Clinicohistopathologic challenges and traps in the diagnosis of nail unit melanoma.

Melanoma of the nail apparatus is challenging to diagnose for both dermatologists and dermatopathologists. Misdiagnosis or delayed diagnosis of nail unit melanoma can have fatal consequences and legal ramifications. This review educates dermatopathologists on challenges and traps they should be aware of to avoid misdiagnosis of nail unit melanoma. We present illustrative difficult cases that introduce several themes regarding challenges in the diagnosis of nail unit melanoma: specimens with subtle histopathologic findings, challenges in immunoperoxidase interpretation, and how clinical knowledge and surgical procedural knowledge are mandatory to make the diagnosis. Dermatopathologists will be aware of when and how to suspect nail unit melanoma in unusual circumstances.

Childhood longitudinal melanonychia: case series from Poland.

INTRODUCTION: Longitudinal melanonychia (LM) is characterized by a tan, brown or black longitudinal streak within nail plate caused by the presence of melanin. LM is relatively common in dark-skinned population, infrequent in Caucasian population, and rare in children. AIM: We report epidemiological, clinicopathological and dermoscopic analysis of 8 cases of childhood LM from Poland, which is the largest series in the Central and Eastern European population. MATERIAL AND METHODS: Three hundred and forty-eight patients presenting with various nail pigmentation (in 2010-2016) were analysed. 72 cases of LM have been identified, including 8 cases of childhood LM (< 16 years of age), which were included in further analysis. RESULTS: Seven patients were boys and one girl, with mean age of 9 years (range: 6-13). More than a half (n = 5) presented skin phototype II. The most common location of melanonychia was the first left fingernail. Dermoscopy revealed heterogeneity of longitudinal lines colour in 5 cases. The irregularity of longitudinal line thickness in 5 cases and irregularity of parallelism in 5 cases was observed. Histopathological evaluation was performed in 4 patients, in 3 cases it revealed the presence of nail matrix nevus, in one case the presence of melanocytic proliferation of the lentiginous pattern along the dermoepidermal junction. CONCLUSIONS: Despite the fact that melanoma was not recognised in any case, such a possibility should always be considered as the cause of LM, even in the paediatric population. Dermoscopy seems to be useful in patient follow-up and management.

Retrospective single-center study evaluating clinical and dermoscopic features of longitudinal melanonychia, ABCDEF criteria, and risk of malignancy.

BACKGROUND: Longitudinal melanonychia (LM) is a common finding in clinical practice; however, it has a broad differential diagnosis, including subungual melanoma (SUM), which can be difficult to distinguish clinically from benign conditions. OBJECTIVE: To identify clinical and dermoscopic features that distinguish histopathologically diagnosed SUM from benign LM and to evaluate the validity of the ABCDEF criteria among patients on whom a biopsy was performed. METHODS: Retrospective cohort study of consecutive patients who underwent nail matrix biopsy for LM at a single center from January 2011 to November 2017. RESULTS: A total of 84 cases in which biopsy was performed (8 cases of SUM and 76 benign) were included in the analysis. The patients with SUM were younger (P = .011), had their melanonychia longer (P = .017), and presented with a wider band (P = .002) and greater width percentage (P < .001) than patients with benign LM did. The number of ABCDEF criteria met did not differ between the groups. LIMITATIONS: Retrospective single-center study; patients who did not undergo biopsy could not be studied. CONCLUSIONS: In the cases of LM in which biopsy was performed, SUM usually presented with a wider band and greater width percentage than benign LM did. The number of ABCDEF criteria met was not different between the groups. Because many of the clinical and dermoscopic signs were less consistent, biopsy should be performed in cases with any concerning band, especially in those with width percentage higher than 40%.

Nail apparatus melanoma: A comparative, clinicoprognostic study of the initial clinical and morphological characteristics of 49 patients.

BACKGROUND: Although nail apparatus melanoma has been widely evaluated, only limited data are available concerning its clinical features, which depend on its initial clinical morphology, broadly defined as a melanonychia or nonmelanonychia lesion. OBJECTIVE: We sought to determine heterogeneity on the basis of the initial clinical morphology of nail apparatus melanoma. METHODS: We searched the Asan Medical Center database for cases of nail apparatus melanoma that were confirmed by skin biopsy specimen. Patients were classified with either nail apparatus melanoma that began as melanonychia (group A) or nail apparatus melanoma that began as nonmelanonychia lesions (group B). RESULTS: We identified 49 patients with nail apparatus melanoma. Of these, 29 and 20 patients were included in groups A or B, respectively. The prediagnosis duration was significantly longer in group A. At the time of diagnosis, advanced stage and deeper Breslow thickness were noted in group B. The median overall survival period of the whole cohort was 93.0 months, and the 5-year overall survival was 67%. Patients in group A demonstrated better survival outcomes. LIMITATIONS: This study is a retrospective, single-center design. CONCLUSION: Nail apparatus melanoma demonstrates different clinical features and survival outcomes depending on whether the lesion begins as melanonychia or nonmelanonychia.

Onychoscopic Analysis of Cyclophosphamide-Induced Polydactylic Bluish-Gray Discoloration in a Case of Pemphigus Foliaceus.

Cyclophosphamide, an alkylating agent, has rarely been observed to cause a bluish discoloration of nails, an occurrence that is typically underreported. We describe the case of a middle-aged male undergoing dexamethasone-cyclophosphamide pulse therapy for pemphigus foliaceus, who exhibited bluish-gray discoloration of the nails. It is crucial to differentiate this presentation from other conditions such as nail apparatus melanoma (NAM), which may manifest in a slightly different manner. We also report the onychoscopic findings observed in this case.

Mutation profile of primary subungual melanomas in Caucasians.

BACKGROUND: Specific genomic profile of cutaneous melanomas is related to UVR exposure, which exerts biological and therapeutic impact. Subungual melanoma (SUM) is an exceedingly rare disease; therefore, it is not well characterized. SUM pathogenesis is not related to UVR induced DNA damage and expected to differ from other melanoma subtypes. Our study aimed to define the mutation profile of SUM in Caucasians. MATERIALS AND METHODS: Next-generation sequencing-based genomic analysis was used to identify frequently mutated loci in 50 cancer-related genes in 31 SUM primary tumors. RESULTS: The most abundant mutations in SUM were found in KIT - in 13% of cases and NRAS - also in 13%, while BRAF - only in 3% of cases. CONCLUSIONS: Our findings confirmed a high frequency of KIT and NRAS mutations in SUM, as well as a low incidence of BRAF mutations. We reported novel KRAS, CTNNB1, TP53, ERBB2, and SMAD4 mutations in SUM. Our findings provide new insights into the molecular pathogenesis of SUM.

Clinicopathological Features and Prognostic Factors of Primary Acral Melanomas in Caucasians.

BACKGROUND: Cutaneous melanomas located on the acral part of extremities (hand and foot melanoma; HFM) comprise a rare group within all melanomas in Caucasians. HFM is associated with a poor prognosis. We aimed to evaluate clinicopathological features, long-term outcomes, and prognostic factors in primary HFM in Caucasians. METHODS: Medical records of all consecutive patients treated between 1997 and 2014 were revised. Patients were diagnosed with primary cutaneous melanoma at I-II clinical stage, and sentinel lymph node biopsy was conducted. The analysis was performed to define the clinicopathological factors influencing outcomes in the HFM and subungual cohort. Among 2537 consecutive patients diagnosed with primary cutaneous melanoma, 247 cases of HFM (9.7%) were found, with a median follow-up time of 7.8 years. RESULTS: Median primary tumor Breslow thickness in subungual melanomas and HFMs was 4.0 mm and 3.3 mm, respectively, significantly higher than in the entire population (median 2.2 mm; p < 0.01). In the HFM group, 37.6% of tumors were ulcerated. Metastases to sentinel lymph node (SLN) were found in 28.3% of HFMs. The 10-year overall survival rate in the HFM group and subungual melanomas was 48.1% and 49.3%, respectively, compared to 63.0% in non-HFM melanomas. CONCLUSIONS: Our results confirm that patients with HFMs display worse overall survival compared to the entire melanoma population, with male gender and positive SLN biopsy status acting as independent negative prognostic factors.

Nail Apparatus Melanoma: Experience of 10 Years in a Single Institution.

BACKGROUND: Nail apparatus melanoma (NAM) is rare. The higher mortality reported in the literature is most likely due to advanced disease associated with delayed diagnosis and treatment. OBJECTIVE: All patients diagnosed with NAM were followed at a single reference center during a period of 10 years, with emphasis on dermatological and histological findings. Clinical outcomes were included. METHODS: A retrospective review of medical records, photographs, and histopathological examination. RESULTS: 73.7% of the patients were female and their mean age was 47 years. Caucasian and African-American patients had a similar incidence (47.4%). There was only 1 Asian patient in this study (5.3%). All patients presented with nail plate pigmentation. The mean prediagnosis duration was 33 months. A total of 63.2% patients had in situ melanoma and an average Breslow index of 2.18 mm in invasive cases. Fifteen patients underwent conservative surgery and 3 underwent phalanx amputation. All patients survived, and 4 have had more than a 5-year follow-up. CONCLUSION: In situ lesions showed longitudinal bands or total melanonychia with no nail dystrophy. Invasive cases presented with dystrophic lesions (longitudinal splitting of the nail). Conservative surgery provides a good option without worsening the prognosis. All dermatologists should be aware of early signs of NAM, since prognosis depends on early treatment.

Dermoscopic evaluation of melanonychia.

The prevalence of melanonychia is approximately 1%, and it is a common symptom encountered in daily practise. However, it may also be the first symptom of melanoma of the nail apparatus. Evaluation of adult melanonychia with clinical information and clinical images is sometimes difficult for clinicians. Dermoscopic observation provides important information based on the algorithm method. Melanonychia in children requires a different approach, because dermoscopic features observed in adult nail apparatus melanoma are generally observed in benign pediatric cases.

Subungual melanoma: Management in the modern era.

Subungual melanoma is a rare subtype of cutaneous melanoma that arises from the structures of the nail apparatus. It presents most commonly in older patients and at an advanced stage. A retrospective review of all patients with subungual melanoma in a single institution over a 15-year period was performed. In total, 54 patients were included (26 males, average age 62.9 years), of which 28 cases involved the upper limb. Median tumour thickness was 4.5 mm. Eighteen patients had lymph node metastasis at diagnosis, including 11 of 36 patients with positive sentinel lymph node biopsy. Median survival was 4.6 years. Subungual melanoma has a poor prognosis that is strongly associated with presence of nodal disease at diagnosis. Sentinel lymph node biopsy should be considered to determine stage and prognosis.

Nail apparatus melanoma in a Japanese population: a comparative study of surgical procedures and prognoses in a large series of 151 cases.

Nail apparatus melanoma (NAM) is a rare subtype of malignant melanoma with a prevalence that varies among populations. Conservative surgical approaches for thin to intermediate NAMs have recently been reported, however, their adoption is controversial, and resulting long-term prognoses are unknown. The purpose of this study was to determine the prognosis of NAM in a sample Asian population, and to investigate whether there is a difference in the local control and overall survival (OS) rates according to the extent of resection of the primary tumour. We performed a retrospective study of NAM patients treated at five medical institutions in Japan between 2000 and 2013. Outcomes according to surgery (amputation vs. resection) and tumour thickness were compared. We identified 151 cases of NAM in 83 men and 68 women; the thumb (n = 50; 33.1%) and hallux (n = 55; 36.4%) were the most common sites. No local recurrence was detected following any of the surgical procedures; Kaplan-Meier survival analysis revealed that the surgical procedure type was not significantly associated with disease-free survival (p = 0.786) or OS (p = 0.997). Five-year OS rates according to tumour thickness were 100% for in situ, 94.4% for ≤1-mm, 91.7% for 1.01-2.0-mm, 72.7% for 2.01-4.0-mm, and 47.6% for ≥4.01-mm tumours. Surgical procedure type does not influence survival as long as total primary tumour resection is accomplished. The prognosis of NAM is comparable to that of other types of melanoma.

Automated evaluation system of dermoscopic images of longitudinal melanonychia: proposition of a discrimination index for detecting early nail apparatus melanoma.

The prognosis of nail apparatus melanoma is generally poor because of difficulty in early stage diagnosis. Most nail apparatus melanomas occur as longitudinal melanonychia, and criteria and algorithms for dermoscopy diagnosis of longitudinal melanonychia have only recently been proposed. However, as with any clinical diagnosis, the diagnosis based on dermoscopy is to some extent subjective. Our goal is to develop an automated dermoscopic screening system for longitudinal melanonychia and to propose a novel objective and quantitative index for discriminating early nail apparatus melanoma from benign longitudinal melanonychia including melanocytic nevus. We propose an automatically calculated index representing degrees of color variegation in dermoscopic images of longitudinal melanonychia. Dermoscopy images of six cases of early stage nail apparatus melanoma and 25 cases of benign longitudinal melanonychia were analyzed with our screening system and a threshold of melanoma discrimination index was determined. This single melanoma discrimination index diagnosed early nail apparatus melanoma with 100% sensitivity and 92% specificity. The automatically calculated index proposed in the present study is valuable for managing longitudinal melanonychia. The results suggest that the degree of color variegation is essentially different between early nail apparatus melanoma and benign longitudinal melanonychia including melanocytic nevus of the nail apparatus.