Melanoma in Organ Transplant Recipients: The Old Enemy Finds a New Battleground

By Quan Q. Dinh, M.D. & Alvin H. Chong, M.D.
Published in Australas J Dermatol 2007, 48;4:199–207

Introduction

There was limited data regarding the incidence and prognosis of melanomas within the population of organ transplant recipients. This study drew attention to particular areas that require further research.

Methods

The authors conducted a Medline literature search for articles within the past 20 years with the terms ‘melanoma,’ ‘transplant’ and ‘transplantation.’ Reference lists of these articles were also searched for additional relevant articles. Thirteen publications were analyzed to determine melanoma incidence rates. A further 9 publications were analyzed for evidence regarding risk factors, biological behavior and prognosis, and treatment of melanoma within this patient group.

Incidence

Data in published studies examining the incidence and mortality of melanoma within the transplant population varied widely in quality, and consequently yield varied results. There were no large studies reporting the melanoma incidence and relative risk in pediatric (aged 18 or less) transplant recipients. The relative contribution of melanomas to the total skin tumor burden in transplant recipients was 12% within the pediatric subgroup, compared with 5% in the adult transplant population. In the transplant population, almost 4% of cutaneous melanomas occurred in patients under 20 years of age, compared with the general population, among which this figure was 2%.

Risk Factors

Within the pediatric transplant population, a retrospective case-control study examining 38 Renal Transplant Recipients (RTR) and 38 age- and sex-matched controls identified an increased number of melanocytic nevi in the RTR population compared with controls. The increase was strongly correlated with increased duration of immunosuppression. For every year of immunosuppression, the study found a increase of nevi of 11.2. The study also found a particularly strong predisposition to nevi on the palms and soles of the RTR population compared with the control population, with 43% of patients in the transplant population compared with 3% in the non-transplant population having one or more nevi on the palms and/or soles. Similar findings were reported in a case-control study conducted within an adult RTR population. Neither of these studies examined whether these nevi were etiologically related to any subsequent melanoma development.

A small case reviewing the histology of melanoma in transplant recipients found that 10/14 had melanocytic nevus in the margin of the tumor, possibly from which the melanomas arose. Thirteen of 14 patients were found to have an abnormal host response to the tumor, characterized by absence of the usual lymphocyte or macrophage infiltrate.

Taken together, these 3 studies suggested that in both the adult and pediatric transplant population, the observed increased number of melanocytic nevi may be associated with an immunosuppressed state. There was also the question of whether particular immunosuppressive drug regimens are more likely to promote melanoma development.

Biological Behavior and Prognosis

Primary melanomas within the renal transplant population generally start to occur 3 years or more after transplantation. The largest data set on primary melanomas occurring in the transplant population came from the Israel Penn International Transplant Tumor Registry (IPITTR), which has collected data on malignancies in more than 15,000 transplant patients since 1968. Examination of the data showed 164 melanomas arising after solid organ transplant or bone marrow transplantation. The site of these tumors was evenly distributed throughout the body. Compared with the general population, there was increased proportion of melanomas found in the head and neck regions, and a reduced proportion found in the lower limbs.

Treatment Guidelines

Data to guide treatment of melanomas pre- and post-transplantation was lacking. Existing guidelines were based primarily on standard guidelines for the treatment of melanoma in the general population. Given that the registry data showed that 6/31 melanomas excised prior to transplantation recurred after transplantation, of which 5/6 were diagnosed less than 5 years prior to transplantation, the authors suggested that, except for in situ melanomas and thin melanomas, patients who develop a melanoma while awaiting transplantation wait a further 5 years before reconsideration of transplantation.

Further treatment recommendations have not yet been supported by research evidence and were based on expert opinion. In patients awaiting transplantation with distant metastasis or extensive regional metastasis, it was suggested that as the prognosis was so poor, transplantation should not be performed. Following transplantation, patients developing melanomas without nodal metastasis could be treated with wide local excision as for the general population. If nodal metastasis was present, experts recommended that, as well as therapeutic lymphadenectomy, consideration should be given to discontinuing both immunosuppressive medication and the administration of adjuvant therapies.

Conclusions

Data on melanomas occurring in the transplant population was limited. Consequently, current treatment guidelines, particularly whether or not to delay transplantation, were based on opinion rather than data of substance. The authors suggest that one way of overcoming small numbers limiting analysis of data is international collaboration. This collaboration could overcome problems with small sample sizes and, over time, could present a more substantial evidence base from which treatment guidelines based on data could be developed.

Reprint requests to: Alvin H. Chong, M.D., Department of Medicine (Dermatology), St. Vincent’s Hospital Melbourne, University of Melbourne, PO Box 2900, Fitzroy, Victoria 3065, Australia.