ratio of 0.462 (95% CI: 0.67, P = 0.204). Pink in melanoma in situ tended to be present throughout the lesion (68% of pink lesions). Pink in invasive melanoma was present in 17% of cases, often presenting as a pink rim. Conclusions. The presence of pink in the periphery or rim of a dermoscopic melanocytic lesion image provides an indication of malignancy. We offer the "pink rim sign" as a clue to the dermoscopic diagnosis of invasive melanoma.
To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma.
A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions.
Predominantly hospital-based clinics from 5 continents.
Sensitivity, specificity, and odds ratios for individual features and models for the diagnosis of melanoma and malignancy.
The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09; 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10; 0.01-0.70), comma vessels as the predominant vessel type (0.16; 0.05-0.52), symmetrical pigmentation pattern (0.18; 0.09-0.39), irregular blue-gray globules (0.20; 0.05-0.87), and multiple blue-gray globules (0.28; 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13; 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4; 2.4-8.0), multiple blue-gray dots (3.5; 1.9-6.4), irregularly shaped depigmentation (3.3; 2.0-5.3), irregular brown dots/globules (3.2; 1.8-5.6), 5 to 6 colors (3.2; 1.6-6.3), and predominant central vessels (3.1; 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. Conclusion Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.
Background
Atypical intraepidermal melanocytic proliferations (AIMP) is a descriptive term sometimes applied to biopsies that do not fulfill diagnostic criteria of melanoma. They are common on sun-damaged skin, but their definition and management are controversial.
Objective
To describe dermoscopic (DS), reflectance confocal microscopic (RCM) and histopathological features of AIMP and identify features associated with subsequent melanoma in situ (MIS).
Methods
A retrospective analysis of AIMP lesions correlated with patient outcome at two melanoma tertiary centers between 2005 and 2015.
Results
Thirty-four patients were included. Nine (26%) patients had MIS in subsequent biopsies. Predictors of later MIS were target-like pattern (OR:12.0 [CI: 1.23, 117.41]; P = 0.032) and high-density vascular network (OR:12 [CI: 1.23–117.41], P: 0.032) on DS, and presence of dendritic cells touching each other (OR:9.1 [CI: 1.54, 54.59], P = 0.014) on RCM. Clinical predictors of worse outcome included a previous history of MIS at the same site. Radiotherapy for AIMP had a high failure rate (all patients presented with recurrent disease, three as AIMP and two as MIS).
Conclusions
Considering that most cases in this series received non-surgical treatment at baseline, we recommend close monitoring for lesions with target-like pattern and density vascular network on DS and treatment for lesions with progression of atypia and/or with “confluent” dendritic cells on RCM. Although the number of patients in this series is very low, early surgery is recommended for MIS cases that recur as AIMP.
In non‐pigmented skin tumors the diagnosis is mainly based on the evaluation of the vascular morphology and vessels´ distribution dermoscopically [1‐4]. However, up to date, no study formally correlated the prevailing vascular morphology with the thickness of melanoma according to Breslow and amount of pigmentation.
Background
Pink skin tumors are difficult to differentiate, clinically and dermoscopically. In previous studies, mainly focused on pigmented lesions, pattern analysis provided the best sensitivity and specificity values, as compared to other algorithms. These findings suggest that the global dermoscopic appearance, based on the evaluation of prevalent features, could represent a valuable and practical approach even when dealing with pink lesions.
Objective
In this study we aimed to evaluate the diagnostic accuracy of a new dermoscopic approach for pink tumors based on the prevalent criterion, as compared to a standard diagnostic method (Menzies algorithm).
Methods
The databases of two referral centers were retrospectively evaluated to retrieve dermoscopic images of amelanotic/hypomelanotic skin lesions. Two experts in dermoscopy, blinded for the final diagnosis and for clinical and demographic information, evaluated separately dermoscopic pictures of 1000 lesions according to the Menzies score and to the prevalent criterion method.
Results
According to the high sensitivity model of the Menzies score, 129 (12.9%) lesions were considered as non‐suspicious (of which 16 were false negative) and 871 (87.1%) as suspicious (of which 212 were false positive), with 97.6% sensitivity, 34.8% specificity. According to the high specificity model, 370 (37%) lesions were evaluated as non‐suspicious (of which 105 were false negative) and 630 (63%) as suspicious (of which 60 were false positive), with 84.4% sensitivity, 81.5% specificity.
Concerning the prevalent criterion method, 316 (31.6%) lesions were evaluated as non‐suspicious (of which 46 were false negative) and 684 (68.4) as suspicious (of which 55 were false positive), with 93.2% sensitivity and 83.1% specificity.
Conclusions
This study demonstrated that focusing on the prevalent dermoscopic features could allow to detect malignant pink tumors with similar sensitivity but higher specificity than using the conventional Menzies scoring system.
This article is protected by copyright. All rights reserved.
Cutaneous amelanotic melanoma (AM) is a rare amelanotic or a hypomelanotic subtype of melanoma, comprising only 0.4–27.5% of all melanoma cases. The mean age of the patients is over 50 years, and the male/female ratio varies from 0.5 to 4. Patients with red hair, type I skin, freckles, lack of nevi on the back, a sun-sensitive phenotype, or previous AM history are more likely to develop AMs. As AMs lack pigmentation, their appearances vary and can mimic many benign and malignant conditions, thus presenting a diagnostic challenge. AMs are composed of greater proportions of nodular melanoma, acral lentiginous melanoma, and desmoplastic melanoma than pigmented melanomas. They also present with thicker Breslow thickness, higher mitotic rate, more frequent ulceration, higher tumor stage, and lower survival than pigmented melanomas.
Dermoscopy is increasingly used by clinicians (dermatologists, family physicians, podiatrists, doctors of osteopathic medicine, etc.) to inform clinical management decisions. Dermoscopic findings and/or images provided to pathologists offer an important insight into the clinician's diagnostic and management thought process. However, with limited dermoscopic training in dermatopathology, dermoscopic descriptions and images provided in the requisition form will provide little value to pathologists. Since most dermoscopic structures have direct histopathological correlates, dermoscopy can act as an excellent communication bridge between the clinician and the pathologist. In the first article of this continuing medical education series we review dermoscopic features and their histopathologic correlates.
Background:
The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge.
Objective:
This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma.
Methods:
A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed.
Results:
There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account.
Limitations:
Single tertiary referral center.
Conclusion:
Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.
Amelanotic/hypomelanotic melanoma (AHM) is a subtype including melanomas with little or no melanin pigmentation, amelanotic melanoma (AM); it represents 2-8 % of all melanomas.1-2 AM may be difficult to diagnose because of lack of pigmentation and symmetry: recently, germline mutations have been reported in the MC1R gene and to a certain extent also in the MITF gene.3 This article is protected by copyright. All rights reserved.
Angiogenesis plays a crucial role in melanoma metastasis and progression. In recent years, numerous studies have investigated the prognostic and clinical significance of this phenomenon, and the development of molecular techniques has enabled us to achieve a better understanding of angiogenesis in melanoma. Herein, we review the current state of knowledge regarding angiogenesis in melanoma, including the pathophysiological, histological and immunohistochemical aspects of this phenomenon. We also review the molecular pathways involved in angiogenesis and the interplay between different components that might be manipulated in the future development of efficient targeted therapies. Recently developed targeted antiangiogenic therapies in clinical trials and included in the treatment of advanced-stage melanoma are also reviewed.
Dermoscopy is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumors. This is because dermoscopy permits the visualization of key vascular structures that are usually not visible to the naked eye. Much work has concentrated on the identification of specific morphologic types of vessels that allow a classification into melanocytic versus nonmelanocytic and benign versus malignant nonpigmented skin tumors. Among a broad spectrum of different types of vascular patterns, six main morphologies can be identified. These are comma-like, dotted, linear-irregular, hairpin, glomerular, and arborizing vessels. With some exceptions, comma, dotted, and linear irregular vessels are associated with melanocytic tumors, while the latter three vascular types are generally indicative of keratinocytic tumors. Aside from vascular morphology, the architectural arrangement of vessels within the tumor and the presence of additional dermoscopic clues are equally important for the diagnosis. This article provides a general overview of the dermoscopic evaluation of nonpigmented skin tumors and is divided into two parts. Part I discusses the dermoscopic vascular patterns of benign and malignant melanocytic skin tumors. Part II discusses the dermoscopic vascular patterns of benign and malignant nonmelanocytic nonpigmented skin tumors. In each part, additional special management guidelines for melanocytic and nonmelanocytic nonpigmented skin tumors, respectively, will be discussed.
The capacity of cutaneous malignant melanoma (CMM) to induce angiogenesis is well established. In addition, dysplastic melanocytic nevi (DMN) have been reported to display prominent vascularity relative to common acquired nevi; but this observation has never been verified objectively.
In the following studies, papillary dermal or tumor vascularity was quantified in 10 examples of normal skin, and in a series of 18 melanocytic nevi, 29 DMN, 37 primary CMM and 5 melanoma metastases. Microvessels were identified with the lectin Ulex europaeus agglutinin I. The number of microvessels were counted with an ocular grid (area 7.84 x 10(-2) mm2) at x400 magnification, and the mean vascularity recorded for five fields for each specimen.
Mean vascular counts were as follows: normal skin 5.9, common acquired nevus 9.1, nevus with features of DMN 10.3, DMN, slight atypia 11.8; DMN, moderate atypia 12.2; DMN, severe atypia 14.8; primary CMM 25.4; and metastatic melanoma 29.5). Significant differences were recorded for DMN, severe atypia versus melanoma (p less than 0.01), DMN, severe versus common nevi (p less than 0.02) and versus nevi with features of DMN (P less than 0.05). When microvessel counts from CMM in the radial growth phase were compared with those from CMM in the vertical growth phase, or CMM less than 1.0 mm versus those greater than 1.0 mm, no significant differences were found. However, CMM in radial growth did differ from severely atypical DMN (22.4 versus 14.8, p less than 0.05).
These results quantify for the first time a gradual rise in vascularity with tumor progression in the melanocytic system and onset of angiogenesis during the radial growth phase of CMM. Other than severely atypical DMN, DMN did not differ substantially from common nevi with reference to overall vascularity.
Amelanotic malignant melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. It may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions.
To evaluate whether dermoscopy is also a useful technique for the diagnosis of amelanotic/hypomelanotic melanoma (AHM).
We conducted a retrospective clinical study of 151 amelanotic/hypomelanotic skin lesions from 151 patients with a mean age of 47 years (+/- 17.5 SD). Digitized images of amelanotic/hypomelanotic skin lesions were converted to JPEG format and sent by e-mail from the five participating centres. Lesions included 55 amelanotic/hypomelanotic nonmelanocytic lesions (AHNML), 52 amelanotic/hypomelanotic benign melanocytic lesions (AHBML), and 44 AHM, 10 (23%) of which were nonpigmented, truly amelanotic melanomas (AM). The 44 AHM lesions were divided into thin melanomas (TnM) </= 1 mm (29 cases) and thick melanomas (TkM) > 1 mm (15 cases), according to the Breslow index. Five clinical features (elevation, ulceration, shape, borders and colour) as well as 10 dermoscopic criteria (pigment network, pigmentation, streaks, dots/globules, blue-whitish veil, regression structures, hypopigmentation, leaf-like areas, multiple grey-bluish globules, central white patch) and eight vascular patterns (comma, arborizing, hairpin, dotted, linear irregular, dotted and linear irregular vessels, and milky-red areas) were evaluated in order to achieve clinical and dermoscopic diagnoses. Statistical analyses were performed with the chi2-test and Fisher's exact test, when appropriate.
The most frequent and significant clinical features for TnM and TkM were asymmetry and ulceration (the latter only for TkM) compared with AHBML. Irregular dots/globules (62% vs. 35%; P </= 0.03), regression structures (48% vs. 27%; P </= 0.03), irregular pigmentation (41% vs. 11%; P </= 0.03) and blue-whitish veil (10% vs. 0%; P </= 0.03) were the most relevant dermoscopic criteria for TnM in comparison with AHBML. TkM differed significantly from AHBML in frequency of occurrence of irregular pigmentation (87% vs. 11%; P </= 0.03), irregular dots/globules (73% vs. 35%; P </= 0.03), regression structures (67% vs. 27%; P </= 0.03), blue-whitish veil (27% vs. 0%; P </= 0.03) and hypopigmentation (13% vs. 55%; P </= 0.03). Linear irregular vessels and the combination of dotted and linear irregular vessels associated with TnM and TkM were not found in our cases of AHBML and were only rarely seen in AHNML (3.6% and 1.8%, respectively). Moreover, TkM differed significantly from AHBML and TnM in frequency of occurrence of milky-red areas (93% vs. 17%; P </= 0.03 and 93% vs. 31%; P </= 0.01, respectively). The dermoscopic diagnosis of melanoma had a higher sensitivity and specificity than the clinical diagnosis (89% and 96% vs. 65% and 88%, respectively). With the limitation of the small number of cases, vascular patterns were the only dermoscopic criteria for 'truly' AM. In the 10 cases of 'truly' AM, we found milky-red areas in more than half of the cases (six of 10), dotted vessels in four, hairpin vessels in two, linear irregular vessels in two, dotted and linear irregular vessels in two.
Because dermoscopy uses criteria reflecting pigmentation (irregular pigmentation and irregular dots/globules) and vascular patterns, it is a useful technique not only for pigmented melanoma but also for hypomelanotic melanoma. In 'truly' AM, vascular patterns alone may not be sufficient to diagnose melanoma. A combined approach with the clinical information should help in the detection of 'truly' AM.