Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis, clinical behavior, and treatment. Owing to their rarity and histologic overlap, accurate diagnosis of sarcomas can be challenging. Our approach has evolved dramatically in the past few decades, where novel insights into the molecular pathogenetic basis for sarcomas has dramatically (re)shaped contemporary diagnosis, building on a largely morphology- and clinical presentation-based strategy. Examples include the introduction of novel immunohistochemical markers that serve as surrogates for molecular genetic alterations and identification of characteristic molecular alterations. Accordingly, cytogenetic and molecular genetic analyses, such as conventional karyotyping, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and targeted sequencing, have increasingly been incorporated into the routine diagnostic work-up of these neoplasms. For those sarcomas with complex cytogenetic changes that lack specific alterations, additional testing is often directed toward identifying lines of differentiation and excluding pathognomonic (cyto-)genetic alterations. Although some gene rearrangements are diagnostic of particular sarcoma types, certain fusion partners, most notably EWSR1, are not tumor specific (and may, in fact, also be found in benign tumors). Correlation with clinical, radiologic, morphologic, and immunohistochemical findings is particularly important in tumors with such rearrangements to establish the correct diagnosis, acknowledging the inherent limitations of diagnostic tests. The recognition of sarcomas occurring in cancer predisposition syndromes is critical, with implications not only for the index patient but also potentially for family members, including the need for genetic counseling and sometimes particular types of surveillance. Together, contemporary sarcoma evaluation involves combining the initial morphologic evaluation with diagnostically relevant cytogenetic, molecular, and immunohistochemical testing methods.

中文翻译：

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当代肉瘤诊断、遗传学和基因组学

肉瘤包括多种间充质肿瘤，其预后、临床行为和治疗各不相同。由于它们的罕见性和组织学重叠，肉瘤的准确诊断可能具有挑战性。在过去的几十年里，我们的方法发生了巨大的变化，对肉瘤的分子病理学基础的新见解极大地（重新）塑造了当代诊断，建立在很大程度上基于形态学和临床表现的策略之上。例子包括引入新的免疫组织化学标记，作为分子遗传改变的替代物和特征分子改变的识别。因此，细胞遗传学和分子遗传学分析，例如常规核型分析、荧光原位杂交、逆转录聚合酶链反应、和靶向测序，越来越多地被纳入这些肿瘤的常规诊断工作中。对于那些具有复杂细胞遗传学变化但缺乏特定改变的肉瘤，额外的测试通常旨在识别分化线并排除病理性（细胞）遗传学改变。尽管某些基因重排可以诊断特定的肉瘤类型，但某些融合伙伴，尤其是 EWSR1，并不是肿瘤特异性的（事实上，也可能在良性肿瘤中发现）。与临床、放射学、形态学和免疫组织化学发现的相关性在具有此类重排的肿瘤中尤为重要，以建立正确的诊断，承认诊断测试的固有局限性。识别癌症易感综合征中发生的肉瘤至关重要，不仅对指示患者而且对家庭成员也有潜在影响，包括需要进行遗传咨询，有时还需要进行特定类型的监测。总之，当代肉瘤评估涉及将初始形态学评估与诊断相关的细胞遗传学、分子和免疫组织化学检测方法相结合。