Nail Unit Research Articles

Melanoma in Patients with Skin of Color.

In comparison to Non-Hispanic White individuals, cutaneous melanoma is far less common in skin of color (SOC) patients but carries a poorer prognosis. Melanomas in SOC populations are more often identified on sun-protected locations such as acral surfaces, nail units, and mucous membranes, providing a challenge to identify in early stages due to unfamiliar clinical and dermatoscopic features. Additionally, racial healthcare disparities compound the difficulty in diagnosis and ultimately contribute to poorer prognosis. We explore the epidemiology, clinical presentation, and healthcare disparities surrounding melanoma in SOC individuals to increase awareness of the intricacies and nuances in identifying these malignancies.

Nail Unit Melanoma Treated with Mohs Micrographic Surgery: Technique, Local Recurrence Rate, and Surgical Outcomes.

Nail unit melanoma (NUM) is increasingly treated with digit-sparing surgery, but few published case series describe Mohs micrographic surgery (MMS) for NUM. To describe the surgical technique, local recurrence rates, and reconstruction method for a large series of NUM treated with MMS using MART-1 immunostaining. Biopsy-proven NUM treated with MMS-MART-1 were identified from a prospectively maintained database (2008-2023). Primary outcome was local recurrence rate. Secondary outcomes included rate of subclinical spread and rate of ablative vs. reconstructive amputation. 69 NUM were identified, including 51 melanomas in situ (73.9%) and 18 invasive melanomas (26.1%) with mean Breslow thickness of 1.07 mm (range 0.2-5.4 mm). One local recurrence (1/69, 1.4%) occurred during a mean follow-up time of 38.2 months. Subclinical spread (>1 Mohs stage) was common (38/69, 55.1%). Amputation was rarely necessary to clear the melanoma (5/69, 7.2%), but amputation at different levels was performed to reconstruct 33 cases (33/69, 47.8%) with extensive exposed bone. Single center cohort and lack of patient-reported outcomes. MMS treats NUM with low local recurrence rates. Amputation is rarely necessary to obtain clear tumor margins, but it may be necessary or desirable to reconstruct MMS defects with extensive exposed bone.

Brunelli (Dorsoulnar) Flap for the Reconstruction of Defect of the Thumb Nail Unit After Oncological Resections With Mohs Micrographic Surgery.

The Brunelli flap is an option in the reconstruction of the thumb after trauma or oncological resections. The arc of movement of the flap makes it possible to resolve defects in the proximal, palmar, dorsal, and lateral regions. We present a case series of 11 patients in whom a Brunelli flap was performed for postoncological reconstruction, melanoma in situ, and invasive squamous cell carcinoma of the thumb nail unit associated with Mohs micrographic surgery. This combination has not been described before. The reconstruction was carried out using a Brunelli flap, incorporating certain variations to the original technique. Clinical follow-up was performed during a 1-year period. All flaps showed good viability. In 3 flaps, there was mild distal suffering that resolved with local healing. Three patients presented hypersensitivity in the distal part, which was managed with physical therapy. The functionality of the thumb was not altered in any case, and there were no complications in the donor site. No tumor recurrence was documented in any patient. The use of the Brunelli flap to reconstruct the nail unit after an oncological resection with Mohs surgery is a good alternative. The advantages include a dorsal artery as a constant vessel and a homodigital flap that does not cause morbidity in the donor area, and with Mohs surgery, amputation is avoided. Disadvantages include lack of sensation of the flap. Some limitations of our study are the sample size and lack of long-term follow-up.

Nail Disorders as clues to systemic disease.

Disorders of the nail unit can provide important clues to underlying systemic diseases. Onychodystrophy or nail abnormalities include altered nail color, shape, or texture, with morphology and growth patterns often related to local anatomic factors such as edema, vascular supply, and neurologic innervation. Associated pain or loss of function can also affect daily activities. Because nail changes may be due to a range of systemic diseases, we chose to provide a systems-based broad overview of the common nail findings in patients with internal disease.

Antimycotic Activity of in silico Validation of Bioactive Compounds of Roccella montagnei Bel. against Clinically Isolated Onychomycosis Fungus Trichophyton mentagrophytes

Dermatophytes are the most common slow growing contagious agents of cutaneous mycosis and persist as a significant public health issues despite of the availability of a number of antifungal medications. Trichophyton mentagrophytes is one of the fungal species which influences the dermatophytic diseases. A wide range of clinical dermatophytosis such as tinea barbae (beards), tinea captis (scalp), tinea corporis (ring worm of the body), tinea faciei (face), tinea manuum (hand), tinea inguinalis (jock itch), tineaunguium or onychomycosis (nail unit),paronychia (proximal and lateral folds of fingernails, toenails and tissue borders sides and root of nail), tinea pedis (feet) and tinea cruris (pubic region) could be produced by this pathogenic species depending on the affected parts. Generally, terbinafine, is used to treat dermatophytosis induced by Trichophyton species. In most of the cases, synthetic anti-mycotic drugs fail over time resulting in development of resistant strains. Sustainable use of herbal sources has been recognised as novel therapeutic drugs to treat dermatophytic disorders. However, few reports are available on antimycotic activity of lichen species. Therefore, in this study, lichen species such as Roccella montagnei Bel. was collected from prime locality of Bhubaneswar, Odisha. Antifungal potency of ethanol and methanol extractives of R. montagnei Bel. was screened by disc diffusion method against the clinical isolates of T. mentagrophytes. The overall study resulted with a positive output and validated through in-silico database. Hence the entire study is based on biomedical evaluation and sustainable use of natural plant supplements for the benefit of human society.

JAAD Game Changers: “A retrospective study of squamous cell carcinoma of the nail unit diagnosed in a Belgian general hospital over a 15-year period”

JAAD Game Changers: “A retrospective study of squamous cell carcinoma of the nail unit diagnosed in a Belgian general hospital over a 15-year period”

Diagnosis and Management of Malignant Epithelial Nail Unit Tumors.

Background: Malignant epithelial nail unit tumors pose significant diagnostic and therapeutic challenges due to their clinical presentation often mimicking benign conditions and due to the need to preserve as much nail unit function as possible during surgery. Early detection is crucial, even if none of these tumors represent a life-threatening disease. Objectives: This review focus on squamous cell carcinoma, verrucous carcinoma, eccrine porocarcinoma, onychocytic carcinoma, basal cell carcinoma, malignant onychopapilloma, malignant onycholemmal cyst and onycholemmal carcinoma. Methods: Existing literature on the aforementioned tumors has been revised and synthesized. Results: Clinical presentation, pathology, diagnostic procedures, risk factors and the challenges associated with surgical management have been described in detail. Conclusions: Malignant epithelial tumors of the nail unit require careful evaluation and management due to their complex presentation. Early detection and an informed surgical approach are essential to improve patient outcomes and minimize complications.

Onychomycosis in the US Pediatric Population-AnEmphasis on Fusarium Onychomycosis.

Onychomycosis is a common nail disease that is often difficult to treat with a high risk of recurrence. To update our current understanding of the etiologic profile in pediatric patients with onychomycosis utilizing molecular diagnosis by polymerase chain reaction (PCR) combined with histopathologic examination. Records of 19,770 unique pediatric patients were retrieved from a single diagnostic laboratory in the United States spanning over a 9-year period (March 2015 to April 2024). This cohort represents patients clinically suspected of onychomycosis seen by dermatologists and podiatrists. Dermatophytes, nondermatophyte molds (NDMs), and yeasts were identified by multiplex real-time PCR corroborated by the demonstration of fungal invasion on histopathology. An average of 37.0% of all patients sampled were mycology-confirmed to have onychomycosis. Most patients were between ages 11 and 16 years, and the rate of mycologically confirmed onychomycosis was significantly higher among the 6- to 8-year (47.2%) and 9- to 11-year (42.7%) age groups compared to the 0- to 5-year (33.1%), 12- to 14-year (33.2%), and 15- to 17-year (36.7%) age groups. The majority of infections were caused dermatophytes (74.7%) followed by NDMs (17.4%). The Trichophyton rubrum complex represents the dominant pathogen with higher detection rates in the 6- to 11-year-olds. Fusarium was the most commonly isolated NDM with an increasing prevalence with age. Elementary school-aged children have a higher risk of contracting onychomycosis which may be attributed to the onset of hyperhidrosis at puberty, use of occlusive footwear, nail unit trauma, and walking barefoot. Fusarium onychomycosis may be more prevalent than expected, and this may merit consideration of management strategies.

A Study of Onychoscopic Findings in Various Dermatological Disorders

Context: About 10% of all the dermatological conditions are comprised nail disorders. It is challenging for the dermatologists to diagnose nail disorders quickly without the help of invasive procedures. Aims: The aim of the study was to evaluate onychoscopic patterns associated with various nail disorders. Settings and Designs: Hospital-based cross-sectional observational study was conducted at a tertiary care teaching institute in Maharashtra, India from November 2019 to May 2021. Materials and Methods: One hundred and fifty patients, with a history and clinical presentation suggestive of nail disorders, were recruited in the study after confirming the clinical diagnosis. Patients having secondarily modified lesions were excluded. Dry as well as wet onychoscopy using polarized and nonpolarized modes was performed with the help of DermLite 4 dermoscope with an attached OnePlus 8T mobile phone camera to capture and save the dermoscopic images. Data were compiled and statistically analyzed using SPSS version 21.0. Statistical Analysis Used: Categorical variables were expressed in frequency and percentages. Data were entered in Microsoft Excel and analyzed using SPSS version 20. P value (using Z-test for proportions) was calculated wherever needed. Results: The majority of the patients were in the age group of 21–50 years with slight male preponderance. Overall most common onychoscopic findings studied in all the disorders were the nail plate alterations followed by chromonychia. The most common nail changes associated with connective tissue disorders were changes in the proximal nail fold capillaries along with changes in the curvature. The most common change observed in onychomycosis was chromonychia. Aurora borealis, spikes, and jagged edges of onycholytic plate with ruin pattern of hyperkeratosis were specific to onychomycosis. Inflammatory disorders of the nail unit (e.g., lichen planus and nail psoriasis) showed nail plate alterations with increased nail plate fragility. Conclusions: Some onychoscopic patterns are observed consistently with certain diseases, and these can be used for their diagnosis, hence, avoiding unnecessary biopsies, thus improving the patient outcome.

Nailing the Nail Biopsy: Surgical Instruments and Their Function in Nail Biopsy Procedures.

Nail surgeries, including nail biopsies (NBs), are performed relatively infrequently-perhaps due to dermatologists' unfamiliarity with nail unit anatomy and lack of formal NB training during residency. To address this educational gap, we sought to create a guide that details the surgical instruments used for the nail matrix tangential excision (shave) biopsy technique-the most common technique used in our nail specialty clinic.

52583 Dermoscopic features of nevi and melanoma of acral surfaces and the nail unit: A systematic literature review

52583 Dermoscopic features of nevi and melanoma of acral surfaces and the nail unit: A systematic literature review

54191 Nail Unit Atypical Intraepidermal Melanocytic Proliferation: Diagnostic Change to Melanoma and Local Recurrence Rate After Mohs Micrographic Surgery

54191 Nail Unit Atypical Intraepidermal Melanocytic Proliferation: Diagnostic Change to Melanoma and Local Recurrence Rate After Mohs Micrographic Surgery

The 2023 WHO updates on skin tumors: advances since the 2018 edition.

Pathology is pivotal in diagnosing skin tumors, and the precision of diagnosis is crucial to devise customized treatment plans and enhance patient care in dermatology. The latest edition of the World Health Organization's classification of skin tumors serves as a comprehensive compendium, summarizing and categorizing all recent advancements in both anatomical-pathological and molecular aspects of cutaneous neoplasms. Several relevant advances have been introduced and new entities have been described. While the fundamental structure of the classification remains unchanged, notable additions include three new sections aimed at providing a more exhaustive description of skin lesions: nail unit tumors, skin metastases, and genetic tumor syndromes associated with skin malignancies. Recent strides in molecular pathology have led to significant breakthroughs in decoding the underlying mechanisms of various skin tumors, ranging from adnexal neoplasms to hematolymphoid neoplasms, soft tissue tumors, and melanocytic lesions. Of particular importance is the evolution in our understanding of melanocytic neoplasms, with the introduction of the term "melanocytoma" reserved for lesions exhibiting "intermediate" biological behavior and characterized by specific molecular mutations. The pathologic diagnosis process integrates morphological, immunohistochemical, and molecular features, playing a crucial role in clinical decision-making. The WHO classification serves as a valuable tool in promoting multidisciplinarity in the management of cutaneous neoplasms with the aim of translating novel pathological discoveries into more effective treatments. This review aims to distill the major updates introduced by the new classification, providing a synthesis of the latest scientific insights.

50627 Dermoscopy of Nail unit Bowen’s disease: a retrospective case series

50627 Dermoscopy of Nail unit Bowen’s disease: a retrospective case series

Ultrasonographic evaluation of nail matrix topography for preservative nail surgery of nail unit melanoma.

Recently, functional or preservative surgery has been preferred for nail unit melanoma; however, complete resection of the nail unit, particularly the matrix, is challenging because of its complex structure. This study aims to measure the distance of important nail structures through ultrasonography. Herein, 14 patients without nail deformity were included. The length from the nail cuticle to the distal interphalangeal joint (distance X), to the attachment part of the extensor muscle (distance A), to the median proximal end of the nail matrix (distance B), and to the lateral proximal end of the nail matrix (distance C) were measured. In the axial plane, the length from the highest point of the nail plate to the bottom of the distal phalanx (distance Y) and to the lateral tip of the nail plate (distance D) were measured. On the first fingernail, third fingernail, first toenail, and third toenail, the mean ratio A:X, ratio B:X, ratio C:X, and ratio D:Y were 78.6%, 44.3%, 57.2%, 40.1%, and 84.6%; 55.9%, 64.9%, 40.2%, and 66.4%; 35.6%, 50.8%, 34.3%, and 81.9%; and 57.2%, 59.6%, and 31.7%, respectively. Nail units are often invisible to the naked eye; thus, this study will help identify the approximate scope of excision.

Recurrence rates after functional surgery versus amputation for nail squamous cell carcinoma not involving the bone: A systematic review.

Background Nail unit squamous cell carcinoma (nSCC) is a malignant subungual tumour. Although it has a low risk of metastasis and mortality, the tumour has a significant local recurrence rate. There is insufficient data to determine whether functional surgery is less effective than amputation for nSCC that does not involve the bone. Objectives We aimed to investigate existing data on the outcomes of functional surgery and amputation for nSCC without bone invasion. Materials and Methods We carried out an extensive search in PubMed, Embase, Cochrane Library, Web of Science, and Scopus for appropriate English-language academic papers, starting with the creation of individual resources until February 23, 2023. The main outcome was local recurrence. Initially, 2191 studies related to nSCC were selected. Information from every research study was retrieved and subdivided, comprising the year of publication, period, number of patients, age, gender distribution, tumour stage, type of intervention, number of recurrences, and follow-up period. Results Ten independent studies (319 lesions) were finally selected. Mohs micrographic surgery was the most reported surgical modality, followed by wide surgical excision and amputation. Local recurrence rates between Mohs micrographic surgery, wide surgical excision and amputation treatment were nearly identical. Other surgical methods included limited surgical excision, partial ablation, and limited excision until the clearing of margins, with recurrence rates up to 50%. Conclusions Given the functional impairment and psychological distress associated with phalanx amputation, functional surgery, including Mohs micrographic surgery and wide surgical excision , should be the preferred therapy for nSCC without bone involvement. Amputation should remain the preferred therapy for nSCC that involves the bone. Partial excision should be avoided. Further studies on whether Mohs micrographic surgery or wide surgical excision is a better option for nSCC not involving the bone are required.

The concept of onychodermis containing onychofibroblasts has histological (microanatomical), immunohistochemical as well as molecular basis.

The terms "onychofibroblast" (nail-specific fibroblast) and onychodermis (nail-specific dermis) were first introduced in 2006 and 2012, respectively, based on distinctive histologic and immunohistochemical features from the dermis of the surrounding skin and have been demonstrated in multiple studies. Recently, based on molecular research, the definition of onychodermis containing onychofibroblasts has been expanded to encompass the area located between the nail matrix and bed epithelium and periosteum. Single-cell RNA sequencing and in situ hybridization demonstrated that onychofibroblasts within the onychodermis express the genes including RSPO4, MSX1, WIF-1, and BMP5, which are implicated in nail formation and/or in disorders with nail phenotype. A mutation in RSPO4, a component of the Wnt signaling pathway, causes anonychia congenita. Nail matrix onychodermis and nail bed onychodermis share many similar characteristics which differ from the surrounding normal dermis of the skin. Comparative spatial transcriptomic and single-cell analyses of human nail units and hair follicles suggest that onychodermis is the counterpart of follicular dermal papilla, which plays a key role in hair follicle growth and morphogenesis. Onychomatricoma, as a nail-specific tumor, has been demonstrated to be a mesenchymal tumor that originates from onychofibroblasts and is associated with the upregulation of Wnt signaling. Collectively, the onychodermis and onychofibroblasts play crucial roles in nail development and these specialized nail mesenchymal elements are key components in the pathogenesis of onychomatricoma. The concept of onychodermis containing onychofibroblasts is very important for nail biology and pathology.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. To target these unique genetic changes, a zebrafish acral melanoma model was exposed to a panel of narrow and broad spectrum multi-RTK inhibitors, revealing that dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration. The potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM patient-derived xenograft (PDX) tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks. Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.

Integrating scRNA-seq and bulk RNA-seq to explore the differentiation mechanism of human nail stem cells mediated by onychofibroblasts.

Introduction: Nail stem cell (NSC) differentiation plays a vital role in maintaining nail homeostasis and facilitating digit regeneration. Recently, onychofibroblasts (OFs), specialized mesenchymal cells beneath the nail matrix, have emerged as potential regulators of NSC differentiation. However, limited understanding of OFs' cellular properties and transcriptomic profiles hinders our comprehension of their role. This study aims to characterize human OFs and investigate their involvement in NSC differentiation. Methods: Human OFs were isolated and characterized for their mesenchymal stem cell (MSC)-like phenotype through flow cytometry and multilineage differentiation assays. Bulk RNA-seq analysis was conducted on three samples of OFs and control fibroblasts from human nail units to delineate their molecular features. Integrated analysis with scRNA-seq data was performed to identify key signaling pathways involved in OF-induced NSC differentiation. Co-culture experiments, siRNA transfection, RT-qPCR, and immunocytochemistry were employed to investigate the effect of OF-derived soluble proteins on NSC differentiation. Drug treatments, RT-qPCR, western blotting, and immunocytochemistry were used to verify the regulation of candidate signaling pathways on NSC differentiation in vitro. Results: Human OFs exhibited slow cell cycle kinetics, expressed typical MSC markers, and demonstrated multilineage differentiation potential. Bulk RNA-seq analysis revealed differential gene expression in OFs compared to control fibroblasts, highlighting their role in coordinating nail development. Integrated analysis identified BMP4 as a pivotal signal for OFs to participate in NSC differentiation through mesenchymal-epithelial interactions, with the TGF-beta pathway possibly mediating this signal. OFs synthesized and secreted more BMP4 than control fibroblasts, and BMP4 derived from OFs induced NSC differentiation in a co-culture model. Recombinant human BMP4 activated the TGF-beta pathway in NSCs, leading to cell differentiation, while the BMP type I receptor inhibitor LDN193189 attenuated this effect. Discussion: This study characterizes the cellular and molecular features of human OFs, demonstrating their ability to regulate NSC differentiation via the TGF-beta signaling pathway. These findings establish a connection between the dermal microenvironment and NSC differentiation, suggesting the potential of OFs, in conjunction with NSCs, for developing novel therapies targeting nail and digit defects, even severe limb amputation.

Cutaneous adverse events to systemic anticancer therapies : Hand-foot syndrome and nail changes

Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies. To provide areview of current evidence in HFS and nail disorders associated with medical tumor treatment. Basis is the current German S3guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized. Two variants of HFS are distinguished: achemotherapy-associated and akinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with ahigh number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is aproposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, avascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds. This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment.