Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and Lausanne University, Lausanne.
Department of Medicine, Division of Hematology.
Am J Surg Pathol. 2021 Jun 1;45(6):773-786. doi: 10.1097/PAS.0000000000001646.
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular helper immunophenotype and similar mutations consisting of TET2 or DNMT3A alterations, IDH2 R172K/M, and RHOA G17V. The 3 patients received chemotherapy. One died of early AITL relapse. The other 2 remained in complete remission of AITL, 1 died with recurrent CLL, and 1 of acute myeloid leukemia. These observations expand the spectrum of T-cell lymphoma entities that occur in association with CLL/SLL, adding AITL to the rare variants of aggressive neoplasms manifesting as Richter syndrome. Given that disturbances of T-cell homeostasis in CLL/SLL affect not only cytotoxic but also helper T-cell subsets, these may contribute to the emergence of neoplasms of T follicular helper derivation.
慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL/SLL)是一种惰性小 B 细胞肿瘤,可能转化为临床侵袭性疾病,即里希特综合征,通常为弥漫性大 B 细胞淋巴瘤。此外,CLL/SLL 发生其他继发性癌症的风险增加,包括各种 T 细胞淋巴瘤,通常为间变性大细胞型或具有细胞毒性表型。在这里,我们报告了一组由 CLL/SLL 和血管免疫母细胞性 T 细胞淋巴瘤(AITL)组成的复合淋巴瘤患者的小系列,这是一种以前未被认识到的关联。这 3 名患者(1 名男性/2 名女性,68 至 83 岁)表现出高级别症状。1 名患者临床疑似里希特综合征,另外 2 名患者同时诊断为 CLL/SLL 和 AITL。CLL/SLL 和 AITL 混合在同一淋巴结(3/3 例)和骨髓(2/2 例)中。在所有病例中,AITL 均包含明显的透明细胞,具有强烈的 T 滤泡辅助免疫表型,以及相似的突变,包括 TET2 或 DNMT3A 改变、IDH2 R172K/M 和 RHOA G17V。3 名患者接受了化疗。1 例死于早期 AITL 复发。另外 2 例仍处于 AITL 完全缓解中,1 例死于复发性 CLL,1 例死于急性髓系白血病。这些观察结果扩展了与 CLL/SLL 相关的 T 细胞淋巴瘤实体的范围,将 AITL 添加到表现为里希特综合征的罕见侵袭性肿瘤的罕见变体中。鉴于 CLL/SLL 中 T 细胞稳态的紊乱不仅影响细胞毒性细胞,还影响辅助性 T 细胞亚群,这可能有助于起源于滤泡辅助 T 细胞的肿瘤的出现。