Department of Anatomic Pathology, Pathology and Laboratory Medicine Institute, The Cleveland Clinic and The Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.
Mod Pathol. 2010 Jan;23(1):93-7. doi: 10.1038/modpathol.2009.138. Epub 2009 Oct 2.
Angiomatoid fibrous histiocytoma is a mesenchymal neoplasm of intermediate malignancy and uncertain histogenesis/line of differentiation, which occurs most commonly in the extremities of children to young adults. It has a characteristic appearance characterized by a proliferation of histiocytoid cells with a lymphoid cuff and fibrous pseudocapsule, simulating the appearance of a neoplasm occurring within a lymph node. However, these classic histological features are not always present. Given the variable appearance of the neoplastic cells and the lack of consistently positive immunohistochemical markers, diagnosis can be problematic. Angiomatoid fibrous histiocytoma has been found to harbor three related translocations, a t(12;16)(q13;p11) resulting in a FUS/ATF1 fusion gene, t(12;22)(q13;q12) resulting in a EWSR1/ATF1 fusion, and t(2;22)(q33;q12) resulting in a EWSR1/CREB1 fusion. Fluorescence in situ hybridization (FISH) probes to EWSR1 and FUS, in theory, should detect all three translocations/gene fusions. We evaluated 18 cases of angiomatoid fibrous histiocytoma for rearrangements of EWSR1 and FUS by FISH, the largest series to date. We found that 13 of 17 (76%) cases of angiomatoid fibrous histiocytoma harbored rearrangements of EWSR1; rearrangements of FUS were not detected in any of the cases. This study affirms that the rearrangement of EWSR1 is a common genetic event in angiomatoid fibrous histiocytoma, and is thus useful diagnostically. This study supports the fact that the rearrangement of FUS is present in only a small minority of angiomatoid fibrous histiocytomas. Interestingly, 24% of the cases were translocation negative, and did not contain rearrangements of EWSR1 or FUS by FISH. Although it is possible that these cases contained cryptic rearrangements of EWSR1 or FUS that were not detectable by our FISH probes, it also raises the possibility that another translocation/gene fusion may be present in angiomatoid fibrous histiocytoma. Finally, we discuss some of the potential pitfalls of this technique, including confusion with other mesenchymal neoplasms containing rearrangement of EWSR1, in particular Ewing's sarcoma/PNET.
血管外皮细胞瘤样纤维组织细胞瘤是一种中等恶性的间叶性肿瘤，其组织发生/分化来源不确定，最常见于儿童至年轻成人的四肢。它具有特征性的外观，表现为组织细胞样细胞的增生，伴有淋巴袖套和纤维假包膜，模拟发生在淋巴结内的肿瘤的外观。然而，这些经典的组织学特征并不总是存在。由于肿瘤细胞的形态变化多样，以及缺乏一致的免疫组织化学标志物阳性，诊断可能存在问题。血管外皮细胞瘤样纤维组织细胞瘤已发现存在三种相关的易位，t(12;16)(q13;p11)导致 FUS/ATF1 融合基因，t(12;22)(q13;q12)导致 EWSR1/ATF1 融合，以及 t(2;22)(q33;q12)导致 EWSR1/CREB1 融合。荧光原位杂交（FISH）探针理论上应该能够检测到所有三种易位/基因融合。我们通过 FISH 评估了 18 例血管外皮细胞瘤样纤维组织细胞瘤的 EWSR1 和 FUS 重排，这是迄今为止最大的系列研究。我们发现，17 例血管外皮细胞瘤样纤维组织细胞瘤中有 13 例（76%）存在 EWSR1 重排；在任何病例中均未检测到 FUS 重排。这项研究证实，EWSR1 的重排是血管外皮细胞瘤样纤维组织细胞瘤中的一种常见遗传事件，因此在诊断上具有重要意义。这项研究支持这样一个事实，即 FUS 的重排在少数血管外皮细胞瘤样纤维组织细胞瘤中存在。有趣的是，24%的病例为易位阴性，通过 FISH 未检测到 EWSR1 或 FUS 的重排。虽然这些病例可能存在我们的 FISH 探针无法检测到的隐匿性 EWSR1 或 FUS 重排，但也提出了另一种易位/基因融合可能存在于血管外皮细胞瘤样纤维组织细胞瘤中的可能性。最后，我们讨论了该技术的一些潜在问题，包括与其他含有 EWSR1 重排的间叶性肿瘤（特别是尤文肉瘤/原始神经外胚层肿瘤）的混淆。
