Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.
Mod Pathol. 2018 Jun;31(6):923-933. doi: 10.1038/s41379-018-0025-7. Epub 2018 Feb 12.
Hyalinizing clear cell carcinoma of the bronchial glands is a very rare tumor. Since only five reports describing six tumors have been published to date, only a little is known about specific histologic findings and clinical features. Because of its rarity, hyalinizing clear cell carcinoma has not been described in the latest WHO classification of pulmonary tumors yet. Here we present three cases of bronchial hyalinizing clear cell carcinomas, confirmed by both fluorescence in situ hybridization (FISH) and RT-PCR, focusing on histologic and immunohistochemical characteristics in a comparison with three cases of salivary gland origin. In addition, we compared immunohistochemical features with bronchial mucoepidermoid carcinoma, a lesion that needs to be taken into account in differential diagnosis of hyalinizing clear cell carcinoma. All our bronchial hyalinizing clear cell carcinoma cases were surgically resected. Histologically, tumor cells showed clear to eosinophilic cytoplasm with hyalinizing stroma in various proportions, resembling those of salivary gland origin. Immunohistochemically, tumor cells were positive for CK7, CK5/6, p40, p63, and ATF1, while they were negative for TTF1, Napsin A, HMB45, and SOX10. The CK5/6 staining pattern varied in mucoepidermoid carcinomas, while that of hyalinizing clear cell carcinoma was uniformly positive. FISH revealed EWSR1-ATF1 fusion, and RT-PCR with sequencing confirmed specificity of the chimeric gene for hyalinizing clear cell carcinoma. Clinically, bronchial hyalinizing clear cell carcinoma was characterized by occurrence in the fourth to sixth decades, no link with smoking history, and a predilection for the right lung, in line with previous reports. In summary, our study confirmed that the bronchial hyalinizing clear cell carcinoma is a histologically and genetically identical tumor to that of salivary gland origin, and that gene rearrangement analysis can play a critical role in distinction from mucoepidermoid carcinoma.
支气管涎腺型透明细胞癌是一种非常罕见的肿瘤。由于迄今为止仅发表了五份描述六个肿瘤的报告，因此对其特定的组织学发现和临床特征知之甚少。由于其罕见性，支气管涎腺型透明细胞癌尚未在最新的 WHO 肺部肿瘤分类中描述。在此，我们通过荧光原位杂交（FISH）和 RT-PCR 证实了 3 例支气管透明细胞癌，并与 3 例涎腺来源的病例进行了组织学和免疫组织化学特征的比较。此外，我们还比较了免疫组织化学特征与需要考虑在透明细胞癌鉴别诊断中的支气管黏液表皮样癌。我们所有的支气管透明细胞癌病例均通过手术切除。组织学上，肿瘤细胞显示出透明至嗜酸性细胞质，伴有透明化的基质，与涎腺来源的肿瘤相似。免疫组织化学上，肿瘤细胞对 CK7、CK5/6、p40、p63 和 ATF1 呈阳性，而对 TTF1、Napsin A、HMB45 和 SOX10 呈阴性。黏液表皮样癌的 CK5/6 染色模式不同，而透明细胞癌的染色模式则是一致阳性。FISH 显示 EWSR1-ATF1 融合，RT-PCR 测序证实了透明细胞癌的嵌合基因的特异性。临床上，支气管透明细胞癌的特点是发生在第四至第六个十年，与吸烟史无关，且偏爱右肺，与以往报道一致。总之，我们的研究证实，支气管透明细胞癌与涎腺来源的肿瘤在组织学和遗传学上是相同的，基因重排分析在与黏液表皮样癌的鉴别中起着至关重要的作用。
