- Email: [email protected]
Multiple melanoma metastases in split-thickness skin graft donor sites
Journal of the American Academy of Dermatology Volume 38, Number 6, Part 1
Brief communications 997
Multiple melanoma metastases in split-thickness skin graft donor sites Uwe Trefzer, MD,a Markus Schwürzer-Voit, MD,a Heike Audring, MD,a Sigbert Jahn, MD,a Ernst Thies, MD,b and Wolfram Sterry, MDa Berlin and Elmshorn, Germany Tumor metastases confined to a skin graft donor site are exceedingly rare. They are thought to represent hematogenous rather than lymphatic spread or iatrogenic implantations of tumor cells during excision of the skin graft. We describe a patient in whom melanoma metastases developed in splitthickness skin graft donor sites as the first cutaneous sign of disseminated disease. CASE REPORT A 76-year-old woman had a pigmented nodule above her left scapula. The tumor excision, performed with a margin of 4 cm, included the removal of subcutaneous tissue. The intraoperative histologic diagnosis was nodular malignant melanoma (Clark level IV, Breslow depth 3.6 mm); all margins were free of tumor. The defect was closed with a rotation flap. Staging examinations revealed melanoma in the lungs, ribs, and the thoracic spine. No metastatic lesions were found in her skin. Subsequently the flap became partially necrotic and 17 days after excision of the primary tumor three small split-thickness (0.4 mm) skin grafts were taken with an electric dermatome from an area above the left hip and used to close the remaining defect by meshgraft technique. About 8 weeks later seven cutaneous metastases developed that were confined to two of the three graft donor sites (Fig. 1). No other skin lesions were found. The lesions were subsequently excised and the diagnosis confirmed by histologic examination. Another 6 weeks later, numerous cutaneous metastases developed that were almost exclusively confined to three areas: the graft donor site, the graft recipient site, and the right leg in an area of chronic venous insufficiency with poikilodermatous skin changes, thickened skin, and scar tissue. Only two lesions were found outside those areas: one on the neck and one on the scalp. From the Department of Dermatology,a Humboldt-University (Charité), Berlin, and the Department of Surgery,b County Hospital Elmshorn. Reprint requests: Uwe Trefzer, MD, Department of Dermatology, Humboldt-University Berlin, Schumannstrasse 20, 10098 Berlin, Germany. J Am Acad Dermatol 1998;38:997-8. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/54/89798
Those metastases were either excised or treated with cryotherapy. The patient died shortly thereafter of her rapidly progressive disseminated disease. DISCUSSION
Distant metastases may reach a skin graft donor site by one of three mechanisms: by intraoperative seeding caused by poor surgical technique, by melanoma cells in transit in the lymphatics producing satellite lesions, and by the blood stream. In our patient, intraoperative seeding during harvest of the skin graft can be ruled out because the removal occurred 17 days after excision of the primary tumor when the recipient site was already covered by granulation tissue and was macroscopically free of tumor. At the time of excision of the melanoma the margins were free of tumor. Moreover, standard surgical procedures were followed, that is, surgical instruments and gloves used while preparing the recipient site were changed for a new set before excising the graft, thus avoiding spread of tumor cells. In transit metastases could be a possibility because the primary tumor was located above the left scapula and the grafts were taken from the left hip. Although lymphoscintigraphy was not performed preoperatively, it is unlikely that the lymphatic drainage was directly toward the left inguinal area, thereby passing the graft donor site. The lymphatic drainage of a tumor on the upper back is almost exclusively toward the ipsilateral axillary lymph node and in some cases toward the contralateral lymph nodes. Cases in which secondary melanoma developed in an ipsilateral donor site have been described only for the extremities, such as the thighs.1 Moreover, the subsequent development of lesions on the right lower leg in this patient cannot be explained by a lymphatic spread. Therefore we consider lymphatic spread improbable. Hematogenous spread seems most likely because at the time of excision of the primary tumor the patient already has inter-
998 Brief communications
Journal of the American Academy of Dermatology June 1998
Fig. 1. Multiple melanoma metastases in skin graft donor site.
nal spread of her melanoma but no manifestations in the skin. The lesions developing in the graft donor site several weeks after excision of the primary tumor thus represent the first wave of cutaneous metastases, with the second wave occurring 6 weeks later involving the skin graft recipient site and the area on the right leg. Epithelial tumors such as basal cell carcinoma have been reported to arise in skin graft recipient sites.2,3 Furthermore, cases of esophageal cancer and adenocarcinoma metastatic to graft donor sites have been described.4,5 To our knowledge, only two cases of metastatic melanoma to a distant skin graft donor site have been reported.6,7 Cutaneous metastases of a malignant melanoma initially confined to the donor site of a split-thickness skin graft suggest that a site with removed epidermis represents a vulnerable point (“locus minoris resistentiae”) for the implantation of circulating tumor cells. This might be the result of increased blood flow and the presence of vascular alterations in fresh scar tissue.8 Those might favor the adhesion and subsequent growth of tumor cells. Another explanation could be the increased expression of chemotactic factors such as hyaluronic acid in scar tissue.9 Hyaluronic acid is a known ligand for the cell surface molecule CD44, which is present in most secondary melanomas and is of importance in metastatic
spread.10 Because metastatic lesions in distant skin grafts are rare and occur only in disseminated disease, recommendations for their avoidance cannot be given. REFERENCES 1. Peterson NC, Bodenhaim DC, Lloyd OC. Malignant melanomas of the skin: a study of the origin, development, etiology, spread, treatment and prognosis. Br J Plast Surg 1962;15:97-102. 2. White JW. Basal cell carcinoma in a hair transplant site. Cutis 1979;23:322-5. 3. Cox NH. Basal cell carcinoma in a skin graft recipient site. Practitioner 1984;228:997-8. 4. Jewell WR, Romdahl MM. Recurrent malignant disease in operative wound not due to surgical implantation from the resected tumor. Surgery 1965;58:806-9. 5. Grenier DJ, Kaplan RP. Occult adenocarcinoma metastatic to a skin graft donor site. J Dermatol Surg Oncol 1985;11:1213-6. 6. McLean NR, Boorman JG. Secondary malignant melanoma arising in a contralateral thigh donor site. Br J Plast Surg 1984;37:386-7. 7. Salmon-Ehr V, Esteve E, Cambie MP, Serpier H, Kalis B. Cutaneous metastases of melanoma localized on the cicatrix at the site of flap taking. Ann Dermatol Venereol 1996;123:194-5. 8. Fisher B, ER, Feduska N. Trauma and the localization of tumor cells. Cancer 196;20:20-3. 9. Clark RAF. Cutaneous tissue repair: basic biologic consideration. J Am Acad Dermatol 1985;13:701-25. 10. Guo YJ, Ma J, Wang J, Che X, Narula J, Bigby M, et al. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 1994;54:1561-5.
Brief communications 997
Multiple melanoma metastases in split-thickness skin graft donor sites Uwe Trefzer, MD,a Markus Schwürzer-Voit, MD,a Heike Audring, MD,a Sigbert Jahn, MD,a Ernst Thies, MD,b and Wolfram Sterry, MDa Berlin and Elmshorn, Germany Tumor metastases confined to a skin graft donor site are exceedingly rare. They are thought to represent hematogenous rather than lymphatic spread or iatrogenic implantations of tumor cells during excision of the skin graft. We describe a patient in whom melanoma metastases developed in splitthickness skin graft donor sites as the first cutaneous sign of disseminated disease. CASE REPORT A 76-year-old woman had a pigmented nodule above her left scapula. The tumor excision, performed with a margin of 4 cm, included the removal of subcutaneous tissue. The intraoperative histologic diagnosis was nodular malignant melanoma (Clark level IV, Breslow depth 3.6 mm); all margins were free of tumor. The defect was closed with a rotation flap. Staging examinations revealed melanoma in the lungs, ribs, and the thoracic spine. No metastatic lesions were found in her skin. Subsequently the flap became partially necrotic and 17 days after excision of the primary tumor three small split-thickness (0.4 mm) skin grafts were taken with an electric dermatome from an area above the left hip and used to close the remaining defect by meshgraft technique. About 8 weeks later seven cutaneous metastases developed that were confined to two of the three graft donor sites (Fig. 1). No other skin lesions were found. The lesions were subsequently excised and the diagnosis confirmed by histologic examination. Another 6 weeks later, numerous cutaneous metastases developed that were almost exclusively confined to three areas: the graft donor site, the graft recipient site, and the right leg in an area of chronic venous insufficiency with poikilodermatous skin changes, thickened skin, and scar tissue. Only two lesions were found outside those areas: one on the neck and one on the scalp. From the Department of Dermatology,a Humboldt-University (Charité), Berlin, and the Department of Surgery,b County Hospital Elmshorn. Reprint requests: Uwe Trefzer, MD, Department of Dermatology, Humboldt-University Berlin, Schumannstrasse 20, 10098 Berlin, Germany. J Am Acad Dermatol 1998;38:997-8. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/54/89798
Those metastases were either excised or treated with cryotherapy. The patient died shortly thereafter of her rapidly progressive disseminated disease. DISCUSSION
Distant metastases may reach a skin graft donor site by one of three mechanisms: by intraoperative seeding caused by poor surgical technique, by melanoma cells in transit in the lymphatics producing satellite lesions, and by the blood stream. In our patient, intraoperative seeding during harvest of the skin graft can be ruled out because the removal occurred 17 days after excision of the primary tumor when the recipient site was already covered by granulation tissue and was macroscopically free of tumor. At the time of excision of the melanoma the margins were free of tumor. Moreover, standard surgical procedures were followed, that is, surgical instruments and gloves used while preparing the recipient site were changed for a new set before excising the graft, thus avoiding spread of tumor cells. In transit metastases could be a possibility because the primary tumor was located above the left scapula and the grafts were taken from the left hip. Although lymphoscintigraphy was not performed preoperatively, it is unlikely that the lymphatic drainage was directly toward the left inguinal area, thereby passing the graft donor site. The lymphatic drainage of a tumor on the upper back is almost exclusively toward the ipsilateral axillary lymph node and in some cases toward the contralateral lymph nodes. Cases in which secondary melanoma developed in an ipsilateral donor site have been described only for the extremities, such as the thighs.1 Moreover, the subsequent development of lesions on the right lower leg in this patient cannot be explained by a lymphatic spread. Therefore we consider lymphatic spread improbable. Hematogenous spread seems most likely because at the time of excision of the primary tumor the patient already has inter-
998 Brief communications
Journal of the American Academy of Dermatology June 1998
Fig. 1. Multiple melanoma metastases in skin graft donor site.
nal spread of her melanoma but no manifestations in the skin. The lesions developing in the graft donor site several weeks after excision of the primary tumor thus represent the first wave of cutaneous metastases, with the second wave occurring 6 weeks later involving the skin graft recipient site and the area on the right leg. Epithelial tumors such as basal cell carcinoma have been reported to arise in skin graft recipient sites.2,3 Furthermore, cases of esophageal cancer and adenocarcinoma metastatic to graft donor sites have been described.4,5 To our knowledge, only two cases of metastatic melanoma to a distant skin graft donor site have been reported.6,7 Cutaneous metastases of a malignant melanoma initially confined to the donor site of a split-thickness skin graft suggest that a site with removed epidermis represents a vulnerable point (“locus minoris resistentiae”) for the implantation of circulating tumor cells. This might be the result of increased blood flow and the presence of vascular alterations in fresh scar tissue.8 Those might favor the adhesion and subsequent growth of tumor cells. Another explanation could be the increased expression of chemotactic factors such as hyaluronic acid in scar tissue.9 Hyaluronic acid is a known ligand for the cell surface molecule CD44, which is present in most secondary melanomas and is of importance in metastatic
spread.10 Because metastatic lesions in distant skin grafts are rare and occur only in disseminated disease, recommendations for their avoidance cannot be given. REFERENCES 1. Peterson NC, Bodenhaim DC, Lloyd OC. Malignant melanomas of the skin: a study of the origin, development, etiology, spread, treatment and prognosis. Br J Plast Surg 1962;15:97-102. 2. White JW. Basal cell carcinoma in a hair transplant site. Cutis 1979;23:322-5. 3. Cox NH. Basal cell carcinoma in a skin graft recipient site. Practitioner 1984;228:997-8. 4. Jewell WR, Romdahl MM. Recurrent malignant disease in operative wound not due to surgical implantation from the resected tumor. Surgery 1965;58:806-9. 5. Grenier DJ, Kaplan RP. Occult adenocarcinoma metastatic to a skin graft donor site. J Dermatol Surg Oncol 1985;11:1213-6. 6. McLean NR, Boorman JG. Secondary malignant melanoma arising in a contralateral thigh donor site. Br J Plast Surg 1984;37:386-7. 7. Salmon-Ehr V, Esteve E, Cambie MP, Serpier H, Kalis B. Cutaneous metastases of melanoma localized on the cicatrix at the site of flap taking. Ann Dermatol Venereol 1996;123:194-5. 8. Fisher B, ER, Feduska N. Trauma and the localization of tumor cells. Cancer 196;20:20-3. 9. Clark RAF. Cutaneous tissue repair: basic biologic consideration. J Am Acad Dermatol 1985;13:701-25. 10. Guo YJ, Ma J, Wang J, Che X, Narula J, Bigby M, et al. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 1994;54:1561-5.