Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei, 11217, Taiwan.
Department of Pathology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Virchows Arch. 2020 Jun;476(6):921-929. doi: 10.1007/s00428-020-02752-5. Epub 2020 Jan 28.
ALK-rearranged renal cell carcinoma is a provisional entity in the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Organs. The reported fusion partners included VCL, TPM3, EML4, STRN, and HOOK1. Herein, we present a peculiar renal cell carcinoma morphologically resembling metanephric adenoma and harboring a novel PLEKHA7-ALK fusion. Microscopically, the tumor is composed of bland epithelial cells with scant to moderate amount of amphophilic cytoplasm, round and uniform nuclei, delicate chromatin, and inconspicuous nucleoli, arranged in tightly packed small acini and angulated tubules. Papillary formation, intraluminal glomeruloid tufts, microcysts, and solid nests were focally observed. Psammomatous calcifications were evident. The tumor cells were diffusely reactive for CK7, AMACR, PAX8, and ALK, while non-reactive for WT1, BRAF V600E, CD57, carbonic anhydrase IX, TFE3, and cathepsin K. Fluorescence in situ hybridization showed breaking apart of ALK. A novel PLEKHA7exon18-ALKexon20 fusion was detected using ArcherDX FusionPlex next-generation sequencing panel and was further confirmed with reverse-transcriptase PCR. Our case demonstrates that in contrast to prior cases showing high-grade tumor cells, ALK-rearranged renal cell carcinoma may also present as a low-grade renal tumor mimicking metanephric adenoma. Immunohistochemistry and molecular testing are helpful to identify this tumor, which may be eligible for ALK inhibitor-targeted therapy.
ALK 重排肾细胞癌是 2016 年世界卫生组织泌尿系统和男性生殖器官肿瘤分类中的一个暂定实体。报道的融合伙伴包括 VCL、TPM3、EML4、STRN 和 HOOK1。在此，我们报告了一例形态上类似于后肾腺瘤的独特肾细胞癌，其携带一种新型 PLEKHA7-ALK 融合。显微镜下，肿瘤由温和的上皮细胞组成，胞质稀少至中等量，圆形且均匀的核，细腻的染色质和不明显的核仁，排列成紧密包裹的小腺泡和角状小管。局灶性观察到乳头状形成、管腔内肾小球样丛、微囊和实性巢。可见砂粒体样钙化。肿瘤细胞弥漫性表达 CK7、AMACR、PAX8 和 ALK，而不表达 WT1、BRAF V600E、CD57、碳酸酐酶 IX、TFE3 和组织蛋白酶 K。荧光原位杂交显示 ALK 断裂。使用 ArcherDX FusionPlex 下一代测序面板检测到一种新型 PLEKHA7exon18-ALKexon20 融合，并通过逆转录聚合酶链反应进一步证实。我们的病例表明，与先前显示高级别肿瘤细胞的病例不同，ALK 重排肾细胞癌也可能表现为低级别肾肿瘤，类似于后肾腺瘤。免疫组化和分子检测有助于识别这种肿瘤，这种肿瘤可能有资格接受 ALK 抑制剂靶向治疗。
