Ohara Nobumasa, Kaneko Masanori, Ikeda Masahiro, Ishizaki Fumio, Suzuki Kazuya, Maruyama Ryo, Komeyama Takeshi, Sato Kazuhiro, Togashi Kenichi, Usuda Hiroyuki, Yamazaki Yuto, Sasano Hironobu, Kaneko Kenzo, Kamoi Kyuzi
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, Niigata, Japan; Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, Niigata, Japan.
Respir Med Case Rep. 2016 Dec 18;20:77-81. doi: 10.1016/j.rmcr.2016.12.002. eCollection 2017.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor gene , which encodes a nuclear protein, menin. MEN1 is characterized by the combined occurrence of tumors involving the pituitary gland, pancreatic islets, and parathyroid glands. Additionally, patients with MEN1 often exhibit adrenal tumors. Although most MEN1-associated tumors are benign, malignant lesions arising in these endocrine organs have been reported. Additionally, malignant diseases of non-endocrine organs concomitant with MEN1 have also been reported. Here, we report a rare case of a MEN1 patient who exhibited adrenocortical carcinoma (ACC) and lung adenocarcinoma (LAC). A 53-year-old Japanese woman was diagnosed with genetically proven MEN1 that initially manifested as parathyroid, pancreatic, and adrenal tumors. During the course of the disease, she developed LAC harboring the epidermal growth factor receptor gene mutations and cortisol-secreting ACC. Both tumors were surgically resected. The tumor cells were immunohistochemically negative for menin. Studies have suggested a causative link between gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role of gene mutations in LAC. Menin is often inactivated in the LACs of patients without MEN1. Thus, our patient's ACC probably occurred as part of MEN1, whereas the latter had no evident etiological association with her LAC. This case demonstrates the need for physicians to consider the potential development of malignant diseases originating from both endocrine and non-endocrine organs in MEN1 patients.
多发性内分泌腺瘤1型（MEN1）是一种常染色体显性疾病，由肿瘤抑制基因的杂合种系突变引起，该基因编码一种核蛋白，即Menin。MEN1的特征是垂体、胰岛和甲状旁腺同时发生肿瘤。此外，MEN1患者常出现肾上腺肿瘤。虽然大多数与MEN1相关的肿瘤是良性的，但这些内分泌器官中也有恶性病变的报道。此外，与MEN1相关的非内分泌器官恶性疾病也有报道。在此，我们报告一例罕见的MEN1患者，该患者表现为肾上腺皮质癌（ACC）和肺腺癌（LAC）。一名53岁的日本女性被诊断为经基因证实的MEN1，最初表现为甲状旁腺、胰腺和肾上腺肿瘤。在疾病过程中，她发展为携带表皮生长因子受体基因突变的LAC和分泌皮质醇的ACC。两种肿瘤均通过手术切除。肿瘤细胞免疫组化检测Menin呈阴性。研究表明基因突变与ACC之间存在因果关系，且Menin表达可能在MEN1相关的ACC中降低。相比之下，很少有报告表明基因突变在LAC中起特定作用。在没有MEN1的患者的LAC中，Menin常常失活。因此，我们患者的ACC可能是MEN1的一部分，而后者与她的LAC没有明显的病因学关联。该病例表明医生有必要考虑MEN1患者发生内分泌和非内分泌器官恶性疾病的潜在可能性。
