Department of Oral & Maxillofacial Surgery, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Division for Health Service Promotion, University of Tokyo, Tokyo, Japan.
BMC Cancer. 2019 Jan 11;19(1):52. doi: 10.1186/s12885-019-5277-1.
Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs.
A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD.
A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.
不明原发灶肿瘤（CUPs）据报道是癌症死亡的第三或第四大常见原因。近年来，基因突变分析和基因组分析技术取得了进展。这些进展可以提高 CUPs 诊断的准确性，并可能改善 CUPs 患者的预后。
一名 76 岁男性患有肺部不明原发灶腺癌，现又出现了另一个腭黏膜肿瘤。胸腔积液中的肿瘤细胞免疫组织化学标志物（TTF-1 和 Napsin A）和肺特异性致癌驱动突变（EGFR 突变和 ALK 易位）均为阴性。腭黏膜肿瘤同样被鉴定为腺癌，细胞与胸腔积液中的肿瘤细胞具有细胞学相似性；TTF-1、Napsin A、EGFR 突变和 ALK 易位均为阴性。这一结果表明，尽管原发灶尚未确定，但腭黏膜肿瘤和肺部肿瘤的起源相同。接下来，我们探讨了腭黏膜肿瘤是否为原发性肿瘤。考虑到可能是一种常见的小涎腺癌（MSGT）——分泌癌（SC），但 mammaglobin 为阴性，未观察到 ETV6-NTRK3（EN）融合。根据组织学和免疫组织化学结果排除了其他 MSGT。此外，进一步检查发现腭部肿瘤和胸腔积液均存在致癌 KRAS 突变密码子 12（p.G12D）。KRAS 突变已知存在于三分之一的肺腺癌（LUAD）中，但在 MSGT 中相当罕见。内窥镜和影像学研究结果提示其他器官转移的可能性不大。这一结果表明，CUP 的原发部位确实是肺部，而腭黏膜肿瘤是 LUAD 的转移灶。
通过基因组改变和组织病理学发现，确定具有诊断困难的腭黏膜肿瘤为转移性 LUAD。
