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Background@#Targeted therapy and immunotherapy such as programmed death-1 (PD-1) targeting have been introduced for treating many types of cancers, including primary cutaneous angiosarcoma (CA). However, studies that examined other targeted molecules in CA are scarce. @*Objective@#We aim to declare the expression of endoglin and survivin in addition to PD-1 and assess the clinical correlation between the expression of these molecules and clinical variables, overall survival (OS), and progressionfree survival (PFS) in CA. @*Methods@#We identified 51 patients diagnosed with CA at Asan Medical Center over the last 14 years, based on the staining results of paraffin sections of tissue samples for endoglin, survivin, and PD-1 that were reviewed by two dermatologists. @*Results@#Statistical analysis for the correlation between results and clinical data of CA revealed that whereas 35 (63.6%) and 30 samples (54.5%) were positive for endoglin and survivin respectively, only nine samples were positive for PD-1 (16.4%). Co-expression of endoglin and survivin was detected in 24 lesions (p=0.013) and was significantly correlated to head, neck, face, and scalp (HNFS) lesions in CA (p=0.005, p=0.038, respectively). However, the expression of these target molecules did not correlate with the OS or PFS of CA. @*Conclusion@#Considering that HNFS type CA is associated with unfavorable clinical outcomes in similar populations, our findings can be helpful in matching patients with CA with effective targeted therapy.
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Background@#Adiponectin is an adipose-derived hormone that plays a role in various metabolic diseases. We previously demonstrated that adiponectin inhibits melanin synthesis through adenosine monophosphate-activated protein kinase (AMPK) activation in melanocytes. However, melanocytes can be affected by neighboring keratinocytes, and the effect of adiponectin on these functional units has not been investigated. @*Objective@#We investigated the effect of adiponectin on melanogenesis in co-cultured models of normal human melanocytes (NHMs), normal human keratinocytes (NHKs), and human dermal fibroblasts (HDFs), and the effect of adiponectin on melanin content in human skin tissues. @*Methods@#Quantitative real-time polymerase chain reaction (qPCR) was performed for tyrosinase and microphthalmia-associated transcription factor (MITF). The degree of phosphorylation of AMPK, cAMP response element binding protein (CREB), and AKT was evaluated by western blot assay, and Fontana-Masson staining was performed on cultured human skin tissues. @*Results@#Adiponectin decreased the melanin content in the co-culture models of NHMs with NHKs, NHMs with HDFs, and NHMs with both NHKs and HDFs. qPCR revealed that both tyrosinase and MITF were decreased after adiponectin treatment in the co-culture system. Following adiponectin treatment, AMPK was activated in all cell groups; however, the phosphorylation of CREB was decreased in HDFs and NHKs. The phosphorylation of AKT was decreased in only NHMs. In the experiment with human skin tissues cultured ex vivo, the densitometric analysis of Fontana-Masson staining revealed that adiponectin treatment reduced the melanin level of ultraviolet-irradiated human skin tissues. @*Conclusion@#Adiponectin inhibited melanogenesis in both co-culture models and human skin tissues ex vivo.
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Background@#Upadacitinib is an oral Janus kinase1 (JAK1)-selective inhibitor, which showed a quick and significant effect on patients with atopic dermatitis in several phase 3 clinical studies. Although, an increasing number of studies have reported data on the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis, no studies have yet been published in Korea. @*Objective@#We assessed the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis in Korean patients. @*Methods@#A total of 17 patients with atopic dermatitis who received 15 mg of oral upadacitinib everyday for 16 weeks, were included in this retrospective single-center study. Based on electronic medical records, the clinical characteristics, Eczema Area and Severity Index (EASI) score, and adverse events were investigated. @*Results@#The mean EASI score was significantly reduced at 4 weeks of upadacitinib treatment (8.81±9.00) and gradually reduced at week 8 (5.70±7.38), week 12 (4.55±6.23), and week 16 (4.58±6.74) (p＜0.001). At week 16, 61.54%, 30.77%, and 15.38% of patients achieved EASI 75, EASI 90, and EASI 100 responses, respectively. There was no statistically significant difference between EASI 75 and EASI 90 by age or gender at week 16 (p＞0.05). A total of 13 people (76.5%) had adverse events, of which acne was the most common. In all patients, the symptoms were mild and self-limited, and no patient discontinued treatment. @*Conclusion@#Upadacitinib was effective and safe for Korean patients with atopic dermatitis in real-world clinical practice.
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The effect of dupilumab on allergic contact dermatitis or patch testing is unknown. Here, we present a case of excited skin syndrome that appeared after patch testing during dupilumab treatment. A 21-year-old woman presented with atopic dermatitis that showed only a partial response to cyclosporine and dupilumab. A patch test was performed to check for underlying allergic contact dermatitis. The result was consistent with excited skin syndrome.Some studies argue that dupilumab suppresses allergic reactions triggered by allergens that activate the Th2 pathway. Others suggest that it does not affect the result of patch testing, regardless of the type of allergen tested. Even if dupilumab suppresses a certain allergic or immunologic pathway, this case shows that it cannot mask excited skin syndrome on patch testing.
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Linear lichen planus pigmentosus is a rare subtype of lichen planus pigmentosus that follows Blaschko’s lines, leaving long-standing residual atrophy and pigmentation, especially in dark-skinned populations. Conventional treatments have several limitations regarding the alleviation of pigmentation and atrophy. We report two cases of Korean women with linear lichen planus pigmentosus on their faces who were successfully treated with fractional lasers and intralesional injection of polydeoxyribonucleotide.
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Background@#Nipple adenoma (NA) is a rare benign tumor arising in the lactiferous ducts of the nipple. It typically presents as a palpable nodule, erosion, or discharge with erythema of the nipple. NA is different from other mammary proliferative diseases of the nipple; however, its clinicopathologic characteristics have been scarcely elucidated. @*Objective@#In this study, we aimed to assess the clinical and histopathological characteristics of NA and compare them with mammary Paget’s diseases and breast carcinomas of the nipple. @*Methods@#We retrospectively reviewed fifteen patients with NA. Furthermore, we reviewed fifteen patients with nipple Paget’s diseases and five patients with breast carcinomas (ductal carcinoma in situ and invasive ductal carcinoma). Skin lesions’ clinical characteristics and general histopathological findings were investigated. @*Results@#NA showed significantly early onset (p=0.014), delayed time for onset to diagnosis (p=0.026), and smaller lesion than other nipple malignant diseases (p＜0.001). NA was predominantly localized on the right side and exhibited as more palpable mass and less nipple discharge as initial symptoms. Estimated prevalence of Korean cases (0.026%) was twice higher than Western countries (0.012%). p16 immunostaining in NA and other malignant diseases did not differ. @*Conclusion@#NA is a benign neoplasm arising on the nipple. NA showed earlier onset with smaller size at initial presentation than other malignant diseases which presented more crusts. Unnecessary surgical procedures for NA should be avoided with preceding clinical differential diagnosis.
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Background@#Omalizumab is a very important drug for the treatment of chronic urticaria. Although omalizumab’s therapeutic efficacy has been demonstrated, data on real-world experiences in Korea, especially regarding chronic inducible urticaria (CIndU), are limited. This study attempted to compare the efficacy of omalizumab in Korean chronic spontaneous urticaria (CSU) and CIndU patients. @*Methods@#Fifty-two CSU and 29 CIndU patients were included and Urticaria Activity Score 7 (UAS7) at baseline, week 4, and week 12 was assessed retrospectively. @*Results@#Omalizumab 150 mg significantly decreased UAS7 in both patients with CSU and CIndU with only one dose (P < 0.001). The significant decrease in the UAS7 scores of both groups of patients continued from weeks 4 to 12. Although there was no significant difference in treatment efficacy between the two groups, the symptoms of patients with CSU tended to improve faster; furthermore, the number of antihistamines administered daily reduced more significantly in this patient group (P = 0.047). Additionally, the decrease in the UAS7 score between baseline and week 12 and the response rate were higher in patients with CSU. @*Conclusion@#Omalizumab may be slightly more effective against CSU than against CIndU. Regarding the CIndU subtypes, dermatographic urticaria was associated with the greatest reduction in the UAS7 score, and patients with this condition showed the highest response rate, indicating the best effect of omalizumab. The duration of chronic urticaria was greater in non-responders than in responders (P = 0.025). Conversely, baseline immunoglobulin E levels were significantly higher in responders (P = 0.039).
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A 64-year old woman who underwent lung transplantation and had T-cannula contracted classic scabies from her daughter. The patient was treated with 5% permethrin 10 times and had two consecutive negative follow-up microscopic examinations. However, the patient had recurrent symptoms and diagnosed with recurrent classic scabies 22 days after the last treatment. Unchanged tie string and unapplied topical agent around the T-cannula skin lesion may be reasons for recurrence. Thus, accurate application of topical treatment and changing the tie string of the t-cannula is needed to prevent a recurrence.
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Background@#Riehl’s melanosis of the face and neck has been reported in middle-aged women who have darker skin types. Recently, cases of Riehl’s melanosis have been on the rise in Korea, which might reflect the increased use of various cosmetic products and procedures. @*Objective@#This study was designed to analyze the clinicopathological characteristics and treatment outcomes of Riehl’s melanosis in Korean patients. @*Methods@#We closely observed 80 patients with Riehl’s melanosis diagnosed in Asan Medical Center and Hanyang University Medical Center between 2005 and 2015. A skin biopsy was analyzed in 51 patients, and a patch test was carried out in 16 patients. @*Results@#Patients with chronic Riehl’s melanosis (＞12 months) had an increased frequency of previous laser treatments. Patients with acute Riehl’s melanosis (＜3 months) reported a previous history of dry skin, itching, or irritation as a result of the use of hair dye. Patients older than 50 years, with darker skin type, and with a longer disease duration (＞12 months) had poor response rates. Chronic Riehl’s melanosis may be preceded by repeated irritation of barrier-compromised skin, and acute Riehl’s melanosis seems to be an allergic form of Riehl’s melanosis. @*Conclusion@#Riehl’s melanosis has different clinical manifestations according to disease duration and different treatment responses based on disease duration.
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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.
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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.
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Halo nevus clinically presents as a nevus with a surrounding ring of depigmentation that histopathologically demonstrates a dense lymphocytic reaction to the melanocytic component of the epidermis. While melanocytic nevi with halo phenomena are common, a halo reaction is uncommon in Spitz nevus. When a halo reaction develops around a Spitz nevus, differential diagnosis from melanoma arising from pre-existing nevus is difficult due to the presence of dense inflammatory components. A halo reaction itself can increase the cytologic atypia of melanocytes and can obscure nest maturation. Herein, we report rare cases of Spitz nevus combined with a halo reaction. It is important to note that the halo phenomenon can occur without a clinically evident white patch and that the architectural features of the nevus components can be used to distinguish Spitz nevus from malignant melanoma.
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Background@#Madelung’s disease (MD) is characterized by multiple symmetric deposits of unencapsulated adipose tissue in the head, neck, and upper trunk. However, the etiology of lipoma tissue in MD remains controversial. @*Objective@#This study determined the clinicopathological and epidemiological features of Korean patients with MD and re-examined the hypothesis that lipomas of MD originate from brown fat. @*Methods@#We performed a single-institution, retrospective medical record review of 20 patients diagnosed with MD between January 1997 and August 2017. Biopsy slides were stained with nuclear factor IA (NFIA) and uncoupling protein 1 (UCP-1). @*Results@#The patients included were 2 women and 18 men with an average age of 64 (range, 27∼75) years. Ten patients reported heavy alcohol intake, and the remaining 10 reported some degree of alcohol intake. Hepatic disease was present in 47.7% of patients, only 16.7% had a body mass index ＞30 kg/m2, and 80% underwent surgical intervention. @*Conclusion@#MD affected mainly alcoholic men in the fourth decade. Alcoholism, hepatic disease, or severe obesity accounted for less than half of the Korean patients with MD. Immunohistochemical staining supported the hypothesis that MD lipomas originate from brown fat. Although the adipose tissue of all patients was stained with NFIA and UCP-1, the staining intensity varied. NFIA, which is a transcription factor required for the induction and maintenance of brown fat-specific gene expression, was more sensitive than UCP-1 for the detection of brown fat.
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Lymphomatoid contact dermatitis is a subset of cutaneous pseudolymphoma that clinically and histopathologically resembles both allergic contact dermatitis and cutaneous lymphoma. A variety of allergens have been reported since the first description of this entity in 1976. Lymphomatoid contact dermatitis is typically related to T cell hyperplasia. We herein describe a case of cutaneous B-cell lymphoid contact dermatitis caused by hair dye. This case demonstrates that lymphomatoid contact dermatitis can present with various clinical features and emphasizes the importance of thorough history-taking and examination for diagnosis.
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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.
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Cutaneous metastases of internal malignancies are relatively rare and originate most frequently from tumors of the breast and lung. Herein, we present an unusual clinical presentation of a skin metastasis from a gastric signet-ring cell carcinoma in an adolescent. A 19-year-old boy presented with asymptomatic subcutaneous nodules on his abdomen and back. Histopathological examination revealed signet-ring cells with cytoplasmic mucin in the dermis. A diagnosis of cutaneous metastasis of a signet-ring cell carcinoma was made and the patient died 12 days after his initial visit to our dermatology clinic. Gastric carcinomas have infrequently been reported in adolescents, and cutaneous metastases from carcinomas in this group are extremely rare. Clinicians should be aware that skin metastases of adolescent gastric carcinoma can be similar in presentation to steatocystoma multiplex and that a skin biopsy is necessary for suspicious skin lesions.
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Dermal melanocytosis is characterized by an increased number of ovoid to elongated melanocytes situated between collagen fibers in the dermis, including blue nevus, Mongolian spots, nevus of Ota and Ito and dermal melanocyte hamartoma. Herein, we present a rare case of a 15-year-old boy presented with both dermal melanocyte hamartoma and Becker's nevus in conjunction with neurofibromatosis. A shared pathophysiologic mechanism between neurofibromatosis and other nevi in the context of organoid hamartoma has been reviewed.
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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.
Subject(s)
Humans , Antibodies , Eczema , Immunotherapy , Lung Neoplasms , Prevalence , PruritusABSTRACT
BACKGROUND: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. OBJECTIVE: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. METHODS: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. RESULTS: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. CONCLUSION: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future.