Merkel Cell Carcinoma in a Vein Graft Donor Site

Metastatic malignancies including metastases from SCC, adenocarcinoma, melanoma, malignant fibrous histiocytoma, angiosarcoma, and osteosarcoma also have been reported to develop in graft donor sites.^11,13,18,19 Many malignancies thought to have developed from iatrogenic seeding may actually be from metastasis either by hematogenous or lymphatic spread. A possible contributing factor may be surgery-induced immunosuppression, which has been linked to increased tumor metastasis formation.²⁰ Surgery or trauma have been shown to have an effect on cellular components of the immune system, causing changes such as a shift in T lymphocytes toward immune-suppressive T lymphocytes and impaired function of natural killer cells, neutrophils, and macrophages.²⁰ The suppression of cell-mediated immunity has been shown to decrease over days to weeks in the postoperative period.²¹ In addition to surgery- or trauma-induced immunosuppression, the risk for metastasis may increase due to increased vascular, including lymphatic, flow toward a skin graft donor site.^13,16 Furthermore, trauma predisposes areas to a hypercoagulable state with increased sludging as well as increased platelet counts and fibrinogen levels, which may lead to localization of metastatic lesions.²² All of these factors could potentially work simultaneously to induce the development of metastasis in graft donor sites.

We found that SCCs and keratoacanthomas, which may be a variant of SCC, are among the only primary malignancies that have been reported to develop in skin graft donor sites.^6-8 Malignancies in these donor sites appear to develop sooner than those found in chronic wounds and are reported to develop within weeks to several months postoperatively, even in as few as 2 weeks.^6,8 Tamir et al⁶ reported 2 keratoacanthomas that developed simultaneously in a burn scar and STSG donor site. The investigators believed it could be a sign of reduced immune surveillance in the 2 affected areas.⁶ It has been hypothesized that one cause of local immune suppression in Marjolin ulcers could be due to poor lymphatic regeneration in scar tissue, which would prevent delivery of antigens and stimulated lymphocytes.²³ Haik et al⁷ considered this possibility when discussing a case of SCC that developed at the site of an STSG. The authors did not feel it applied, however, as the donor site had only undergone a single skin harvesting procedure.⁷ Ponnuvelu et al⁸ felt that inflammation was the underlying etiology behind the 2 cases they reported of SCCs that developed in STSG donor sites. The inflammation associated with tumors has many of the same processes involved in wound healing (eg, cellular proliferation, angiogenesis). Ponnuvelu et al⁸ hypothesized that the local inflammation caused by graft harvesting produced an ideal environment for early carcinogenesis. Although in chronic wounds it is believed that continual repair and regeneration in recurrent ulceration contributes to neoplastic initiation, it is thought that even a single injury may lead to malignant change, which may be because prior actinic damage or another cause has made the area more susceptible to these changes.^24,25 Surgery-induced immunosuppression also may play a role in development of primary malignancies in graft donor sites.

There have been a few reports of SCCs and basal cell carcinomas occurring in other surgical scars that healed without complications.^24,26-28 Similar to the malignancies in graft donor sites, some authors differentiate malignancies that occur in surgical scars that heal without complications from Marjolin ulcers, as they do not occur in chronically irritated wounds. These malignancies have been reported in scars from sternotomies, an infertility procedure, hair transplantation, thyroidectomy, colostomy, cleft lip repair, inguinal hernia repair, and paraumbilical laparoscopic port site. The time between surgery and diagnosis of malignancy ranged from 9 months to 67 years.^24,26-28 The development of malignancies in these surgical scars may be due to local immunosuppression, possibly from decreased lymphatic flow; additionally, the inflammation in wound healing may provide the ideal environment for carcinogenesis. Trauma in areas already susceptible to malignant change could be a contributing factor.

Conclusion

Our patient developed an MCC in a vein graft donor site 18 years after vein harvesting. It was likely a primary tumor, as vein harvesting was done for coronary artery bypass graft. There was no evidence of any other lesions on physical examination or computed tomography, making it doubtful that an MCC serving as a primary lesion for seeding or metastasis was present. If such a lesion had been present at that time, it would likely have spread well before the time of presentation to our clinic due to the fast doubling time and high rate of metastasis characteristic of MCCs, further lessening the possibility of metastasis or implantation.

The extended length of time from procedure to lesion development in our patient is much longer than for other reported malignancies in graft donor sites, but the reported time for malignancies in other postsurgical scars is more varied. Regardless of whether the MCC in our patient is classified as a Marjolin ulcer, the pathogenesis is unclear. It is thought that a single injury could lead to malignant change in predisposed skin. Our patient’s legs did not have any evidence of prior actinic damage; however, it is likely that he had local immune suppression, which may have made him more susceptible to these changes. It is unlikely that surgery-induced immunosuppression played a role in our patient, as specific cellular components of the immune system only appear to be affected over days to weeks in the postoperative period. Although poor lymphatic regeneration in scar tissue leading to decreased immune surveillance is not generally thought to contribute to malignancies in most surgical scars, our patient underwent vein harvesting. Chronic edema commonly occurs after vein harvesting and is believed to be due to trauma to the lymphatics. Local immune suppression also may have led to increased susceptibility to infection by the MCC polyomavirus, which has been found to be associated with many MCCs. In addition, the area may have been more susceptible to carcinogenesis due to changes from inflammation from wound healing. We suspect together these factors contributed to the development of our patient’s MCC. Although rare, graft donor sites should be examined periodically for the development of malignancy.