Department of Pathology and Laboratory Medicine Dartmouth Health, Lebanon, 03766, NH, USA; Geisel School of Medicine at Dartmouth, Lebanon, 03766, NH, USA.
Corewell Health's Beaumont Hospital, Department of Pathology, Royal Oak, MI, 48073, USA.
Hum Pathol. 2024 May;147:129-138. doi: 10.1016/j.humpath.2024.03.005. Epub 2024 Mar 21.
Bone and soft tissue tumors (BST) are a highly heterogeneous group largely classified by their line of differentiation, based on their resemblance to their normal counterpart in adult tissue. Yet, rendering a specific diagnosis can be challenging, primarily due to their rarity and overlapping histopathologic features or clinical presentations. Over the past few decades, seemingly histogenetic-specific gene fusions/translocations and amplifications have been discovered, aiding in a more nuanced classification, leading to well-established objective diagnostic criteria and the development of specific surrogate ancillary tests targeting these genetic aberrations (e.g., immunohistochemistry). Ironically, the same research also has revealed that some specific tumor subtypes may be the result of differing and often multiple gene fusions/translocations, but, more interestingly, identical gene fusions may be present in more than one phenotypically and biologically distinct neoplasm, sometimes with entirely different clinical behavior. Prime examples include, EWSR1::ATF1 and, less commonly, EWSR1::CREB1 gene fusions present in both clear cell sarcoma, a malignant high-grade tumor with melanocytic differentiation, and angiomatoid fibrous histiocytoma, a mesenchymal neoplasm of intermediate malignancy with a generally indolent course. Similarly, MDM2 amplification, once deemed to be pathognomonic for atypical lipomatous tumor/well differentiated and dedifferentiated liposarcoma, has been documented in a range of additional distinct tumors, including low grade osteosarcomas (e.g. low grade central and surface parosteal) and high-grade intimal sarcomas, amongst others. Such findings reinforce the importance of careful attention to morphological and clinicoradiological features and correlation with molecular testing before rendering a specific diagnosis. Future classification systems in BST neoplasms cannot be solely based on molecular events and ideally will balance morphologic features with molecular analysis. Herein, we provide a narrative literature review of the more common BST neoplasms with shared genetic events but differing demographics, morphology, immunophenotype, and clinical behavior, re-emphasizing the importance of the hematoxylin and eosin slide and the "eye" of the practicing pathologist.
骨与软组织肿瘤（BST）是一组高度异质性的肿瘤，主要根据其分化来源进行分类，类似于成人组织中的正常对应物。然而，做出明确的诊断具有挑战性，主要是因为它们的罕见性以及组织病理学特征或临床表现的重叠。在过去的几十年中，已经发现了一些似乎具有组织发生特异性的基因融合/易位和扩增，这有助于更细致的分类，从而建立了明确的客观诊断标准，并开发了针对这些遗传异常的特定替代辅助测试（例如免疫组织化学）。具有讽刺意味的是，同样的研究也表明，一些特定的肿瘤亚型可能是不同的，而且通常是多种基因融合/易位的结果，但更有趣的是，相同的基因融合可能存在于一种以上表型和生物学上不同的肿瘤中，有时具有完全不同的临床行为。主要的例子包括 EWSR1::ATF1，以及较少见的 EWSR1::CREB1 基因融合，这两种融合均存在于透明细胞肉瘤中，这是一种具有黑色素细胞分化的恶性高级别肿瘤，和血管脂肪瘤样纤维组织细胞瘤，这是一种间充质肿瘤，恶性程度中等，病程通常较为惰性。同样，MDM2 扩增曾经被认为是典型的脂肪肉瘤/高分化和去分化脂肪肉瘤的特征，但已在一系列其他不同的肿瘤中记录到，包括低度恶性的骨肉瘤（例如低度中央和表面骨旁）和高级内膜肉瘤等。这些发现强调了在做出明确诊断之前，仔细注意形态学和临床影像学特征并与分子检测相关联的重要性。未来的 BST 肿瘤分类系统不能仅基于分子事件，理想情况下应将形态特征与分子分析相平衡。在此，我们提供了具有共同遗传事件但具有不同人口统计学、形态学、免疫表型和临床行为的更常见的 BST 肿瘤的叙述性文献综述，再次强调了苏木精和伊红切片以及执业病理学家的“眼睛”的重要性。
