title: Lung adenocarcinoma and adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1.
abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor geneMEN1, 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 betweenMEN1gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role ofMEN1gene 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.
authors.affiliation: 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.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Ohara
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Ishizaki
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Urology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Komeyama
authors.affiliation: Department of Respiratory Medicine, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Thoracic Surgery, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Togashi
authors.affiliation: Department of Pathology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Usuda
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Internal Medicine, Ojiya General Hospital, Niigata, Japan; Center of Diabetes, Endocrinology and Metabolism, Joetsu General Hospital, Niigata, Japan.
authors.forename: Kyuzi
authors.initials: K
authors.lastname: Kamoi
keywords: ACC, adrenocortical carcinoma; ALK, anaplastic lymphoma kinase; Adrenocortical carcinoma; CT, computed tomography; EGFR, epidermal growth factor receptor; Epidermal growth factor receptor gene mutation; Immunohistochemistry; LAC, lung adenocarcinoma; Lung adenocarcinoma; MEN1, multiple endocrine neoplasia type 1; MRI, magnetic resonance imaging; Menin; Multiple endocrine neoplasia type 1; SF-1, steroidogenic factor; TTF-1, thyroid transcription factor-1