Hong Sun Jang

Comparison of Melanoma Subtypes among Korean Patients by Morphologic Features and Ultraviolet Exposure

Background Genetic alterations have been identified in melanomas according to different levels of sun exposure. Whereas the conventional morphology-based classification provides a clue for tumor growth and prognosis, the new classification by genetic alterations offers a basis for targeted therapy. Objective The purpose of this study is to demonstrate the biological behavior of melanoma subtypes and compare the two classifications in the Korean population. Methods A retrospective chart review was performed on patients found to have malignant melanoma in Severance Hospital from 2005 to 2012. Age, sex, location of the tumor, histologic subtype, tumor depth, ulceration, lymph node invasion, visceral organ metastasis, and overall survival were evaluated. Results Of the 206 cases, the most common type was acral melanoma (n=94, 45.6%), followed by nonchronic sun damage-induced melanoma (n=43, 20.9%), and mucosal melanoma (n=40, 19.4%). Twenty-one patients (10.2%) had the chronic sun-damaged type, whereas eight patients (3.9%) had tumors of unknown primary origin. Lentigo maligna melanoma was newly classified as the chronic sun-damaged type, and acral lentiginous melanoma as the acral type. More than half of the superficial spreading melanomas were newly grouped as nonchronic sun-damaged melanomas, whereas nodular melanoma was rather evenly distributed. Conclusion The distribution of melanomas was largely similar in both the morphology-based and sun exposure-based classifications, and in both classifications, mucosal melanoma had the worst 5-year survival owing to its tumor thickness and advanced stage at the time of diagnosis.

Delayed Reconstruction for the Non-Amputative Treatment of Subungual Melanoma

Background In cases of early stage subungual melanoma (SUM), conservative treatment with non-amputative wide excision of the nail unit and subsequent skin graft is preferred over amputation to preserve the involved digit. Objective We report a series of patients with SUM treated with conservative surgery and suggest an effective supplementary treatment process. Methods We retrospectively reviewed 10 patients (2 males, 8 females) who were diagnosed with in situ or minimally invasive SUM on the first biopsy and underwent non-amputative wide excision of the nail unit. All patients underwent secondary intention healing during the histopathological re-evaluation of the entire excised lesion, and additional treatment was administered according to the final report. Results In two of 10 patients, amputation was performed because of the detection of deep invasion (Breslow thickness: 4.0, 2.3 mm) from the final pathologic results, which differed from the initial biopsy. In six patients who received delayed skin graft, the mean total time required for complete healing after secondary intention healing and the skin graft was 66.83±15.09 days. As a result of this delayed skin graft, the final scarring was similar to the original shape of the nail unit, scored between 5 and 10 on a visual analogue scale. Most patients were satisfied with this conservative surgery except one patient, who had volar portion involvement and received an interpolated flap instead of a skin graft. Conclusion Our treatment process can reduce the risk of incomplete resection and improve cosmetic outcomes in patients with SUM.

Segmental vitiligo and facial palsy associated with a concurrent ipsilateral acoustic schwannoma

1 Berk DR, Bayliss SJ. Milia: a review and classification. J Am Acad Dermatol 2008; 59: 1050–1063. 2 Langley RG, Walsh NM, Ross JB. Multiple eruptive milia: report of a case, review of the literature, and a classification. J Am Acad Dermatol 1997; 37: 353–356. 3 Wolfe SF, Gurevitch AW. Eruptive milia. Cutis 1997; 60: 183–184. 4 Batra P, Tsou HC, Warycha M, Votava HJ, Stein J. Multiple eruptive milia. Dermatol Online J 2009; 15: 20. 5 Cho E, Cho SH, Lee JD. Idiopathic multiple eruptive milia occurred in unusual sites. Ann Dermatol 2010; 22: 465–467. 6 Cairns ML, Knable AL. Multiple eruptive milia in a 15-year-old boy. Pediatr Dermatol 1999; 16: 108–110. 7 Diba VC, Al-Izzi M, Green T. A case of eruptive milia. Clin Exp Dermatol 2005; 30: 677–678. 8 Connelly T. Eruptive milia and rapid response to topical tretinoin. Arch Dermatol 2008; 144: 816–817. 9 Diba VC, Handfield-Jones S, Rytina E, et al. Multiple eruptive milia in a 9-year-old boy. Pediatr Dermatol 2008; 25: 474–476. 10 Sharma R, Singal A, Sonthalia S. Multiple eruptive milia over both external ears. Indian J Dermatol Leprol 2011; 77: 519–520. 11 Khaled A, Zeglaoui F, Hawilo A, et al. Multiple eruptive milia in a 26 month-old boy. Tunis Med 2012; 90: 270–271.

Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation

Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild‐type cell lines (SK‐MEL‐2 and HaCaT) but not in BRAF mutant cell lines (SK‐MEL‐24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase in a CRAF‐dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)‐2 and MMP‐9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen‐activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion.

Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions

Purpose Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected. Materials and Methods In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions. Results Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. GNAQ/11 mutation showed 100% homogeneity in uveal melanoma patients. Conclusion Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

Unusual manifestation of molluscum contagiosum: eruptive papules on the face and neck of an immunocompetent patient.

Dear Editor: Molluscum contagiosum (MC) is a common benign skin disease caused by the pox virus and usually affects young children. Most MC in adults occurs in people with an immunosuppressive status, but it can also appear in immunocompetent adults who have experienced friction or scrubbing. We herein report a case of MC that presents multiple pinhead-sized eruptive skin-coloured papules covering the whole face and neck in a patient without a history of epidermal trauma. A 60-year-old Korean woman with a history of recent onset diabetes presented to our clinic with sudden eruptive papules on her face and neck, which had been persistent for the past 6 months. She had been treated with topical hydrocortisone in the local clinic, but no improvements were observed. Even though she was mostly asymptomatic, the patient complained of occasional mild pruritus. She had no history of towel scrubbing or massage. Upon physical examination, multiple 2 to 3-mm-sized skin-coloured papules were observed on her face and neck (Fig. 1). Fig. 1 (A) Multiple 2- to 3-mm-sized skin-coloured papules observed on the face and neck. (B) Close up view of the skin-coloured papules. Keratin-like material was observed after extractions of some lesions, resulting in the performance of punch biopsy under the initial impression of milium. Histopathologic examination revealed epidermal cells bearing large eosinophilic cytoplasmic inclusion bodies, typical of the molluscum body, and the lesion was diagnosed as MC (Fig. 2). Due to diffuse distributions across the face and neck, imiquimod cream, oral gamma linolenic acid 360 mg and oral cimetidine 2,000 mg were used daily for 3 months, until all the lesions were resolved. We believe that the immunomodulating effects from imiquimod cream and oral cimetidine could have contributed to the resolution. Fig. 2 Epidermal cells bearing large eosinophilic cytoplasmic inclusion bodies, typical of the molluscum body (H&E, ×100). There have been several reports of disseminated molluscum contagiosum in patients with hematologic malignancies, human immunodeficiency (HIV) infection, or in patients taking immunosuppresants such as methotrexate or azathioprine1,2. Cases associated with traumas and contacts have also been reported, such as molluscum folliculitis after shaving or molluscum developed after use of a nylon towel at a public spa3,4. In this case, the patient was a healthy woman without any evidence of systemic diseases other than diabetes and was not taking any medicine that could impair cellular immunity. Lab data including complete blood counts and routine chemistry were within normal values and venereal disease research laboratory (VDRL) was non-reactive. Anti-HIV antibodies were also negative. In addition, she had no history of shaving, friction or massage, which might cause the inoculation of pox virus from epidermal trauma. However, an incidental MC infection could have spread to her whole face and neck due to the application of hydrocortisone cream after a misdiagnosis. In conclusion, our case suggests that dermatologists should perceive various clinical features of MCs in order to avoid misdiagnosis due to unusual clinical features. Additionally, the diagnosis of mollosum contagiosum should not be excluded, even if the patient is a healthy person without immunodeficiency.