Two Cases of Linear Lichen Planus Pigmentosus of the Chin in Korean Women Treated by Fractional Lasers and Polydeoxyribonucleotide Injection

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.

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. @*Materials and Methods@#Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. @*Results@#We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. @*Conclusion@#Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Glossopharyngeal Neuralgia Caused by Nerve Compression and Traction by Tortuous Vertebral and Posterior Inferior Cerebellar Arteries

Glossopharyngeal neuralgia is a condition characterized by lancinating pain in the tongue, soft palate, and pharynx. This condition can be caused by the combination of traction and compression of the glossopharyngeal nerve by tortuous vertebral and posterior inferior cerebellar arteries, which tug down and exert pressure on the nerve. Medical treatments including carbamazepine and gabapentin have been found to effectively manage glossopharyngeal neuralgia, even in cases with overt compression and traction of the nerve.

Real-World Experience of the Efficacy and Safety of Upadacitinib 15 mg in Patients with Atopic Dermatitis in Korea / 대한피부과학회지

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.

Clinical Implications of Expression of Endoglin and Survivin in Patients with Primary Cutaneous Angiosarcoma in an Asian Population / 대한피부과학회지

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.

Excited Skin Syndrome after Patch Testing in a Patient with Atopic Dermatitis Treated with Dupilumab / 대한피부과학회지

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.

May-Thurner Syndrome Appearing as Recurrent Swelling and Cellulitis in the Left Leg and Foot / 대한족부족관절학회지

The authors have diagnosed and treated patients with May-Thurner syndrome who presented with recurrent edema and redness in the left lower leg and foot. Although May–Thurner syndrome is a rare vascular disease, its primary symptoms manifest as edema and redness in the left lower leg and foot, leading the patients to seek foot and ankle surgery. Suspicion should be directed towards May-Thurner syndrome if an obese individual who spends prolonged periods sitting repeatedly complains of edema and redness in the left lower leg and foot area, in which a blood clot forms due to compression of the left common iliac vein within the pelvis.

Clinicopathologic Characteristics of Nipple Adenoma: Comparison with Malignant Proliferative Diseases / 대한피부과학회지

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.

Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma

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.

Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma

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.

Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrastenhanced MRI pilot study

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp , both, p = 0.062), left thalamus and in left putamen (Ktrans , p = 0.062), and left insula and right amygdala (Vp , p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = −0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.

Diagnostic model for pancreatic cancer using a multi-biomarker panel

Purpose@#Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. @*Methods@#Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). @*Results@#The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. @*Conclusion@#This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.

Revisiting Riehl’s Melanosis in Korean Patients: Clinicopathological Features, Blood Chemistry, and Immunohistochemistry / 대한피부과학회지

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.

A Case of Lymphomatoid Contact Dermatitis Secondary to Hair Dye / 대한피부과학회지

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.

Benign Symmetric Lipomatosis in Korean Patients / 대한피부과학회지

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.

Case Reports of Spitz Nevus with a Halo Phenomenon / 대한피부과학회지

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.

Longevity of Cross-linked Hyaluronic Acid Filler Depending on Injection Depth: In Vivo Study Using a Small Animal Model / 대한피부과학회지

Background@#Hyaluronic acid (HA) is the material used most often for soft tissue augmentation. Both agent factors, such as type of fillers and host factors, including technical manipulation, are known to affect the longevity of HA fillers. Although the relationship between longevity and filler composition has been widely studied, quantitative analysis to evaluate the difference in longevity of HA filler depending on injection depth has not yet been reported.Objective This study estimates injection depth-dependent degradation of HA filler in vivo using a rat model to evaluate its longevity. @*Methods@#Three Sprague–Dawley rats were assigned to each group based on sampling timepoints. Four injections were administered intradermally on one side of the back of rats and four more injections were administered subcutaneously on the other side. Histological specimens from the injected site were obtained at 2 (Group 1), 5 (Group 2), 9 (Group 3), 13 (Group 4), 20 (Group 5), and 33 (Group 6) weeks after initial implantation. External size of the implant site was calculated using caliper measurement at sampling timepoints. @*Results@#Although caliper-based analysis did not reveal a significant difference between intradermal and subdermal sites in all groups (p＞0.05), volumetric analysis of histological specimens demonstrated a difference in injection depth-dependent degradation rate. The volume ratio decreased over time in the subdermal injection sites, but it maintained a greater volume ratio than intradermal injection sites during the experiment (Groups 1∼6, p＜0.007).At 20 weeks after implantation, approximately half of the HA filler remained in the subdermal injection sites, whereas ＞80% of the filler was lost from intradermal injection sites. After the initial injection, time taken for the implant volume to reduce to half of its original value at intradermal and subdermal sites was 13 and 20 weeks, respectively. @*Conclusion@#This study demonstrates histological changes occurring in implanted HA filler materials over time and compares the injection depth-dependent longevity of materials. Caliper-based analysis did not show a significant difference between the intradermal and subdermal sites. However, quantitative analysis based on histological volumetric analysis revealed that subdermal injection lasts longer than intradermal injection.

A Case of Pseudomyogenic Hemangioendothelioma of the Lower Extremity

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.

Comprehensive Cancer Panel Sequencing Defines Genetic Diversity and Changes in the Mutational Characteristics of Pancreatic Cancer Patients Receiving Neoadjuvant Treatment

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDA) is associated with an extremely poor prognosis. This study assessed the genetic diversity among patients with PDA and compared their mutational profiles before and after treatment. METHODS: Tumors and matched blood samples were obtained from 22 PDA patients treated with neoadjuvant chemoradiation therapy. The somatic mutations were analyzed with comprehensive cancer gene panel (CCP). In addition, the biopsy samples obtained at diagnosis and the surgically resected samples after treatment were compared for seven patients. The CCP provided formalin-fixed paraffin-embedded sample-compatible multiplexed target selection for 409 genes implicated in cancer. RESULTS: Assessments of the MLH1, MLH3, MSH2, and PMS2 genes showed that the four patients with the highest relative burdens of mutations harbored somatic mutations in at least three of these genes. Genes in the histone-lysine N-methyltransferase 2 (KMT2) family, such as KMT2D, KMT2A, and KMT2C, were frequently mutated in tumor samples. Survival was worse in patients with ARID1A gene mutations than those without ARID1A gene mutations. Mutation patterns were compared between tissue samples before and after neoadjuvant treatment in seven patients who underwent surgical resection. The allelic fraction of mutations in KRAS codon 12 was lower in the surgically resected samples than in the endoscopic ultrasonography-guided fine needle aspiration biopsy samples of six patients. The number of mutant alleles of the histone lysine methyltransferase gene WHSC1 also decreased after treatment. CONCLUSIONS: These results indicate that tumor tissue from PDA patients is genetically diverse and suggest that ARID1A mutations may be a potential prognostic marker for PDA.

A Skin Metastasis from a Gastric Signet-Ring Cell Carcinoma in an Adolescent that Mimicked Steatocystoma Multiplex / 대한피부과학회지

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.