University of the Ryukyus · Faculty of Medicine · 教授

Research keywordssalivary gland tumors・neuroendocrine neoplasms・gynecologic pathology・mesonephric-like adenocarcinoma・PD-L1 expression・HLA status・cervical adenocarcinoma

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• A Case of Leiomyoadenomatoid Tumor of the Epididymis Mimicking Epithelioid Mesothelioma.2025 · Sanematsu A, Teruya K, Nabeshima K, Tanaka K, Inokuchi J, Nishie A, Kawakami F
• Multi-institutional study of mesonephric-like adenocarcinoma: its clinicopathological characteristics and histogenetic association with ectopic endometrium.2025 · To explore the clinicopathological features and origin of mesonephric-like adenocarcinomas (MLAs), 83 cases diagnosed or suspected to be MLAs were collected from various institutions in Japan. We clearly classified 78 as MLAs (uterus: 47, ovary: 31) and 5 as non-MLAs (all ovary) based on our morphological and immunohistochemical criteria. In uterine MLAs (uMLAs), lymphovascular space invasion was an independent prognostic factor for progression-free survival (PFS) (P = 0.03). Patients with uMLAs had significantly shorter PFS and overall survival (OS) than those diagnosed with endometrial endometrioid carcinomas (EECs) (P < 0.0001 and P < 0.001, respectively) and comparable PFS and OS to those with copy number-high tumors. PFS and OS of ovarian MLAs (oMLAs) were similar to those of ovarian endometrioid carcinomas (OECs) overall but worse for patients with stage II-IV. Endometriosis was observed with oMLAs as often as with OECs (94% vs 93%, respectively). Adenomyosis was more frequently observed with uMLAs than with EECs (62% vs 28%, respectively, P = 0.0005). Six uMLAs were confined to the myometrium and adjacent to adenomyosis. In an analysis of molecularly speculated origin, among 29 oMLAs harboring a KRAS hotspot mutation, 23 (79%) instances of endometriosis in the background had the same mutation. Among 36 uMLAs carrying the KRAS hotspot mutation, common mutations were observed in 12 (33%) instances of adjacent adenomyosis (12/21 [67%] of adenomyosis). These findings suggest a histogenetic link between MLAs and ectopic endometrium, implicating both ovarian endometriosis and adenomyosis in MLA pathogenesis, with potential clinical significance.
• A Rare Case of Brain Metastasis of Gastric Neuroendocrine Carcinoma.2025 · Gastric neuroendocrine carcinoma (small cell neuroendocrine carcinoma [small cell NEC]) is a rare type of gastric cancer that is rarely encountered in clinical practice. Although solitary brain metastasis from gastric cancer is exceptionally rare, we present a case of solitary brain metastasis of gastric NEC. The patient was a 71-year-old man who had undergone surgery and chemotherapy for gastric NEC two years prior. During follow-up, computed tomography (CT) scans of the neck, chest, abdomen, and pelvis, along with tumor marker evaluations, revealed no evidence of metastasis. However, he developed left homonymous hemianopsia, prompting a head CT and magnetic resonance imaging (MRI). Imaging revealed a subcortical hemorrhage in the right temporal lobe and tumors in two locations: the right temporal lobe and the upper surface of the cerebellum. Tumor resection and hematoma removal were performed for diagnostic and decompressive purposes. Histopathological examination confirmed the diagnosis of brain metastasis from gastric NEC. Brain metastases from gastric cancer are rare, and to the best of our knowledge, only one English-language case report of solitary brain metastasis from gastric NEC has been published. We report this case and provide a discussion based on the available literature.
• Immune cell densities, HLA status, and PD-L1 expression in stage I neuroendocrine neoplasm of the uterine cervix.2025 · Neuroendocrine neoplasms (NENs) of the uterine cervix are highly malignant tumors associated with a poor prognosis. Human papillomavirus test-based uterine cervical cancer screening methods can detect early-stage uterine cervical NENs, so therapeutic strategies for the earliest stages are urgently needed. This study aimed to investigate and evaluate the prognostic significance of intratumoral and stromal immune cell densities, as well as human leukocyte antigen (HLA) and programmed cell death ligand 1 (PD-L1) expression in stage I uterine cervical NENs. Sixteen NENs were identified, including 8 large cell neuroendocrine carcinomas (LCNECs), 4 small cell neuroendocrine carcinomas (SCNECs), 3 neuroendocrine tumors (NETs), and 1 LCNEC with an SCNEC component. Only 3 cases were pure NENs, while 13 cases included a component of adenocarcinoma or squamous cell carcinoma. Eight of the 16 patients experienced postoperative recurrence. The recurrence-free group exhibited significantly higher densities of intratumoral CD3- and CD8-positive cells compared to the recurrence group (median densities: 136 vs. 48 cells/mm2, P = 0.0281 and 91 vs. 27 cells/mm2, P = 0.0359, respectively). No significant differences in clinicopathological characteristics, other immune cell densities, or expression of HLA class I, HLA-DR, or PD-L1 were observed between groups. HLA-DR expression was nearly absent in uterine cervical NENs, whereas adjacent non-NEN components displayed varying degrees of HLA-DR expression. PD-L1 expression was observed in 25 % of cases, with CD3- and CD8-positive T-cell-rich stroma. The observed modifications to tumor microenvironments could offer clues to future treatments for uterine cervical NEN. (240/250 words).

• WHO第5版診断基準適応困難例を手がかりとしたHPV関連子宮頸部腺癌の悪性度評価2025 · 基盤研究(C)
• 沖縄県特有の土壌分布は特発性間質性肺炎の経過に影響をおよぼすのか？2025 · 基盤研究(C)
• 子宮頸部分葉状頸管腺過形成の悪性化リスク評価のための 網羅的分子遺伝学的解析研究2023 · 若手研究(S)
• 分子基盤に基づいた HPV 関連子宮頸部腺癌の治療選択基準の提唱－子宮温存のために2023 · 基盤研究(C)

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