Küsters-Vandevelde Heidi V N, Keunen Jan E E, Wesseling Pieter, Verdijk Marian A J, Ligtenberg Marjolijn J L, Blokx Willeke A M
Department of Pathology C66, Canisius Wilhelmina Hospital, P.O. Box 9015, 6500 GS Nijmegen, The Netherlands.
Virchows Arch. 2008 Mar;452(3):331-6. doi: 10.1007/s00428-007-0555-8.
The differential diagnosis between primary uveal melanoma and cutaneous melanoma metastasis in the eye may be difficult, both clinically and histologically. We report successful application of combined mutational analysis of the NRAS and the CDKN2A gene to discriminate between these two entities. The patient had a history of a superficial spreading cutaneous melanoma of the left shoulder. Nine years later, she developed a lymph node metastasis in the left axilla, and 13 years later she presented with an atypical, pigmented tumor in the uvea. Histologically, the origin of the uveal melanoma could not be determined with certainty. We performed molecular analysis on the skin melanoma, the lymph node metastasis and the uveal melanoma. We detected an NRAS codon 61 mutation (c.182A>G, p.Gln61Arg) in all three tumor specimens. This mutation was absent in the normal control tissue of the patient, thereby excluding a germline mutation. To confirm a clonal relationship between the tumors, we also performed CDKN2A mutational analysis. We detected a CDKN2A mutation ((p16) c.238C>T, p.Arg80X, (p14) c.404C>T, p.Pro135Leu)) in the tumor samples, but not in the normal control tissue of the patient. We concluded that the uveal melanoma is a metastasis from the cutaneous melanoma removed 13 years before.
原发性葡萄膜黑色素瘤与皮肤黑色素瘤眼部转移之间的鉴别诊断在临床和组织学上都可能存在困难。我们报告了成功应用NRAS和CDKN2A基因联合突变分析来区分这两种实体。该患者有左肩浅表扩散性皮肤黑色素瘤病史。9年后，她出现左腋窝淋巴结转移，13年后她出现了葡萄膜非典型色素性肿瘤。组织学上，无法确定葡萄膜黑色素瘤的起源。我们对皮肤黑色素瘤、淋巴结转移灶和葡萄膜黑色素瘤进行了分子分析。我们在所有三个肿瘤标本中均检测到NRAS密码子61突变（c.182A>G，p.Gln61Arg）。该患者的正常对照组织中不存在此突变，从而排除了种系突变。为了确认肿瘤之间的克隆关系，我们还进行了CDKN2A突变分析。我们在肿瘤样本中检测到CDKN2A突变（（p16）c.238C>T，p.Arg80X，（p14）c.404C>T，p.Pro135Leu），但在患者的正常对照组织中未检测到。我们得出结论，葡萄膜黑色素瘤是13年前切除的皮肤黑色素瘤的转移灶。
