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Background/Objectives: Mohs micrographic surgery (MMS) is a precise skin surgery technique that is particularly useful in the treatment of high-risk skin cancers and tumors located in challenging anatomical areas. Methods: we report two cases of basal cell carcinoma located in the acral areas effectively treated using MMS. Results: the presented cases demonstrate that MMS is an excellent surgical modality providing outstanding medical, cosmetic, and functional outcomes. Moreover, this study provides another dermoscopic presentation of acral basal cell carcinoma in a patient without the diagnosis of hereditary genetic syndromes associated with an increased risk of skin cancer. Conclusions: basal cell carcinoma located on hands and feet, albeit rare, should be included in the differential diagnosis of amelanotic skin tumors in acral areas. [ABSTRACT FROM AUTHOR]

Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer‐gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre‐clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M‐specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas. [ABSTRACT FROM AUTHOR]

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from endothelial dysfunction and prothrombotic effects induced by the tumor through a paraneoplastic mechanism. This case underscores the importance of recognizing acral vascular syndrome, prompting thorough investigation for an underlying malignancy. Ultimately, collective efforts aimed at enhancing our understanding of PAVS and optimizing its management hold promise for improving outcomes and alleviating the burden of this condition on affected patients.

Simple Summary: This study aimed to assess the 3-year time to relapse (TTR) and overall survival (OS) of melanoma, including acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or the combination of dabrafenib and trametinib. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). This study suggests that both acral and mucosal types in the adjuvant setting are less effective than non-acral cutaneous melanoma at the 3-year TTR. Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint. [ABSTRACT FROM AUTHOR]

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis. [ABSTRACT FROM AUTHOR]

Paraneoplastic acral vascular syndrome (PAVS) is a captivating enigma in the landscape of oncological pathology, characterized by vascular disturbances of the extremities. PAVS is linked to rapidly progressing trajectory and understanding the intricate interplay between cancer and this vascular dysfunction is imperative for timely diagnosis. We describe the case of a 45-year-old cachectic male who presented at the ICU with bilateral tumefied, cyanotic digits, accompanied by acute pain and numbness in both hands. A Digital Angiography described complete obstruction of the digital arteries. Imaging showed a laterocervical tumor mass with pulmonary metastases. This form of digital ischemia likely stems from endothelial dysfunction and prothrombotic effects induced by the tumor through a paraneoplastic mechanism. This case underscores the importance of recognizing acral vascular syndrome, prompting thorough investigation for an underlying malignancy. Ultimately, collective efforts aimed at enhancing our understanding of PAVS and optimizing its management hold promise for improving outcomes and alleviating the burden of this condition on affected patients. [ABSTRACT FROM AUTHOR]

Background: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. Methods: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. Results: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. Conclusion: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

Calcified chondroid mesenchymal neoplasm is a recently recognized bone and soft tissue entity primarily found in the extremities and the temporomandibular joint. This neoplasm is typically driven by the fusion of the FN1 gene with a kinase. In this case report, we provide a detailed account of a rare superficial calcified chondroid mesenchymal neoplasm located on the left big toe, characterized by an FN1::FGFR2 fusion. The tumor exhibited a peripheral collarette and consisted of large intradermal histiocytoid to epithelioid cells with no mitotic activity. These cells displayed fine chromatin and abundant pale eosinophilic cytoplasm, forming a swirling syncytium. They were interspersed with localized areas of glassy chondromyxoid matrix containing randomly mineralized calcific material and isolated osteoclast‐like giant cells. RNA sequencing confirmed the presence of an FN1 (exon 29)::FGFR2 (exon 7) gene fusion. Our report emphasizes the importance for dermatopathologists to consider this entity when evaluating superficial lesions displaying mesenchymal, chondroid, and calcified attributes. [ABSTRACT FROM AUTHOR]

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas.

Objective: Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other. Materials and Methods: The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated. Results: A total of 30 patients were diagnosed with Gorlin syndrome of whom 36.7% were children. BCC was the most common finding (90%) followed by OKCs (83.3%), skeletal system anomalies (76.7%), and palmoplantar pitting (76.7%). While classical BCC (63.3%) lesions were the predominant clinical subtype among all patients, acrochordon-like or small-sized papular BCCs were seen in 45.4% of pediatric patients. Three patients, 2 of whom were children, had BCC lesions in the palmoplantar region in association with palmoplantar pitting. Epidermoid cysts presenting clinically as solitary (n = 12) or a few nodules (n = 4) without punctum, located more commonly in acral areas (n = 10) were seen in 16 (53.3%) patients of whom 7 were children. Epidermoid cysts were seen in 60% of patients with OKCs, and the relationship between epidermoid cysts and OKCs was not statistically significant (P = .15). Extracutaneous tumors such as medulloblastoma (n = 3), cardiac fibroma (n = 1), and ameloblastoma (n = 1) were also recorded. Conclusion: The awareness of papular or acrochordon-like BCCs, palmoplantar BCCs, and acral epidermoid cysts without punctum may facilitate early diagnosis of Gorlin syndrome in children. [ABSTRACT FROM AUTHOR]

A PTEN deficiency leads to the activation of phospho‐Akt at serine 473 (p‐Akt) and promotes the tumorigenesis of melanomas by coupling with NUAK2 amplification. We tested the prognostic impact of p‐Akt and/or NUAK2 expression on the relapse‐free survival (RFS) and overall survival (OS) of melanoma patients. Primary tumors from patients with acral melanomas (112), Low‐cumulative sun damage (CSD) melanomas (38), and High‐CSD melanomas (18) were examined using immunohistochemistry and their prognostic significance was analyzed statistically. The expression of p‐Akt was found in 32.1%, 68.4%, and 55.6% of acral, Low‐CSD, and High‐CSD melanomas, while NUAK2 expression was found in 46.4%, 76.3%, and 50.0%, respectively. Either p‐Akt or NUAK2 expression was inversely correlated with the RFS of primary melanoma patients and acral melanoma patients (p‐Akt: p <.0001, p <.0001; NUAK2; p =.0005, p <.0001, respectively). Strikingly, multivariate analyses revealed that p‐Akt had a significant impact on RFS (Hazard ratio = 4.454; p <.0001), while NUAK2 did not. Further subset analyses revealed that p‐Akt expression had an inferior RFS of patients with acral melanomas (Hazard ratio = 4.036; p =.0005). We conclude that the expression of p‐Akt has a significant impact on RFS of patients with primary melanomas and can predict the relapse of patients with acral melanomas. Research Highlights: The expression of p‐Akt has a significant impact on relapse‐free survival in primary melanoma patients and can predict the relapse of acral melanoma patients. The expression of p‐Akt can be a promising biomarker to stratify acral melanomas for clinical trials. [ABSTRACT FROM AUTHOR]

Background: Noncultured epidermal cell suspension (NCECS) is a commonly used surgical treatment for resistant stable acral vitiligo and vitiligo overlying joints. Platelet‐rich plasma (PRP) has been reported to enhance the repigmentation response of different therapeutic modalities for vitiligo, including vitiligo surgery. Objective: To assess the value of adding of PRP to NCECS in the surgical treatment of acral vitiligo and vitiligo overlying joints. Patients and Methods: This self‐controlled randomised trial included 15 patients with 30 lesions in which NCECS suspended in PRP was performed for one lesion and NCECS in ringer's lactate for another comparable lesion. Following NCECS, patients underwent thrice weekly excimer light sessions for 3 months. After 8 weeks, patients underwent preliminary assessment. By the end of the 3 months, both lesions were compared as regards improvement in surface area and pigmentation. Additionally, physician global assessment was made by a blinded investigator. Results: Significant improvement was reported in both lesional extent and pigmentation (after PRP and lactated ringer NCECS) with no statistical difference between them. Conclusion: Despite previous promising results, suspending NCECS in PRP offered no privilege in surgical treatment of acral vitiligo and vitiligo overlying joints, which are quite resistant to treat. Pan African Clinical Trial registry ID: PACTR202108873035929, Date: 16 August 2021. [ABSTRACT FROM AUTHOR]

Background: Autologous noncultured, nontrypsinized melanocyte–keratinocyte grafting (Jodhpur technique [JT]) is an unconventional innovative surgical modality for the treatment of stable vitiligo. Acral vitiligo is considered an area that is difficult to treat with variable results in different studies. Purpose: The aim of this study was to assess the efficacy and safety of JT in stable acral vitiligo. Methods: This was an open, nonrandomized, and single-arm study. Ninety patches of stable acral vitiligo were included in this study. JT was performed over these patches. The total duration of the study was 48 weeks. The degree of repigmentation was graded into poor (

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

Compared with sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors, but their genetic heterogeneity is not well studied. We investigated the genomic profile of acral, mucosal, and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features. We performed whole transcriptome messenger RNA and DNA (1711 genes) sequencing, messenger RNA expression profiling, tumor mutational burden, ultraviolet signature, and copy number variants analysis on 29 volar/digital acral, 7 mucosal, and 6 vulvovaginal melanomas. There was significant genetic heterogeneity, particularly in acral melanomas, with 36% having BRAF alterations, whereas other melanomas had none (P =.0159). Nonzero ultraviolet signatures were more frequent in acral melanomas, suggesting greater ultraviolet involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified, such as AURKA and ERBB2 , in mucosal and acral melanomas, respectively. The sample size was a small. There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1+) CD8 T cells and PD-1 ligand (PD-L1+) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells' capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy. [ABSTRACT FROM AUTHOR]

Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands. [ABSTRACT FROM AUTHOR]

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods: Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results: Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM. [ABSTRACT FROM AUTHOR]

Introduction: Nodular melanoma (NM) is a rare subtype of melanoma, responsible for more than 40% of melanoma deaths, characterized by rapid growth and high metastatic potential. Only a few case studies concerning the dermoscopic presentations of giant nodular melanoma have been reported so far. Objectives: The aim of the study was to assess dermoscopic features of giant nodular melanomas in special locations, along with their clinical and histopathologic aspects. Methods: Among 120 patients with histopathologically confirmed melanoma treated by the Skin Cancer and Melanoma Team between September 2020 and February 2021, we identified six patients with giant nodular melanoma in special locations. We retrospectively assessed the archived dermoscopic images to determine the dermoscopic features of these tumors. Results: The group consisted of six cases of giant melanoma in special locations, including the scalp (4/6) and the heel (2/6). The giant tumors were large in size (at least 5 cm in diameter). The most common dermoscopic structures in polarized light included asymmetric distribution of dermoscopic structures, the presence of structureless, multicolored zones (showing three or more colors), and the presence of white perpendicular lines or small, pink globules. Conclusions: It seems that there are no significant differences in dermoscopy between small and giant melanomas; however, further studies should be conducted on a larger scale. [ABSTRACT FROM AUTHOR]

Background: The immunohistochemical (IHC) marker PReferentially expressed Antigen in MElanoma (PRAME) has shown promise in the diagnosis of melanocytic lesions. A few studies have investigated PRAME IHC expression in acral melanomas, but PRAME expression in subungual melanomas is largely unknown. We evaluated the utility of PRAME IHC expression in distinguishing subungual melanomas (SUM) and non‐subungual acral melanomas (AM) from acral nevi (AN). Methods: Twenty‐two SUM, 20 AM, and 14 AN were identified. IHC studies were performed using an anti‐PRAME antibody. The percentage of lesional cells with PRAME expression was recorded and categorized as follows: 0%, 0; 1%–25%, 1+; 26%–50%, 2+; 51%–75%, 3+; and >75%, 4+. Patient demographics and other relevant clinicopathologic parameters were recorded. Results: Diffuse (4+) PRAME IHC expression was identified in 55% (12/22) SUM and 70% (14/20) AM, respectively. Any PRAME expression (1+ to 4+) was identified in 73% (16/22) SUMs and 95% (19/20) AM, respectively. One of 14 (7%) AN exhibited PRAME expression; interestingly, the pattern of expression was diffuse. Conclusions: In our study, PRAME IHC expression was useful in identifying AM, including SUM. However, there are exceptions of PRAME‐negative melanomas and PRAME‐positive nevi. [ABSTRACT FROM AUTHOR]

Background: Physiologic volar melanotic macules (P-VMM) are understudied. Trauma has been a suggested predisposing factor. Little has been published over the last several decades., Objective: To evaluate clinical/historical/dermatoscopic features of P-VMM in Skin-of-Color (SOC) persons., Method: This cross-sectional study enrolled 200 SOC adults from Jamaica and Massachusetts. In those with P-VMM, clinical and dermatoscopic images were taken with size, color, localization, distribution, and dermatoscopic patterns recorded. Questionnaires recorded demographic, occupational and trauma history in both groups., Results: For those with P-VMM, most (91.8%, n=89) were Black followed by mixed-race (5.2%, n=5), Indian Asian (2.1%, n=2), and Hispanic (1%, n=1). The F:M ratio was 2.5:1. Both palms/soles were involved in 67%. Light-to-dark brown, round/oval macules/patches were common and were similar to each other. No significant difference in trauma was found, nor predilection for weight-bearing areas. Occupations involving manual labor were associated with the presence of P-VMM (p=0.019). Dermatoscopically, >90% had a homogenous pattern, while bland ridge, beaded, and fibrillar patterns were rarely seen., Limitations: Lack of histopathology and unbalanced proportions of SOC subgroups., Conclusion: P-VMM is common in Black adults. It lacks association with major trauma or predilection for weight-bearing sites. Dermoscopy primarily reveals a homogenous pattern., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Diagnosis of acral melanocytic lesions can be challenging. The BRAAFF checklist was introduced as a tool to help differentiate between acral nevi and melanoma but has not been validated., Methods: We asked raters with varying expertise in dermatoscopy to diagnose dermatoscopic images of 533 acral nevi and 144 melanomas via an online platform with and without use of the BRAAFF checklist. From the ratings, we calculated sensitivity, specificity, and interrater agreement. Additionally, a new simplified version of the checklist was also tested., Results: We collected 6,880 ratings from 175 readers. The BRAAFF checklist achieved a sensitivity of 92.5% and a specificity of 65.0%, which was similar to diagnosis from pattern recognition (sensitivity 90.0%, specificity: 72.1%). Interrater agreement for the BRAAFF criteria ranged from fair to moderate, with lowest agreement for parallel ridge and fibrillar pattern (alpha = 0.31) and highest for asymmetry of colors and structures (alpha = 0.46). Agreement and diagnostic accuracy were higher for more experienced readers. A simplified version with only two criteria achieved similar sensitivity (95.0%) and lower specificity (60.0%) as the original BRAAFF checklist., Conclusion: The BRAAFF checklist is a useful tool for the diagnosis of melanocytic acral lesions with acceptable sensitivity and reasonable specificity but is not superior to pattern recognition. A simplified version of the checklist could be easier to use with equal sensitivity while exhibiting a modest reduction in specificity., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Early recognition of a pituitary secretor tumor offers a better prognostic; thus acromegaly might be recognized before the actual clinical picture of acromegaly is detectable. This is a 59-year old, non-smoking female admitted for: post-operatory evaluation of acromegaly. The clinical evaluation is non-specific. One year prior she was diagnosed with acromegaly based on cerebral imaging assessment due to intermittent headache. She was treated with cabergoline a few months before neurosurgery was done; post-operatory panel showed complete remission of acromegaly. Prompt detection of the disease allowed the early intervention with a very good outcome. The remission of GH excess after neurosurgery depends on tumor size and practical experience of the surgeon. The longer time of high growth hormone levels exposure the higher is the risk of cardio-metabolic and oncologic complications.

The anatomic site of primary melanoma is significantly correlated with survival, and extremity melanomas have better prognosis than trunk or head and neck melanomas. The aim of this study was to review and evaluate the prognostic factors and survival outcomes associated with both upper and lower extremity melanomas. A total of 524 limb-located melanomas were analyzed retrospectively. Lower extremity melanomas were predominant in number and feet/toes melanomas were more frequently found in the elderly. Acral lentiginous melanomas were found to affect more frequently lower limbs and showed mainly distal distributions for both limbs. However, acral melanomas were more often ulcerated and they were more frequently BRAF wild-type melanomas associated with significant lymphovascular invasion. Foot and toe melanomas relapsed more frequently than leg melanomas. The 5-year overall survival rates for upper and lower limbs were the same, 62%. The finger (p =.0001) and toe (p =.005) melanomas had worse overall survivals than arm and leg melanomas, respectively. Both overall and disease-free survivals of acral melanoma patients were found worse than those of nonacral melanoma patients, p =.0001 and p =.001 respectively. Despite not having adjusted by Breslow, ulceration and nodal involvement status, acral location per se could be associated with poorer outcome in our retrospective study. Even though they were not found to be correlated with major predictors of poor prognosis, acral melanomas significantly predict poor survival. [ABSTRACT FROM AUTHOR]

Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas). PRAME was scored as % positive nuclei: negative = 0%; 1% to 25% = 1+; 25% to 50% = 2+; 50% to 75% = 3+, or positive: 75% to 100% = 4+. p16 expression was defined as retained (homogeneous or checkerboard) or lost (complete or partial/regionally). PRAME expression was negative in all benign, dysplastic, and Spitz nevi. Conversely, all acral melanomas were diffusely (4+) positive for PRAME expression. p16 expression was retained in all benign acral nevi (8/11 homogeneous, 3/11 checkerboard), completely lost in one dysplastic nevus, and retained in all acral Spitz nevi (3/7 homogeneous, 4/7 checkerboard). p16 was retained in five of 10 acral melanomas (3/10 homogeneous; 2/10 checkerboard), and negative in five of 10 acral melanomas (absent in 3/10, partially lost in 2/10). Our data suggest that 4+ PRAME expression is highly sensitive and specific in the setting of acral melanomas and is a more predictive diagnostic tool compared with p16 immunohistochemistry. [ABSTRACT FROM AUTHOR]

RHOA‐related neuroectodermal syndrome is characterised by linear skin hypopigmentation along Blaschko's lines associated with alopecia, leukoencephalopathy, facial and limb hypoplasia, and ocular, dental, and acral anomalies. Herein, we report a patient with patterned cutaneous hypopigmentation with a similar phenotype due to a novel postzygotic RHOA variant (c.210G>T; p.Arg70Ser). This illustrates that the complexity of the orchestration of morphogenesis and organogenesis can be affected by different variants in the same gene. [ABSTRACT FROM AUTHOR]

Abstract Cellular digital fibroma is a benign fibrous lesion that typically occurred on either a finger or a toe. Cellular digital fibroma was introduced as a distinctive cluster of differentiation 34 (CD34)-positive lesion in July 2005. Cellular digital fibroma has been described in 20 patients: 12 men and 8 women. The patients ranged in age from 27 to 83 years old (median, 52 years old) at diagnosis. The tumor had been present from 2 months to 2 years (median, 11 months) prior to seeking medical attention. The cellular digital fibroma was usually slowly growing and asymptomatic; there has been no prior history of trauma at the tumor site. The lesion typically presented as either an erythematous or a flesh-colored, solitary papule of 5 mm or smaller. It frequently occurred on either the dorsal, lateral or ventral side of a digit. Yet, some of the lesions were located on the nail fold of the digit. Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis; diffuse and strongly positive CD34 staining is present throughout the entire tumor. There is no erosion by the tumor of the bony phalanx. Other acral tumors, such as superficial acral fibromyxoma (which also has diffuse strongly positive CD34 staining) and acquired digital fibrokeratoma (which is either CD34-negative or only focal CD34 positive), are in the clinical and pathologic differential diagnosis of cellular digital fibroma. Conservative complete excision is the treatment of cellular digital fibroma; however, even for tumors that have only been partially removed during biopsy, recurrence has not been observed. In conclusion, cellular digital fibroma is a unique CD34-positive acral lesion of the distal fingers and toes whose diagnosis requires correlation of the clinical morphology and the pathologic features of the tumor.

Abstract Background/objective Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma. Methods Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion. Results Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami’s criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami’s or Gaiser’s criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma. Conclusions We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas., Competing Interests: C.S.H., D.H., T.J.P., S.R., J.D.W., T.M., and R.J.B. are inventors on multiple patents filed by MSK covering CAR T cell technology, including the CAR T cells discussed in this manuscript. S.R. serves on the Scientific Advisory Board of Celyad Oncology. R.J.B. has licensed intellectual property to and collects royalties from BMS, Caribou, and Sanofi. R.J.B. received research funding from BMS. R.J.B. is a consultant to BMS, Atara Biotherapeutics Inc., and Triumvira, and was a consultant for Cargo Tx and CoImmune but ended in the past 3 months, and Gracell Biotechnologies Inc. but ended employment in the past 24 months. R.J.B. is a member of the scientific advisory board for Triumvira and was a member of the scientific advisory board for Cargo Tx and CoImmune, but that ended in the past 6 months. J.D.W. is a consultant for Apricity, Ascentage Pharma, AstraZeneca, BeiGene, Bicara Therapeutics (ending 4/1/2024), Bristol Myers Squibb, Daiichi Sankyo, Dragonfly, Imvaq, Larkspur, Psioxus, Recepta, Takeda, Tizona, Trishula Therapeutics, and Sellas. J.D.W. received grant/research support from Bristol Myers Squibb and Enterome. J.D.W. has equity in Apricity, Arsenal IO/CellCarta, Ascentage, Imvaq, Linneaus, Larkspur, Georgiamune, Maverick, Tizona Therapeutics, and Xenimmune. J.D.W. is an inventor on the following patents: Xenogeneic DNA Vaccines, Newcastle Disease viruses for Cancer Therapy, Myeloid-derived suppressor cell (MDSC) assay, Prediction of responsiveness to treatment with immunomodulatory therapeutics and method of monitoring abscopal effects during such treatment, Anti-PD1 Antibody, Anti-CTLA4 antibodies, Anti-GITR antibodies and methods of use thereof. T.M. is a consultant for Immunos Therapeutics, Daiichi Sankyo Co, TigaTX, Normunity, and Pfizer. T.M. is a cofounder of and equity holder in Imvaq Therapeutics. T.M. receives research grant funding from Bristol Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals, Peregrine Pharmaceuticals, Adaptive Biotechnologies, Leap Therapeutics, and Aprea Therapeutics. T.M. is an inventor on patent applications related to work on oncolytic viral therapy, alpha virus-based vaccine, neo-antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4., (© 2024 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Synovial sarcoma is a malignant soft tissue tumor of uncertain differentiation. It is typically seen in the deep soft tissue of the extremities; however, it has been reported to occur anywhere in the body. Synovial sarcoma by histomorphology has multiple subtypes, including monophasic spindle cell, biphasic and poorly differentiated subtypes. Synovial sarcomas measuring less than one centimeter in diameter are termed "minute" synovial sarcomas. "Minute" synovial sarcomas have only been reported so far in the acral region of the hands and feet. They are extremely rare and can often be misinterpreted as benign neoplasms. Herein, we report the findings in a 30-year-old female presenting with a palpable mass within the deep subcutaneous tissue along the anterior aspect of her right rectus abdominis muscle. The mass was excised and measured 0.6 cm in greatest dimension with histomorphology findings, immunohistochemical and molecular workup confirming the diagnosis of "minute" synovial sarcoma. Our findings represent the first documented case of a "minute" synovial sarcoma occurring at an extra-acral site. With such unique finding not yet reported in the literature, this case highlights the importance of considering synovial sarcoma in the differential diagnosis of subcutaneous abdominal masses., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Grove et al.)

Primary cutaneous acral CD8+ T‐cell lymphoma (PCACTL) is currently a provisional entity defined as a rare cutaneous proliferation of atypical CD8+ lymphocytes that preferentially involves acral sites and has a good prognosis. We present a case of primary cutaneous CD8+ T‐cell lymphoma involving the eyelid of an adolescent male. The case shares features with PCACTL, including indolent clinical behavior and expression of CD68 in a Golgi‐associated dot‐like pattern; however, other features differ significantly from PCACTL as currently defined by the World Health Organization (WHO). These features include ulceration, expression of CD56, granzyme B, and perforin, and a high proliferative index. Given these discrepancies, our case is currently best classified as a CD8+ primary cutaneous peripheral T‐cell lymphoma, not otherwise specified. We review the differential diagnosis for this case and suggest expanding the definition of PCACTL. [ABSTRACT FROM AUTHOR]

Background: Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face.Objective: To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT).Methods: This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded.Results: BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P < .0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P < .0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P = .0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT.Limitations: Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK.Conclusion: BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated. [ABSTRACT FROM AUTHOR]

COVID‐19‐associated cutaneous manifestations are one of the most important and relatively common extra‐respiratory presentations of SARS‐COV‐2 infection. The exact identification and classification of these lesions can facilitate the accurate diagnosis and treatment. There are several case reports and small case series which describe cutaneous lesions in hands and feet. Currently, there is no scoping review about acral skin manifestations associated with COVID‐19. This paper covers the COVID‐related acral skin manifestations in 10 entities including acral papulo‐vesicular eruption, acral urticarial lesion, acral non‐inflammatory purpura and necrosis, acro‐ischemia associated COVID‐19, acral vasculitis, chilblain‐like lesion (COVID Toe), acral erythema multiform (EM) like lesion, hand and foot skin lesions associated with multisystem inflammatory syndrome in children (MISC), acral peeling conditions and red half‐moon nail sign. Future studies should focus on exact investigation of etiologies of these lesions including role of immune senescence, environment, gender, immunogenetics and relation of these lesion with major organ involvements. [ABSTRACT FROM AUTHOR]

Early recognition of a pituitary secretor tumor offers a better prognostic; thus acromegaly might be recognized before the actual clinical picture of acromegaly is detectable. This is a 59-year old, non-smoking female admitted for: post-operatory evaluation of acromegaly. The clinical evaluation is non-specific. One year prior she was diagnosed with acromegaly based on cerebral imaging assessment due to intermittent headache. She was treated with cabergoline a few months before neurosurgery was done; post-operatory panel showed complete remission of acromegaly. Prompt detection of the disease allowed the early intervention with a very good outcome. The remission of GH excess after neurosurgery depends on tumor size and practical experience of the surgeon. The longer time of high growth hormone levels exposure the higher is the risk of cardio-metabolic and oncologic complications. [ABSTRACT FROM AUTHOR]

Specialty site melanomas on the head and neck, hands and feet, genitalia, and pretibial leg have higher rates of surgical complications after conventional excision with postoperative margin assessment (CE-POMA) compared with trunk and proximal extremity melanomas. The rule of 10s describes complication rates after CE-POMA of specialty site melanomas: ∼10% risk for upstaging, ∼10% risk for positive excision margins, ∼10% risk for local recurrence, and ∼10-fold increased likelihood of reconstruction with a flap or graft. Trunk and proximal extremity melanomas encounter these complications at a lower rate, according to the rule of 2s. Mohs micrographic surgery (MMS) with frozen section melanocytic immunostains (MMS-I) and slow Mohs with paraffin sections decrease complications of surgery of specialty site melanomas by detecting upstaging and confirming complete tumor removal with comprehensive microscopic margin assessment before reconstruction. This article reviews information important for counseling melanoma patients about surgical treatment options and for developing consensus guidelines with clear indications for MMS-I or slow Mohs. [ABSTRACT FROM AUTHOR]

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris is an autoimmune disorder with many clinical variants. In this report, we present a 57-year-old female patient who presented with unilateral acral erosions, pustulations, and crusts, which was diagnosed as localized pemphigus vulgaris, which is a very rare variant of pemphigus.

Abstract Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Pityriasis rosea (PR) is a common, selflimited inflammatory skin condition, usually affects the trunk and proximal extremities. A variety of atypical manifestations of PR have been recognized ranging from the difference in the morphology, distribution, and course. Herein, the rare form of acral PR in an adult has been illustrated as the 29- year-old Thai female who presented with generalized erythematous papules and plaques with peripheral collarette scales on the trunk and extremities, prominently on the hands and feet.[...]

Excimer light, topical vitamin D analogues, and topical steroids have been reported to be effective treatments for vitiligo. However, monotherapy often demonstrates unfavorable results for acral vitiligo. This study aimed to evaluate the efficacy and safety of combination treatment with 308‐nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. A prospective, randomized, double‐blind, and intraindividual study was conducted. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, and monotherapy (topical medication alone) was used in the later 12 weeks. Both hands were irradiated with excimer light three times a week for 12 weeks. Calcipotriol ointment was randomly assigned to one hand, whereas clobetasol ointment was assigned to the other hand. The ointments were applied twice daily for a total of 24 weeks. Repigmentation, clinical improvement, and adverse reactions were assessed. A total of 26 hands completed the study. Of the hands treated with excimer light and calcipotriol, approximately 8% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol‐based and clobetasol‐based regimens showed some repigmentation at the end of the study, respectively (P <.05). Nevertheless, no significant difference was found between the treatments. No serious adverse reactions were observed. In conclusion, the combination of excimer light and topical calcipotriol followed by topical calcipotriol alone is effective and might be a promising treatment regimen for acral vitiligo. [ABSTRACT FROM AUTHOR]

We report the largest series to date (N = 6) of EWSR1‐SMAD3 rearranged fibroblastic tumor. Initially described in 2018, the tumor features a marked female predominance (F:M, 5:1, mean age 44‐years, median age 45.5 years; range 27‐57), with most cases (5/6, 83%) arising in acral locations (4 on foot/toe, 1 on hand). One case presented on the lower extremity. The lesions presented as nodules and were composed of short, variably cellular, intersecting fascicles of uniform spindled cells in a collagenous to myxoid stroma. In four cases, the tumor abutted the epidermis without a grenz zone. In one case, there was an abrupt transition to a central, acellular hyalinized area. Two other cases had admixed smaller collagenous areas, reminiscent of collagen rosettes. One had a concentric arrangement of tumor cells around blood vessels. Mitotic activity was low (<1/10 HPFs). All were positive for ERG by immunohistochemistry and negative for CD34 (6/6). An EWSR1‐SMAD3 fusion was identified in three cases tested by next‐generation sequencing (3/3). Rearrangement of EWSR1 by fluorescence in situ hybridization was showed in 1/1 case. Our series reaffirms prior findings and expands the known histopathologic spectrum of this emerging entity. [ABSTRACT FROM AUTHOR]

Metastatic hand tumors are uncommon but important to include in the differential diagnosis for hand masses. In this study, we report the case of a patient presenting initially with hand pain and swelling with no other pertinent medical history except for an extensive smoking history. Subsequent mass biopsy and work-up revealed metastatic lung cancer. Acral metastases to the hand as the first manifestation of a primary tumor are a rare but debilitating condition with a poor prognosis. Hand surgeons must remain aware of the potential for metastatic hand tumors in patients without known malignancy and advocate for the prompt initiation of multidisciplinary care and treatment to maximize patient outcomes., Competing Interests: No benefits in any form have been received or will be received related directly to this article., (© 2024 The Authors.)

MicroRNAs (miRNAs) are small ∼22nt single stranded RNAs that negatively regulate protein expression by binding to partially complementary sequences in the 3' untranslated region (3' UTRs) of target gene messenger RNAs (mRNA). Recently, mutations have been identified in both miRNAs and target genes that disrupt regulatory relationships, contribute to oncogenesis and serve as biomarkers for cancer risk. KIT, an established oncogene with a multifaceted role in melanogenesis and melanoma pathogenesis, has recently been shown to be upregulated in some melanomas, and is also a target of the miRNA miR-221. Here, we describe a genetic variant in the 3' UTR of the KIT oncogene that correlates with a greater than fourfold increased risk of acral melanoma. This KIT variant results in a mismatch in the seed region of a miR-221 complementary site and reporter data suggests that this mismatch can result in increased expression of the KIT oncogene. Consistent with the hypothesis that this is a functional variant, KIT mRNA and protein levels are both increased in the majority of samples harboring the KIT variant. This work identifies a novel genetic marker for increased heritable risk of melanoma.