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Background: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma that has a poor prognosis., Objectives: To investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM)., Methods: Differences in the spatially resolved transcriptomic profiles of 9 patients with AAM with 29 regions of interest (ROIs) and 11 patients with PAM with 46 ROIs were investigated using S100b and CD3 morphology markers., Results: In S100b+ tumour cell areas, we detected 11 upregulated differentially expressed genes (DEGs; including chaperone/ubiquitin--associated DEGs) and 82 downregulated DEGs (including human leucocyte antigen) in AAMs vs. PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signalling and melanin biosynthesis pathways in S100b+ ROIs of AAMs compared with PAMs. In tumour-associated immune cell areas, the numbers of CD8 T cells (P = 0.04) and M1 macrophages (P = 0.01) were significantly decreased, whereas those of monocytes (P = 0.04) and endothelial cells (P = 0.04) were increased in AAMs compared with PAMs., Conclusions: These findings could widen our understanding of the biological differences between AAMs and PAMs, which might result in a different clinical course., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time., (© 2024. The Author(s).)

Background: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers., Objective: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM., Methods: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data., Results: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion., Limitations: Single-center, retrospective design., Conclusion: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest the authors declare no conflicts of interest.

Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess cancer risks in patients with psoriasis and the effect of TNF-α inhibitor and interleukin (IL)-12/23 inhibitor therapy on those cancer risks., Methods: Using the Korean Health Insurance Review and Assessment Service database, patients with newly diagnosed psoriasis between 2008 to 2019 were included. Standardized incidence ratios (SIRs) of overall and specific cancers were calculated in patients with psoriasis. The effect of TNF-α inhibitor and IL-12/23 inhibitor exposure on the risk of cancers was assessed by multivariable Cox regression models., Results: In total, 191,678 patients with psoriasis were included in this study. The overall risk of cancer was significantly higher in patients with psoriasis than in the general population (SIR, 1.12; 95% confidence interval (CI), 1.09-1.14). TNF-α inhibitor users had a significantly higher risk for overall cancer (adjusted hazard ratio (aHR), 1.41; 95% CI 1.01-1.97). In contrast, IL-12/23 inhibitor exposure had a significantly lower risk for overall cancer (aHR, 0.57; 95% CI 0.37-0.87). Among specific cancers, the risks of non-Hodgkin lymphoma (aHR, 2.98; 95% CI 1.02-8.69) were increased by TNF-α inhibitor therapy, while the risk of other cancers, including nonmelanoma skin cancer (aHR, 2.31; 95% CI 0.51-10.46), was not significantly altered by TNF-α inhibitor therapy., Conclusion: TNF-α inhibitor therapy in psoriasis is associated with a significantly increased risk of overall cancer and lymphoma, while the risk of solid organ cancer was not affected by this therapy. The IL-12/23 inhibitor is not associated with an increased risk of any cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with high mortality. However, its clinical characteristics in Asian patients remain uncertain owing to its low incidence., Objective: To analyze the clinicopathological features of MCC and identify factors associated with its prognosis., Methods: The medical records of 62 patients with MCC were retrospectively reviewed. Data on clinical features, survival outcomes, prognostic factors, histopathology and immunohistochemical profile of the patients were collected and analyzed. Merkel cell polyomavirus status was evaluated using immunohistochemistry., Results: The incidence of MCC significantly increased over time. The mean duration of follow-up was 51.2 months, with an overall 5-year survival of 80.6%. More female patients with MCC were identified than male patients (1.3:1). Approximately half of the patients had stage I disease at the time of initial presentation. The primary tumor was frequently located in the lower extremities (40.3%), followed by the head and neck (32.3%), upper extremities (22.6%), and the trunk (4.8%). Male sex was associated with poorer overall survival (p = 0.003). Post-resection adjuvant radiotherapy significantly improved the overall survival (p = 0.023). Sentinel lymph node biopsy during surgery ameliorated the progression-free survival (p = 0.036) in patients with stage I or II cancer. Lymphovascular and perineural invasion were associated with a poor prognosis. Old age, immunohistochemical profiles, and Merkel cell polyomavirus-positivity were not associated with prognosis., Conclusion: Post-surgical adjuvant radiotherapy and sentinel lymph node biopsy significantly improve the course of MCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Background: Nail apparatus melanoma (NAM) is a subtype of cutaneous melanoma occurring at nail units and belongs to the acral lentiginous melanoma subgroup. Due to its unique anatomical structure to protect the acral site, mechanical trauma may have a clinicoprognostic impact on NAM. Therefore, we investigated the clinicoprognostic and histopathological characteristics of NAM according to the presence of trauma history prior to melanoma development., Methods: Clinicopathological and follow-up data of patients with NAM according to trauma history were obtained., Results: We included 87 patients with NAM, 21.8% of whom had a previous trauma history. Trauma-related NAMs were more likely to involve the toenail (p = 0.040), include a high proportion of amelanotic melanomas (p = 0.038) as well as nail bed tumor (p = 0.013), and have a longer time interval between the onset of nail change and confirmed diagnosis (p = 0.012). Moreover, survival analysis revealed that trauma-related NAMs more frequently showed progression in general (p = 0.034) and nodal metastasis (p = 0.047) and had worse prognosis in terms of progression-free survival (p = 0.004)., Conclusion: In conclusion, NAMs with previous trauma have unique clinicoprognostic characteristics. The specific clinicopathological features of NAMs according to trauma indicate that trauma may play a role in melanoma development., (© 2022 S. Karger AG, Basel.)

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms., (© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumour of unknown pathogenesis with intermediate malignant potential. Although trauma has been hypothesized as a predisposing factor for DFSP development, clinicopathological characteristics of trauma-related DFSP have not been investigated., Objective: This study investigated the differences between trauma-associated DFSP and trauma-unrelated DFSP., Methods: Patients histopathologically diagnosed with DFSP from January 2000 to December 2019 at the Dermatology Department were included. Clinical, histopathological, prognostic features and trauma history were analysed., Results: We recruited 141 patients with DFSP (mean age, 36.1 years; male: female, 1:1.01). Recurrence and systemic metastasis were observed in 15.6% and 2.8% of patients, respectively. Older patients were likely to develop DFSP at the trauma sites more frequently on the face and lower legs. The active-growing lesions were more frequently associated with trauma-related DFSP. Multivariable logistic regression revealed that age at diagnosis (OR: 1.031; 95% CI: 1.004-1.059; p = 0.024) and tumour growth (OR: 3.336; 95% CI: 1.162-9.578, p = 0.025) were significantly associated with trauma-related DFSPs., Conclusions: The age at diagnosis, lesion location and tumour growth were associated with DFSPs in this study. Analysis of DFSP with trauma history provides a deeper understanding of long-term trauma effects on sarcoma development., (© 2022 Australasian College of Dermatologists.)

Trial Design: This was a single-center, unmasked, paralleled, randomized controlled trial., Methods: A randomized trial was conducted in a tertiary care institute in South Korea to validate whether artificial intelligence (AI) could augment the accuracy of nonexpert physicians in the real-world settings, which included diverse out-of-distribution conditions. Consecutive patients aged >19 years, having one or more skin lesions suspicious for skin cancer detected by either the patient or physician, were randomly allocated to four nondermatology trainees and four dermatology residents. The attending dermatologists examined the randomly allocated patients with (AI-assisted group) or without (unaided group) the real-time assistance of AI algorithm (https://b2020.modelderm.com#world; convolutional neural networks; unmasked design) after simple randomization of the patients., Results: Using 576 consecutive cases (Fitzpatrick skin phototypes III or IV) with suspicious lesions out of the initial 603 recruitments, the accuracy of the AI-assisted group (n = 295, 53.9%) was found to be significantly higher than those of the unaided group (n = 281, 43.8%; P = 0.019). Whereas the augmentation was more significant from 54.7% (n = 150) to 30.7% (n = 138; P < 0.0001) in the nondermatology trainees who had the least experience in dermatology, it was not significant in the dermatology residents. The algorithm could help trainees in the AI-assisted group include more differential diagnoses than the unaided group (2.09 vs. 1.95 diagnoses; P = 0.0005). However, a 12.2% drop in Top-1 accuracy of the trainees was observed in cases in which all Top-3 predictions given by the algorithm were incorrect., Conclusions: The multiclass AI algorithm augmented the diagnostic accuracy of nonexpert physicians in dermatology., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, the clinicopathologic features and survival outcomes of patients with hyperpigmented MF from a single tertiary referral center database were retrospectively evaluated. Hyperpigmented MF accounted for 10.9% (14/128) of all MF cases. The mean age at diagnosis was 46.9 years, and the female-to-male ratio was 1:1.3. Concurrent hypopigmented, ichthyosiform, and poikilodermatous lesions were detected in 21.4%, 14.3%, and 14.3% of the patients, respectively. Histopathologically, most patients (85.7%) showed interface change with pigment incontinence. Double negative (CD4- and CD8-) immunophenotypes were more frequent in patients with hyperpigmented MF (25%) than in those with other MF subtypes (9.8%). Most patients (85.7%) had early-stage disease at diagnosis. The survival outcomes did not differ significantly between hyperpigmented and other MF subtypes. In conclusion, hyperpigmented MF often accompanies other atypical MF variants and is frequently associated with atypical immunophenotypes. The outcomes of hyperpigmented MF are comparable to those of other MF subtypes.

Background: The clinical and pathological features of lymphomatoid papulosis (LYP) are diverse. The objective of this study is to evaluate the clinical and pathological features associated with the prognosis and clinical course of LYP., Patients and Methods: The clinical and pathological features of LYP in a medical center database were retrospectively retrieved., Results: Overall, 58 LYP patients were included in the study. The mean age at diagnosis was 39.1 years and the female-to-male ratio was 1:1.2. More than two-thirds (40/58, 69.0%) of the patients showed a chronic and recurrent disease course. A longer pre-diagnosis duration (odds ratio (OR), 1.01; 95% confidence interval (CI), 1.00-1.03) was significantly associated with secondary lymphoma development. Lower extremity involvement (OR, 10.40; 95% CI, 1.17-92.28) and the absence of eosinophils in the lesions (OR, 11.28; 95% CI, 1.01-126.24) were found to be significantly associated with the chronic and recurrent course of LYP., Conclusion: A longer pre-diagnosis duration is associated with secondary lymphoma, while a lower extremity involvement and the absence of lesional eosinophil infiltration are associated with the chronicity of LYP., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The clinicoprognostic implications of head and neck involvement of mycosis fungoides (MF) are poorly understood., Objectives: To evaluate the association of head and neck involvement on the clinicoprognostic features of MF., Methods: The clinical features and survival outcomes of patients with MF in a Korean academic medical center database were retrospectively evaluated according to the presence of head and neck involvement at diagnosis., Findings: Cases of MF with (group A, n = 39) and without (group B, n = 85) head and neck involvement at diagnosis were identified. Advanced-stage disease (stages IIB-IVB) was more common in group A (43.6%) than in group B (5.9%) (P < .001). MF progression, extracutaneous dissemination, and large-cell transformation more commonly occurred in group A than in group B. The 10-year overall survival rate was worse in group A (53.4%) compared with group B (81.6%) (P < .001). Head and neck involvement at diagnosis was associated with poor prognosis in early-stage MF (stages IA-IIA) and was independently associated with worse progression-free survival (hazard ratio, 24.4; 95% confidence interval, 2.2-267.6; P = .009)., Limitations: A single center, retrospective design., Conclusion: Head and neck involvement of MF was associated with a poor prognosis., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although deep neural networks have shown promising results in the diagnosis of skin cancer, a prospective evaluation in a real-world setting could confirm these results. This study aimed to evaluate whether an algorithm (http://b2019.modelderm.com) improves the accuracy of nondermatologists in diagnosing skin neoplasms., Methods: A total of 285 cases (random series) with skin neoplasms suspected of malignancy by either physicians or patients were recruited in two tertiary care centers located in South Korea. An artificial intelligence (AI) group (144 cases, mean [SD] age, 57.0 [17.7] years; 62 [43.1%] men) was diagnosed via routine examination with photographic review and assistance by the algorithm, whereas the control group (141 cases, mean [SD] age, 61.0 [15.3] years; 52 [36.9%] men) was diagnosed only via routine examination with a photographic review. The accuracy of the nondermatologists before and after the interventions was compared., Results: Among the AI group, the accuracy of the first impression (Top-1 accuracy; 58.3%) after the assistance of AI was higher than that before the assistance (46.5%, P = .008). The number of differential diagnoses of the participants increased from 1.9 ± 0.5 to 2.2 ± 0.6 after the assistance (P < .001). In the control group, the difference in the Top-1 accuracy between before and after reviewing photographs was not significant (before, 46.1%; after, 51.8%; P = .19), and the number of differential diagnoses did not significantly increase (before, 2.0 ± 0.4; after, 2.1 ± 0.5; P = .57)., Conclusions: In real-world settings, AI augmented the diagnostic accuracy of trainee doctors. The limitation of this study is that the algorithm was tested only for Asians recruited from a single region. Additional international randomized controlled trials involving various ethnicities are required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:Han founded IDerma, Inc. for the development and clinical application of artificial neural networks in Dermatology.

Background: Mycosis fungoides (MF) shows racial and regional differences in terms of clinical features. The availability of therapeutic options as well as drugs differs from one country to another. There are only limited data on the clinical characteristics and treatment experience of MF from South Korea., Methods: Medical records of 97 patients with MF were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Assessment of prognostic variables was done using univariate Cox proportional hazard models., Results: Median age at time of diagnosis was 45 years. The median time from onset of skin lesion to diagnosis of MF was 36 months with a median follow-up period of 96 months. A number of clinical variants of MF were observed. Treatment mainly consisted of narrow-band UVB, systemic retinoids, methotrexate, chemotherapy, and regional radiotherapy. Complete remission was observed in 78% of patients with records on their clinical course. About 12% experienced disease progression. No clinical prognostic factor apart from TNM staging was identified., Conclusion: Despite delay in diagnosis, most cases of MF in Korea were diagnosed in early stages. Prognosis of our patients was more favorable than those of other geographic regions as reported in previous studies. Good response to treatment, consisting mainly of phototherapy and radiation therapy, and relatively indolent clinical behavior of disease were observed in this homogeneous cohort of Korean patients with MF., (© 2021 the International Society of Dermatology.)

Comprehensive studies of primary cutaneous extranodal natural killer/T-cell lymphoma (PCENKTL) are scarce. The objectives of this study are to describe PCENKTL in terms of its clinical features, histopathology, immunophenotypes, and prognosis, and to analyze factors affecting patient survival outcomes. We searched four databases and include studies with extractable data. We also searched the Asan Medical Center database for cases of PCENKTL. We include a total of 289 patients. The mean age at diagnosis was 52.8 years and the female to male ratio was 1:1.2. The most common clinical morphology was a subcutaneous nodule, followed by ulceration. About half of the patients presented with disseminated skin lesions. The median overall survival was 12.0 months and the 5-year survival rate was 22.0%. There was no correlation between the clinical morphology or the histopathological features of the skin lesions with the patient outcomes. Advanced TNM stage, a disseminated skin lesion, tumor location on the leg or trunk, the presence of B symptoms, and a high International Prognostic Index score were associated with a worse prognosis, and chemoradiotherapy was associated with a better survival outcome as compared with chemotherapy alone in univariable analyses. In multivariable analyses, only advanced TNM stage and tumor location on the leg were associated with a worse prognosis. In conclusion, PCENKTL is an aggressive cutaneous lymphoma and its prognosis is associated with TNM stage and tumor location., (© 2021 Japanese Dermatological Association.)

Background: Kaposi sarcoma (KS) is a mesenchymal tumor with distinct histopathological features according to stage of progression. Programmed death-1 (PD-1) and its ligand PD-L1 play major roles in the immune escape strategy of tumors., Objectives: This study evaluated expression of PD-1 and PD-L1 in various stages of KS and investigated associations between their expression and clinical characteristics., Methods: Fifty cases with histopathologically diagnosed KS were classified as early or late stage. These specimens were stained with anti-PD-1 and anti-PD-L1 antibodies. The extent of expression in the intratumoral and peritumoral areas was judged by two dermatopathologists., Results: PD-1 and PD-L1 were expressed in 72.2% (13/18) and 11.1% (2/18) of early-stage cases, respectively, compared with 43.8% (14/32) and 28.1% (9/32) of late-stage cases, respectively. At the late stage, PD-1 expression was significantly higher in the peritumoral area than in the intratumoral area (P = 0.001). PD-1 expression in the intratumoral area was significantly higher at the early stage than at the late stage (P = 0.013). PD-L1 expression in the peritumoral area was significantly higher at the late stage than at the early stage (P = 0.038)., Conclusions: The pattern of PD-1 and PD-L1 expression differs according to the stage of KS, but is unaffected by clinical variables., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Nevoid basal cell carcinoma syndrome (NBCCS) is mainly characterised by multiple basal cell carcinomas (BCCs) caused by PTCH1, PTCH2, and SUFU. However, clinical and genetic data on Asian NBCCS patients are limited. We aimed to analyse the clinical phenotypes and genetic spectrum of Korean patients with NBCCS. Fifteen patients with NBCCS at Seoul National University Hospital were included, and their clinical data were analysed. Whole-exome sequencing and/or multiplex ligation-dependent probe amplification using peripheral blood were performed to identify genetic causes. Genetic analysis revealed that 73.3% (11/15) of the patients carried 9 pathogenic variants, only in the PTCH1 gene. Variants of uncertain significance (VUS) and likely benign were also detected in 2 (13.3%) and 2 (13.3%) patients, respectively. BCCs were found in the majority of the cases (93.3%) and the number of BCCs increased with age (ρ = 0.595, P = 0.019). This study revealed that PTCH1 pathogenic variants were the main cause of NBCCS in Korean patients. As BCCs are commonly detected, a periodic dermatologic examination is recommended. Finally, our results support the addition of genetic screening to the existing criteria for NBCCS diagnosis.

Background: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma., Aims: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes., Methods: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database., Results: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma., Limitations: This study is a retrospective, single-center design., Conclusion: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive cancer characterised by angiocentric and angiodestructive infiltration by NK-cells, or cytotoxic T-cell types. Histopathologically, ENKTL shows a multinodular or diffuse infiltration localised to vascular structures, resulting in angiodestruction and necrosis. We present a patient with an initially suspected diagnosis of benign interface dermatitis with a differential diagnosis of mycosis fungoides that was later found to be an aggressive extranodal natural killer/T-cell lymphoma of a nasal type and with a dismal prognosis., (© 2020 The Australasian College of Dermatologists.)

Background: Although cutaneous melanoma has been widely evaluated, data elucidating the clinical features and prognostic factors of cutaneous metastatic melanoma are limited., Objective: To determine and compare the clinicoprognostic features of cutaneous metastasis in acral and nonacral melanoma., Methods: The Asan Medical Center database was reviewed for cases of cutaneous metastatic melanoma that had been confirmed by skin biopsy between January 1996 and December 2017., Results: Cutaneous metastasis occurred in 12.4% (61 of 492 cases) of our cohort. The frequency of cutaneous metastasis was higher in nonacral melanoma than that in acral melanoma. The mean duration between the initial diagnosis of a primary tumor and cutaneous dissemination was 19.8 months. Cutaneous metastasis developed earlier during the disease course in acral melanoma than that in nonacral melanoma. Cutaneous metastasis was more disseminated, involving multiple anatomy sites in nonacral melanoma than that in acral melanoma. In-transit metastasis was significantly more common in acral melanoma than that in nonacral melanoma. The disease stage at the time of cutaneous metastasis was not significantly different between acral and nonaral melanoma. In-transit metastasis was commonly associated with visceral involvement in acral melanoma but not in nonacral melanoma. The extent and multiplicity of cutaneous metastasis were dependent on the status of other viscera during the cutaneous metastasis. No significant difference in survival during the cutaneous metastasis was observed between acral and nonacral melanoma., Conclusion: Clinicoprognostic features of cutaneous metastasis were different between acral and nonacral melanoma., (© 2020 the International Society of Dermatology.)

There have been limited studies comparing the clinical significance of lymphatic invasion in melanoma according to tumour site. The objective of this study was to evaluate the impact of lymphatic invasion on the clinicoprognostic features of acral and non-acral melanoma. Clinical and histopathological features and survival outcomes of 532 patients with acral melanoma or non-acral melanoma in the database of the Asan Medical Center, Korea, were retrospectively evaluated according to the presence of lymphatic invasion. Lymphatic invasion was significantly more common in acral melanoma than non-acral melanoma. In acral melanoma, lymphatic invasion was significantly associated with a higher frequency of lymph node involvement and advanced stages, but not associated with Breslow thickness or visceral dissemination. By contrast, lymphatic invasion in non-acral melanoma was significantly associated with a higher rate of visceral involvement, deeper Breslow thickness, as well as a higher rate of lymph node involvement and advanced stages. When acral melanoma and non-acral melanoma both with lymphatic invasion were compared, Breslow thickness was significantly shallower and vertical growth phase was significantly less common in acral melanoma. Meanwhile, visceral involvement was significantly more frequent in non-acral melanoma than acral melanoma. In conclusion, lymphatic invasion was more common in acral melanoma than non-acral melanoma and occurred in acral melanoma cases with relatively thin Breslow thickness, suggesting acral melanoma is lymphotropic., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Because primary skin cancers in organ transplant recipients are rare, little is known about the characteristics and risk factors for skin cancers in organ transplant recipients. We searched the Asan Medical Center database of 13 469 organ transplant recipients for cases of all skin cancers from January 1990 to December 2018. Characteristics of and risk factors for skin cancers were analyzed and compared according to the period of transplantation. Of the identified 113 patients with skin cancers, squamous cell carcinoma was the most common cancer followed by basal cell carcinoma and Kaposi sarcoma. The cumulative incidence of skin cancers at 28 years was 5.3%. Over the 10-year period from January 2009 to December 2018, the standardized incidence ratio for premalignant in situ skin lesions increased, whereas the standardized incidence ratio for skin cancers decreased. Age at transplantation and treatment with more than two immunosuppressive agents were risk factors for the development of new skin cancers in organ transplant recipients. Over the most recent 10-year period, post-transplant skin cancers have been found earlier and diversified compared with in the previous period., (© 2020 Japanese Dermatological Association.)

V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor. We evaluated correlations among the expression of VISTA, the myeloid-derived suppressor cell marker CD33, and programmed death-1 (PD-1), and determined their relationships with clinicopathological characteristics and disease outcomes in melanoma. Diagnostic tissue from 136 cases of melanoma was evaluated by immunohistochemistry for CD33, VISTA, and PD-1 expression. Dual immunofluorescence using CD33 and VISTA antibodies was performed. VISTA expression positively correlated with CD33 expression in melanoma tissue. Dual immunofluorescence staining revealed that VISTA was expressed by CD33-positive myeloid cells. PD-1 expression correlated with CD33 and VISTA expression. CD33 and VISTA expression were significantly associated with negative prognostic factors, including a deeper Breslow thickness and an advanced stage of disease. High expression of either CD33 or VISTA was associated with worse survival. Positivity for both VISTA and PD-1 predicted worse survival. Multivariate analysis showed that both CD33 and VISTA expression were independent prognostic factors in cutaneous melanoma. VISTA and CD33 expression are independent unfavourable prognostic factors in melanoma, which suggests their potential as therapeutic targets.

Background: Primary cutaneous angiosarcoma (CA) is a rare but aggressive tumor with a high rate of local recurrence. This study was designed to analyze the clinicopathological features of primary CA and identify factors of cutaneous manifestations associated with the prognosis of angiosarcoma., Methods: Medical records of 55 patients with primary CA were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Anatomical location of tumor was classified to the scalp, face, and neck, and sites outside the head and neck., Results: Primary CA presented cutaneous nodules (31/55, 47.2%), patches (13/55, 23.6%), and indurated plaques (11/55, 20.0%). Nodular lesion was significantly more common in CA on the scalp compared to CA on sites outside the scalp. Histologically, tumors presenting as nodular lesions on the scalp was predominantly composed of solid sheets of large pleomorphic cells, whereas non-nodular lesions composed of tumor cells between collagen bundles forming irregular vascular spaces. Cutaneous angiosarcoma on the scalp showed a worse prognosis compared to CA on sites outside the scalp. Patients presenting clinical morphology with nodules and multiple skin lesions showed significantly reduced overall survival (OS)., Conclusion: In primary CA, location on the scalp, morphology with nodules, and multiplicity of skin lesions significantly affected survival outcomes., (© 2020 The International Society of Dermatology.)

Background: Epstein-Barr virus (EBV) positivity frequently presents in patients with nodal angioimmunoblastic T-cell lymphoma (AITL). However, the presence of EBV in skin lesions and its clinicopathologic significance have not been evaluated., Objective: To analyze the clinical and histopathologic features of cutaneous AITL and evaluate EBV positivity in skin tissue and its effects on clinicopathologic features of AITL., Methods: Clinicopathologic variables in patients with cutaneous AITL were analyzed and compared depending on EBV in situ hybridization status in skin lesions by using patients' medical records., Results: Of the 86 patients with AITL, 42 had a cutaneous presentation. In situ hybridizations positive for EBV were noted in 19 of 42 patients with cutaneous AITL. EBV positivity was more common in papular and nodular skin lesions than other cutaneous morphologies, such as nonspecific rash or purpuric patches. An EBV-positive in situ hybridization was associated with a pattern of dense, superficial and deep infiltrates of pleomorphic, large-sized, atypical lymphocytes. EBV positivity in skin lesions was an independent negative prognostic factor in patients with AITL., Limitations: Retrospective study at a single institution., Conclusion: EBV-positive cutaneous AITL is associated with distinctive clinicopathologic features., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins., Objective: We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma., Methods: Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1., Results: LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive of survival., Limitations: Retrospective study in a single institution and possibility of type 1 error., Conclusion: Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic value of CD30 expression in cutaneous extranodal natural killer/T-cell lymphoma is controversial., Methods: Clinicopathological features, survival outcomes, and prognostic implications of CD30 were retrospectively analyzed in 55 patients with cutaneous extranodal natural killer/T-cell lymphoma. We classified patients into (i) primary cutaneous extranodal natural killer/T-cell lymphoma and (ii) cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease depending on the primary tumor site., Results: CD30+ cutaneous extranodal natural killer/T-cell lymphoma was more common in patients with cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease than in those with primary cutaneous disease. CD30+ cases were more likely to present nodular lesions or cellulitis-like swelling than CD30- cases. Histologically, CD30+ cutaneous extranodal natural killer/T-cell lymphoma predominantly comprised large tumor cells compared with CD30- cases. However, the clinical morphology and tumor cell size were not associated with survival outcomes. CD30 expression was associated with better survival outcomes in patients with cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease., Conclusion: CD30+ cutaneous extranodal natural killer/T-cell lymphoma presented peculiar clinicopathological features and had more favorable disease course in patients with cutaneous dissemination from nasal disease., (© 2018 The International Society of Dermatology.)

Background: Cutaneous lymphomas are a heterogeneous group of tumors with various clinical manifestations, histological features, and prognoses., Methods: Among 425 cases of cutaneous lymphoma, we describe eight cases of peripheral T-cell lymphoma, unspecified, presenting with generalized benign-looking dermatitis., Results: Our case series included eight cases of secondary cutaneous peripheral T-cell lymphoma, unspecified. The observed clinical morphology features included drug eruption-like generalized morbilliform maculopatches in two cases, generalized folliculitis-like papules in two cases, and generalized eczematous dermatitis-like papules and patches in four cases. Histopathological examination demonstrated tumor cell infiltrates of mainly atypical, small-to-medium lymphoid cells that were perivascularly or periadnexally distributed throughout the dermis. Immunohistochemical staining results for CD2, CD3, CD4, and CD8 revealed that the tumor cells were T-cells., Conclusion: This collection of cases and literature review emphasizes the need for clinical suspicion of peripheral T-cell lymphoma, unspecified, in the differential diagnosis of adult patients with refractory eczematous or benign-looking skin lesions., (© 2017 The International Society of Dermatology.)

Few studies have evaluated the histopathological features of cutaneous extranodal NK/T-cell lymphoma (ENKTL). The authors' study aims to describe cases of cutaneous ENKTL that histopathologically mimic benign inflammatory dermatosis. The authors searched the database of Asan Medical Center to identify cases of cutaneous ENKTL that were confirmed by skin biopsy between January 1998 and December 2014. The authors included cases that were initially diagnosed as benign inflammatory disorders on the histopathological examination, but finally diagnosed as cutaneous ENKTL on further evaluation. This study included 10 cases of cutaneous ENKTL. Six cases demonstrated nonspecific perivascular cellular infiltration, 2 cases demonstrated lupus erythematosus-like histological features, 1 case demonstrated psoriasiform lichenoid reaction, and 1 case demonstrated vasculitis-like features on histopathological examination. All cases were positive for CD56 and Epstein-Barr virus in situ hybridization. Perivascular infiltrations throughout the superficial and deep dermis with vasculopathy and panniculitic infiltration were common histopathological findings. The clinical features included 7 cases of erythematous to purpuric patches, 2 cases of facial swelling, and 1 case of cellulitis-like swelling. In conclusion, cutaneous ENKTL can histopathologically mimic benign inflammatory dermatosis. Cutaneous ENKTL should be suspected when histopathology shows perivascular dermal infiltration with vasculopathy and panniculitic cellular infiltration.

Long-term changes in the relative frequency of cutaneous lymphoma (CL) have not been investigated in Asian populations. The aim of this study was to investigate the relative frequency, clinical characteristics, and survival outcomes of CL in Korean patients, and to evaluate the changes in relative frequency of CL over a 20-year period. The present retrospective cohort study included 395 patients, of whom 289 had primary CL and 106 secondary CL, seen at a tertiary referral hospital in Seoul, Korea. Primary CL included T-/NK-cell linage lymphoma (CTCL, 85.1%) and B-cell lineage lymphoma (CBCL, 14.9%). The relative frequency of CBCL increased over time, as shown by a decrease in the CTCL/CBCL ratio from 10.3 in 1994 to 2003 to 4.5 in 2004 to 2013. CTCL was more commonly associated with multiple and extensive skin lesions than CBCL. Extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma were commonly associated with extensive skin lesions. The 5-year overall survival rate for all patients with primary CL was 81%.

Background: Cutaneous lymphomas (primary and secondary lymphomas involving the skin) are a heterogeneous group with various clinical manifestations, histological features, and prognoses., Methods: We describe eight cases of cutaneous lymphoma presenting with facial swelling., Results: Our case series included three cases of primary cutaneous extranodal natural killer/T-cell lymphoma, one case of secondary cutaneous extranodal natural killer/T-cell lymphoma, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of cutaneous CD4+ small/medium pleomorphic T-cell lymphoma, and two cases of peripheral T-cell lymphoma (unspecified)., Conclusions: This collection of cases and literature review emphasizes the need for clinical suspicion of cutaneous lymphoma in the differential diagnosis of patients with refractory facial swelling., (© 2016 The International Society of Dermatology.)