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Abstract and Introduction
Abstract
Organ transplant recipients have a higher incidence of melanoma compared to the general population but the prognosis of this potentially fatal skin cancer in this group of patients has not yet been established. To address this, we undertook a multicenter retrospective analysis to assess outcome for 100 melanomas (91 posttransplant and 9 pretransplant) in 95 individuals. Data were collected in 14 specialist transplant dermatology clinics across Europe belonging to the Skin Care in Organ Transplant Patients, Europe (SCOPE) Network, and compared with age, sex, tumor thickness and ulceration status-matched controls from the American Joint Committee on Cancer (AJCC) melanoma database. Outcome for posttransplant melanoma was similar to that of the general population for T1 and T2 tumors (≤2 mm thickness); but was significantly worse for T3 and T4 tumors (>2 mm thickness); all nine individuals with a pretransplant melanoma survived without disease recurrence following organ transplantation. These data have implications for both cutaneous surveillance in organ transplant recipients and management of transplant-associated melanoma.
Introduction
Melanoma is an aggressive cutaneous malignancy accounting for just 4% of skin cancers but resulting in 80% of all skin-cancer related deaths. Its incidence in the general population is rising rapidly with estimated rates likely to treble over the next 30 years. There is compelling evidence for a causative link with sunlight exposure, with intermittent, intense sun exposure in early life correlating best with melanoma risk. In the immunocompetent population other risk factors for developing melanoma include skin phototype, family history, multiple and atypical naevi and past history of nonmelanoma (basal [BCC] and squamous cell) carcinoma [SCC] (Supplementary Table S1). The clinicopathological classification of cutaneous melanoma is primarily based on anatomic location and patterns of growth (Supplementary Table S2). Noncutaneous melanoma accounts for 5% of melanoma and includes ocular and mucosal malignancies. The etiology, prognostic features and treatment of these differ from that of cutaneous subtypes.
The American Joint Committee on Cancer (AJCC) predicted 5-year survival for immunocompetent patients with early (stage I/II) melanoma disease to be 85%. Increases in Breslow thickness (the vertical distance measured in millimeters from the granular cell layer to the deepest part of the tumor) and microscopic ulceration are the most important histological determinants of prognosis, both inversely correlated with survival (Supplementary Table S3). However, nodal status as determined by sentinel lymph node biopsy (SNB) -- has emerged as the most powerful predictor of recurrence and survival and in patients with stage III regional nodal disease the 5-year survival ranges from 24% to 69.5% depending on the number of lymph nodes affected and the tumor burden. With visceral metastases, 5-year survival falls to approximately 6%, and the median survival is 7.5 months. Early diagnosis and surgery remains the cornerstone of treatment for melanoma and little progress has been made with adjuvant therapy and treatment for advanced disease over the past three decades.
An increased incidence of skin malignancies following organ transplantation is well established, in particular SCC and BCC, where the excess risk is in the order of 50-100-fold and 10-fold, respectively, with a resulting reversal in the usual SCC:BCC ratio of 1:3-4 seen in the general population. Evidence also suggests an increased relative risk of melanoma in organ transplant recipients (OTRs), but information on outcome is scarce.
Melanoma arises in three main clinical settings in relation to solid organ transplantation; donor-derived melanoma, melanoma preceding solid organ transplantation and de novo melanoma following solid organ transplantation. Melanoma acquired from the transplanted organ accounts for 28% of cases of transplanted tumors making this the most common type of transplanted tumor in OTRs. It has a high mortality rate, with a reported 5-year survival of 5%. Only one study has previously addressed outcome in OTRs with a pre-existing melanoma and the limited data similarly suggest a poor prognosis.De novo melanoma following solid organ transplantation is the most common clinical scenario, with an excess relative risk attributable to transplantation of up to 12 in several studies. Immunological factors are implicated in both development and progression of melanoma, thus, in OTRs a worse prognosis might be anticipated although, to date, no study has had sufficient power to address this issue.
In the current study, we determine prognosis for melanoma in transplant recipients compared with the general population, and also examine outcomes for OTRs with a history of melanoma prior to transplantation. A multi-centered European collaborative study was coordinated for this purpose involving a network of clinicians within the organization -- 'Skin Care in Organ Transplant Patients, Europe (SCOPE). The study comprises 14 cohorts of OTRs under routine surveillance in dedicated transplant dermatology clinics across Europe.
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