Department of Pathology, Radboud University Medical Center, P,O, Box 9101, 6500 HB Nijmegen, The Netherlands.
Diagn Pathol. 2014 Jul 1;9:131. doi: 10.1186/1746-1596-9-131.
Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3)(p36;q25), a consistent WWTR1-CAMTA1 fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases.
Thirty-nine tumors, from 24 females and 15 males with an age range 9-85 years, were located in soft tissue (head and neck [8], trunk [5], upper extremities [3], lower extremities [2], mediastinal [1], and paratesticular [1]), lymph node (1), breast (1), skin (2), bone (6), lung (7), and liver (2). The cases were investigated using a panel of immunohistochemical markers. The aforementioned fusion-genes were examined using RT-PCR and/or FISH in order to validate their diagnostic value.
Follow-up available for 17 patients ranged from 3 months to 7 years (median interval 1.5 years). Eleven patients were alive without disease, 2 patients were alive with disease after 1.5 and 2 years, respectively. Four patients died of disease after 4 months (n = 1), 5 months (n = 2), and 1.5 years (n = 1).The size, known for 30 lesions, was >3 cm in 9 of them. Histologically, all lesions had classical features, at least focally. Four tumors counted >3 mitoses/50 HPF. Immunohistochemically, all cases tested stained positive for ERG (21), FLI1 (5) and CD31 (39). CD34 and D2-40 positivity was seen in 81% and 71% of the examined cases, respectively. 11/35 cases expressed pan-keratin and 6/20 cases CK8.18. TFE3 showed a nuclear reaction in 21/24 cases, irrespective of TFE3 rearrangement.Molecular genetically, 35/35 cases revealed one of the fusion genes by FISH and/or RT-PCR with WWTR1-CAMTA1 in 33 cases and YAP1-TFE3 in 2 cases.
These results demonstrate the high diagnostic value of FISH and RT-PCR in detecting the fusion genes of EHE. The immunohistochemical utility of TFE3 appears questionable in this study.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4010279141259481.
上皮样血管内皮细胞瘤是一种恶性、常为惰性的血管肿瘤，可发生于各种解剖部位。基于相互易位 t（1;3）（p36;q25），发现了一致的 WWTR1-CAMTA1 融合基因。在一小部分明显不同的病例中，检测到了另一种 YAP1-TFE3 融合。
39 例肿瘤来自 24 名女性和 15 名男性，年龄 9-85 岁，位于软组织（头颈部[8]、躯干[5]、上肢[3]、下肢[2]、纵隔[1]和副睾[1]）、淋巴结（1）、乳腺（1）、皮肤（2）、骨（6）、肺（7）和肝（2）。使用一组免疫组织化学标志物对这些病例进行了研究。使用 RT-PCR 和/或 FISH 检查了上述融合基因，以验证其诊断价值。
17 例患者的随访时间为 3 个月至 7 年（中位间隔 1.5 年）。11 例患者无疾病存活，2 例患者分别在 1.5 年和 2 年后疾病存活。4 例患者分别在 4 个月（n=1）、5 个月（n=2）和 1.5 年后（n=1）死于疾病。已知 30 个病变中的 30 个病变的大小>3cm。组织学上，所有病变至少局灶性地具有典型特征。4 个肿瘤计数>3/50 HPF 的有丝分裂。免疫组织化学检查，所有病例均检测到 ERG（21）、FLI1（5）和 CD31（39）阳性。CD34 和 D2-40 的阳性率分别为 81%和 71%。35/35 例表达泛角蛋白，20/20 例 CK8.18。24 例中的 21 例 TFE3 显示核反应，不论 TFE3 重排如何。分子遗传学上，35/35 例通过 FISH 和/或 RT-PCR 检测到融合基因，其中 WWTR1-CAMTA1 融合基因在 33 例中，YAP1-TFE3 融合基因在 2 例中。
这些结果表明 FISH 和 RT-PCR 在检测 EHE 的融合基因方面具有很高的诊断价值。在这项研究中，TFE3 的免疫组织化学效用似乎值得怀疑。
