Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China.
Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.
Front Immunol. 2023 Sep 18;14:1270365. doi: 10.3389/fimmu.2023.1270365. eCollection 2023.
Discriminating between cutaneous anaplastic large cell lymphoma (cALCL) and CD30-positive transformed mycosis fungoides (CD30+ TMF) is challenging, particularly when they arise in the context of pre-existing mycosis fungoides. The development of molecular diagnostic tools was hampered by the rarity of both diseases and the limited understanding of their pathogenesis.
In this study, we established a cohort comprising 25 cALCL cases and 25 CD30+ TMF cases, with transcriptomic data obtained from 31 samples. We compared the clinicopathological information and investigated the gene expression profiling between these two entities. Furthermore, we developed an immunohistochemistry (IHC) algorithm to differentiate these two entities clinically.
Our investigation revealed distinct clinicopathological features and unique gene expression programs associated with cALCL and CD30+ TMF. cALCL and CD30+ TMF displayed marked differences in gene expression patterns. Notably, CD30+ TMF demonstrated enrichment of T cell receptor signaling pathways and an exhausted T cell phenotype, accompanied by infiltration of B cells, dendritic cells, and neurons. In contrast, cALCL cells expressed high levels of HLA class II genes, polarized towards a Th17 phenotype, and exhibited neutrophil infiltration. An IHC algorithm with BATF3 and TCF7 staining emerged as potential diagnostic markers for identifying these two entities.
Our findings provide valuable insights into the differential molecular signatures associated with cALCL and CD30+ TMF, which contribute to their distinct clinicopathological behaviors. An appropriate IHC algorithm could be used as a potential diagnostic tool.
鉴别皮肤间变大细胞淋巴瘤（cALCL）和 CD30 阳性蕈样肉芽肿（CD30+TMF）具有挑战性，尤其是当它们出现在蕈样肉芽肿之前。由于这两种疾病的罕见性和对其发病机制的有限了解，分子诊断工具的发展受到了阻碍。
本研究建立了一个包含 25 例 cALCL 病例和 25 例 CD30+TMF 病例的队列，其中 31 例样本获得转录组数据。我们比较了这两种实体的临床病理信息并研究了它们的基因表达谱。此外，我们开发了一种免疫组织化学（IHC）算法来临床区分这两种实体。
我们的研究揭示了 cALCL 和 CD30+TMF 之间存在明显的临床病理特征和独特的基因表达程序。cALCL 和 CD30+TMF 的基因表达模式存在显著差异。值得注意的是，CD30+TMF 表现出 T 细胞受体信号通路的富集和耗竭的 T 细胞表型，伴有 B 细胞、树突状细胞和神经元浸润。相比之下，cALCL 细胞表达高水平的 HLA Ⅱ类基因，向 Th17 表型极化，并伴有中性粒细胞浸润。BATF3 和 TCF7 染色的 IHC 算法可能成为识别这两种实体的潜在诊断标志物。
我们的研究结果提供了关于 cALCL 和 CD30+TMF 相关差异分子特征的宝贵见解，有助于了解它们不同的临床病理行为。适当的 IHC 算法可以作为一种潜在的诊断工具。
