Wei Calvin, Sirikanjanapong Sasis, Lieberman Seth, Delacure Mark, Martiniuk Frank, Levis William, Wang Beverly Y
Department of Otolaryngology, New York University School of Medicine, New York, NY, USA.
Ear Nose Throat J. 2013 Jan;92(1):36-40. doi: 10.1177/014556131309200112.
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.
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。