Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Am J Dermatopathol. 2023 Aug 1;45(8):539-543. doi: 10.1097/DAD.0000000000002475.
Epithelioid fibrous histiocytoma (EFH) is a distinctive benign cutaneous neoplasm composed of uniform epithelioid cells, often with binucleated cells. EFH are characterized by the presence of anaplastic lymphoma kinase ( ALK ) gene rearrangements with a variety of binding partners. These rearrangements result in the overexpression of ALK , which can be detected using immunohistochemistry. Cytoplasmic ALK expression is by far the most common pattern encountered. Here, we describe a case of EFH with a distinctive intranuclear dot-like ALK expression pattern. Subsequent next-generation DNA sequencing revealed a novel SP100::ALK gene fusion. Speckled protein-100 (SP100) is a constituent of nuclear dots, also known as promyelocytic leukemia bodies, which are still poorly understood membraneless subnuclear structures. Thus, this novel ALK fusion partner seems to explain this distinctive pattern of ALK localization. We examined ALK expression patterns in 11 other cases of EFH, but all showed typical cytoplasmic localization. This study expands the morphologic and molecular spectrum of EFH, provides a dramatic illustration of the ability of fusion partners to control protein localization, and implies that tumorigenic ALK signaling may occur at a variety of subcellular locations.
上皮样纤维组织细胞瘤（EFH）是一种独特的良性皮肤肿瘤，由均匀的上皮样细胞组成，常伴有双核细胞。EFH 的特征是存在间变性淋巴瘤激酶（ALK）基因重排，与多种结合伴侣结合。这些重排导致 ALK 的过度表达，可以通过免疫组织化学检测到。细胞质 ALK 表达是迄今为止最常见的模式。在这里，我们描述了一例具有独特核内点状 ALK 表达模式的 EFH。随后的下一代 DNA 测序显示了一种新的 SP100::ALK 基因融合。 speckled protein-100（SP100）是核点的组成部分，也称为早幼粒细胞白血病体，这些结构仍然是膜内无核亚结构中理解甚少的部分。因此，这种新的 ALK 融合伙伴似乎可以解释这种独特的 ALK 定位模式。我们检查了 11 例其他 EFH 的 ALK 表达模式，但均显示典型的细胞质定位。本研究扩展了 EFH 的形态和分子谱，生动地说明了融合伙伴控制蛋白定位的能力，并暗示致癌性 ALK 信号可能发生在多种亚细胞位置。
