대한족부족관절학회지 : 제 10 권제 1 호 2006 J Korean Foot Ankle Soc. Vol. 10. No. 1. pp.18-23, 2006 가천의과학대학교정형외과학교실 문성훈 박홍기 Malignant Melanoma of the Foot Sung Hoon Moon, M.D., Hong Gi Park, M.D. Department of Orthopaedic Surgery, Gachon University College of Medicine and Science, Incheon, Korea =Abstract= Purpose: We reviewed the clinical finding of malignant melanoma of the foot in korean because it's advanced stage and extended lesion at diagnosis. Materials and Methods: Retrospective study was enforced about the 11 cases who has diagnosed to malignant melanoma of the foot from February 1995 to March 2004. The mean follow up period was 61 months. In this study we used age, sex, site, depth, histology, clinical stage, precursor lesion, misdiagnosis, interval to diagnosis, survival time, survival. Results: Average age was 58 years and number of female was six. Common site of involvement were heel of plantar surface (6 cases) and subungual area (2 cases). Depths of involvement were 0.3 to 10 mm, most common histological type was acral lentiginous melanoma (7 cases), stage 5 according to classification of Clark were 5 cases and stage 2 or more according to clinical staging were 8 cases. precursor lesion were benign melanocytic nevi (2 cases) and ill defined (9 cases). Chief complaint were increasing of size, color change, pain and ulceration. Conclusion: Malignant melanoma of the foot usually arise at nonvisible area and is easy to be misdiagnosed or delayed treatment. So it is hard to early diagnosis and have poor prognosis. So we need education and effort to early detection and diagnosis. Key Words: Foot, Malignant melanoma 서 론 악성흑색종은멜라닌이라는암색소를만들어내는세포인멜라닌세포 (melanocyte) 의악성증식을특징으로하는피부암의한유형이며족부에발생하는가장흔한악성피부병변의하나로, 발병률은지역에따라차이가있다. 미국 Address for correspondence Hong Gi Park, M.D. Department of Orthopedic Surgery, Gachon University of Medicine, Gil Hospital 1198, Guwol-dong, Namdong-gu, Incheon, 405-760, Korea Tel: +82-2-460-3384 Fax: +82-2-468-5437 E-mail: luteus@empal.com 의경우남자에발생하는 4번째흔한침윤성암이며일생동안흑색종으로진행하는누적위험도는 5.7% 이나, 중국, 인도, 일본, 싱가폴등의아시아인에서는비교적낮은것으로보고되었다 4,8,28). 모든악성종양이그렇듯조기발견및진단그리고적절
한치료는생존율증가에매우중요하다 1,9,11). 그런데은신체의다른부위에발생한경우에비해초기에발견이어렵고오진등으로진단이지연되어병변의깊이가증가하고임상적병기가진행되어환자의생존율이낮다. 조갑부에서악성흑색종의생존율은매우낮으며, 조기악성흑색종의경우, 아시아인에서백인에비해생존율이낮은경향이다 6,7,10,12,14,19-21). 이에저자는동양인에비교적드문피부의원발성악성흑색종이족부에발생한 11예의임상소견에대해후향적연구를시행하였다. 대상및방법 본원에서치료한 1995 년 5월에서 2004 년 3월까지족부에발생한악성흑색종 11예를대상으로하였으며추시기간은평균 61개월이었다. 연구방법은조직학적정보와의무기록을검토하고전화상담을시행하여다음과같은사항을확인하였다. 진단당시환자의연령및성별그리고, 침범부위는족저부, 족배부, 조갑하병변으로구분하였으며, 표피의육아조직층에서종양의가장깊은부위까지의수직거리를접안마이크로미터 (ocular micrometer) 를사용하여 Breslow 의침습깊이를측정하였다 2,18,29). 침습깊이에따른분류는 Clark 에의해다섯단계로구분하였으며, I기는표피및그부속기관에국한되어있고, II기는종양세포가유두상진피까지확대된것이며, III기는유두상진피전체에종양세포가확산된것이다. IV기는망상진피까지침습한상태이며, V기는피하지방층까지침습한상태로분류하였다 5). 임상병리학적으로악성흑자 (lentigo maligna), 표재확장성흑색종 (superficial spreading melanoma), 말단흑자성흑색종 (acral lentiginous melanoma) 및결절성흑색종 (nodular melanoma) 으로구분하였고 15), 임상적병기는네개의병기로나누었다. 제 1기는피부표재층에서만존재하고두께가 1.5 mm 미만인경우, 제 2기는피부표재층에서만존재하고두께가 1.5 mm 이상이거나, 흑색종의주병변주위에작은흑색종세포병변이있는경우, 제 3기는피부내에존재하고흑색종에인접한림프절에확장되었고, 또는흑색종의주병변으로부터 5 cm 이상되는부위에흑색종세포가있는경우, 제 4기는흑색종세포가폐, 간, 뇌등의신체다른부위로전이된경우, 그리고, 재발성악성흑색종은초기치료후에흑색종이재발한경우이다. 전구병변유무와주증상및초진에서오진유무와조직검사로확진까지기간을확인하였으며, 사망유무와생존기간은확진한시기에서부터계산하였다. Figure 1. This photograph shows malignant melanoma on lateral plantar surface of the forefoot. Figure 2. This photograph shows anterolateral thigh free flap operation after wide excision.
문성훈 박홍기 치료는질환의임상적병기에따라절단, 광범위국소적절제및유리피판술 (Fig. 2), 전층피부이식, 서혜림프절절제, 항암치료등을병합하였으며사망한 5예에서국소적재발과타장기전이가관찰되었다. 결과 증례의평균연령은 58세 ( 범위, 29~73 세 ) 이며남녀의구성은남자 5명, 여자 6명, 침범부위는족저부 9예, 조갑하유형이 2예이었으며, 족저부의가장흔한침범부위는후족부로 6예이었으며족무지원위부가 3예이었다 (Fig. 1). 병변의깊이 (criteria of Breslow) 는 0.3 mm에서 10 mm이내이었으며 ( 증례 5 제외 ) 사망한 5명은평균 4.5 mm이며생존군에서는 0.6 mm 이었다 ( 증례 11 제외 ). Clark 에의한 Table 1. Summary of Cases Case Age/ Sex Involvement site Mean deapth (mm) Clark stage Hitology Clinical stage Precursor lesion/chief complaint Misdiagno sis/ Interval* (months) Treatment modality Survival time (months)/ Survival 1 39/M SU 4.3 V ALM 4 Nonspecific/Bleed ing, Ulceration 2 40/F PS (heel) 8 V ALM 3 Nonspecific/ Pain, Size increasing -/36 AMP, ILND, CTx +/7 WE&FF, 41/Death 22/Death 3 73/F PS (big toe) 0.3 II SSM 1 Nonspecific/ Urticaria 4 29/M PS (big toe) 0.3 II NM** 1 Nonspecific/ Mass -/3 AMP 86/Survival -/8 FTSG 100/Survival 5 72/M SU bone involve ment V ALM 3 Previous mole/necrosis, Ulceraion, Pain +/48 AMP, ILND, CTx 44/Death 6 69/F PS (heel) 1 IV ALM 1 Previous mole /Bleeding -/36 FTSG, ILND 85/Survival 7 60/F PS (heel) 8 V ALM 3 Nonspecific/ Size increasing, Bleeding, Ulceration -/36 WE&FF, 18/Death 8 69/F PS (big toe) 0.4 III SSM 1 Nonspecific/Size increasing -/60 AMP 87/Survival 9 68/F PS (heel) 1 IV NM 2 Nonspecific/Size increasing, Pain, Mass 10 53/M PS (heel) 10 V ALM 2 Nonspecific/Size increasing, Pain, Ulceration, Infection +/36 WE&FF, +/12 WE&FF, 91/Survival 31/Death 11 67/M PS (heel) 3 IV ALM 2 Nonspecific/Size increasing -/60 WE&FF, 24/Survival * Interval; time to be diagnosed from first visit via bipsy, Survival time; period that is counted from diagnosis, SU; subungal area, PS; plantar surface, ALM; acral lentiginous melanoma, SSM; superficial spreading melanoma, **NM; nodular melanoma, AMP; amputation, ILND; inguinal lymph node dissection, CTx; chemotherapy, WE&FF; wide excision and free flap, FTSG; full thickness skin graft.
분류는 II가 2예, III가 1예, IV가 3예, V가 5예로 IV이상이 8예이었다. 임상병리학적분류에서말단흑자성흑색종이 7예이며그외에각각 2예씩표재확장성흑색종과결절성흑색종이있었다. 임상적병기는 1기가 3예, 2기가 5예, 3 기가 2예, 4기가 1예이었으며 2기이상이 8예이었다. 전구병변은 2예에서양성흑자성모반 (benign melanocytic nevi) 이었고 9예에서는불분명하며주증상은병변의크기가증가하고색깔이진해지며, 출혈, 궤양, 두드러기, 괴사등의동반이었다. 초진에서오진되었던 4예중후족부에발생한 3예는혈관종, 종괴, 피하감염으로오진되었고, 조갑하유형의 1예는원위지골골수염으로오진되었다. 그리고, 병변의인지후확진까지평균 35 개월 ( 범위, 3~60 개월 ) 이소요되었으며, 생존한 6예는 34개월, 사망한 5예는 28 개월이었다. 추시기간내사망한 5명의발생부위는후족부 3예, 조갑하 2예이며전례에서말단흑자성흑색종형이며병변의평균깊이가 7.6 mm ( 범위, 4.3~10 mm) 이며전례에서 Clark 에의한분류 V이고 4예에서주증상은궤양이동반된진행된상태이었으며임상적병기 2기가 1예, 3기가 3예, 4 기가 1예였다. 그중 3예에서오진으로진단이지연되었다. 그리고생존기간은평균 33개월이며치료도중재발및전이가발생하였다반면, 생존한 6예에서는전례에서족저부에발생하였고, 평균깊이가 0.6 mm이며 Clark 에의한분류 IV이하였고임상적병기는 1기가 4예, 2기가 2예로모든예에서 2기이하였다. 오진으로진단된예는 1예였다 (Table 1). 현재생존하고있는 6예에서나머지추시기간이짧은 1예 ( 증례 11) 를제외한 5예는평균 7년 6개월동안재발및전이가발생하지않았다. 각증례에관한치료방법과그에따른예후는주목할만한연관성은보이지않았다. 고찰일반적으로악성흑색종은주로백인에서발생하고유색인종에는드물며, 남성에서흔하고호발연령은 30~40 대이다. 서구에서는병리학적으로 70% 에서표재확장성흑색종이며일차적으로상배부와하지에주로발생하고남녀공히이부위에서는증가하는추세이나전체적인발병률은증가하지않고있다 6). 1995 년족부에발생한악성흑색종 60 예를분석한내용에따르면여성이 2.3 배 (42/18) 더흔하며, 평균연령도 57세이고말단흑자성흑색종이흔하였으며 22), 유색인종에서악성흑색종은사지의원위부를주로침범하고, 일본인에서는이중 10% 가조갑부를침범했다 17,25). 저자의증례도주로수부와족부에발생하는 15) 말단흑자성흑색 종이 7예이며평균연령도 58세이었고, 2예에서조갑하병변이었다. 은진단당시병변의깊이및임상적병기가진행되어환자의생존율이낮다고하며, 특히아시아인에서는초기병기에서도생존율이백인에비해낮다고보고하고있어다른부위에발생하는악성흑색종에비해불량한예후를보이고있다 6,10,12,14,19,20). 저자의증례에서도사망한 5예에서진단당시병변의평균깊이가 7.6 mm이고, 임상적병기가 3기이상인예가 4예였으며모두사망하였고 Clark 에의한분류도모두 V였다. 생존한군에서도 3 예에서 Clark 에의한분류가 IV였으나, 임상적병기는 2이하로낮았다. 이러한결과로미루어볼때진단시병변의깊이및 Clark 에의한분류그리고, 임상적병기는환자의예후에중요한영향을미친다고할수있다. 그외에악성흑색종의위험인자로모반, 연령, 유전인자 (P53) 그리고환경적요인으로자외선조사및외상등이거론되고있다 14,16,22,24,30). The United States Surveillance, Epidemiology and End Results (SEER) 에의하면병기의차이와병변의깊이에있어서병기분포는점차침윤성흑색종 (invasive melanoma) 에서상피내흑색종 (in situ melanoma) 으로이동되며병변의깊이는점차감소하고있다고한다 25). 그러나, 의경우오진과진단의지연으로진단당시병기및병변의깊이가진행되어하지의다른부위에비해불량한예후와짧은생존기간을보인다 1,3,22,26,27). 저자의증례에서도오진한예가 4예였고확진까지의기간이평균 26개월 ( 범위, 7~48 개월 ) 이었으며이중 3예가사망하였다. 진단의지연과오진의이유로는족부의병변이시야에가려져신체의타부위에비하여쉽게인지할수없고양성모반, 조갑하또는외상성혈종, 수포, 만성조갑주위염, 사마귀, 화농성육아종, 에크린한공종, 피부섬유종및낭종등과초기에감별이어려우며 12,14,19,20), 일본인의 11% 에존재하는선상흑조증 (melanonychia striata) 의경우 13), 대부분양성병변이지만조상및조기질에발생하는악성흑색종과감별진단에어려움이있다. 피부암의첫번째징후는일반적으로모반의존재, 또는새로운모반의생성, 또는특정피부의변화등이고, 색, 크기, 모양의변화등을포함한모반또는피부병변의변화, 동통, 미란, 또는가려움증등이동반되는경우피부암가능성을의심해야한다. 그러나환자의악성피부암에대한일반의학적상식부족으로이러한변화의의미를환자및보호자가인지하지못하여출혈및궤양등의진행피부암을시사하는병변등으로악화되어내원하여조기진단이불가능하였다. 또한
문성훈 박홍기 멜라닌성양성모반의존재와흑자의존재, 3개또는그이상의비정형적또는이형성적멜라닌성모반도위험인자로알려져있으므로주기적진료를요하나단지 2예에서피부과진료기록에서양성멜라닌성모반에서진행하였음을확인할수있어피부병변에대한진료가부적절함을알수있었다 16). 증례 1은개인병원에서조직검사를시행하여진단되었음에도불구하고악성흑색종에대한지식부족으로인하여 1년동안치료를시행하지않았고고령의환자에서는악성흑색종의임상적위험성에대한충분한설명에도불구하고장기간외래추시에어려움이있었다. 그러나조기진단으로비교적조기치료가가능하였던 5예는평균 7년 6개월동안재발및타장기전이를발견할수없어조기진단이치료결과와예후에매우중요함을알수있었다. 결 론 족부에발생하는악성흑색종은일반적으로육안으로잘보이지않는부위에발생하고의사의오진과환자의진료지연등으로조기진단에어려움이있으므로일반인을대상으로한교육과의료진의조기발견및진단을위한노력이필요하리라사료된다. REFERENCES 1. Balch CM, Murad TM, Soong SJ, Ingalls AL, Richards PC and Maddox WA: Tumor thickness as a guide to surgical management of clinical stage I melanoma patients. Cancer, 43: 883-888, 1979. 2. Balch CM, Urist MM, Karakousis CP, et al: Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg, 218: 262-267, 1993. 3. Barnes BC, Seigler HF, Saxby TS, Kocher MS and Harrelson JM: Melanoma of the foot. J Bone Joint Surg, 76-A: 892-898, 1994. 4. Booher RJ and Pack GT: Malignant melanoma of the feet and hands. Surgery, 42: 1084-1121, 1957. 5. Clark WH: A classification of malignant melanoma in man correlated with histogenesis and biologic behavior. Adv Biol Skin, 8: 621-647, 1967. 6. Chang AE, karnell LH and Menck HR: The national cancer data report on cutaneous and noncutaneous melanoma. Cancer, 83: 1664-1678, 1998. 7. Feibleman CE, Stoll H and Maize JC: Melanoma of the palm, sole and nail bed; a clinicopathologic study. Cancer, 46: 2492-2504, 1980. 8. Ferlay J, Bray F, Pisani P, et al: GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. version 1.0. IARC cancer base no.5. Lyon: IARC Press; 2001. 9. Friedman RJ, Riger DS, Silverman MK, Kopf AW and Vossaert KA: Malignant melanoma in the 1990s: the continued importance of early detection and the role of physician examination and self-examination of the skin. Cancer J Clin, 41: 201-226, 1991. 10. Gallagher RP and Elwood JM: Epidermiological aspects of cutaneous malignant melanoma. 1st ed, Boston, Kluwer Academic Publishers: 1994. 11. Ho VC and Sober AJ: Therapy for cutaneous melanoma: an update. J Am Acad Dermatol, 22: 159-176, 1990. 12. Hughes LE, Horgan K, Taylor BA and Laidler P: Malignant melanoma of the hand and foot: diagnosis and management. Br J Surg, 72: 811-815, 1985. 13. Kawamura T, Nishihara K, Kawasakiya S, et al: Pigmentation longitudinalis striata unguium and the pigmentation of nail plate in Addison's disease (Abstract). Jpn J Dermatol, 68: 10, 1958. 14. Kukita A and Ishihara K: Clinical features and distribution of malignant melanoma and pigmented nevi on the soles of the feet in Japan. J Invest Dermatol, 92 (Supplement 5): 210S-213S, 1989. 15. Lim CW: Melanoma. In: Dermatology. 3rd ed. J Korean Dermatol, 452-456. 1994. 16. Mackie RM: Incidence, risk factors and prevention of melanoma. Eur J Cancer, 34(Suppl 3): S3-6, 1998. 17. Miura S and Jimbow K: Clinical characteristics of subugual melanoma in Japan: case report and questionnaire survey of 108 cases. J Dermatol, 12: 393-402, 1985 18. NIH consensus conference: Diagnosis and treatment of early melanoma. JAMA, 268: 1314-1319, 1992. 19. Pack GT and Oropeza R: Subungual melanoma. Surg Gynec Obstet, 124: 571-582, 1967. 20. Papachristou DN and Fortner JG: Melanoma arising under the nail. J Surg Oncol, 21: 219-222, 1982. 21. Patterson RH and Helwig EB.: Subungal malignant melanoma: a clinical-pathologic study. Cancer, 46: 2074-2087, 1980. 22. Paul TF, Andrew AF, Riley Rees, Vernon KS, Timothy MJ and Ann A: Malignant melanoma of the foot and ankle. J Bone Joint Surg, 77-A: 1396-1403, 1995. 23. Pedlow PJ, Walsh MY, Patterson CC, et al: Cutaneous malignant melanoma in Northern Ireland. Br J Cancer, 76: 124-126, 1997. 24. Peterson NC: Malignant melanoma of the foot. Scand J Plast Reconstr Surg, 2: 144-153, 1968. 25. Resmond RA and Soong SJ: Epidemilolgy of malignant melanoma. Surg Clin N Am, 83: 1-29, 2003. 26. Rigby HS and Briggs JC: Subungual melanoma: a clinico-pahological study of 24 cases. Br J Plast Surg, 45: 275-278, 1992.
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