Abstract：
BACKGROUND: Leukemic infiltration of the eye and ocular adnexal site is rare with unknown risk factors and clinical outcomes.
OBJECTIVE: To describe the clinical characteristics of extramedullary ocular adnexal (OA) leukemia in patients with myeloid malignancies.
METHODS: In a retrospective analysis, we screened all patients treated at our center between 1993 and 2022. We identified 50 patients with myeloid malignancies who presented with vision changes with available magnetic resonance imaging of the orbits.
RESULTS: Among all 50 patients, 38 had their symptoms attributed to an infection, 2 to retinal hemorrhage with thrombocytopenia, 1 to chronic graft-vs-host disease and 1 to dacrocystocele. The remaining 8 patients (7 AML, 1 MDS) had leukemic infiltration of the eye and OA, diagnosed by imaging (7/8) or biopsy (1/8). The median age was 47 years (18-82), 6 (75%) were females. The optic nerve was most frequently affected in 7/8 patients, followed by infiltration of the cranial nerve (CN) III and intraconal soft tissues in 2/8 patients, each. Infiltration of the retina, lateral rectus muscle, CN IV, CN VI, and extraconal soft tissue was seen in 1/8 patient, each. Spinal fluid evaluation identified no evidence of leukemia in all 8 patients. Interestingly, 4/8 patients (50%) had abnormalities in chromosome 3q26 or MDS1 and EVI1 complex locus (MECOM) rearrangements, 2 (25%) had Lysine Methyltransferase 2A (KMT2A) rearrangement and the remaining two had trisomy 8 and a diploid karyotype respectively. Patients with KMT2A rearrangement also had other sites of extramedullary disease, while orbital adnexal involvement was the only extramedullary leukemia site in those with MECOM rearrangements. Intrathecal chemotherapy and concurrent local radiation were given to 6/8 patients while the other 2 received either intrathecal chemotherapy or radiation. Symptoms improved or resolved following these measures in 4/8 patients. These visual findings were detected during salvage therapy (median 4, range 1-9 lines). Overall survival following appearance of these findings was short with a median of 5.8 months (range: 0.4-17.5).
CONCLUSIONS: Leukemic infiltration of the orbital adnexa in myeloid malignancies is rare and associated with an inordinately high proportion of MECOM rearrangements in addition to adverse outcomes.
OBJECTIVE: To describe the clinical characteristics of extramedullary ocular adnexal (OA) leukemia in patients with myeloid malignancies.
METHODS: In a retrospective analysis, we screened all patients treated at our center between 1993 and 2022. We identified 50 patients with myeloid malignancies who presented with vision changes with available magnetic resonance imaging of the orbits.
RESULTS: Among all 50 patients, 38 had their symptoms attributed to an infection, 2 to retinal hemorrhage with thrombocytopenia, 1 to chronic graft-vs-host disease and 1 to dacrocystocele. The remaining 8 patients (7 AML, 1 MDS) had leukemic infiltration of the eye and OA, diagnosed by imaging (7/8) or biopsy (1/8). The median age was 47 years (18-82), 6 (75%) were females. The optic nerve was most frequently affected in 7/8 patients, followed by infiltration of the cranial nerve (CN) III and intraconal soft tissues in 2/8 patients, each. Infiltration of the retina, lateral rectus muscle, CN IV, CN VI, and extraconal soft tissue was seen in 1/8 patient, each. Spinal fluid evaluation identified no evidence of leukemia in all 8 patients. Interestingly, 4/8 patients (50%) had abnormalities in chromosome 3q26 or MDS1 and EVI1 complex locus (MECOM) rearrangements, 2 (25%) had Lysine Methyltransferase 2A (KMT2A) rearrangement and the remaining two had trisomy 8 and a diploid karyotype respectively. Patients with KMT2A rearrangement also had other sites of extramedullary disease, while orbital adnexal involvement was the only extramedullary leukemia site in those with MECOM rearrangements. Intrathecal chemotherapy and concurrent local radiation were given to 6/8 patients while the other 2 received either intrathecal chemotherapy or radiation. Symptoms improved or resolved following these measures in 4/8 patients. These visual findings were detected during salvage therapy (median 4, range 1-9 lines). Overall survival following appearance of these findings was short with a median of 5.8 months (range: 0.4-17.5).
CONCLUSIONS: Leukemic infiltration of the orbital adnexa in myeloid malignancies is rare and associated with an inordinately high proportion of MECOM rearrangements in addition to adverse outcomes.
摘要：
背景：眼部和眼附属器部位的白血病浸润很少见，其危险因素和临床结局未知。
目的：描述髓系恶性肿瘤患者的髓外眼附属器（OA）白血病的临床特征。
方法：在回顾性分析中，我们筛选了1993年至2022年间在我们中心接受治疗的所有患者.我们确定了50例髓系恶性肿瘤患者，这些患者通过可用的眼眶磁共振成像表现出视力变化。
结果：在所有50名患者中，38人的症状归因于感染，2视网膜出血伴血小板减少症，1为慢性移植物抗宿主病，1为红细胞膨出。其余8例患者（7例AML，1MDS）有眼部白血病浸润和OA，通过影像学（7/8）或活检（1/8）诊断。中位年龄为47岁（18-82岁），6（75％）为女性。视神经在7/8患者中最常见，其次是2/8患者的颅神经（CN）III和内软组织的浸润，each.视网膜浸润,外侧直肌，CNIV,CNVI,1/8的患者可见外侧软组织，each.在所有8例患者中，脑脊液评估均未发现白血病。有趣的是,4/8患者（50%）染色体3q26或MDS1和EVI1复合物基因座（MECOM）重排异常，2个（25％）具有赖氨酸甲基转移酶2A（KMT2A）重排，其余两个分别具有三体性8和二倍体核型。KMT2A重排患者也有其他部位的髓外疾病，而眼眶附件受累是MECOM重排患者中唯一的髓外白血病部位。对6/8例患者进行了鞘内化疗和同时进行的局部放疗，而其他2例接受了鞘内化疗或放疗。4/8的患者在这些措施后症状得到改善或缓解。这些视觉发现是在抢救治疗期间检测到的(中位数4,范围1-9行)。出现这些发现后的总生存期很短，中位数为5.8个月（范围：0.4-17.5）。
结论：在骨髓性恶性肿瘤中，眼眶附件的白血病浸润是罕见的，并且与MECOM重排比例过高以及不良结局相关。
目的：描述髓系恶性肿瘤患者的髓外眼附属器（OA）白血病的临床特征。
方法：在回顾性分析中，我们筛选了1993年至2022年间在我们中心接受治疗的所有患者.我们确定了50例髓系恶性肿瘤患者，这些患者通过可用的眼眶磁共振成像表现出视力变化。
结果：在所有50名患者中，38人的症状归因于感染，2视网膜出血伴血小板减少症，1为慢性移植物抗宿主病，1为红细胞膨出。其余8例患者（7例AML，1MDS）有眼部白血病浸润和OA，通过影像学（7/8）或活检（1/8）诊断。中位年龄为47岁（18-82岁），6（75％）为女性。视神经在7/8患者中最常见，其次是2/8患者的颅神经（CN）III和内软组织的浸润，each.视网膜浸润,外侧直肌，CNIV,CNVI,1/8的患者可见外侧软组织，each.在所有8例患者中，脑脊液评估均未发现白血病。有趣的是,4/8患者（50%）染色体3q26或MDS1和EVI1复合物基因座（MECOM）重排异常，2个（25％）具有赖氨酸甲基转移酶2A（KMT2A）重排，其余两个分别具有三体性8和二倍体核型。KMT2A重排患者也有其他部位的髓外疾病，而眼眶附件受累是MECOM重排患者中唯一的髓外白血病部位。对6/8例患者进行了鞘内化疗和同时进行的局部放疗，而其他2例接受了鞘内化疗或放疗。4/8的患者在这些措施后症状得到改善或缓解。这些视觉发现是在抢救治疗期间检测到的(中位数4,范围1-9行)。出现这些发现后的总生存期很短，中位数为5.8个月（范围：0.4-17.5）。
结论：在骨髓性恶性肿瘤中，眼眶附件的白血病浸润是罕见的，并且与MECOM重排比例过高以及不良结局相关。
