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Use of stem cells to treat various diseases in dermatology has been of interest. Conditioned media with the growth factors secreted from stem cells has been used as a topical agent. We report a case of foreign body granulomas that appeared days after dermal injection of the conditioned media mimicking scars at all injection sites.

Background Distinguishing benign lesion from early malignancy in melanocytic lesions of the nail unit still remains a diagnostic challenge, both clinically and histopathologically. While several immunohistochemistry (IHC) stainings have been suggested to help discriminate benign subungual melanocytic proliferation (SMP) and subungual melanoma in situ (MIS), the diagnostic utility of IHC staining for cyclin D1 and PRAME has not been thoroughly investigated in melanocytic lesions of nail unit. Methods This retrospective study included cases of benign SMP and subungual MIS confirmed by biopsy at Asan Medical Center from January 2016 to December 2020. Cases of melanocytic activation without proliferation and melanoma where dermal invasion was identified were excluded. Cyclin D1 and PRAME expression was assessed by counting proportion of melanocytes with nuclear positivity under 200x magnification. Results A total of 14 patients with benign SMP and 13 patients with subungual MIS were included in this study. 11 patients with benign SMP (71.4%) and 5 patients with subungual MIS (38.5%) showed > 60% nuclear immunostaining for cyclin D1, respectively. While 13 patients with benign SMP (92.9%) showed totally negative staining for PRAME, 10 patients with subungual MIS (76.9%) exhibited > 50% nuclear immunostaining for PRAME. Using the cutoff of 10%, PRAME exhibited good overall discrimination between benign SMP and subungual MIS (AUC = 0.849, 95% CI = 0.659–0.957). Conclusions This study suggests that PRAME IHC staining as a reliable discriminator in distinguishing subungual MIS from benign SMP.

This was a single-center, unmasked, paralleled, randomized controlled trial.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 aged19 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.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; P0.0001) 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.The multiclass AI algorithm augmented the diagnostic accuracy of nonexpert physicians in dermatology.

Several studies have determined the correlation between programmed cell death protein-1 (PD-1) and chronic plaque psoriasis (CPP). However, limited studies have assessed the association between PD-1 expression and the clinicoprognostic and distinct clinicopathological characteristics of CPP and guttate psoriasis (GP). Twenty-nine patients with skin biopsy-confirmed CPP were recruited at the Asan Medical Center between January 2018 and June 2020, and 33 patients with biopsy-confirmed GP were enrolled between January 2002 and June 2020. The clinicoprognostic and histopathological characteristics were analyzed according to immunohistochemical PD-1 expression in the epidermal or dermal inflammatory infiltrates. The CPP and GP lesions were divided into PD-1-low and PD-1-high groups. The CPP epidermal PD-1-high group had typical histopathological changes and significantly higher psoriasis area and severity index scores (p = 0.014) and disease duration (p = 0.009) than the epidermal PD-1-low group. In patients with GP, compared with the dermal PD-1-high group, the dermal PD-1-low group exhibited significantly higher disease duration (p = 0.002) and relapse rate of plaque psoriasis (p = 0.005) and significantly lower relapse-free survival (p = 0.016). Upregulated epidermal PD-1 expression was correlated with the chronicity and severity of CPP, while downregulated dermal PD-1 expression was correlated with poor prognosis of GP.

With the increasing incidence of skin cancer, many noninvasive technologies to detect its presence have been developed. This review focuses on reflectance confocal microscopy (RCM), optical coherence tomography (OCT), high-frequency ultrasound (HFUS), electrical impedance spectroscopy (EIS), pigmented lesion assay (PLA), and Raman spectroscopy (RS) and discusses the basic principle, clinical applications, advantages, and disadvantages of each technology. RCM provides high cellular resolution and has high sensitivity and specificity for the diagnosis of skin cancer. OCT provides lower resolution than RCM, although its evaluable depth is deeper than that of RCM. RCM and OCT may be useful in reducing the number of unnecessary biopsies, evaluating the tumor margin, and monitoring treatment response. HFUS can be mainly used to delineate tumor depths or margins and monitor the treatment response. EIS provides high sensitivity but low specificity for the diagnosis of skin malignancies. PLA, which is based on the genetic information of lesions, is applicable for the detection of melanoma with high sensitivity and moderate-to-high specificity. RS showed high accuracy for the diagnosis of skin cancer, although more clinical studies are required. Advances in these technologies for the diagnosis of skin cancer can lead to the realization of optimized and individualized treatments.

Inflammatory skin diseases, such as rosacea and acne, are major causes of facial erythema and accompanying skin barrier dysfunction. Several methods to restore the impaired skin barrier and improve facial erythema, such as medication, radiofrequency, laser, and ultrasound therapy were attempted. This study evaluated the efficacy and safety of dual-frequency ultrasound with impulse mode, for improving skin hydration and erythema in Asian subjects with rosacea and acne. Twenty-six subjects with facial erythema received an ultrasound treatment once per week, for 4 weeks, over both cheeks. The erythema index and transepidermal water loss (TEWL) were measured at each visit. Clinicians assessed the erythema improvement and patients evaluated their satisfaction level. The average decrease in TEWL and erythema index at 6 weeks was 5.37 ± 13.22 g·h−1·m−2 (p = 0.020) and 39.73 ± 44.21 (p = 0.010), respectively. The clinician’s erythema assessment and the subject satisfaction questionnaire score significantly improved at final follow-up (p &lt, 0.001, p = 0.003, respectively). No serious adverse effects were observed during the treatment and follow-up periods. The dual-frequency ultrasound with impulse mode appears to be effective and safe for improving skin hydration and erythema in patients with rosacea and acne.

The association between tumor-associated macrophages (TAMs) and the expression of immune checkpoint molecules has not been well described in cutaneous melanoma. We evaluated the correlations between the expression of markers of TAMs, cluster of differentiation 163 (CD163), and immune checkpoint molecules, programmed cell death protein-1 (PD-1), and lymphocyte activating gene-3 (LAG-3). We also determined their relationships with the clinicopathological features and disease outcomes in melanoma. Diagnostic tissues collected from melanoma patients were evaluated using immunohistochemistry for CD163, PD-1, and LAG-3 expression. CD163 expression positively correlated with PD-1 and LAG-3 expression. High expression of both CD163 and PD-1 expressions was significantly associated with negative prognostic factors and worse prognosis than high expression of the single markers. High co-expression of CD163 and LAG-3 was associated with poor clinicopathological indexes of melanoma and worse survival compared to the high expression of the single markers. The expression of immune checkpoint molecules PD-1 and LAG-3 positively correlated with the M2-TAM density in melanoma tissue. Simultaneous high M2-TAM density and immune checkpoint molecules expression acted as independent poor prognostic factors in cutaneous melanoma.

Background: Pyoderma gangrenosum is a rare autoinflammatory neutrophilic dermatosis that rapidly evolves. However, little is known about the clinicopathological features and prognosis of pyoderma gangrenosum. Aims: We aimed to document clinicopathologic and prognostic data of the patients with pyoderma gangrenosum. Methods: In this retrospective observational study, we reviewed case records of patients diagnosed with pyoderma gangrenosum between 1999–2019. Results: Fifty-three patients were identified by reviewing medical records for skin biopsy; of these, 37 were men and 16 were women. Mean age at onset was 43.3 ± 18.5 years. The most frequently affected area was the lower extremities (60.4%), followed by the head and neck (17.0%). The most common subtype was ulcerative (47.2%), followed by bullous (22.6%). 30 cases had underlying diseases and the most common were malignancy (24.5%), followed by inflammatory bowel diseases (18.9%). The proportion of cases with history of trauma were significantly higher in post-operative type (100%) as compared to the bullous type (8.3%). Histologic features of granulation tissue were frequently found in post-operative type (66.7%) and bullous type (58.3%). Granulomas were predominantly found in bullous type (58.3%). Age Limitations: This study was a single-centre study with a retrospective design. Conclusion: Pyoderma gangrenosum appears to have ethnic differences. Underlying haematologic disorders and bullous subtype have a worse prognosis. However, the type of histopathology did not correlate with the clinical outcome of pyoderma gangrenosum.

Importance Large population-based studies investigating the risks of overall and specific cancers among patients with hidradenitis suppurativa (HS) are limited. Objective To assess the overall and specific cancer risks in patients with HS compared with the risks in patients without HS in the Republic of Korea. Design, Setting, and Participants A nationwide population-based cohort study, using the Korean Health Insurance Review and Assessment Service database was conducted over a 2-year period from January 1, 2007, to December 31, 2008. Individuals in the control group who were never diagnosed with HS or cancer during the washout period were randomly extracted and matched by age, sex, index year, and insurance type at a case-control ratio of 1:8, and patients with newly diagnosed HS between January 1, 2009, and December 31, 2017, were included. Follow-up data on incident cancer from January 1, 2009, to December 31, 2018, were included. Main Outcomes and Measures The overall and specific cancer incidence rates were calculated per 100 000 person-years in patients with HS and in the matched control cohort. The risk for cancers was assessed by multivariable Cox regression models in patients with HS compared with the matched control cohort. Results In total, 22 468 patients with HS and 179 734 matched controls were included in the study. The mean (SD) age was 33.63 (17.61) years and 63.7% of the participants in both groups were male. The adjusted hazard ratio (aHR) of overall cancer in patients with HS was 1.28 (95% CI, 1.15-1.42). Patients with HS had significantly higher risk for Hodgkin lymphoma (aHR, 5.08; 95% CI, 1.21-21.36), oral cavity and pharyngeal cancer (aHR, 3.10; 95% CI, 1.60-6.02), central nervous system cancer (aHR, 2.40; 95% CI, 1.22-4.70), nonmelanoma skin cancer (HR, 2.06; 95% CI, 1.12-3.79), prostate cancer (aHR, 2.05; 95% CI, 1.30-3.24), and colorectal cancer (aHR, 1.45; 95% CI, 1.09-1.93). Conclusions and Relevance In this study, HS appeared to be associated with a significantly increased risk of overall cancer as well as several specific cancers.

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.

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

Natural killer/T-cell lymphoma is a rare, Epstein–Barr virus-associated type of cytotoxic lymphoma thatpresents mainly in the nasal cavity and its vicinity. Very few cases of primary cutaneous extranodal natural killer/T-cell lymphoma have been reported till date. All the previously reported cases of primary cutaneous extranodalnatural killer/T-cell lymphoma presented as lesions resembling cellulitis, subcutaneous nodules or ulcers. We report a rare case which presented as erythematous and purpuric round patches on the arms and was finally diagnosed as primary cutaneous extranodalnatural killer/T-cell lymphoma, following a skin biopsy. The atypical patchy lesions presented a diagnostic challenge. We herein describe this clinically novel atypical patch-like presentation of primary cutaneous extranodalnatural killer/T-cell lymphoma together with the key histopathologic features and highlights of the previously reported cases.

Background To achieve optimal clinical outcomes in patients with gastrointestinal stromal tumor (GIST), it is crucial to maintain sufficient dosing of imatinib. Skin rash is a common imatinib-associated adverse event and may affect compliance. This phase II study was conducted to evaluate whether imatinib-associated severe skin rash can be managed with systemic steroids without dose reduction or interruption of imatinib. This study is registered at ClinicalTrials.gov, number NCT03440515. Patients and Methods Between 2014 and 2016, 29 patients with imatinib-associated severe skin rash were enrolled. Skin rash of grade 2 with grade ≥2 pruritus or of grade 3 was considered severe. Oral prednisolone was administered 30 mg/day for 3 weeks, then tapered off over 12 weeks. The primary endpoint was treatment success rate (TSR). Treatment success was defined as maintaining imatinib for more than 15 weeks after completion of the steroid administration schedule without skin rash that led to additional steroid treatment or dose reduction or interruption of imatinib. Results Of the 29 patients enrolled, 22 patients with skin rash were treated successfully (TSR, 75.8%), 2 (6.9%) were evaluated as treatment failures, and 5 (17.2%) were not evaluable. The 2-year rash-free and imatinib reduction-free interval rate was 67.2% with median follow-up of 22.0 months (range, 0.4–30.3). Recurrence of severe skin rash occurred in seven patients (24.1%). Systemic steroids were well tolerated except in one patient who experienced pneumocystis pneumonia. Conclusion This study demonstrated that imatinib-associated severe skin rash can be effectively controlled by systemic steroid treatment without interruption or dose reduction of imatinib in patients with GIST. Implications for Practice Imatinib has been the standard treatment of gastrointestinal stromal tumor in both adjuvant and palliative settings. It is crucial to maintain sufficient dosing of imatinib to achieve optimal clinical outcomes. Imatinib commonly causes imatinib-associated skin rash, which may worsen drug compliance. This phase II study demonstrated that systemic steroids could help maintaining the efficacy of imatinib by preventing interruption or dose reduction of imatinib. The present study provides a new administration strategy of systemic steroids and its efficacy and safety data. Thus, this study can be a cornerstone to establish treatment guidelines for imatinib-associated skin rash.

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.

Background Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. Methods We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. Results Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1–378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. Conclusion Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response., Graphical Abstract

It has long been believed that histamine is associated with cutaneous melanogenesis. Specifically, H2-receptor antagonists reportedly inhibit melanogenesis, but H1-receptor antagonists, which are some of the most commonly prescribed medicines in dermatology, have not been studied to determine whether and how they regulate melanogenesis. Therefore, we screened H1-receptor antagonists to determine whether they inhibit melanogenesis and found that loratadine was particularly effective, in this regard without compromising cellular viability. Loratadine downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase in melanocytes. To determine the intracellular signaling pathways, Akt was consistently activated by loratadine. PI3K/Akt pathway inhibitor, LY294002, restored the reduced melanin content that was induced by loratadine. In addition, phospho-GSK-3β also was found to be increased following loratadine treatment. Loratadine reduced the amount of PKC-βII in the membrane fraction, thereby decreasing its activity. Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-βII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.

Background Epidermal growth factor receptor (EGFR) is overexpressed in many cancers. However, EGFR expression in melanoma and its role are conflicting. Objective This study aimed to evaluate EGFR expression in distant metastatic melanoma and analyze its relationship with histologic and clinical characteristics and survival. Methods Diagnostic tissues from 55 cases of distant metastatic melanoma was evaluated by immunohistochemistry for EGFR expression. Clinicopathologic features and survival outcomes were analyzed according to EGFR expression. Results The positive EGFR expression in distant metastatic melanoma was significantly correlated with the absence of ulceration. The EGFR expression in distant metastatic melanoma was significantly associated with poor survival, under the conditions of male sex and primary cutaneous melanoma without ulceration or Breslow thickness ≤4.0 mm. This study bears limitations of a retrospective study in a single institution. Conclusion EGFR immunostaining had predictive values for survival outcome. The EGFR expression in distant metastatic melanoma in male, no ulcer, or Breslow thickness ≤4.0 mm appeared to be involved in disease progression.

Background Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions. Objective We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis. Methods Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a). Results In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-α. Further, exposure of keratinocytes to IL-1α, TNF-α, transforming growth factor-α, and interferon-γ downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1. Conclusion Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.

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%.

Cutaneous lymphoid hyperplasia (CLH) is a heterogeneous type of reactive lymphocytic infiltration resembling cutaneous lymphoma clinically and histopathologically. Few studies describe the relationship between the causative agents and histopathological and immunohistochemical characteristics of CLH. We investigated the clinical and histopathological characteristics of 50 patients with cutaneous CLH and analyzed them according to causative factors and predominant cell types (B or T cells). We retrospectively reviewed medical records to identify causative agents, and histopathological and immunohistochemical features. The majority of infiltrating lymphocytes were T cells (60%). T cell-dominant CLH showed papuloplaque lesions, whereas B cell-dominant CLH lesions were nodular. The infiltration pattern differed between T and B cells. In terms of prognosis, B-cell-predominant lesions tended to respond better to treatment than T-cell-predominant lesions. Hair dyes tended to be associated with multiple CLH lesions in older patients. CLH lesions associated with drugs were located on the head and neck. Insect bites were likely to cause a solitary papular lesion. Histopathologically, infiltration depth was located more superficially than other causes and featured intense eosinophilic infiltration. Thus, our study demonstrated that CLH presents different clinicopathological features according to causative agents and predominant lymphocytic types.

Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor and was recently recognized as a distinct entity. It has a predilection for young male adults and it frequently occurs in distal extremities. Although it is known to follow an indolent course, multi-focal presentation and local recurrence are common. PMH should be differentiated from epithelioid sarcoma, epithelioid hemangioendothelioma, dermatofibrosarcoma protuberans, and rhabdomyosarcoma. Its characteristic immunohistochemical staining pattern and recurrent translocation t(7:19)(q22:q13) are the basis for its diagnosis. Surgical excision is the mainstay treatment, although chemotherapy can be considered in non-operable patients. We present a rare case of a 40-year-old Korean male patient diagnosed with PMH through an excisional biopsy to facilitate the recognition PMH in the clinical practice.

Background Reactive oxygen species (ROS) play an important role in the induction of apoptosis under pathological conditions. Recently, a significant increase in ROS production and disrupted apoptosis mechanisms in keloids have been reported. Nuclear factor erythroid 2-related factor 2 (Nrf2) represents one of the most important cellular defense mechanisms against oxidative stress and is implicated in the regulation of apoptosis. Recently, it has been reported that Nrf2 upregulates Bcl-2, an anti-apoptotic protein. Objective To compare Nrf2 protein expression in normal skin tissues to keloid tissues. Methods ROS generation in keloid tissues was evaluated with OxyBlot analysis. Western blotting and/or immunohistochemical staining approaches were used to study expression of Nrf2 or Bcl-2 in keloid and normal skin tissues. Cellular fractionation was performed to examine subcellular distribution of Nrf2. Transfection of fibroblasts with Nrf2-specific small interfering RNA (siRNA) was conducted to understand the relationship between Nrf2 expression and apoptosis induction. Results Protein oxidation, a marker of oxidative stress, is increased in keloid tissues. Western blot analysis clearly showed that Nrf2 and Bcl-2 are downregulated in keloid tissues. Immunohistochemical staining of Nrf2 confirmed the results of the western blot analysis. Transfection of fibroblasts with the Nrf2-specific siRNA results in increased apoptosis and decreased cell viability. Conclusion Collectively, our data indicate that Nrf2 expression is downregulated in keloid tissues, and that Nrf2 is involved in the development of apoptosis in Nrf2 siRNA-transfected fibroblasts. We propose that a defective antioxidant system and apoptotic dysregulation may participate in keloid pathogenesis.

Purpose This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. Materials and methods A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. Results Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). Conclusion By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions.

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

Background Skin cancer is the most common other primary cancer in patients with lymphoma. However, an intriguing association between cutaneous lymphoma and other primary cancers has been suggested in a few studies. Objective This study investigated other primary cancers in patients with cutaneous lymphoma to evaluate the risk for occurrence of each type of cancer. Methods We screened for other primary cancers in 428 patients with cutaneous lymphoma. Clinical features were analyzed according to the lineage and origin of the lymphomas. We calculated the standardized incidence ratio with statistical analysis for each group according to age. Results Among 330 patients with cutaneous T cell lymphoma and 98 with cutaneous B cell lymphoma, a total of 43 cancers in 38 patients were finally included. Other primary cancers were prevalent in patients with cutaneous B cell lymphoma and patients with secondary cutaneous lymphoma. However, those differences were not significant when the age was calibrated by multiple logistic regression. Metachronously higher standardized incidence ratios were observed for primary lung (standardized incidence ratio [SIR], 14.81; 95% confidence interval [CI], 3.05~39.54), skin (SIR, 68.05; 95% CI, 14.03~181.62), and breast (SIR, 12.91; 95% CI, 1.56~41.41) cancers with statistical significance. Conclusion Other primary cancers more preferentially occurred in patients with cutaneous lymphoma. Clinicians should carefully examine patients with cutaneous lymphoma for other cancers, especially lung, skin, and breast cancers.

Epithelioid hemangioma (EH) is an uncommon benign vascular tumor, of controversial etiology that usually presents as a slowly growing nodule on the face or digit of a middle-aged woman. 1 Most lesions have a nonspecific nodular appearance with frequent secondary changes such as excoriation and bleeding. Multiplicity is also a common finding. Histopathologically, EH is characterized by a mixture of vascular proliferation and marked mixed inflammatory cell infiltration, and was first de scribed by Wells and Whimster 2 as angiolymphoid hyperplasia with eosinophilia. The proliferation of vascular structures lined with prominent endothelial cells is a distinguishing feature of EH. The epithelioid endothelial cells that protrude into the vascular lumen create a characteristic “cobble-stone” or “tombstone” appearance. A chronic inflammatory cell infiltration in cluding lymphoplasma cells and eosinophils is a consistent find ing. EH has a diverse range of microscopic features, depending on the composition and distribution of the vascular and inflam matory cellular components. EH has been described in the literature as an inflammatory angiomatous nodule or, an atypical or pseudopyogenic granuloma, 3,4 when infiltration of various inflammatory cells is predominant, and a histiocytoid hemangi oma 5 when cobble stone-like endothelial cells are conspicuous. Some cases of EH consist entirely of solid sheets of epithelioid to spindled cells without fully canalized vascular structures. The solid form of EH can be difficult to diagnose and is occa sionally misdiagnosed as a malignant vascular tumor. EH is a benign neoplasm and surgical excision is sufficient for its treat ment. Recently, we experienced a solid form of EH with no inflammatory component, which showed a dramatic change into the typical morphology on the consecutive biopsy. This is the first reported Korean case of a solid form of EH, which patholo gists should include in the differential diagnosis of epithelioid vascular lesions to avoid overdiagnosis of epithelioid vascular malignancies.