Diagnosis and Management of Longitudinal Erythronychia: A Clinical Review by an Expert Panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of one nail) or polydactylous (involvement of more than one nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia (LLE) are most frequently benign subungual neoplasms, and less often malignancies. Polydactylous longitudinal erythronychia (PLE) is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common, but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Clinical, onychoscopic, nail clipping, and histopathological findings of malignant onychopapilloma.

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.

Onychomycosis.

This Patient Page describes the risk factors, clinical features, diagnosis, and treatment of onychomycosis.

Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2­dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

Adult and Pediatric Nail Unit Melanoma: Epidemiology, Diagnosis, and Treatment.

Nail unit melanoma (NUM) is an uncommon form of melanoma and is often diagnosed at later stages. Approximately two-thirds of NUMs are present clinically as longitudinal melanonychia, but longitudinal melanonychia has a broad differential diagnosis. Clinical examination and dermoscopy are valuable for identifying nail findings concerning malignancy, but a biopsy with histopathology is necessary to confirm a diagnosis of NUM. Surgical treatment options for NUM include en bloc excision, digit amputation, and Mohs micrographic surgery. Newer treatments for advanced NUM include targeted and immune systemic therapies. NUM in pediatric patients is extremely rare and diagnosis is challenging since both qualitative and quantitative parameters have only been studied in adults. There is currently no consensus on management in children; for less concerning melanonychia, some physicians recommend close follow-up. However, some dermatologists argue that the "wait and see" approach can cause delayed diagnosis. This article serves to enhance the familiarity of NUM by highlighting its etiology, clinical presentations, diagnosis, and treatment options in both adults and children.

Update on nail unit histopathology.

Histopathologic evaluation of the nail unit is an essential component in the diagnosis of nail unit disorders. This review highlights recent updates in nail unit histopathology and discusses literature covering a wide range of nail disorders including melanoma/melanocytic lesions, squamous cell carcinoma, onychomatricoma, onychopapilloma, onychomycosis, lichen planus, and other inflammatory conditions. Herein we also discuss recent literature on nail clipping histopathology, a useful and noninvasive diagnostic tool that continues to grow in popularity and importance to both dermatologists and dermatopathologists.

Diagnosis and surgical treatment of benign nail unit tumors.

Little is known about benign non-melanocytic nail tumors, probably due to their low pathogenicity. They are commonly misdiagnosed as inflammatory or infective diseases. They have various features, depending on the type of tumor and its location in the nail apparatus. The typical sign of a tumor is the presence of a mass and/or secondary nail changes from damaged nail structures. In particular, if a single digit is affected by a dystrophic sign or a symptom is reported without any explanation, the presence of a tumor should always be ruled out. Dermatoscopy helps to enhance visualization of the condition and in many cases supports the diagnosis. It may also assist in identifying the right place to biopsy, but it never replaces surgery. Most common non-melanocytic nail tumors are analyzed in this paper, including glomus tumor, exostosis, myxoid pseudocyst, acquired fibrokeratoma, onychopapilloma, onychomatricoma, superficial acral fibromyxoma and subungual keratoacanthoma. The aim of our study is to review the main clinical and dermatoscopic characteristics of the most common benign non-melanocytic nail tumors, to correlate them with the histopathology and to advise practitioners of the best surgical management.

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.

A call for nail clipping histopathology to become an essential component of the routine evaluation of melanonychia: Benefitting patients as a triage and surgical planning maneuver.

We call on dermatologists and dermatopathologists to include nail clipping histopathology as an essential component of the routine evaluation of melanonychia. This manuscript demonstrates a case where an adult woman with broad melanonychia of the right thumbnail declined a nail matrix biopsy, but was amenable to a nail clipping.The nail clipping showed pigmentation, melanocyte remnants, and small cavities in the nail plate. These features have been published previously by our group as a clue to nail unit melanoma within nail clippings.This patient was rapidly triaged for nail matrix biopsy, which demonstrated nail unit melanoma in situ. Every patient with melanonychia can benefit from a nail clipping by examination of the location of the pigmentation within the nail plate for surgical planning, and if melanocyte remnants are detected, the nail clipping also serves as a rapid triage mechanism for nail matrix biopsy to evaluate for nail unit melanoma. Fontana-stained sections will highlight the pigmentation in the nail plate, and its location in the nail plate can easily be described by the dermatopathologist. Nail clippings performed in the setting of clinically apparent melanonychia may show helpful histopathologic findings of pigmented fungi, hemorrhage, external pigmentation, features of other pigmented nail unit tumors, as well as other entities. Nail clipping histopathology can provide extensive information in the evaluation of melanonychia with minimal discomfort for a patient, and little disruption to a physician's clinic flow. With this additional case of a nail unit melanoma diagnosed after initial concern found in a nail clipping, as well as other information in the literature, it is clear that melanocyte remnants found in nail clippings are reliable concerning features related to nail unit melanoma in adults. With knowledge of these histopathologic features in nail clippings and the significance of melanocyte remnants, the dermatopathologist can play a crucial role in the use of a nail clipping as a life-saving diagnostic maneuver. Accordingly, given the potential benefit to patients in this setting, as well as other uses of a nail clipping in the evaluation of melanonychia, we call on dermatologists and dermatopathologists to innovate the routine evaluation of melanonychia through the routine employment of nail clippings for histopathologic evaluation.

Pleomorphic acquired digital fibrokeratoma: A novel clinicopathologic entity.

A 26-year-old male presented with a 2-year history of a hyperkeratotic growth from the left index finger. Histopathology was consistent with an acquired digital fibrokeratoma with changes of a pleomorphic fibroma. Lesional cells were negative for CD34, Rb, and p53, and were positive for FXIIIa. We introduce the pleomorphic acquired digital fibrokeratoma as a novel clinicopathologic entity.