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

이의형,김지은,장홍선,박규현,오병호,신상준,정기양,노미령,라선영 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

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/11mutation 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 NRASmutation, and 28.6% of KIT amplification. GNAQ/11mutation 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/11mutation 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.

P051 : Study of primary systemic cancers accompanying melanoma

( Soo Hyeon Bae ),( Jee Bum Lee ),( Seong Jin Kim ),( Seung Chul Lee ),( Young Ho Won ),( Sook Jung Yun ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: While the genetics and pathogenesis of melanoma still remains unclear, there have been previous few case reports regarding possible genetic relevance and clinical coexistence of primary cutaneous melanoma and systemic cancers other than melanoma. But, there are no studies aboutprimary systemic cancer and melanoma in Korea Objectives: To analyze the epidemiologic and clinical features, and incidences of primary systemic cancers accompanied with primary cutaneous melanoma Methods: Cross-sectional study was done with 465 melanoma patients who visited our hospital from 1994 to 2014. We reviewed cancer registry datas, medical charts, clinical photographs, and histopathologic results of the patients Results: Acral lentiginous melanoma was the most common histopathologic subtype (62.3%) followed by mucosal melanoma (22.1%), nodular melanoma (7.6%), superficial spreading melanoma (17.4%), and amelanotic melanoma (1.4%). A total of 64 patients with melanoma (13.8%) were diagnosed with other systemic cancer. Among those, lung cancer (17.2%) and thyroid cancer (17.2%) were most commonly diagnosed, followed by colon cancer (15.6%), and stomach cancer (10.9%) Conclusion: In this study, we identified 13.8% patients of melanoma accompanying other systemic cancer, which ishigher than 2.2%, the total cancer prevalence of the general population. Further studies are necessary regarding incidence, progression, and survival of concomitant systemic carcinomas with melanoma for better comprehension

Different progression pattern between acral and non-acral melanoma: a comparative, clinicoprognostic study of 492 cases of primary cutaneous melanoma according to tumor site

( Dong Jun Lim ),( Joon Min Jung ),( Chang Jin Jung ),( Chong Hyun Won ),( Sung Eung Chang ),( Mi Woo Lee ),( Jee Ho Choi ),( Woo Jin Lee ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2

Background: There are limited data regarding the difference in progression pattern between acral melanoma and non-acral melanoma. Objectives: The objectives of this study were to compare the progression pattern between acral and non-acral melanoma and evaluate its impact on clinical outcome. Methods: Clinical and histopathological features, survival outcomes, and prognostic factors of 492 patients with acral melanoma or non-acral melanoma were retrospectively evaluated using medical records. 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 non-acral melanoma (n = 243), respectively. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than non-acral melanoma, vertical growth phase was more common in non-acral melanoma than acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than non-acral melanoma. Dissemination to lymph node was more common in acral melanoma than non-acral melanoma. Overall survival was worse in acral melanoma than non-acral melanoma. The prognostic value of Breslow thickness was more remarkable in non-acral melanoma than acral melanoma. Conclusion: Acral melanoma has a longer radial growth phase compared with non-acral melanoma. However, acral melanoma is more commonly associated with lymph node dissemination, which contributed to worse survival in acral melanoma than non-acral melanoma.

P050 : Dermoscopic patterns of m alignant melanomas on the trunk and extremities in Koreans

( Je Ho Mun ),( Woo Il Kim ),( Gun Wook Kim ),( Hyun Ho Cho ),( Won Jeong Kim ),( Margaret Song ),( Hoon Soo Kim ),( Hyun Chang Ko ),( Byung Soo Kim ),( Moon Bum Kim ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Dermoscopy has been proven to increase diagnostic accuracy of malignant melanomas. However, dermoscopic features of melanomas in Asians have been scarcely reported. Objectives: To investigate dermoscopic patterns and evaluate diagnostic algorithmic approach in Korean patients with melanomas in trunk and extremities. Methods: Dermoscopic evaluation of histopathologically confirmed melanomas at 2 university hospitals from 2007 to 2014 was performed. Dermoscopic scores were evaluated using various dermoscopic algorithmic methods. Results: Sixteen patients with 16 primary melanomas and 5 patients with 15 metastatic melanomas were included. In primary melanomas, several dermoscopic melanoma-associated features were found: blue-white veil (76%), blotches (62%), atypical dots/globules (52%), ulcer (48%), atypical pigment network (43%), irregular peripheral streaks (43%), atypical vessels (38%), shiny white lines (29%), and regression (10%). Mean scores of 7-point checklist, revised 7-point checklist, 3-point checklist, ABCD rule, and CASH algorithm were 6.3, 4.1, 2.6, 7.6, and 10.9. In metastatic melanomas, the algorithmic approaches were not accurate as the mean scores were 1.7, 0.9, 0.8, 2.0, 4.1. Conclusion: Dermoscopy can be useful in diagnosingmalignant melanomas in trunk and extremities in Koreans. Dermoscopic algorithmic approaches were useful in detecting primary melanomas; however, they were not precise in identifying metastatic melanomas.

Slow mohs micrographic surgery and wide local excision for melanoma treatment in Korean patients

( Jimyung Seo ),( Jee Eun Kim ),( Jihee Kim ),( Dae San Yoo ),( Kyoung Ae Nam ),( Sang Kyum Kim ),( Mi Ryung Roh ),( Kee Yang Chung ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: It is not always possible to use conventional wide local excision (WLE) for melanoma in areas that have anatomical complexity and lack a local skin Also, considering the prominent radial growth features of acral melanomas common in darker-pigmented individuals, a new strategy for entire margin evaluation is needed. Objectives: We aimed to show the potential benefits of slow Mohs micrographic surgery (MMS) for treatment of melanoma. Methods: This retrospective study evaluated 244 melanoma patients treated using slow MMS (n = 72) or WLE (n = 144) by a single dermatologic surgeon from 2005 to 2015. We performed slow MMS in melanomas that showed features of radial growth phase or had high recurrence risks; conventional melanomas were treated using WLE. Results: The slow MMS group had greater proportions of acral lentiginous and lentigo maligna melanomas and had more patients with melanoma in situ, suggesting the preferential use of Slow MMS in radial growth feature melanomas. Cox regression analysis of the study cohort revealed that melanoma stage and acral location were the significant factors for recurrence and survival. Kaplan-Meier analysis showed that patients treated with slow MMS had significantly higher disease-free proportions, compared with those treated using WLE. Conclusion: Slow MMS may be a useful alternative in treating difficult-to-manage melanomas for WLE, providing better local control with maximum conservation of surrounding skin.

Characteristics and Treatment of Cutaneous Melanoma of the Foot

Nam, Kyung Wook,Bae, Yong Chan,Nam, Soo Bong,Kim, Joo Hyung,Kim, Hoon Soo,Choi, Young Jin Korean Society of Plastic and Reconstructive Surge 2016 Archives of Plastic Surgery Vol.43 No.1

Background In East Asia, the foot is the most common site of cutaneous melanoma. The purpose of this study was to investigate the differences between cutaneous melanoma of the foot and melanomas of other sites. Methods We studied 52 patients who underwent surgical treatment for cutaneous melanoma of the foot from September 2000 to January 2015. Through a retrospective review of their medical records, we collected data relating to their sex, age, histopathological subtype, Clark level, tumor thickness, lymph node involvement, stage, and survival rate, and we compared these parameters to those of 61 patients treated for melanoma of other sites. Moreover, we analyzed the surgical procedures, complications, and mortality rates associated with cutaneous melanoma on various parts of the foot. Results Melanoma of the foot differed from other melanomas only in the histopathological subtype. Other clinical features, including survival rate, did not differ significantly between the two groups heel was the most common site of melanoma of the foot (22 cases, 42.3%). The method of reconstruction varied depending on the region involved. Conclusions A comparison of melanoma of the foot to other melanomas showed that melanoma of the foot was associated with a significantly different distribution of histological subtypes. Consistent with previous findings, we found that the acral lentiginous subtype was the most common among melanomas of the foot. Furthermore, in contrast with previous studies, we did not find a worse prognosis or lower survival rate for melanoma of the foot in comparison with other melanomas.

Frequency of Trauma, Physical Stress, and Occupation in Acral Melanoma: Analysis of 313 Acral Melanoma Patients in Korea

( Ji Hong Lee ),( Yoo Duk Choi ),( Jae Ha Hwang ),( Min-ho Shin ),( Sook Jung Yun ) 대한피부과학회 2021 Annals of Dermatology Vol.33 No.3

Background: Traumatic events are thought to be a cause of acral melanoma. However, little is known about the role of mechanical trauma or physical stress in the development of acral melanoma. Objective: In our study, we evaluated the frequency of trauma, physical stress, and occupation in patients with acral melanoma and aimed to identify any pathological correlates of these factors. Methods: We conducted a retrospective study of 313 acral melanoma patients from Chonnam National University Hospital. We mapped melanoma- developed anatomical sites of acral areas and assessed patients’ history of trauma, physical stress, and occupation. Results: Among the 313 acral melanoma patients, many reported a traumatic event (84 of 313; 26.8%) or physical stress (91 of 313; 29.1%) before the melanoma developed. The most common anatomical sites in these patients were on the borders of the foot (136 of 313; 43.5%). Trauma was more commonly associated with the fingernails and toenails than other sites. The frequency of each type of physical stress depended on the site of the lesion. Farmer and fisherman were the most common occupations (130 of 313; 41.5%) of the acral melanoma patients. Conclusion: Our results demonstrate that traumatic events, physical stress, and certain occupations are common in acral melanomas. Further studies are needed to establish whether these are risk factors for acral melanomas. (Ann Dermatol 33(3) 228∼236, 2021)

Clinical effect of dermal invasion in subungual melanoma: a comparative study of melanoma in situ and invasive melanoma.

( Chan Seong Park ),( Youngkyoung Lim ),( Jae Ho Lee ),( You Jin Lee ),( Ji-hye Park ),( Jong Hee Lee ),( Dong-youn Lee ),( Joo-heung Lee ),( Jun-mo Yang ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Background: Subungual melanoma has higher incidence in Asian than Caucasians. Clinical manifestations of subungual melanoma include melanonychia, nail dystrophy, and Hutchinson’s sign. However, only limited data are available concerning clinical correlation of histopathological features. Objectives: To evaluate clinical effect of dermal invasion in subungual melanoma by comparing clinical features of subungual melanoma in situ and invasive melanoma. Methods: A total of 25 patients diagnosed subungual melanoma were enrolled. All cases were earlier than pathological stage IB. They were divided into two groups according to presence of dermal invasion. Age of onset, sex, width of melanonychia, nail dystrophy, and Hutchinson’s sign were regarded as clinical variables and compared. Results: Nail dystrophy was more frequently observed in invasive melanomas. (30.76% and 75.00%, respectively in in situ and invasive melanoma. p=0.024). Other clinical variables were not significantly different between in situ and invasive subungual melanoma. Total melanonychia and Hutchinson’s sign were found in most cases regardless of dermal invasion. Conclusion: In our investigation, an association between nail dystrophy and dermal invasion was identified. Nail matrix injury due to dermal invasion might be a pathological mechanism. Total melanonychia and periungual pigmentation were not significantly correlated to dermal invasion, but these features can be common features of subungual melanoma.

BRAF mutation in acral melanomas: clinicopathological features and correlation with VE1 immunostains

( Min Song Suh ),( Yoo Duk Choi ),( Seung-chul Lee ),( Young Ho Won ),( Jee Bum Lee ),( Sook Jung Yun ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Background: BRAF mutation is frequently detected in non-chronically sun damaged melanomas, and those melanomas usually occur on the trunk and extremities. Acral melanomas are known to have low frequency of BRAF mutation. Recently, VE1 immunostain is reported to have good correlation with BRAF mutation status Objectives: To evaluate clinicopathologic features of BRAF mutated acral melanoma. Also we wanted to validate VE1 immunostain in those cases Methods: 33 patients of acral melanoma were reviewed with clinicopathologic features, and analyzed anatomic site, melanoma cell morphology, pagetoid scatter, and pigmentation grade. We performed sequencing to detect BRAF mutation status. We did VE1 stains to correlate with BRAF mutation status Results: 3 patients had melanomas on the thumbnail, 12 melanomas on the sole, and 2 melanomas on the toe. Histopathologic features revealed melanoma cells had variable sized nests of large epithelioid cells, many pagetoid scatter, and mild to moderate melanin pigmentation. On the other hand, BRAF-negative acral melanomas show more lentiginous proliferation of spindle to epitheloid cells. The VE1 immunostain results showed positive stains in all 17 cases of acral melanomas, and negative in 18 cases without BRAF mutation Conclusion: Histopathologic features of BRAF mutated acral melanomas have nested epithelioid cells with many pagetoid scatter. VE1 immunostains have quite good correlation with BRAF mutation status, and can substitute mutation sequencing analysis

FC 1-2 A preliminary study about genetic phenotyping of acral melanoma, comparison of gene expressions among melanoma subtypes

( Jae Hwan Kim ),( Jong Mi Lee ),( James G. Krueger ),( Chang Min Kim ),( Aeree Kim ),( Soo Hong Seo ),( Chil Hwan Oh ),( Il-hwan Kim ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Background: Acral Melanoma (AM) is a subtype of melanomas that preferentially occurs on hands and feet. It is of particular interest to understand melanoma pathogenesis, because it has different genetic factors from other melanoma subtypes and treatment. Therefore a thorough study about genomic characteristics of AM is needed to develop new treatment options. We preliminarily investigated the gene expression profiles of melanomas. Objectives: In this study, we tried to compare genomic patterns of melanomas with normal tissues and also compare gene expressions of AM with those of superficial spreading melanomas (SSM). Methods: We obtained fresh frozen tissue samples from AM and SSM, as well as normal skin and carried out cDNA microarray analysis. We also compared the gene expressions of AM, SSM, and normal tissues by RT-PCR. Results: We identified 742 up-regulated and 1518 down-regulated probe sets in melanoma compared to normal skin. Top 20 up-regulated genes in melanoma compared to normal skin include MLANA, PMEL, TYR, C6orf218, TRPM1, PRAME, RGS1. Conclusion: We collected data about differences in gene expression between melanomas and normal tissues, and also between AM and SSM. With this information we look forward to finding out specific genomic traits of AM and developing new biologic targets treating AM.