Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
Mod Pathol. 2023 Jun;36(6):100182. doi: 10.1016/j.modpat.2023.100182. Epub 2023 Apr 5.
Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.
黏液腺腺瘤（MGA）是一种罕见的良性肿瘤，通常发生在近端气道，由类似于支气管腺体的分泌黏液细胞组成。在这里，我们报告了 2 例 MGA 病例，并比较了 19 例其他 5 种组织学类型（浸润性黏液性腺癌、黏液表皮样癌、混合鳞状细胞和腺性乳头状瘤、细支气管腺瘤/纤毛黏液性乳头状肿瘤和唾液腺乳头瘤）的肿瘤的形态、免疫组织化学和分子特征。2 例 MGA 分别位于 1 例男性患者和 1 例女性患者的支气管和气管中。对 1 例 MGA 进行了 RNA 测序，未发现潜在的驱动突变（包括 BRAF、KRAS 和 AKT1 突变）或基因融合。在另 1 例 MGA 中，BRAF 的 V600E 突变和 AKT1 的 E17K 突变分别未通过等位基因特异性实时 PCR 或数字 PCR 检测到。然而，基因表达分析显示，MGA 呈现出特定的 RNA 表达谱，多个基因在唾液腺中富集。与正常对照肺相比，MGA 病例的 NKX3.1 基因表达显著升高（P<0.001）。然后，我们对 2 例 MGA 和 5 种其他组织学类型的 19 例肿瘤进行了 NKX3.1 免疫组织化学检测。MGA 中 NKX3.1 阳性（2/2，100%），而在其他组织学类型中，所有成分细胞（包括黏液细胞）均为 NKX3.1 阴性（0%，0/19）。在正常肺组织中，NKX3.1 阳性表达于支气管腺的黏液性腺泡细胞。总之，基因表达谱、MGA 与支气管腺之间的组织学相似性以及肿瘤的好发位置（近端气道伴黏膜下腺）提示 MGA 是黏液性支气管腺的肿瘤性对应物。NKX3.1 免疫组织化学检测可作为一种敏感而特异的辅助标志物，有助于将 MGA 与其他组织学模拟物区分开来。
