Early acral melanoma in situ: correlation between the parallel ridge pattern on dermoscopy and microscopic features

In non-white populations, acral skin is the most prevalent site of malignant melanoma. Early melanomas of this anatomic site are often misdiagnosed as melanocytic nevi, which are not uncommon on acral skin. In fact, clinical and/or histopathological features of melanocytic nevi occasionally mimic those of early acral melanoma and vice versa, and thus differentiation of early acral melanoma from melanocytic nevus is sometimes very difficult for clinicians as well as for histopathologists. Our dermoscopic investigation has revealed that the parallel ridge pattern, a band-like pigmentation on the ridges of the skin markings, is highly specific to malignant melanoma in situ on acral volar skin. In the present study, we reviewed 22 acral melanocytic lesions that showed the parallel ridge pattern on dermoscopy but had very subtle clinical and/or histopathological presentations. We diagnosed 20 of them as early melanoma in situ by careful histopathological examination, which revealed histopathological features very similar to those seen in macular portions of overt acral melanoma, but fundamentally different from features found in melanocytic nevi on acral skin. In correspondence with their dermoscopic pattern, in these early lesions of acral melanomas, proliferation of solitary arranged melanocytes was mainly detected in the crista profunda intermedia, the epidermal rete ridge underlying the ridge of the skin marking. The two remaining lesions were diagnosed as possible cases of acquired melanocytic nevus because of the formation of well-demarcated nests of melanocytes in the epidermal rete ridges. We propose that a finding of preferential proliferation of solitary arranged melanocytes in the crista profunda intermedia is an important clue for the histopathological diagnosis of early phases of acral melanoma.     

Homogeneous blue pattern in an acral congenital melanocytic nevus

Dermoscopy in acquired acral melanocytic nevi has been widely studied. This is in contrast with the little information about the dermoscopic characteristics in congenital acral melanocytic nevi. We report a 46-year-old man who was referred due to a lesion on his right sole present since childhood corresponding to an acral congenital nevus. Dermoscopy showed a homogeneous blue pattern not previously described in acral benign tumors. The homogeneous blue pattern has previously been associated with blue nevus and skin metastasis of melanoma. The recognition of this pattern in benign acral congenital nevi is relevant in the clinical decision making concerning acral tumors.     

178例掌跖部位黑素细胞性皮损的皮肤镜特点

目的 探讨掌跖部位黑素细胞性皮损的皮肤镜特点。方法 回顾性分析2009年9月至2011年10月在北京大学第一医院皮肤科行皮肤镜检查的掌跖部位黑素细胞性皮损的皮肤镜图像。结果 共分析了121例患者的155个良性黑素细胞性损害,22例患者的23个黑素瘤皮损。掌跖部位良性黑素细胞性皮损中最多见的皮肤镜模式为平行沟模式（占34.2%）,其次为纤维样模式（占22.6%）,有2个（1.3%）良性皮损表现为平行脊结构。23个黑素瘤皮损中12个（52.2%）出现平行脊结构,14个（60.9%）出现弥漫不规则的色素,且后者见于所有侵袭性黑素瘤中。纤维样结构作为肢端色素痣常见的一种良性皮肤镜模式,亦见于39.1%的黑素瘤中。结论 皮肤镜在区分掌跖部位良性黑素细胞痣和黑素瘤方面有一定价值     

Specific dermoscopy patterns and amplifications of the cyclin D1 gene to define histopathologically unrecognizable early lesions of acral melanoma in situ

OBJECTIVE: To define early lesions of acral melanoma in situ that cannot be recognized histopathologically. DESIGN: A retrospective review of the clinical, dermoscopic, and histopathological findings. SETTING: University department of dermatology. PATIENTS: Thirty-three patients with melanocytic lesions on acral volar skin that were clinically suspected of being early melanomas. MAIN OUTCOME MEASURES: Fluorescent in situ hybridization studies to detect the cyclin D1 gene amplification in proliferating melanocytes, which is a characteristic genetic aberration recently found in acral melanoma. RESULTS: Seventeen of 33 lesions were histopathologically diagnosed as either melanoma in situ (8 lesions) or benign melanocytic nevi (9 lesions). Amplification of the cyclin D1 gene was observed in 2 (25%) of the 8 melanomas in situ. None of the 9 nevi showed the amplification. The remaining 16 lesions were, however, difficult to classify histopathologically because most of them showed only a slight increase of nonatypical melanocytes in the basal cell layer of the epidermis. On dermoscopic examination, 9 of these 16 lesions exhibited the parallel ridge pattern that has been reported to be highly specific to melanoma in situ, and 4 (44%) of them had amplifications of the cyclin D1 gene. Amplifications were not found in any of the remaining 7 lesions that showed dermoscopic patterns suggestive of melanocytic nevi. CONCLUSIONS: Cyclin D1 gene amplification detected by fluorescent in situ hybridization identified a very early progression phase of acral melanoma that precedes histopathologically defined melanoma in situ. The present study also indicates the specificity of the parallel ridge pattern on dermoscopy to detect melanomas on acral volar skin at such a very early developmental phase.     

Key points in dermoscopic differentiation between early acral melanoma and acral nevus

Acral skin is the most prevalent site of malignant melanoma in non-Caucasian populations. On acral skin, other various kinds of pigmented lesions are also detected. Particularly, melanocytic nevus is commonly seen on acral volar skin; approximately 10% of Japanese have a nevus on their soles. Prognosis of acral melanoma is still generally poor because of delayed detection in the advanced stages. To improve the prognosis, early detection is essential. Early acral melanoma is seen as a brownish macule, which is clinically quite similar to acral nevus. Therefore, clinicians often face a dilemma when they see a pigmented macule on acral volar skin. Introduction of dermoscopy was a great epoch in this field. Pigmentation pattern on dermoscopy is completely opposite between early acral melanoma and acral nevus; pigmentation on the ridges of the surface skin markings is detected in early acral melanoma, whereas pigmentation along the furrows of the skin markings is seen in acral nevus. We termed these dermoscopic patterns the parallel ridge pattern and the parallel furrow pattern, respectively. These features are highly helpful in the differentiation between the two biologically distinct entities. The sensitivity and specificity of the parallel ridge pattern in diagnosing early acral melanoma is 86% and 99%, respectively. However, we must be aware that dermoscopic features in acral nevus sometimes mimic the parallel ridge pattern and that other conditions also could show dermoscopic features similar to the parallel ridge pattern. In this review article, we summarize key points of the dermoscopic diagnosis of early acral melanoma and then describe the three-step algorithm for the management of acral melanocytic lesions, which surely aids us in effectively detecting early acral melanoma and in reducing unnecessary resection of benign nevus.     

Dermoscopic Findings of an Unusual Acral Nevus on the Hand of a Child

Distinguishing benign acral nevi from small early acral melanomas may be challenging in certain cases. Dermoscopy is a noninvasive imaging technique that can help clinicians better visualize deeper lesion structures and thus more easily differentiate benign nevi from melanoma. We report the case of a 13‐year‐old girl with a changing dark brown to black macule with a central papular component on the volar surface of the right third finger. Dermoscopy revealed asymmetrically distributed irregular black blotches on a bluish‐black background. Histopathology revealed a traumatized compound melanocytic nevus. Certain melanocytic nevi, although histologically benign, may not conform to the limited selection of reassuring benign dermoscopic patterns. Nevi in children are often dynamic and have a high likelihood of dermoscopic change.     

Significance of dermoscopic patterns in detecting malignant melanoma on acral volar skin: results of a multicenter study in Japan

OBJECTIVE: To determine diagnostic variables such as sensitivity and specificity of the major dermoscopic patterns observed in melanocytic lesions on acral volar skin, with particular attention to the significance of the parallel ridge pattern and irregular diffuse pigmentation in detecting acral melanoma. DESIGN: Multicenter, retrospective study. SETTING: University hospitals in Japan. PATIENTS: Patients with melanocytic lesions on acral volar skin. A total of 712 melanocytic lesions (103 malignant melanomas, including 36 in situ lesions, and 609 melanocytic nevi) were consecutively collected from the files of 3 hospitals. Diagnoses of all the lesions had been determined histopathologically. INTERVENTIONS: Dermoscopic examination. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the major dermoscopic patterns seen in benign and malignant melanocytic lesions on acral volar skin. RESULTS: The parallel ridge pattern and irregular diffuse pigmentation showed extremely high specificity (99.0% and 96.6%, respectively) and very high negative predictive value (97.7% and 97.5%, respectively) in malignant melanoma. For melanoma in situ, the positive predictive value and diagnostic accuracy of the parallel ridge pattern were significantly higher than those of irregular diffuse pigmentation (P = .009 and P = .006, respectively). In melanocytic nevi, the specificity and positive predictive value of the parallel furrow pattern and/or the latticelike pattern were found to be very high (93.2% and 98.3%, respectively). CONCLUSIONS: Dermoscopy is immensely helpful in differentiating malignant melanomas from melanocytic nevi on acral volar skin. Moreover, the parallel ridge pattern aids in detecting acral melanomas in early, curable stages.     

Dermoscopy of a plantar combined blue nevus: a simulator of melanoma

Dermoscopy allows early detection of melanoma also on acral volar skin. The majority of melanocytic nevi on palms and soles may show three major dermoscopic patterns: the parallel-furrow pattern, the lattice-like pattern, and the fibrillar pattern. Melanomas at these sites are characterized by the parallel ridge pattern. We present the case of a 59-year-old woman who had an oval papule of bluish color, measuring 0.6 x 0.9 cm, localized on her left sole, that had been present, unchanged, for more than 10 years. Dermoscopy showed a parallel ridge pattern. The histopathological examination revealed a combined blue nevus. We present this case to underline that on acral volar skin also intradermal nevi, such as combined blue nevi, may dermoscopically exhibit a parallel ridge pattern, simulating melanoma.     

Congenital acral melanocytic nevi clinically simulating acral lentiginous melanoma

Three cases of congenital acral melanocytic nevi with unusual clinical characteristics are reported. In all of the cases the surface changes and their growth were clinically suggestive of acral lentiginous melanoma, but biopsies revealed their benign nature. This exceptional presentation of congenital acral melanocytic nevi merits recognition by physicians and underscores the need for histologic diagnosis prior to definitive surgery in any cases suspected of being malignant melanoma.     

Limitations of dermoscopy in the recognition of melanoma

OBJECTIVE: To compare dermoscopic features of melanocytic nevi with those of early melanomas that were not excised initially because of their uncharacteristic clinical and dermoscopic appearance. DESIGN: Retrospective study of the baseline images of 325 melanocytic skin lesions that were observed by digital dermoscopy and finally excised because of changes over time. SETTING: A dermatologic clinic and a dermatologic department at a university hospital. MAIN OUTCOME MEASURES: Comparison of baseline images of melanomas and melanocytic nevi by pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist. RESULTS: Baseline dermoscopic images of 262 melanocytic nevi and 63 melanomas from 315 patients were included in the analysis. The patterns of dermoscopic features observed in the baseline images of melanocytic lesions finally diagnosed as melanomas during follow-up did not differ substantially from the patterns observed in the baseline images of melanocytic nevi. Pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist failed to achieve adequate diagnostic accuracy for melanoma. In retrospect, no dermoscopic feature or pattern of features could be identified that reliably differentiated between melanomas and melanocytic nevi at the time of the first presentation. CONCLUSION: Dermoscopy depends on the appearance of classic dermoscopic features and is therefore limited in the diagnosis of very early and mainly featureless melanomas.     

Pilot study on the correlation between dermoscopic patterns and fluorescence in situ hybridization findings using whole‐slide digital imaging for acral volar melanocytic lesions

Dermoscopic evaluation of acral volar skin is helpful in differentiating malignant melanomas (MM) from benign melanocytic nevi. However, histological diagnosis remains difficult because sufficient evidence of histopathological changes to establish a diagnosis of MM are not easily obtained. The aim of the present study was to evaluate the effective use of fluorescence in situ hybridization (FISH) in the diagnosis of acral volar melanocytic lesions, and to determine whether acral volar melanocytic lesions show characteristic molecular biological features of malignant melanoma via FISH. We classified acral volar melanocytic lesions showing junctional findings into three groups: (A) parallel ridge pattern (PRP) on dermoscopic examination with melanoma in situ; (B) PRP with insufficient melanocyte proliferation and atypia to diagnose malignant melanoma using hematoxylin–eosin staining; and (C) junctional nevi. We performed FISH analysis using the same tissue section that was used for hematoxylin–eosin staining. FISH positivity was seen in 80% (4/5) of the group A sections, and in 80% (4/5) of the group B sections. One case in group C was only 0.3% over the established criteria line (63.3% > 63% in RREB1). Our results suggest that FISH using whole‐slide digital imaging may be useful in the diagnosis of early in situ MM when a typical PRP is observed in an acral volar skin lesion with non‐diagnostic histopathology.     

Epidermolysis bullosa nevus: an exception to the clinical and dermoscopic criteria for melanoma

BACKGROUND: Large acquired melanocytic nevi that occur in patients with epidermolysis bullosa (EB), referred to as EB nevi, may pose a diagnostic challenge because of their clinical and dermoscopic resemblance to melanoma. These unconventional melanocytic nevi have been encountered in all categories of hereditary EB, most of them in childhood. Although some of the reported cases have an alarming clinical appearance that is indistinguishable from melanoma, long-term follow-up has confirmed the benign nature of these rarely encountered melanocytic lesions. The histopathologic patterns of these nevi range from a banal congenital pattern to the problematic persistent pseudomelanoma pattern. OBSERVATION: We describe the clinical, dermoscopic, and histopathologic features of a large EB nevus in a toddler. Clinically, the lesion was markedly asymmetrical and irregularly pigmented with foci of stippled pigmentation and scarring, which easily fulfilled the ABCD criteria for melanoma. Accordingly, a false-positive score resulted when dermoscopy was performed. Histopathologically, a pattern of persistent melanocytic neoplasm was observed. In the following 18 months, dynamic changes of the lesion included near-complete disappearance of the pigment, which was replaced by scar, milia, and areas of healing ulcers. CONCLUSION: Epidermolysis bullosa nevi are dynamic melanocytic lesions that may simulate melanoma.     

Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs

Evaluation of the three benign lesions discussed here form the basis for dermoscopic evaluation of other pigmented skin lesions. The features of seborrheic keratosis, including [figure: see text] the various forms of fissures, comedo-like openings, and milia-like cysts, often allow easy interpretation of seborrheic keratosis; however, similar structures are commonly associated with melanocytic neoplasms, notably congenital nevi. Understanding solar lentigo and its dermoscopy features allows for the appreciation of pigment networks common in lentiginous melanocytic nevi and melanoma. The lichenoid keratosis is the model for lichenoid inflammation elsewhere, notably in halo nevi, regressing melanoma, and other melanocytic neoplasms with significant host inflammatory reactions.     

Dispelling the myth of the "benign hair sign" for melanoma

The vast majority of melanocytic lesions with hair, such as congenital melanocytic nevi, are benign. However, there is a notion that the presence of one or more hairs in a melanocytic lesion is confirmatory for the benign nature of the lesion. To dispel this notion, we present 3 examples of melanocytic lesions that showed terminal hairs on clinical and dermoscopic evaluation, but in which the final diagnosis was invasive melanoma. Thus, integrating all clinical and dermoscopic findings, rather than relying on a single criterion for the lesion at hand should guide clinicians to the correct diagnosis.     

Dermoscopic patterns of acral melanocytic nevi and melanomas in a white population in central Italy

OBJECTIVE: To investigate the dermoscopic features of acral melanocytic lesions in a white population in central Italy. DESIGN: Retrospective review. SETTING: University dermatology department. PATIENTS: Six hundred fifty-one Italian subjects, ranging in age from 6 months to 78 years. MAIN OUTCOME MEASURES: We retrospectively investigated all digital dermoscopic images of acral melanocytic lesions included in our database from January 1996 to May 2005. RESULTS: We retrieved digital images of 723 benign acral melanocytic lesions in 641 patients (235 males and 406 females; mean age, 26.5 years) and of 10 acral melanomas in 10 patients (7 males and 3 females; mean age, 65 years). Individual lesions were located on the soles (n=520), fingers (n=146), and palms (n=67). Among acral nevi, the parallel furrow (42.1%) was the most common pattern, followed by the latticelike (14.9%), nontypical (13.7%), fibrillar (10.8%), homogeneous (9.3%), globular (5.4%), and reticular (2.1%) patterns. The frequency of distribution of the latticelike, nontypical, fibrillar, and homogeneous patterns significantly differed (P<.001, P=.03, P<.001, and P=.03, respectively) between anatomical sites. Also, 13 acral nevi (1.8%), mainly located on the fingers, showed a new combined pattern (transition pattern) consisting of a brownish black network associated with a parallel furrow or latticelike pattern. All 10 acral melanomas showed a multicomponent dermoscopic pattern. CONCLUSIONS: In our series of acral nevi, we observed 8 dermoscopic patterns, with varying distribution by anatomical site. Identification of a specific pattern is highly suggestive of the benign or the malignant nature of any given acral melanocytic lesion.     

Melanocytic nevi with special features: clinical‐dermoscopic and reflectance confocal microscopic‐findings

Histopathology is considered the ‘gold’ standard for the diagnosis and classification of melanocytic nevi, but the widespread use of in vivo diagnostic technologies such as dermoscopy and reflectance confocal microscopy (RCM), has enriched profoundly the knowledge regarding the morphological variability in nevi. This is because most morphological observations made via these in vivo tools are closely correlated with features seen in histopathology. Dermoscopy has allowed for a more detailed classification of nevi. As such, dermoscopy identifies four main morphologic groups (i.e. globular, reticular, starburst and structureless blue nevi), one group of nevi located at special body sites (i.e. face, acral, nail) and one group of nevi with special features. This latter category consists of nevi of the former categories, which are typified by peculiar clinical‐histopathological findings. They can be subdivided into ‘melanoma simulators’ including combined nevi, recurrent nevi and sclerosing nevus with pseudomelanomatous features, ‘targetoid’ nevi (i.e. halo, cockade, irritated targetoid haemosiderotic and eczematous nevus) and uncommon histopathological variants such as desmoplastic, white dysplastic or ballon cell nevus. While the dermoscopic and RCM patterns of the former categories have been studied in detail, little is currently known about the clinical morphology of the heterogeneous group of ‘special’ nevi. In this article, we describe the clinical, dermoscopic and RCM features of ‘special’ nevi and review the current literature on this group of melanocytic proliferations.     

Characteristic distribution of melanin columns in the cornified layer of acquired acral nevus: an important clue for histopathologic differentiation from early acral melanoma

Clinical and histopathologic differentiation between early acral melanoma and acral nevus is often difficult. Dermoscopy is helpful in this differentiation. On dermoscopy, early acral melanoma shows the parallel ridge pattern showing band-like pigmentation on the ridges of the surface skin markings, whereas a representative dermoscopic pattern in acquired acral nevus is the parallel furrow pattern showing parallel linear pigmentation along the surface furrows. The parallel furrow pattern suggests that melanocytes of acral nevus preferentially proliferate in the crista profunda limitans, an epidermal rete ridge underlying the surface furrow. In the present study, however, we found that in 13 of 18 acquired acral nevi, proliferation of melanocytes were detected not only in the crista profunda limitans but also in the crista profunda intermedia (CPI), an epidermal rete ridge underlying the surface ridge. Very interestingly, Fontana-Masson staining of these acral nevi revealed that even when proliferation of melanocytes was prominent in the CPI, melanin granules in the cornified layer were observed as regular melanin columns situated under the surface furrows and were hardly detected under the surface ridges. These findings indicate that in acral nevus, melanin granules produced by melanocytes in the CPI are not transferred to the upper epidermis. Hence, we must be careful not to overdiagnose an acral melanocytic lesion in which an increased number of melanocytes are detected in the CPI. Even in such a case, if melanin granules in the cornified layer are detected as melanin columns regularly distributed under the surface furrows, the lesion is strongly suggested to be a benign acral nevus.     

Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management

Congenital melanocytic nevi occur in approximately 1% of newborns and are usually classified according to their size. Giant congenital melanocytic nevi are most simply defined as melanocytic nevi that are greater than 20 cm in largest dimension; whereas small congenital nevi are defined as melanocytic nevi less that 1.5 cm in largest dimension. Congenital nevi can exhibit distinctive histologic features that can help in differentiating them from common acquired nevi. Giant congenital melanocytic nevi are associated with an increased risk of the development of melanoma. On the other hand, there is evidence of an increased melanoma risk in patients with small congenital nevi. Nevertheless, the risk of malignant transformation in small congenital nevi and the lifetime melanoma risk in patients with small congenital nevi remain controversial. In large part due to inconsistency in the reported literature describing patients with congenital melanocytic nevi, the risk of melanoma in these patients remains unclear and consistent guidelines for clinical management do not exist. We review the literature and comment on the course of management for these patients at the Massachusetts General Hospital Pigmented Lesion Clinic.     

The histology of "congenital features" in early acquired melanocytic nevi

To test the specificity of certain histologic features claimed to be frequent in congenital melanocytic nevi, 66 of 313 consecutive newborn infants without congenital nevi (verified by perinatal examination) were addressed in a questionnaire 2 1/2 years after birth. Fifty children with acquired melanocytic nevi were reexamined clinically and biopsies were performed in 15. Congenital features were found in seven biopsy specimens from the indubitably acquired melanocytic nevi. These nevi were larger and more speckled in color than melanocytic nevi without "congenital features." It is concluded that the histologic features said to be specific for congenital nevi are, in fact, not specific. The possible relationship between these features and an increased melanoma risk cannot be refuted by the present study, but the risk of misinterpretation based on congenital features as the sole criterion in the prediction of the potential malignancy of melanocytic nevi is real.