Lévêque L, Dalac S, Dompmartin A, Louvet S, Euvrard S, Catteau B, Hazan M, Schollhamer M, Aubin F, Dreno B, Daguin P, Chevrant-Breton J, Frances C, Bismuth M J, Tanter Y, Lambert D
Service de Dermatologie, Hôpital Le Bocage, 21034 Dijon Cedex, France.
Ann Dermatol Venereol. 2000 Feb;127(2):160-5.
The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas.
This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years.
Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5.
Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.
在过去几十年中,皮肤黑色素瘤的发病率在白人人群中迅速上升。据估计,全球发病率每10年翻一番。已确定了不同的风险因素,包括免疫抑制。我们研究的目的是确定器官移植人群中发生黑色素瘤的相对风险及其黑色素瘤的临床和组织学特征。
这项回顾性研究是在9个大学医院中心的合作下进行的:贝桑松、布雷斯特、卡昂、第戎、里尔、里昂、南特、巴黎(皮提耶-萨尔佩特里埃医院)和雷恩。向这些医院的不同皮肤科发送了一份问卷,以获取1971年至1997年间移植后出现黑色素瘤患者的信息。在此期间,这9家医院的移植单位共有12477名器官移植受者。这些患者的平均随访时间约为5年,免疫抑制治疗的平均持续时间约为4.5年。
在12477名器官移植受者中,我们发现了17例黑色素瘤,但有1例无法获取数据:14例发生在肾移植受者中,3例发生在心脏移植受者中。临床和组织学数据仅在16名患者中可用。移植与黑色素瘤诊断之间的平均时间为63个月,但对于2名移植前有黑色素瘤病史的患者,该时间缩短了5倍。2名患者患有黏膜黑色素瘤;对于皮肤黑色素瘤,2例出现在杜布雷伊黑色素沉着病上,2例为原位黑色素瘤,7例为浅表扩散性黑色素瘤,3例为结节性黑色素瘤。对11例皮肤黑色素瘤的组织学检查显示,6例有前驱痣,7/7例宿主细胞对肿瘤的反应较弱或无反应。除1例肛管直肠黑色素瘤患者外,所有患者均对黑色素瘤进行了完整切除。4例患者因内脏转移在平均15个月内死亡。其他12例患者自肿瘤治疗后平均3年仍存活。我们试图确定肾移植人群(14例)中发生黑色素瘤的相对风险。黑色素瘤的预期病例数为5.54,相对风险为2.5。
只有4项研究表明肾移植人群中黑色素瘤的发病率有所增加:约为2至5倍。在我们的研究中,黑色素瘤增加了2.5倍,平均随访5年,平均免疫抑制治疗5年。这可能是对风险的低估,因为即使移植受者比参照人群接受了更多的体格检查,我们也无法详尽收集黑色素瘤病例。与其他研究一样,从移植到黑色素瘤诊断的平均潜伏期为63个月。组织学检查显示,前驱痣很常见,宿主细胞对肿瘤的反应较弱。这些黑色素瘤的预后仍然难以预测,但在我们的研究中,似乎并不像预期的那么差。除非存在转移,否则似乎没有必要停止免疫抑制治疗。最后,我们的研究表明,即使在因黑色素瘤持续风险导致移植排斥后,对患者进行良好的随访也很重要。