Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, US.
Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, US.
Am J Clin Pathol. 2023 Jun 1;159(6):522-537. doi: 10.1093/ajcp/aqad022.
To report findings from the 2021 Society for Hematopathology/European Association for Haematopathology Workshop within the category of B-cell lineage neoplasms' transdifferentiation into histiocytic/dendritic cell neoplasms (HDCNs).
The workshop panel reviewed 29 cases, assigned consensus diagnoses, and summarized findings.
The specific diagnoses of transdifferentiated HDCN tumors were histiocytic sarcoma (16); Langerhans cell histiocytosis/sarcoma (5); indeterminate DC tumor (1); and HDCN, unclassifiable (1). Approximately one-third of the patients reviewed had follicular lymphoma; lymphoblastic leukemia/lymphoma; or another B-cell lymphoma, most commonly chronic lymphocytic leukemia/small lymphocytic lymphoma. There was a 3:1 preponderance toward women, median patient age was 60 years, and the median interval between the initial diagnosis of B-cell lineage neoplasm and HDCN was 4 to 5 years. The submitted cases have demonstrated substantial heterogeneity as well as overlapping immunophenotypic and other features. Comprehensive genomic DNA sequencing revealed alterations enriched in the MAPK pathway. Based on shared and distinct alterations seen in HDCNs and the preceding lymphomas, both linear and divergent clonal evolutionary pathways were inferred. Furthermore, RNA sequencing performed in a subset of cases yielded new insights into markers that could be useful for more precise cell lineage identification. The panel has thus proposed an updated algorithm for HDCN lineage assignment. The outcome of transdifferentiated HDCNs was poor, but the MAPK signaling pathway emerges as a potentially attractive therapeutic target.
Transdifferentiated HDCNs demonstrate heterogeneity and pose diagnostic challenges with regard to exact classification, but the in-depth characterization of the submitted cases have added to our understanding of the secondary HDCNs transdifferentiated from B-cell lymphoma/leukemia. Continuous efforts focusing on deciphering the specific cell lineage and differentiation state of these tumors will be critical for their accurate classification. Comprehensive molecular characterization of HDCNs may be informative in this regard. With the list of novel pharmacologic inhibitors of the MAPK pathway continuing to expand, improved outcomes for HDCN can be expected.
报告 2021 年血液病理学协会/欧洲血液病理学协会工作组在 B 细胞谱系肿瘤向组织细胞/树突状细胞肿瘤（HDCN）转化这一类别中的发现。
工作组小组审查了 29 例病例，做出了共识诊断，并总结了发现。
转化的 HDCN 肿瘤的具体诊断为组织细胞肉瘤（16 例）；朗格汉斯细胞组织细胞增生症/肉瘤（5 例）；未确定的树突状细胞肿瘤（1 例）；以及分类不明的 HDCN（1 例）。审查的患者中约有三分之一患有滤泡淋巴瘤；淋巴母细胞白血病/淋巴瘤；或另一种 B 细胞淋巴瘤，最常见的是慢性淋巴细胞白血病/小淋巴细胞淋巴瘤。女性患者占 3 比 1，中位患者年龄为 60 岁，B 细胞谱系肿瘤与 HDCN 之间的中位间隔为 4 至 5 年。提交的病例表现出明显的异质性以及免疫表型和其他特征的重叠。综合基因组 DNA 测序显示 MAPK 通路中的改变丰富。基于在 HDCN 和先前的淋巴瘤中看到的共享和独特改变，推断出线性和发散的克隆进化途径。此外，对部分病例进行的 RNA 测序为更精确的细胞谱系鉴定提供了有用的标记物。该小组因此提出了用于 HDCN 谱系分配的更新算法。转化的 HDCN 的结果较差，但 MAPK 信号通路作为一个有吸引力的治疗靶点出现。
转化的 HDCN 表现出异质性，并在精确分类方面提出了诊断挑战，但对提交病例的深入特征分析增加了我们对源自 B 细胞淋巴瘤/白血病的继发性 HDCN 的理解。专注于解码这些肿瘤的特定细胞谱系和分化状态的持续努力对于它们的准确分类至关重要。全面的 HDCN 分子特征分析可能对此有所帮助。随着 MAPK 通路的新型药理学抑制剂的不断增加，预计 HDCN 的预后会得到改善。
