Department of Diagnostics and Public Health, Section of Anatomic Pathology, University of Verona, Verona, Italy.
ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy.
Neuropathology. 2022 Apr;42(2):160-166. doi: 10.1111/neup.12789. Epub 2022 Feb 10.
We report a case of oligodendroglioma that had consistent histopathological features as well as a distinct change in 1p/19q status in the second recurrence, after temozolomide chemotherapy and radiotherapy. The first tumor recurrence had oligodendroglial morphology, IDH1 R132H and TERT promoter mutations, and 1p/19q codeletion detected by fluorescent in situ hybridization (FISH). Copy number analysis, assessed by next-generation sequencing, confirmed 1p/19q codeletion, and disclosed loss of heterozygosity (LOH) of chromosomes 4 and 9 and chromosome 11 gain. The second recurrence featured not only oligodendroglial morphology but also the appearance of admixed multinucleated giant cells or neoplastic cells having oval nuclei and mitoses and showing microvascular proliferation; it maintained IDH1 R132H and TERT promoter mutations, acquired TP53 mutation, and showed 19q LOH, but disomic 1p, detected by FISH. Copy number analysis depicted LOH of chromosomes 3p, 13, and 19q, 1p partial deletion (1p chr1p34.2-p11), and gain of chromosomes 2p25.3-p24.1, 8q12.2-q24.3, and 11q13.3-q25. B-allele frequency analysis of polymorphic sites disclosed copy-neutral LOH at 1p36.33-p34.2, supporting the initial deletion of 1p, followed by reduplication of 1p36.33-p34.2 alone. These findings suggest that the two tumor recurrences might have originated from an initial neoplastic clone, featuring 1p/19q codeletion and IDH1 and TERT promoter mutations, and have independently acquired other copy number alterations. The reduplication of chromosome 1p might be the result of temozolomide treatment, and gave rise to false negative 1p deletion detected by FISH. The possibility of 1p copy-neutral LOH should be considered in recurrent oligodendrogliomas with altered 1p/19q status detected by FISH.
我们报告了一例在替莫唑胺化疗和放疗后第二次复发的少突胶质细胞瘤,其具有一致的组织病理学特征以及 1p/19q 状态的明显变化。第一次肿瘤复发具有少突胶质细胞形态、IDH1 R132H 和 TERT 启动子突变,并通过荧光原位杂交(FISH)检测到 1p/19q 缺失。通过下一代测序评估的拷贝数分析证实 1p/19q 缺失,并揭示染色体 4 和 9 的杂合性丢失(LOH)和染色体 11 的增益。第二次复发不仅具有少突胶质细胞形态,而且还出现混合多核巨细胞或肿瘤细胞,具有椭圆形核和有丝分裂,并表现出微血管增生;它保持 IDH1 R132H 和 TERT 启动子突变,获得 TP53 突变,并显示 19q LOH,但通过 FISH 检测到二倍体 1p。拷贝数分析描绘了染色体 3p、13 和 19q 的 LOH、1p 部分缺失(1p chr1p34.2-p11)以及染色体 2p25.3-p24.1、8q12.2-q24.3 和 11q13.3-q25.3 的增益。多态性位点的 B-等位基因频率分析显示 1p36.33-p34.2 处的拷贝数中性 LOH,支持 1p 的初始缺失,随后单独重复 1p36.33-p34.2。这些发现表明,两个肿瘤复发可能源自最初的肿瘤克隆,具有 1p/19q 缺失和 IDH1 和 TERT 启动子突变,并独立获得了其他拷贝数改变。染色体 1p 的重复可能是替莫唑胺治疗的结果,并导致 FISH 检测到的 1p 缺失呈假阴性。在通过 FISH 检测到改变的 1p/19q 状态的复发性少突胶质细胞瘤中,应考虑 1p 拷贝数中性 LOH 的可能性。