Subungual melanoma: molecular analysis of 31 cases from early stage to invasive melanoma.

AIMS: The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole-genome copy number variations (CNV) as well as targeted next-generation sequencing (NGS) in SUM. METHODS AND RESULTS: This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16-39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM. CONCLUSION: To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

Nearly complete hair re-pigmentation in an older patient treated with hydroxyurea for essential thrombocytosis.

INTRODUCTION: Employed in the treatment of malignancies and non-neoplastic conditions, hydroxyurea is associated with integumentary adverse effects, including skin discoloration, xerosis, pruritus, cutaneous atrophy, chronic leg ulcers, oral ulcerations, alopecia, and some nail abnormalities. CASE REPORT: A 77-year-old woman was diagnosed with essential thrombocytosis and started on low dose hydroxyurea. After 20 weeks of treatment, she experienced an unexpected change in hair color from gray to dark brown, without using hair dye or supplements. She later developed bilateral dorsal hand melanoderma, melanonychia, and onychodystrophy. MANAGEMENT AND OUTCOME: It was decided to monitor the patient with no action taken as she was happy with this side effect of hydroxyurea. The platelet count has remained in excellent control. The dark brown hair color persisted over time. DISCUSSION/CONCLUSION: Hair hyperpigmentation likely occurred through melanocyte activation via hydroxyurea. Severe side effects may require dosage adjustments, while milder effects can be monitored closely. The newly observed hair color restoration in this case highlights potential dual (therapeutic and aesthetic) applications of this class of agents.

Melanoma-like features in pediatric longitudinal melanonychia: A systematic review and meta-analysis.

BACKGROUND: Pediatric longitudinal melanonychia (LM) can exhibit atypical features that mimic red-flag signs for subungual melanoma in adults and lead to diagnostic uncertainty. Nail biopsy may be unnecessary if clinical inspection and dermoscopy suggest a benign nature. METHODS: We searched PubMed and Embase from inception to February 2023 for studies of any design reporting either the number or proportion of clinical and dermoscopic features in at least five children (≤18 years) with LM. Non-English articles, reviews, and abstracts were excluded. We performed a systematic review and meta-analysis to collate all existing data. RESULTS: A total of 1218 articles were screened and 24 studies with 1391 pediatric patients were included. Nevus was the most common diagnosis (86.3%). The most prevalent sites were fingernails (76.2%) and first digits (45.4%). Pooled proportions of common features were: dark-color bands (69.8%), multi-colored bands (47.6%), broad bandwidth (41.1%), pseudo-Hutchinson sign (41.0%), irregular patterns (38.1%), Hutchinson sign (23.7%), dots and globules (22.5%), nail dystrophy (18.2%), and triangular sign (10.9%). Outcomes included progression (widening or darkening, 29.9%), stability (23.3%), and spontaneous regression (narrowing or fading, 19.9%). Only eight cases of subungual melanoma in situ were reported, and no invasive melanomas were identified. CONCLUSION: Although atypical characteristics are common in pediatric LM, the probability of malignant transformation is exceedingly low. Appropriate evaluation and management of pediatric LM includes careful clinical and dermoscopic inspection with attention to benign features followed by long-term interval follow-up.

Frontal Examination of the Distal Nail Unit. / Visión frontal distal de la uña.

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice.

[Translated article] Frontal Examination of the Distal Nail Unit.

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice.

Melanoma in skin of color: Part I. Epidemiology and clinical presentation.

Although there is a higher incidence of melanoma among non-Hispanic White individuals, melanoma is diagnosed at more advanced stages and associated with worse survival rates among individuals with skin of color (SOC). The proportions of melanoma subtypes differ across racial groups, with acral lentiginous melanoma and mucosal melanoma representing higher proportions of melanoma diagnoses in individuals with SOC compared to White individuals. The recognition of distinct differences in anatomic locations and dermatoscopic patterns may facilitate the appropriate differentiation of physiologic from pathologic pigmentation. The first article of this continuing medical education series will focus on the epidemiology and clinical presentation of melanoma in individuals with SOC, with the aim of improving early diagnoses and clinical outcomes.

Clinical and dermoscopic features of nail unit melanoma in an Australian nail clinic cohort.

Nail unit melanoma carries diagnostic challenges conferring with its poor prognosis. This audit aims to characterise both clinical and dermoscopic features of nail unit malignant lesions and compare them with biopsied benign lesions. It focuses on informing future practice by aiding in the stratification and recognition of malignant diagnostic patterns in the Australian context.

Clinical and dermoscopic findings of benign longitudinal melanonychia due to melanocytic activation differ by skin type and predict likelihood of nail matrix biopsy.

BACKGROUND: Longitudinal melanonychia (LM) is a common dermatologic finding in clinical practice with a broad differential diagnosis. Melanocytic activation is the most common LM etiology. OBJECTIVE: To investigate clinical and dermoscopic differences of benign LM based on Fitzpatrick skin type and in biopsied versus nonbiopsied patients. METHODS: A 10-year retrospective cohort of 248 benign LM cases at Weill Cornell Dermatology was identified and analyzed. RESULTS: Darker-skinned versus lighter-skinned patients had higher band width percentage (P = .0125), had lower band brightness (P < .001), had more band changes (P = .0071), and received more biopsies (P = .032). Biopsied (n = 47) versus nonbiopsied patients (n = 201) had less multidigit band involvement (P = .0008), higher band width percentage (P = .0213), lower band brightness (P = .0003), and more band changes (P < .0001). Darker skin types more often had brown versus gray coloration on dermoscopy (P = .0232). The mean band width percentage for all biopsied patients was 30.81% (range: 5.80%-100%). LIMITATIONS: Single-center retrospective design. Subungual melanoma and other benign LM etiologies were not analyzed. Only 18.95% of patients received a biopsy. CONCLUSION: Darker versus lighter skin types more often present with darker and wider bands, present with brown versus gray coloration on dermoscopy, and receive more biopsies. Multi-institutional studies on LM are needed to determine nail matrix biopsy criteria in different skin types.

Clinical features and natural course of pediatric longitudinal melanonychia: A retrospective cohort study in Korea.

BACKGROUND: Large studies on the clinical features and natural course of pediatric longitudinal melanonychia (LM) are lacking. OBJECTIVE: To investigate the clinical features and natural course of pediatric LM. METHODS: Retrospective cohort analysis of pediatric patients (age ≤ 18 years) with LM. RESULTS: We examined 703 LM lesions in 381 children. Single, narrow, and homogeneously pigmented fingernail lesions were most frequently observed. Our results suggested that within 3, 4.5, and 9.5 years after onset, approximately 3%, 5%, and 10% of LM lesions, respectively, will completely regress and that single, left-sided, and homogeneously pigmented lesions are more likely to disappear completely. The age of onset, sex, finger/toe position, Hutchinson's sign, and nail dystrophy were not associated with complete regression. During follow-up, most cases demonstrated no change in color or width between the first and last visit, and early darkening/widening before stabilization or lightening/narrowing was common. The lightning of pigmentation was associated with complete regression, whereas change in width was not. LIMITATIONS: Retrospective study at a tertiary center. CONCLUSION: Our results suggest that clinicians ought to follow pediatric patients with LM without intervention for several years even if lesions grow darker or wider. Single, left-sided, and homogeneously colored lesions are more likely to regress.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Clinical and onychoscopic features of histopathologically proven onychopapillomas and literature update.

BACKGROUND: Onychopapilloma is a benign tumor of the distal nail matrix and proximal nail bed with heterogeneous clinical presentations. It poses a diagnostic challenge because it could mimic subungual malignancies and inflammatory conditions. Clinical, onychoscopic, and histopathological clues play critical roles in diagnosis. METHODS: We performed a retrospective chart review of onychopapilloma cases collected over 10 years, and characterized the clinical, onychoscopic, and histopathological features of onychopapilloma at an academic institution. RESULTS: We obtained 17 biopsy-confirmed cases of onychopapilloma. Among our cases, we found manifestation of onychopapilloma as longitudinal erythronychia, longitudinal leukonychia, yellow-brown chromonychia, and longitudinal melanonychia. Long longitudinal or short splinter hemorrhages may be present. Distal fissuring with V-shaped notch, subungual keratotic mass, and onycholysis are other discernable features. Histopathological features include papillomatosis, epidermal hyperplasia, acanthosis of the distal nail bed, premature keratinization, matrix metaplasia, hyperkeratosis, and splinter hemorrhages; histopathological signs of malignancy were not observed in any of our cases. CONCLUSIONS: Onychopapilloma has polymorphic clinical and morphological features. Onychoscopic and histopathological studies are important to help exclude malignant mimickers. Consider onychopapilloma in the differential diagnoses of a monodactylous longitudinal streak in the nail, especially on the left thumb of an adult female.

Distribution of cellular remnants of melanocytes in the nail plate: Clue to the diagnosis of subungual melanoma.

BACKGROUND: Previous studies reported that cellular remnants in the nail plate could be a diagnostic clue for subungual melanoma (SUM). We sought to characterize the histopathologic features of cellular remnants in the nail plates of SUM patients. METHODS: A retrospective case-control study was conducted in a single tertiary center from 2012 to 2019. Twenty-three patients with pathologically diagnosed SUM and eight nail matrix nevi (NMN) patients were recruited. The analysis of the nail plate specimens focused on large cellular remnants of melanocytes (LCRMs). Longitudinal linear density and vertical distribution pattern of the LCRMs were scrutinized for possible features distinguishing SUM from NMN. RESULTS: The median linear density of the LCRMs was significantly higher in the SUM samples than in the NMN samples. LCRMs in the SUM samples were more dorsally distributed than those in the NMN samples. In invasive SUM, LCRMs were more likely to be found in the dorsal part of the nail plate compared to SUM in situ. CONCLUSION: Nail plate specimens should not be overlooked in the histopathological examination of melanonychia. High-density LCRMs with more dispersion to the dorsal side might be suggestive of SUM.

[Laugier-Hunziker syndrome : A rare differential diagnosis of mucocutaneous hyperpigmentation]. / Laugier-Hunziker-Syndrom : Eine seltene Differenzialdiagnose der mukokutanen Hyperpigmentierung.

Laugier-Hunziker syndrome (LHS) is characterized by lentiginous hyperpigmentation of the oral mucosa and lips. In addition, longitudinal melanonychia and palmoplantar hyperpigmented lesions may occur. LHS is a clinical diagnosis of exclusion. Herein, we report the case of a 66-year-old woman with LHS. The clinical and histopathologic features of LHS are presented and important differential diagnoses are discussed.

Subungual Melanocytic Lesions in Pediatric Patients. / Lesiones melanocíticas subungueales en la edad pediátrica.

The study of subungual melanocytic lesions can present challenges because of the clinical and histologic characteristics of the nail unit and the difficulty of performing nail biopsies and processing specimens. These lesions can be even more challenging in children due to differences in clinical and epidemiological profiles between the adult and pediatric populations. Many of the clinical features of subungual melanocytic lesions that would raise alarm in an adult do not have the same implications in children. Consensus is also lacking on when a nail biopsy is needed to rule out malignancy in the pediatric setting. In view of these considerations and the rarity of subungual melanoma in childhood, the recommended approach in most cases is a watch-and-wait strategy. Subungual melanocytic lesions in children may also show atypical histopathologic features that are not necessarily associated with aggressive behavior. Subungual melanoma is very rare in childhood, with just 21 cases described to date. None of the patients developed visceral metastasis or died as a result and the diagnosis was controversial in many of the cases. Considering the above and the significantly higher frequency and particular characteristics of longitudinal melanonychia with a benign etiology in children, subungual melanocytic lesions should be managed differently in this setting than in adults. In most cases, a watch-and-wait approach is the most appropriate strategy.

Retrospective analysis of nail biopsies performed using the Medicare Provider Utilization and Payment Database 2012 to 2017.

Subungual melanoma (SUM) is subset of acral melanoma that develops within the nail unit and is associated with a poor prognosis. Nail biopsy is the only way to definitively diagnosis SUM. Our objectives were to analyze the Medicare database for nail biopsy utilization and to compare the annual nail biopsy rate with the estimated incidence of SUM in the United States. A retrospective study on nail biopsy data was performed using the Medicare Provider Utilization and Payment Database 2012 to 2017. The number of nail biopsies performed per 100 000 people was compared to SUM incidence per 100 000 people. Podiatrists, dermatologists, other physicians, and NP/PAs respectively performed 12.12, 0.42, 0.08, 0.07 nail biopsies per 100 000 people annually. Dermatologists performed adequate nail biopsies to cover the minimum (0.7%), but not the maximum (3.5%) estimated incidence of SUM. Only 0.28% and 1.01% of general dermatologists and Mohs surgeons, respectively, performed nail biopsies in 19/50 (38.00%) states and 69/929 (7.42%) zip codes. Limitations of our study were that nail biopsies on patients less than 65 years, and those with no or commercial health insurance were not analyzed. In sum, very few dermatologists performed nail biopsies in the Medicare database. Increased efforts are needed to educate dermatologists on nail surgery.

Association of occupational direct radiation exposure to the hands with longitudinal melanonychia and hand eczema in spine surgeons: a survey by the society for minimally invasive spinal treatment (MIST).

PURPOSE: To investigate the association between occupational direct radiation exposure to the hands and longitudinal melanonychia (LM) and hand eczema in spine surgeons. METHODS: A web-based questionnaire survey of the Society for Minimally Invasive Spinal Treatment (MIST) in Japan was conducted. The proportion of LM and hand eczema in hands with high and low-radiation exposure was compared using Fisher's exact test. The odds ratios (ORs) and their 95% confidence intervals (CIs) for the prevalence of LM and hand eczema in the high-radiation exposure hands were calculated using generalized estimating equations for logistic regression as control for the correlation of observations among the same individuals and possible confounders. RESULTS: Among 324 members of the society, responses were received from 229 members (70.7%). A total of 454 hands from 227 participants were analysed. The prevalence of LM and hand eczema was 43% and 29%, respectively. In a hand-by-hand comparison, more hands had LM in the high-radiation exposure group than the low-radiation exposure group (90 [40%] vs. 39 [17%], respectively, p < 0.001). A similar trend was observed for hand eczema (63 [28%] vs. 33 [15%], respectively, p = 0.001). The adjusted OR for high-radiation exposure hands was 3.18 (95% CI: 2.24-4.52). Consistent results were obtained for hand eczema, with an adjusted OR of 2.26 (95% CI: 1.67-3.06). CONCLUSION: The present study suggests that direct radiation exposure to physician's hands is associated with LM and hand eczema. Those with LM and radially biased hand eczema may have had high direct radiation exposure.

Nail discoloration in pediatric skin of color patients.

Nail pigmentation in children can cause significant anxiety in parents and clinicians. Different pigments of the nails, such as yellow, orange, and green, can all occur; however, this paper will focus on the dark pigments: brown, gray, and black pigmentation of the nails. Many causes of dark coloration of the nails exist; almost all causes in pediatric patients are benign and require no treatment. Melanoma is the one diagnosis that physicians do not want to miss. Fortunately, this is extremely rare in children.

Clinicopathological diversity and outcome of longitudinal melanonychia in children and adolescents: analysis of 35 cases identified by excision specimens.

AIMS: Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood. METHODS AND RESULTS: We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P < 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count. CONCLUSIONS: Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.

A case of adult-onset longitudinal melanonychia due to nail matrix compound nevus.

A case of adult-onset longitudinal melanonychia caused by a compound nevus is described. Longitudinal melanonychias are mainly caused by melanocytic activation (hypermelanosis), lentigo (benign melanocytic hyperplasia), nevus, and melanoma. Nevi are more commonly seen in children than adults; however, melanocytic activation, atypical melanocytic proliferation, and melanoma are more frequent in adults. The majority of nail matrix nevi causing longitudinal melanonychia first appear in childhood and are junctional. Rarely, compound nevi are reported to cause longitudinal melanonychia in childhood.

Dermoscopic findings of fungal melanonychia.

INTRODUCTION: There are very few studies about dermoscopic findings of fungal melanonychia (FM) apart from the case reports. AIM: To reveal and identify dermoscopic findings which facilitate diagnosis of the FM. MATERIAL AND METHODS: The study included a total of 42 nails from 33 patients diagnosed with FM on the basis of the clinical history, physical examination, dermoscopic findings and microbiological investigation. All of the dermoscopic images were retrospectively reviewed and the findings identified were recorded in a period of 1 year. RESULTS: The most common presentation was homogenous brown pigmentation (n = 15, 35.7%). The other presentations included: homogenous black (n = 9, 21.4%), homogenous grey (n = 9, 21.4%), clumped/granular black (n = 7, 16.6%) and irregular longitudinal black (n = 4, 9.5%) pigmentation. Superficial transverse striation was observed in 11 (26.1%) nails. Twenty (47.6%) nails showed white streaks (white longitudinal striae) and 6 (14.2%) nails showed distal white jagged edge (also known as "spikes"). Twenty-two (52.3%) nails had at least one of white streaks and jagged edge findings. 4 (9.5%) nails showed pseudo Hutchinson's sign. CONCLUSIONS: To the best of our knowledge, this is the most comprehensive study regarding the dermoscopic patterns of FM. Here, we also evaluated onychomycosis associated dermoscopic findings like white longitudinal striae and jagged edges. Our study, along with the previous studies, showed that dermoscopy can be a very helpful method in the diagnosis of FM. Long disease duration, homogenous pigmentation pattern, presence of white streaks and jagged edges are the main clues to FM.