ALK Expression in Angiomatoid Fibrous Histiocytoma A Potential Diagnostic Pitfall
ALK Expression in Angiomatoid Fibrous Histiocytoma A Potential Diagnostic Pitfall
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DOI：
10.1097/pas.0000000000001103
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Goldblum, John R.
中科院分区：
文献类型：
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作者：
Cheah, Alison L.;Zou, Youran;Goldblum, John R.
我们最近遇到一个原发性肺血管瘤样纤维组织细胞瘤（AFH）的病例，最初被误诊为炎性肌纤维母细胞瘤（IMT），部分原因是免疫组化（IHC）检测到间变性淋巴瘤激酶（ALK）表达。基于这一经验，我们使用3种不同的抗体克隆：D5 F3、5A 4和ALK 1，评价了11例AFH、15例IMT和11例滤泡树突状细胞肉瘤中ALK的表达。ALK IHC阳性病例采用双色ALK断裂探针试剂盒进行荧光原位杂交（FISH）分析。研究的大多数AFH病例的ALK IHC阳性，至少有1种抗体（9/11例D5 F3、6/9例5A 4、1/9例ALK 1），大多数显示中度至重度细胞质染色。ALK IHC阳性的AFH通过FISH显示无ALK基因重排（0/8），ALK拷贝数范围为1.6 - 2.1。免疫组化检测ALK阳性率为67%（10/15例D5 F3、8/15例5A 4、7/15例ALK 1），FISH检测ALK基因重排阳性率为9/10例。所有滤泡性树突状细胞肉瘤经IHC检测均为ALK阴性（D5 F3和5A 4）。我们的研究结果表明，ALK在AFH中的表达是常见的，特别是在高度敏感的D5 F3和5A 4抗体和增强的检测系统中，并且可能是与IMT诊断混淆的潜在来源。ALK在AFH中表达的潜在机制尚不清楚，尽管它似乎不是来自ALK重排或扩增。
We recently encountered a case of primary pulmonary angiomatoid fibrous histiocytoma (AFH), which was initially misdiagnosed as inflammatory myofibroblastic tumor (IMT) based in part on anaplastic lymphoma kinase (ALK) expression by immunohistochemistry (IHC). Prompted by this experience, we evaluated ALK expression in 11 AFH, 15 IMT, and 11 follicular dendritic cell sarcomas using 3 different antibody clones: D5F3, 5A4, and ALK1. ALK IHC positive cases were analyzed with fluorescence in situ hybridization (FISH) using dual color ALK break-apart probe kit. The majority of AFH cases studied were positive for ALK IHC with at least 1 antibody (9/11 D5F3, 6/9 5A4, 1/9 ALK1), most demonstrating moderate to strong cytoplasmic staining. AFH with positive ALK IHC showed no ALK gene rearrangement by FISH (0/8) with ALK copy number ranging from 1.6 to 2.1. Sixty-seven percent of IMT were ALK positive by IHC (10/15 D5F3, 8/15 5A4, 7/15 ALK1), and 9 of the 10 cases were positive for ALK gene rearrangement by FISH. All follicular dendritic cell sarcomas were negative for ALK by IHC (D5F3 and 5A4). Our results indicate that ALK expression in AFH is common, particularly with the highly sensitive D5F3 and 5A4 antibodies and enhanced detection systems, and may be a potential source of diagnostic confusion with IMT. The underlying mechanism of ALK expression in AFH is unclear, although it does not appear to be from ALK rearrangement or amplification.