Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.

Clinical characteristics and survival analysis of cutaneous metastases in a single tertiary centre in Korea.

BACKGROUND: Cutaneous metastasis (CM) refers to the spread of malignancy to the skin. CM is perceived as an advanced stage. It might be the first sign of a primary cancer or an indicator of recurrence. OBJECTIVES: To identify primary cancers associated with CMs and perform a survival analysis according to advanced stage of cutaneous metastasis at a single tertiary centre in Korea. METHODS: A total of 219 patients from Samsung Medical Center from January 2009 to April 2020 were retrospectively analysed to identify cases with biopsy-proven CMs. According to advanced stage of metastasis, patients were divided into three stages, CM only (CMO), CM with lymph node metastasis (CM/LM) and CM with distant metastasis (CM/DM), to analyse clinical characteristics and survival rate. RESULTS: The most common CM from primary cancer was breast cancer, followed by lung cancer, stomach cancer, colorectal cancer and others. When all primary cancers were included, the median survival period was 4.82 years for the CMO stage, 2.15 years for the CM/LM stage and 0.80 years for the CM/DM stage, with a tendency to deteriorate with advancing stage. At 1- and 3-year after occurrence of CM, the CM/DM stage showed a significantly poorer survival rate than the other two stages. CONCLUSIONS: This study showed a median survival period of 22 months for CM patients overall. Breast cancer has greater accessibility to the skin than other cancers. Therefore, breast cancer can metastasize to the skin without involving lymph nodes or other sites.

Impact of Pediatric Alopecia Areata on Quality of Life of Patients and Their Family Members: A Nationwide Multicenter Questionnaire Study.

BACKGROUND: Pediatric alopecia areata (AA) can affect the quality of life (QoL) of patients and their family members. Research on the QoL and burden on family members in pediatric AA is limited. OBJECTIVE: This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA. METHODS: This nationwide multicenter questionnaire study enrolled AA patients between the ages of 5 and 18 years from March 1, 2017 to February 28, 2018. Enrolled patients and their parents completed the modified Children's Dermatology Life Quality Index (CDLQI) and the modified Dermatitis Family Impact (mDFI). The disease severity was measured using the Severity of Alopecia Tool (SALT) survey scores. RESULTS: A total of 268 patients with AA from 22 hospitals participated in this study. Our study found that the efficacy and satisfaction of previous treatments of AA decreased as the severity of the disease increased. The use of home-based therapies and traditional medicines increased with the increasing severity of the disease, but the efficacy felt by patients was limited. CDLQI and mDFI scores were higher in patients with extensive AA than those with mild to moderate AA. The economic and time burden of the family members also increased as the severity of the disease increased. CONCLUSION: The severity of the AA is indirectly proportional to the QoL of patients and their family members and directly proportional to the burden. Physicians need to understand these characteristics of pediatric AA and provide appropriate intervention to patients and their family members.

Incidence and Prevalence of Skin Cancers in South Korea from 2008 to 2016: A Nation-Wide Population Based Study.

Background: In South Korea, there have been few nationwide epidemiologic studies about premalignant actinic keratosis (AK), squamous cell carcinoma in situ (Bowen's disease), nonmelanoma skin cancer (NMSC), malignant melanoma of the skin (MM), Kaposi's sarcoma (KS), connective and soft tissue cancers, or mycosis fungoides (MF). Objective: Using a nationwide population-based study, we attempted to measure the incidence and the prevalence of the above-mentioned tumors in South Korea. Methods: The database we used included all claims in the Korean National Health Insurance program and the Korean Medical Aid program from 2008 to 2016. The International Classification of Diseases, 10th revision (ICD-10) was used to record diagnoses in this database. This data included AK, Bowen's disease, NMSC, MM, KS, connective and soft tissue cancers, and MF. Results: The age-standardized incidence and prevalence rate of AK, Bowen's disease, NMSC, MM, KS, connective and soft tissue cancers, as well as MF increased during the periods we investigated. The incidence and prevalence rate of AK and NMSC have increased two- to three-fold. In the case of Bowen's disease, MM, KS, connective and soft tissue cancers, or MF, we observed no significant tendency in age-standardized incidence or prevalence. Conclusion: We confirmed that the age-standardized incidence and prevalence rates of NMSC and AK tended to increase. These results might contribute to developing preventive and therapeutic strategies for skin cancers and may become a source for further studies.

Immunohistochemical Analysis of Prurigo Nodularis in 209 Patients: Clinicopathological Analysis between Atopic and Non-Atopic Patients and between Treatment Response Groups.

BACKGROUND: Prurigo nodularis (PN) is a highly pruritic disease that significantly impairs patient quality of life. Although the mechanism that causes pruritus is not clear, one hypothesis argues that neural hyperplasia, mast cell, and Merkel cell neurite complexes may be associated with PN pathogenesis. OBJECTIVE: The objective of this study was to analyze whether special staining outcomes differed depending on the presence of atopic dermatitis (AD) and treatment response. METHODS: A total of 209 patients diagnosed with PN was analyzed retrospectively. Patients were divided into two groups according to presence or past history of AD and by treatment response. Histopathologic features were obtained using the following stains: Giemsa, S-100, neuron-specific enolase, cytokeratin (CK)-20, CAM5.2, and CK8/CK18. RESULTS: A total of 126 patients (60.29%) had AD, and 68 (32.54%) showed clinical improvement. There were no statistically significant differences in the staining results between the PN groups with AD (PN c AD) and without AD (PN s AD). Additionally, there were no statistically significant differences in staining results between the improved and non-improved groups. CONCLUSION: Implementing the special stains helped to identify PN pathogenesis. Because there were no statistically significant differences in the special stain results between the improved and non-improved groups, we conclude that mast cell proliferation, neural hyperplasia, and Merkel cell hyperplasia may not have a significant effect on treatment response.

A Case Report of Multiple Capillary Hemangioma in a Chronic Myeloid Leukemia Patient Taking Tyrosine Kinase Inhibitors.

A capillary hemangioma is a vascular tumor with small capillary sized vascular channel. Multiple capillary hemangioma in relation with drugs have been rarely reported. Here in, we report a case of multiple capillary hemangioma in patient diagnosed with chronic myeloid leukemia who received tyrosine kinase inhibitors (TKIs). Histopathological findings have shown capillary proliferation in the upper dermis, which is consistent with capillary hemangioma. Since TKIs can paradoxically activate the MEK/ERK pathway which is required for angiogenesis, we presumed that the lesions as the cutaneous side effects of TKIs.

Identification of genetic mutations related to invasion and metastasis of acral melanoma via whole-exome sequencing.

Many studies have analyzed the genes related to melanoma. However, only a limited number of studies have been conducted to identify the genes that are involved in the invasion and metastasis of acral melanoma (AM). Here, we attempted to investigate the genetic mutations associated with invasion and metastasis of AM. We analyzed five multi-regional samples of primary and metastatic AM and histologically normal tissue adjacent to the tumor (NAT) in two AM patients by whole-exome sequencing (WES). We identified single nucleotide variations and small indels present in tissue samples but not in saliva. We compared the sequencing results of superficial and deep lesions and primary and metastatic lesions of AM. We identified significantly deleterious mutations (SDM) that are likely to be related to invasion and metastasis of AM, respectively. SDM such as SKA3, MAST4, CNNM1, KIAA1549L, and SLC26A10 were found only in the deep lesion, but not in the superficial lesion. SDM present only in the metastatic lesion were ANO1, CPEB1, EP300, INADL, MAP1B, MAP7D1, MARCH6, NETO1, PRKCE, SBK1, TNRC6A, USP13, WDR74, and ZNF827. In conclusion, we applied multi-region WES to investigate possible pathogenic mutations related to invasion and metastasis in AM. Several genes including CNNM1, USP13, ZNF827, WDR74, CPEB1, and EP300 might be related to invasion and metastasis of AM. This study might facilitate the exploration of the evolutionary pathogenesis of advanced AM.

Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center.

Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have demonstrated their efficacy in the treatment of various malignancies. Despite their benefits, their immunomodulatory activities can cause unpredictable cutaneous adverse events (CAE). This study aimed to identify characteristics of CAE in patients treated with PD-1/PD-L1 inhibitors through the medical records, photographs, and pathology reports. Fifty CAE occurred in 47 (2.75%) of 1711 patients treated with PD-1/PD-L1 inhibitors. Pruritic, psoriasiform, urticarial, and acneiform eruptions were the four most common types. Melanoma patients showed CAE more frequently than other malignancies. Acneiform eruption occurred more often at ages under 60 years. Urticarial eruption appeared earlier, while keratoacanthoma appeared later after immunotherapy. The overall survival times were not significantly different between the two groups with and without CAE by Kaplan-Meier analysis (p = 0.055). Studies on CAE may provide more information to understand these drugs and to help manage the patients.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Effect of photobiomodulation therapy on radiodermatitis in a mouse model: an experimental animal study.

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Evaluation for Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-term Narrowband UV-B Phototherapy.

Importance: Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. Objectives: To investigate the risks of skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions. Design, Setting, and Participants: This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed. Exposures: The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients). Main Outcomes and Measures: Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment. Results: Among the 60 321 patients with vitiligo in this study (33 617 women; mean [SD] age, 50.2 [14.9] years), the risks of Bowen disease (<50 sessions of phototherapy: hazard ratio [HR], 0.289 [95% CI, 0.060-1.392]; 50-99 sessions: HR, 0.603 [95% CI, 0.125-2.904]; 100-199 sessions: HR, 1.273 [95% CI, 0.329-4.924]; ≥200 sessions: HR, 1.021 [95% CI, 0.212-4.919]), nonmelanoma skin cancer (<50 sessions: HR, 0.914 [95% CI, 0.533-1.567]; 50-99 sessions: HR, 0.765 [95% CI, 0.372-1.576]; 100-199 sessions: HR, 0.960 [95% CI, 0.453-2.034]; ≥200 sessions: HR, 0.905 [95% CI, 0.395-2.073]), and melanoma (<50 sessions: HR, 0.660 [95% CI, 0.286-1.526]; 50-99 sessions: HR, 0.907 [95% CI, 0.348-2.362]; 100-199 sessions: HR, 0.648 [95% CI, 0.186-2.255]; ≥200 sessions: HR, 0.539 [95% CI, 0.122-2.374]) did not increase after phototherapy. The risk of actinic keratosis increased significantly for those who had undergone 200 or more NBUVB phototherapy sessions (HR, 2.269 [95% CI, 1.530-3.365]). A total of 717 patients with vitiligo underwent at least 500 sessions of NBUVB phototherapy; their risks of nonmelanoma skin cancer and melanoma were no greater than those of the patients who did not undergo NBUVB phototherapy (nonmelanoma skin cancer: HR, 0.563 [95% CI, 0.076-4.142]; melanoma: HR, not applicable). Conclusions and Relevance: Our results suggest that long-term NBUVB phototherapy is not associated with an increased risk of skin cancer in patients with vitiligo and that NBUVB phototherapy may be considered a safe treatment.

Is the survival rate for acral melanoma actually worse than other cutaneous melanomas?

It is still not clear whether the survival rate for acral melanoma (AM) is better or worse than that of cutaneous melanoma developed at other sites. We sought to evaluate the difference in survival depending on the primary tumor site of cutaneous melanoma. We retrospectively reviewed primary cutaneous melanoma cases diagnosed at Samsung Medical Center, a tertiary institution in Korea, from January 1995 to July 2017. The cohort consisted of 642 patients, with 389 non-acral cutaneous melanoma (NACM) patients and 253 AM patients. The AM patients had a higher percentage of stage 0 diagnoses than the NACM patients (31.6% vs 6.9%, respectively). The factors associated with overall survival were primary tumor site, sex, age, American Joint Committee on Cancer stage, surgery and medical treatment (P < 0.05). Non-acral sites showed worse survival in multivariable analysis (hazard ratio [HR], 1.457; 95% confidence interval [CI], 1.051-2.020; P = 0.0240). Among the NACM, melanomas on the trunk were associated with a higher risk of mortality compared with AM (HR, 1.883; 95% CI, 1.142-3.107; P = 0.0131). Acral melanoma was associated with a better prognosis than non-acral melanoma, specifically when located on the trunk, in Korean patients.

A Case of Cutaneous Leukocytoclastic Vasculitis Associated with Granulocyte Colony-Stimulating Factor: An Unusual Presentation.

Drug-induced vasculitis is an inflammation of small-sized blood vessel caused by the use of drugs. It accounts for approximately 10% of acute cutaneous vasculitis. Propylthiouracil, hydralazine, and allopurinol have been widely known as causative agents. The most common clinical feature of drug-induced vasculitis is palpable purpura on lower extremities. A 66-year-old Korean female presented with erythematous nodules on upper chest and back. She had been on medication for multiple myeloma. Laboratory results showed neutropenia. After a single injection of filgrastim (recombinant granulocyte colony-stimulating factor), she developed cutaneous lesions with concurrent increase in absolute neutrophil count. A skin biopsy revealed leukocytoclastic vasculitis. After discontinuation of filgrastim injection, her skin lesions disappeared spontaneously.