Abdulla Farah R, Zhang Weiwei, Wu Xiwei, Honda Kord, Qin Hanjun, Cho Hyejin, Querfeld Christiane, Zain Jasmine, Rosen Steven Terry, Chan Wing C, Parekh Vishwas, Song Joo Y
Department of Surgery, City of Hope National Medical Center, Duarte, California, USA.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
JID Innov. 2021 Nov 15;2(1):100068. doi: 10.1016/j.xjidi.2021.100068. eCollection 2022 Jan.
Primary cutaneous CD30 T-cell lymphoproliferative disorders are the second most common cutaneous lymphomas. According to the World Health Organization, CD30 T-cell lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. C-ALCL and LyP are thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms but share the same histology of medium to large CD30 atypical lymphoid cell infiltrates. Because the behavior of these entities is different clinically and prognostically, we aim to search for oncogenic genomic variants using whole-exome sequencing that drive the development of LyP and C-ALCL. Clinical information, pathology, immunohistochemistry, and T-cell rearrangements on six cases of LyP and five cases of C-ALCL were reviewed to confirm the rendered diagnosis before whole-exome sequencing of all specimens. Both LyP and C-ALCL had recurrent alterations in epigenetic modifying genes affecting histone methylation and acetylation (, , , and ). However, they also harbor unique differences with mutations in signal transducer and activator of transcription gene of the Jak/signal transducer and activator of transcription pathway and , a transcription factor involved in lymphocyte development, only noted in C-ALCL specimens. Genomic characterization of LyP and C-ALCL in this series confirms the role of multiple pathways involved in the biology and development of these lymphomatous processes. The identification of similar aberrations within the epigenetic modifying genes emphasizes common potential development mechanisms of lymphomagenesis within lymphoproliferative disorders being shared between LyP and C-ALCL; however, the presence of differences may account for the differences in clinical course.
原发性皮肤CD30 T细胞淋巴增殖性疾病是第二常见的皮肤淋巴瘤。根据世界卫生组织的分类，CD30 T细胞淋巴增殖性疾病包括原发性皮肤间变性大细胞淋巴瘤（C-ALCL）和淋巴瘤样丘疹病（LyP）以及交界性病变。C-ALCL和LyP被认为代表了一系列疾病的两端，它们在经典形式下具有不同的临床表现、临床病程和预后，但具有相同的组织学特征，即中等至大的CD30非典型淋巴细胞浸润。由于这些实体在临床和预后方面的行为不同，我们旨在通过全外显子测序寻找驱动LyP和C-ALCL发生发展的致癌基因组变异。在对所有标本进行全外显子测序之前，回顾了6例LyP和5例C-ALCL的临床信息、病理、免疫组化和T细胞重排情况，以确认诊断。LyP和C-ALCL在影响组蛋白甲基化和乙酰化的表观遗传修饰基因中均有反复改变（……）。然而，它们也存在独特差异，Jak/信号转导及转录激活因子途径的信号转导和转录激活因子基因 以及参与淋巴细胞发育的转录因子 的突变仅在C-ALCL标本中被发现。本系列中LyP和C-ALCL的基因组特征证实了多种途径在这些淋巴瘤形成过程的生物学和发展中所起的作用。表观遗传修饰基因中相似畸变的鉴定强调了LyP和C-ALCL之间在淋巴增殖性疾病中淋巴瘤发生的共同潜在发展机制；然而，差异的存在可能解释了临床病程的不同。
