Cork University Hospital, Cork, Ireland.
Virchows Arch. 2014 Feb;464(2):241-5. doi: 10.1007/s00428-013-1520-3. Epub 2013 Dec 7.
There have been recent reports of a rare variant of renal cell carcinoma associated with upregulation of the anaplastic lymphoma kinase gene (ALK) arising as a consequence of chromosomal translocations. The tumours were described as having a characteristic morphology. Here, we describe a case with similar morphology characterised by eosinophilic cells, abundant intracytoplasmic lumina and scattered large ganglion-like tumour cells. There was focal staining for ALK demonstrated by immunohistochemistry. However, rather than exhibiting a chromosomal translocation involving ALK, the use of FISH and a break-apart probe demonstrated that there was increased copy number of intact 2p23, the chromosomal region containing the ALK gene. Furthermore, the use of comparative genomic hybridisation showed increase of the whole of chromosome 2 along with chromosomes 6 and 17. There was no evidence of loss of 3p nor of trisomy of 7 associated with clear cell and papillary carcinoma, respectively. We suggest that this demonstrates a novel mechanism of upregulation of ALK activity by increased copy number occurring during the development of a renal carcinoma with the characteristic ALK-associated morphology.
最近有报道称，一种罕见的肾细胞癌变异型与间变性淋巴瘤激酶基因 (ALK) 的上调有关，这种基因的上调是由于染色体易位引起的。这些肿瘤具有特征性的形态。在这里，我们描述了一例具有相似形态的病例，其特征为嗜酸性细胞、丰富的细胞内腔和散在的大神经节样肿瘤细胞。免疫组织化学显示 ALK 有局灶性染色。然而，与涉及 ALK 的染色体易位不同，使用 FISH 和断裂探针表明完整的 2p23 染色体区域（包含 ALK 基因）的拷贝数增加。此外，比较基因组杂交显示整条 2 号染色体以及 6 号和 17 号染色体的增加。没有证据表明 3p 的缺失，也没有与 clear cell 和 papillary carcinoma 分别相关的 7 号染色体三体。我们认为，这表明在具有特征性 ALK 相关形态的肾癌的发展过程中，通过增加拷贝数而导致 ALK 活性上调的一种新机制。
