Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema.

Nummular eczema, a chronic dermatitis characterized by coin-shaped lesions, was first documented in 1857. However, its pathophysiological characteristics are still not well known. To investigate differences in the regulation of the desquamation process in the stratum corneum of lesional and nonlesional skin of patients with nummular eczema and healthy control subjects, tape-stripped stratum corneum samples from patients with nummular eczema and healthy volunteers were analysed using immunofluorescence staining and western blot analysis. In the nummular eczema lesional skin, expression of desmoglein-1, desmocollin-1, and corneodesmosin exhibited a disorganized, dense or partially diffuse non-peripheral pattern with increased intensity, compared with the peripheral patterns observed in healthy or nonlesional skin, suggesting the impaired desquamation process in nummular eczema. Furthermore, although the expression of the desquamation-related serine proteases, kallikrein-related peptidase 7 and 5, was increased in nummular eczema lesional skin, the immunofluorescence staining of lympho-epithelial Kazal-type-related inhibitor-1, an endogenous inhibitor of various kallikrein-related peptidases, and its fragments were significantly increased in the nummular eczema lesional skin, suggesting its contribution to the inhibition of corneodesmosomal degradation. Therefore, the increased detection of corneodesmosomal proteins in nummular eczema lesions may be due to the increased amount of the fragments of lympho-epithelial Kazal-type-related inhibitor-1, which could contribute to delayed desquamation.

Spatial transcriptomic analysis of tumour-immune cell interactions in melanoma arising from congenital melanocytic nevus.

BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden.

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated ß-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of ß-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

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.

Tumor invasion in the hyponychium is associated with distant metastasis and poor prognosis in subungual melanoma: A histologic landscape of 44 cases.

BACKGROUND: Subungual melanoma (SUM) has a poor prognosis because of delayed diagnosis. Its progression, consensus on surgical treatment, and correlation with clinical outcomes remain unclear. OBJECTIVE: We aimed to identify the pattern of dermal invasion in different locations of the nail apparatus and its relationship with prognosis. METHODS: In this retrospective review of surgically treated SUM patients between January 2011 and April 2019, the nail apparatus was divided into 5 anatomic subunits: the dorsal roof of proximal nail fold, ventral floor of proximal nail fold, germinal matrix, nail bed, and hyponychium. Invasions in the subunits were categorized using 3 criteria: no tumor, in situ tumor, or invasion. RESULTS: Among 44 cases of SUM, dermal invasion occurred mostly in the distal areas, with 11, 30, 18, 7, and 4 in the hyponychium, nail bed, germinal matrix, ventral floor of proximal nail fold, and dorsal roof of proximal nail fold, respectively. The patients with hyponychial invasion showed a significantly greater Breslow depth (P = .009), a higher rate of lymph node metastasis (P = .019), distant metastasis (P = .036), and shorter disease-free survival (P = .001). CONCLUSION: Hyponychial invasion is an important prognostic predictor of SUM, given its strong association with invasion depth, metastatic progression, and disease-free survival. Patients with invasion in the hyponychium should undergo more strict workup, treatment, and surveillance.

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.

Histopathologic findings of idiopathic trachyonychia: An analysis of 30 adult patients.

BACKGROUND: Trachyonychia, a rare inflammatory disease of the nail matrix, has a more chronic course in adults compared with that in children. However, the histopathologic features of the disease have not been sufficiently reported in the literature. METHODS: We retrospectively reviewed the pathologic features of idiopathic trachyonychia in adult cases at our center. RESULTS: A total of 30 cases were included. The median age was 55.5 years (range, 27-77 years). Median disease duration was 84 months (range, 8-384 months). Histopathologic analysis showed upper dermal lymphocytic infiltrates (93.3%), acanthosis (86.7%), exocytosis (63.3%), spongiosis (63.3%), parakeratosis (46.7%), psoriasiform hyperplasia (40%), eosinophilic infiltrates (33.3%), vacuolar degeneration (33.3%), lichenoid pattern (13.3%), Civatte body (6.7%), and collection of neutrophils in the stratum corneum (3.3%). Statistical analysis among pathologic parameters revealed associations of spongiosis with exocytosis (P < 0.001) and lichenoid infiltration with vacuolar degeneration (P = 0.008). Three patients (10%) showed fungal co-infection. CONCLUSION: The majority of cases revealed inflammatory cell infiltration with epidermal changes. Given the inflammation and chronic course of idiopathic trachyonychia in adulthood, active treatment with anti-inflammatory agents should be considered. Additionally, mycological tests should be considered during initial evaluation as there are cases with fungal coinfection.

Dermoscopic Evaluation of Inflammatory Nail Disorders and Their Mimics.

Nail dermoscopy (onychoscopy) is a valuable diagnostic tool for evaluating diseases in the nail apparatus. It is non-invasive, allowing clinicians to prioritize particular nails for biopsy. Thus, it can improve diagnostic accuracy and expedite treatment. Evaluating inflammatory nail disorders using onychoscopy is a relatively new approach to clinical assessment and has the potential to augment clinical care. This review highlights key dermoscopic features of major inflammatory nail disorders, including trachyonychia, nail psoriasis, nail lichen planus, onychotillomania, nail lichen striatus and allergic contact dermatitis due to artificial nails. It also illustrates their management and differential diagnoses, including onychomycosis, onycholysis, nail dystrophy due to systemic amyloidosis and malignant nail tumours. Limitations of this review included the low amount of literature on this topic and non-standardized terminology used among research-ers. As onychoscopy is a relatively new technique, further studies and standardization of terminology are warranted to consolidate the role of dermoscopy in evaluating inflammatory nail disorders.

Sleep during Mohs micrographic surgery: A prospective study.

Mohs micrographic surgery (MMS) is a highly specialized technique for treating skin cancer. Drawbacks of MMS are the multi-step procedure and long surgery time. Some patients sleep during surgery and involuntary movements during sleeping can interfere with surgery, which increases the risk of a fall injury. However, to our knowledge, there have been no studies regarding the characteristics of patients' sleep during MMS. This study aimed to investigate the prevalence and characteristics of sleeping patients during MMS. We performed a prospective study and included patients with skin cancers impending MMS. All patients rated their anxiety levels and sleep status using the State-Trait Anxiety Inventory, an anxiety visual analog scale, the Pittsburgh Sleep Quality Index, and the Leeds Sleep Evaluation Questionnaire. Our data showed that 21.9% of patients were asleep during MMS. Multivariable analysis showed that older age (odds ratio [OR], 1.142; p=0.003), lesion size >150 mm2 (OR, 7.904; p=0.031), and multi-stage MMS (OR, 12.201; p=0.011) were significantly associated factors of sleep. This study is the first to report the prevalence and associated factors of sleep during MMS. Physicians should monitor patients with risk factors during MMS to prevent possible medical accidents.

Surgical management of lipomas: Proposal of the Z-incision design and surgical algorithm based on tumor size.

Surgical excision is the treatment of choice for lipomas. However, linear incision methods or minimal extraction techniques often do not provide a sufficient surgical view. Therefore, removing large lipomas is often difficult. To present the Z-incision and half Z-incision designs for lipoma extraction, this retrospective study analyzed lipomas surgically excised at our institution between September 2015 and December 2018. The area of surgical field exposed by the Z-incision versus that exposed by the linear incision was calculated using a schematic model. Cure rate, complications, and surgical field area were investigated. A total of 84 lipomas were included. A Z- or half Z-incision was used to treat 30 lipomas, while a linear incision was used to treat 54 lipomas. The mean diameter of the mass in the Z- or half Z-incision group was 47.7 mm (range, 15-160 mm), larger than that in the linear incision group (25.5 mm; range, 7-59 mm) (p < .001). The Z-incision involved making rectangular windows by lifting 2 triangular flaps. According to our mathematical model, the Z-incision provided a larger surgical field area than that provided by the linear incision based on stretched angles (1.81 times larger at 30° and 3.14 times larger at 15°). The Z- and half Z-incisions were successfully performed in all but 1 lipoma (29 lipomas, 96.7%). There was 1 lipoma that resulted in postoperative complications (seroma, 3.3%). The Z-incision design can be a useful alternative technique for the extirpation of lipomas, especially large lipomas. Here, we proposed a surgical algorithm for lipoma surgery based on tumor size.

Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-ß1-Induced Fibrosis in Keloids.

Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor ß1 (TGF-ß1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-ß1-induced expression of procollagen type 1 in keloid fibroblasts (p < 0.05). Moreover, it inhibited the TGF-ß1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase (p < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-ß1-induced fibrosis (p < 0.05). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.

Functional surgery versus amputation for in situ or minimally invasive nail melanoma: A meta-analysis.

BACKGROUND: Evidence on whether functional surgery is not inferior to amputation for the treatment of in situ or minimally invasive (Breslow thickness ≤0.5 mm) nail melanoma is limited. OBJECTIVE: To investigate the difference in local recurrence between the 2 interventions for in situ or minimally invasive nail melanoma using available published studies. METHODS: We performed systematic search on PubMed, Embase, Cochrane Library, trial registers, and grey literature databases from inception to June 28, 2018. We included observational studies with at least 5 patients with in situ or minimally invasive nail melanoma. Main outcome was local recurrence. RESULTS: The odds ratio synthesized from 5 studies including 109 patients (88 functional operations and 21 amputations) was 1.57 (95% confidence interval, 0.31-8.00). LIMITATIONS: Small sample size and possible interstudy heterogeneity. CONCLUSIONS: Our meta-analysis revealed no difference in local recurrence between the 2 interventions. Considering the functional deficit after amputation, conservative surgery should be the treatment of choice for in situ or minimally invasive nail melanoma.

Early detection of acral melanoma: A review of clinical, dermoscopic, histopathologic, and molecular characteristics.

Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages and delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress in understanding the key features of this disease, the diagnosis of early-stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histologic findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful. In this review, we have summarized our current understanding of this disease entity from articles that were published between 1969 and 2018. We have outlined clinical and dermoscopic features as well as pathologic and molecular findings regarding acral melanoma and have presented an algorithm for diagnosis. Understanding and integrating these characteristics may assist clinicians in the early detection of acral melanomas.

Association between Breslow thickness and dermoscopic findings in acral melanoma.

BACKGROUND: Dermoscopy is a useful tool for the diagnosis of acral melanomas (AMs). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM. OBJECTIVE: To investigate the affect Breslow thickness (BT) has on the dermoscopic patterns of AM. METHODS: Data on cases of AM on the glabrous skin were collected from 4 university hospitals. We investigated the frequency of each dermoscopic feature of AM according to the BT. Statistical analysis was performed to investigate the association between the specific dermoscopic patterns and BT. RESULTS: Multivariable analysis revealed that the colors red (odds ratio [OR] 16.482, 95% confidence interval [CI] 3.605-99.016); blue (OR 7.092; 95% CI 1.707-37.435); and white (OR 5.048, 95% CI 1.152-22.897) were more common in AM with BT >2 mm than those with BT ≤2 mm. Regarding patterns, atypical vascular (OR 34.589, 95% CI 6.458-305.852); blue-white veils (OR 9.605, 95% CI 1.971-72.062); and ulcers (OR 5.084, 95% CI 1.145-24.152) were more frequently detected in cases with BT >2 mm than those with BT ≤2 mm. LIMITATIONS: A retrospective study design and small sample size. CONCLUSION: This study showed an association between dermoscopic patterns and tumor thickness among patients with AM. Dermoscopy can be a useful adjuvant tool for predicting BT in AM.