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Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

检查点抑制时代的玻璃体内皮肤转移性黑色素瘤: 揭穿和伪装。

  • 影响因子:4.19
  • DOI:10.1016/j.ophtha.2019.09.018
  • 作者列表:"Francis JH","Berry D","Abramson DH","Barker CA","Bergstrom C","Demirci H","Engelbert M","Grossniklaus H","Hubbard B","Iacob CE","Jaben K","Kurli M","Postow MA","Wolchok JD","Kim IK","Wells JR
  • 发表时间:2020-02-01

PURPOSE:Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN:Multicenter, retrospective cohort study. PARTICIPANTS:Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS:Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES:Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS:The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS:The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.


目的: 皮肤黑色素瘤转移至玻璃体是非常罕见的。本研究调查了转移性皮肤黑色素瘤至玻璃体患者的临床发现、治疗和结局。大多数患者接受检查点抑制治疗全身性疾病,并探讨其意义。 设计: 多中心、回顾性队列研究。 对象: 转移性皮肤黑色素瘤至玻璃体 11 例 14 眼。 方法: 回顾性分析临床记录,包括眼底照相和超声结果,并记录每例患者眼的相关数据。 主要结局指标: 就诊时的临床特征、眼科和全身治疗以及结局。 结果: 眼科疾病就诊时的中位年龄为 66 岁 (范围 23-88 岁),眼科疾病诊断后的中位随访时间为 23 个月。11 例患者中 10 例在治疗过程中的某个时间点进行免疫检查点抑制治疗。从开始免疫治疗到眼部症状的中位时间为 17 个月 (范围 4.5-38 个月)。一半的眼睛表现出无色素性玻璃体碎片。5 只眼表现为眼压升高,4 只眼表现为视网膜脱离。6 例患者表现为中枢神经系统转移性疾病。眼科治疗: 外照射 (30-4 0 Gy) 6 眼,玻璃体内美法仑 (1 0-2 0 μ g) 4 眼,眼球摘除 1 眼,2 眼在接受全身治疗的同时进行局部观察。3 只眼接受玻璃体内注射贝伐单抗治疗新生血管。最终Snellen视力从 20/20 到无光感。 结论: 转移性皮肤黑素瘤背景下玻璃体碎片的鉴别诊断疾病包括玻璃体内转移,这在这个检查点抑制治疗的时代似乎尤为明显。外照射、玻璃体内美法仑和全身检查点抑制可用于眼科疾病的治疗。可能发生新生血管性青光眼和视网膜脱离,大多数眼睛显示出较差的视觉潜能。大约四分之一的患者表现出中枢神经系统转移前的眼部疾病。在转移性皮肤黑色素瘤背景下出现视觉症状或玻璃体碎片的患者将受益于眼科肿瘤学家的评估。



作者列表:["Zhang B","Li L","Zhang N","Zhao M","Liu Y","Wei L","Ma L","Xu Z"]

METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.

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作者列表:["Pham CT","Juhasz M","Sung CT","Mesinkovska NA"]

METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

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作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.

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