Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Eye Clinic, University Hospital Basel, Basel, Switzerland.
Hematol Oncol. 2020 Aug;38(3):284-292. doi: 10.1002/hon.2718. Epub 2020 Feb 16.
The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS. The study included 34 OA-MZL, 11 chronic conjunctivitis, five mature small cell B-cell lymphomas spreading to the OA, five diseases with increase of IgG4+ plasma cells, three Burkitt lymphomas (BL), three diffuse large B-cell lymphomas (DLBCL), three mantle cell lymphomas, three idiopathic orbital inflammations/orbital pseudo tumors (PT), and three OA lymphoid hyperplasia. All cases were negative for Chlamydia. The mutational number was highest in BL and lowest in PT. The most commonly (and exclusively) mutated gene in OA-MZL was TNFAIP3 (10 of 34 cases). Altogether, 20 out of 34 patients harbored mutually exclusive mutations of either TNFAIP3, BCL10, MYD88, ATM, BRAF, or NFKBIE, or nonexclusive mutations of IRF8, TNFRSF14, KLHL6, and TBL1XR1, all encoding for NK-κB pathway compounds or regulators. Thirteen patients (38%) had, to a great part, mutually exclusive mutations of chromatin modifier-encoding genes: KMT2D, CREBBP, BCL7A, DNMT3A, EP300, or HIST1H1E. Only four patients harbored co-occurring mutations of genes encoding for NK-κB compounds and chromatin modifiers. Finally, PTEN, KMT2D, PRDM1, and HIST1H2BK mutations were observable in reactive lymphoid lesions too, while such instances were devoid of NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes. In conclusion, 80% of OA-MZL display mutations of either NK-κB compounds or chromatin modifiers. Lymphoid lesions of the OA bearing NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes highly likely represent lymphomas.
大多数眼附属器（OA）淋巴瘤（OAL）是结外边缘区淋巴瘤（MZL）。首次针对 OA-MZL 的高通量测序（HTS）研究结果不一致，并且该解剖区域的反应性淋巴病变的突变分布尚未得到充分解决。我们通过靶向 HTS 对 OAL 和 OA 的淋巴病变进行了表征。该研究包括 34 例 OA-MZL、11 例慢性结膜炎、5 例成熟小 B 细胞淋巴瘤扩散至 OA、5 例 IgG4+浆细胞增多症、3 例 Burkitt 淋巴瘤（BL）、3 例弥漫性大 B 细胞淋巴瘤（DLBCL）、3 例套细胞淋巴瘤、3 例特发性眼眶炎症/眶假瘤（PT）和 3 例 OA 淋巴组织增生。所有病例均为沙眼衣原体阴性。突变数量在 BL 中最高，在 PT 中最低。在 OA-MZL 中最常见（且唯一）突变的基因是 TNFAIP3（34 例中有 10 例）。总的来说，34 例患者中有 20 例存在 TNFAIP3、BCL10、MYD88、ATM、BRAF 或 NFKBIE 的相互排斥突变，或 IRF8、TNFRSF14、KLHL6 和 TBL1XR1 的非排他性突变，所有这些突变都编码 NK-κB 途径化合物或调节剂。13 名患者（38%）具有很大程度上相互排斥的染色质修饰基因编码突变：KMT2D、CREBBP、BCL7A、DNMT3A、EP300 或 HIST1H1E。只有 4 名患者同时存在编码 NK-κB 化合物和染色质修饰基因的突变。最后，在反应性淋巴病变中也可观察到 PTEN、KMT2D、PRDM1 和 HIST1H2BK 的突变，而这些病例缺乏 NF-κB 化合物突变和/或乙酰转移酶编码基因的突变。总之，80%的 OA-MZL 显示 NK-κB 化合物或染色质修饰基因的突变。携带 NF-κB 化合物突变和/或乙酰转移酶编码基因突变的 OA 淋巴病变极有可能代表淋巴瘤。
