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Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation.起源于咽鼓管且伴有细胞毒性T淋巴细胞相关抗原4(CTLA-4)、白细胞介素-17A(IL-17A)、白细胞介素-17C(IL-17C)和白细胞介素-17E(IL-17E)上调的原发性黏膜黑色素瘤
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Primary Middle Ear Mucosal Melanoma: Case Report and Comprehensive Literature Review of 21 Cases of Primary Middle Ear and Eustachian Tube Melanoma.原发性中耳黏膜黑色素瘤:病例报告及21例原发性中耳和咽鼓管黑色素瘤的综合文献综述
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引用本文的文献

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Mucosal Melanoma of Eustachian Tube: A Case Report.咽鼓管黏膜黑色素瘤:一例报告。
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本文引用的文献

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CTLA4 blockade increases Th17 cells in patients with metastatic melanoma.CTLA4阻断可增加转移性黑色素瘤患者的Th17细胞。
J Transl Med. 2009 May 20;7:35. doi: 10.1186/1479-5876-7-35.
2
Effects of high-dose IFNalpha2b on regional lymph node metastases of human melanoma: modulation of STAT5, FOXP3, and IL-17.高剂量干扰素α2b对人黑色素瘤区域淋巴结转移的影响:信号转导和转录激活因子5、叉头框蛋白P3及白细胞介素-17的调节作用
Clin Cancer Res. 2008 Dec 15;14(24):8314-20. doi: 10.1158/1078-0432.CCR-08-0705.
3
CTLA-4 control over Foxp3+ regulatory T cell function.细胞毒性T淋巴细胞相关抗原4对叉头框蛋白3阳性调节性T细胞功能的调控
Science. 2008 Oct 10;322(5899):271-5. doi: 10.1126/science.1160062.
4
MR imaging features of primary mucosal melanoma of the eustachian tube: report of 2 cases.咽鼓管原发性黏膜黑色素瘤的磁共振成像特征:2例报告
AJNR Am J Neuroradiol. 2009 Feb;30(2):431-3. doi: 10.3174/ajnr.A1270. Epub 2008 Sep 3.
5
CTLA-4 is a direct target of Wnt/beta-catenin signaling and is expressed in human melanoma tumors.细胞毒性T淋巴细胞相关抗原4(CTLA-4)是Wnt/β-连环蛋白信号通路的直接靶点,且在人类黑色素瘤肿瘤中表达。
J Invest Dermatol. 2008 Dec;128(12):2870-9. doi: 10.1038/jid.2008.170. Epub 2008 Jun 19.
6
CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion.细胞毒性T淋巴细胞相关抗原4(CTLA4)阻断以剂量依赖的方式扩增叉头框蛋白P3(FoxP3)+调节性和活化效应性CD4+T细胞。
Blood. 2008 Aug 15;112(4):1175-83. doi: 10.1182/blood-2007-11-125435. Epub 2008 Jun 3.
7
Mucosal melanoma of the head and neck.头颈部黏膜黑色素瘤
Am J Clin Oncol. 2008 Feb;31(1):43-8. doi: 10.1097/COC.0b013e318134ee88.
8
IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis.白细胞介素-17B和白细胞介素-17C与肿瘤坏死因子-α的产生相关,并促使炎性关节炎加重。
J Immunol. 2007 Nov 15;179(10):7128-36. doi: 10.4049/jimmunol.179.10.7128.
9
Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant.白细胞介素-23作为癌症疫苗佐剂的免疫及抗肿瘤作用
J Immunol. 2006 May 1;176(9):5213-22. doi: 10.4049/jimmunol.176.9.5213.
10
Mucosal melanoma arising in the eustachian tube.起源于咽鼓管的黏膜黑色素瘤。
J Laryngol Otol. 2006 Mar;120(3):E17. doi: 10.1017/s0022215106004762.

起源于咽鼓管且伴有细胞毒性T淋巴细胞相关抗原4(CTLA-4)、白细胞介素-17A(IL-17A)、白细胞介素-17C(IL-17C)和白细胞介素-17E(IL-17E)上调的原发性黏膜黑色素瘤

Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation.

作者信息

Wei Calvin, Sirikanjanapong Sasis, Lieberman Seth, Delacure Mark, Martiniuk Frank, Levis William, Wang Beverly Y

机构信息

Department of Otolaryngology, New York University School of Medicine, New York, NY, USA.

出版信息

Ear Nose Throat J. 2013 Jan;92(1):36-40. doi: 10.1177/014556131309200112.

DOI:10.1177/014556131309200112
PMID:23354891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3969881/
Abstract

Primary malignant melanoma arising from the eustachian tube is extremely rare. We report the case of a 63-year-old white man who presented with a 1-month history of left-sided hearing loss and aural fullness. Flexible fiberoptic laryngoscopy detected a blue-purple mass that appeared to arise from the left lateral nasopharynx. Computed tomography demonstrated an enhancing mass arising from an orifice of the left eustachian tube. The tumor was debulked endoscopically and was confirmed to have originated in the left eustachian tube. Histologically, the tumor was made up of heavily pigmented pleomorphic spindle cells with frequent mitoses. The tumor cells were immunohistochemically positive for S-100 protein, HMB-45, Melan-A, and PNL-2. The final diagnosis was a mucosal malignant melanoma. We also performed a nested polymerase chain reaction assay for several genes of interest, including CTLA-4, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, PLZF, Foxp3, RORγt, CD27, and CD70. These genes have been studied mainly in cutaneous melanomas, especially for the development of immunotherapy, but only very limited studies have been done on mucosal melanomas. Our investigation found upregulation of CTLA-4, IL-17A, IL-17C, and IL-17E. Based on our finding of CTLA-4 upregulation, it may be suggested that our patient might have had low antitumor immunity and that he might have benefited from CTLA-4 blockade. On the other hand, upregulation of IL-17A and IL-17E might reflect increased antitumor immunity, which could suggest that patients with a mucosal melanoma might benefit from immunomodulators associated with the effect of Th17. These genes also have great potential to help melanoma patients obtain tailored treatment, and they can be used as biomarkers for predicting prognosis.

摘要

起源于咽鼓管的原发性恶性黑色素瘤极为罕见。我们报告了一例63岁白人男性病例,该患者有1个月的左侧听力损失和耳闷病史。纤维软性喉镜检查发现一个蓝紫色肿物,似乎起源于左侧鼻咽部。计算机断层扫描显示一个强化肿物起源于左侧咽鼓管开口处。肿瘤通过内镜进行了减瘤手术,并证实起源于左侧咽鼓管。组织学上,肿瘤由大量色素沉着的多形性梭形细胞组成,有频繁的有丝分裂。肿瘤细胞免疫组化检测S-100蛋白、HMB-45、Melan-A和PNL-2呈阳性。最终诊断为黏膜恶性黑色素瘤。我们还对多个感兴趣的基因进行了巢式聚合酶链反应检测,包括CTLA-4、IL-17A、IL-17B、IL-17C、IL-17D、IL-17E、IL-17F、PLZF、Foxp3、RORγt、CD27和CD70。这些基因主要在皮肤黑色素瘤中进行了研究,特别是用于免疫治疗的开发,但对黏膜黑色素瘤的研究非常有限。我们的研究发现CTLA-4、IL-17A、IL-17C和IL-17E上调。基于我们发现的CTLA-4上调,可能提示我们的患者抗肿瘤免疫力较低,他可能会从CTLA-4阻断治疗中获益。另一方面,IL-17A和IL-17E上调可能反映抗肿瘤免疫力增强,这可能提示黏膜黑色素瘤患者可能会从与Th17效应相关的免疫调节剂中获益。这些基因在帮助黑色素瘤患者获得个性化治疗方面也有很大潜力,并且可以用作预测预后的生物标志物。