研究者詳細 - 中黒　匡人

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan 査読有り

Kawakita, D; Murase, T; Ueda, K; Kano, S; Tada, Y; Tsukahara, K; Okami, K; Onitsuka, T; Fujimoto, Y; Matoba, T; Sakurai, K; Nagao, T; Hanai, N; Kawata, R; Hato, N; Nibu, KI; Urano, M; Taguchi, K; Nakaguro, M; Kusafuka, K; Yamamoto, H; Nagao, T; Inagaki, H

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 25 巻 ( 10 ) 頁： 1774 - 1785 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Clinical Oncology

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

DOI： 10.1007/s10147-020-01731-9

その他リンク： http://link.springer.com/article/10.1007/s10147-020-01731-9/fulltext.html

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment 査読有り国際誌

Nakaguro, M; Tada, Y; Faquin, WC; Sadow, PM; Wirth, LJ; Nagao, T

CANCER CYTOPATHOLOGY 128 巻 ( 10 ) 頁： 693 - 703 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Cytopathology

Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50 years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in well-known oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.

DOI： 10.1002/cncy.22288

Microsecretory adenocarcinoma of the hard palate: A case report of a recently described entity 査読有り国際誌

Kawakami, F; Nagao, T; Honda, Y; Sakata, J; Yoshida, R; Nakayama, H; Inoue, S; Kitajima, M; Ikeda, O; Nakaguro, M; Mikami, Y

PATHOLOGY INTERNATIONAL 70 巻 ( 10 ) 頁： 781 - 785 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.

DOI： 10.1111/pin.12987

表在型食道扁平上皮癌におけるLinked Color Imagingで観察される色情報と深達度および血管径との相関に関する検討

小林健一, 宮原良二, 舩坂好平, 古川和宏, 澤田つな騎, 前田啓子, 山村健史, 石川卓也, 大野栄三郎, 中村正直, 川嶋啓揮, 中黒匡人, 奥村結希, 廣岡芳樹, 藤城光弘

日本消化器内視鏡学会雑誌 62 巻 ( 9 ) 頁： 1624 - 1633 2020年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本消化器内視鏡学会

【背景】食道扁平上皮癌の治療方針決定に正確な深達度診断が重要であるが，MM/SM1の正診率は低く解決すべき課題となっている．本研究の目的はLED光源を用いたLCIにおける食道表在癌に対する色と深達度の関連性について検討することである．【方法】表在型食道癌と診断された病変に対し白色光につづいてLCIで観察を行った．色合いの評価についてはCIE-L＊a＊b＊空間を用いて色値を算出し，深達度ごとの癌部と非癌部の色差を算出した．血管径およびintrapapillary capillary loopの分岐角を病理的に算出し，色合いとの相関を検討した．【結果】48症例52病変が登録された．深達度別の正常と病変部の色差において，MM/SM1以深群ではEP/LPM群に比べて有意に色差が大きかった（P＝0.025）．血管径はb＊値と弱い正の相関を認めた（相関係数＝0.302，P＝0.033）．【結論】LED光源を用いたLCI観察は，表在型食道癌における深達度診断の向上に有用である可能性があるが，その有用性を示すのにはさらなる検討が必要である．

DOI： 10.11280/gee.62.1624

表在型食道扁平上皮癌におけるLinked Color Imagingで観察される色情報と深達度および血管径との相関に関する検討査読有り

CiNii Research

Gastroenterological Endoscopy 62 巻 ( 9 ) 頁： 1624 - 1633 2020年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：(一社)日本消化器内視鏡学会

【背景】食道扁平上皮癌の治療方針決定に正確な深達度診断が重要であるが,MM/SM1の正診率は低く解決すべき課題となっている.本研究の目的はLED光源を用いたLCIにおける食道表在癌に対する色と深達度の関連性について検討することである.【方法】表在型食道癌と診断された病変に対し白色光につづいてLCIで観察を行った.色合いの評価についてはCIE-L*a*b*空間を用いて色値を算出し,深達度ごとの癌部と非癌部の色差を算出した.血管径およびintrapapillary capillary loopの分岐角を病理的に算出し,色合いとの相関を検討した.【結果】48症例52病変が登録された.深達度別の正常と病変部の色差において,MM/SM1以深群ではEP/LPM群に比べて有意に色差が大きかった(P=0.025).血管径はb*値と弱い正の相関を認めた(相関係数=0.302,P=0.033).【結論】LED光源を用いたLCI観察は,表在型食道癌における深達度診断の向上に有用である可能性があるが,その有用性を示すのにはさらなる検討が必要である.(著者抄録)

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma 査読有り国際誌

Hirai, H; Tada, Y; Nakaguro, M; Kawakita, D; Sato, Y; Shimura, T; Tsukahara, K; Kano, S; Ozawa, H; Okami, K; Sato, Y; Fushimi, C; Shimizu, A; Okamoto, I; Takase, S; Okada, T; Sato, H; Imanishi, Y; Otsuka, K; Watanabe, Y; Sakai, A; Ebisumoto, K; Togashi, T; Ueki, Y; Ota, H; Saigusa, N; Takahashi, H; Ando, M; Urano, M; Hanazawa, T; Nagao, T

VIRCHOWS ARCHIV 477 巻 ( 2 ) 頁： 291 - 299 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Virchows Archiv

Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)–positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism–related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.

DOI： 10.1007/s00428-020-02777-w

Central pathology review of salivary gland adenoid cystic carcinoma 査読有り国際誌

Ueda, K; Murase, T; Nagao, T; Kusafuka, K; Urano, M; Yamamoto, H; Nakaguro, M; Taguchi, K; Masaki, A; Hirai, H; Kawakita, D; Tsukahara, K; Hato, N; Nagao, T; Fujimoto, Y; Sakurai, K; Hanai, N; Kano, S; Onitsuka, T; Okami, K; Nibu, K; Tada, Y; Kawata, R; Inagaki, H

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 42 巻 ( 8 ) 頁： 1721 - 1727 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Head and Neck

Background: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC). Methods: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation. Results: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants. Conclusions: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.

DOI： 10.1002/hed.26081

Steroid-responsive recurrent tumefactive demyelination with multiple petechial hemorrhages along non-displaced medullary veins 査読有り国際誌

Tsuboi, T; Harada, Y; Suzuki, M; Ando, T; Atsuta, N; Ohka, F; Takeuchi, K; Taoka, T; Ohba, S; Nakaguro, M; Abe, M; Nakashima, I; Yoshida, M; Katsuno, M

CLINICAL NEUROLOGY AND NEUROSURGERY 193 巻頁： 105764 - 105764 2020年6月

A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation 査読有り国際誌

Kitano, A; Nakaguro, M; Tomotaki, S; Hanaoka, S; Kawai, M; Saito, A; Hayakawa, M; Takahashi, Y; Kawasaki, H; Yamada, T; Ikeda, M; Onda, T; Cho, K; Haga, H; Nakazawa, A; Minamiguchi, S

DIAGNOSTIC PATHOLOGY 15 巻 ( 1 ) 頁： 48 - 48 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Diagnostic Pathology

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients. Case presentation: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels. Conclusions: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.

DOI： 10.1186/s13000-020-00972-6

Enhanced performance of the Milan System for Reporting Salivary Gland Cytopathology: Point of view from an Asian country 査読有り国際誌

Higuchi, K; Urano, M; Nakaguro, M

CANCER CYTOPATHOLOGY 128 巻 ( 5 ) 頁： 305 - 306 2020年5月

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma Proposal of a Novel Histologic Risk Stratification Model 査読有り国際誌

Nakaguro, M; Sato, Y; Tada, Y; Kawakita, D; Hirai, H; Urano, M; Shimura, T; Tsukahara, K; Kano, S; Ozawa, H; Okami, K; Sato, Y; Fushimi, C; Shimizu, A; Takase, S; Okada, T; Sato, H; Imanishi, Y; Otsuka, K; Watanabe, Y; Sakai, A; Ebisumoto, K; Togashi, T; Ueki, Y; Ota, H; Saigusa, N; Takahashi, H; Ando, M; Hanazawa, T; Nagao, T

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 44 巻 ( 4 ) 頁： 526 - 535 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Surgical Pathology

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

DOI： 10.1097/PAS.0000000000001413

【免疫組織化学実践的な診断・治療方針決定のために】(第3部)腫瘍の鑑別に用いられる抗体(各臓器別) 唾液腺査読有り

中黒匡人, 長尾俊孝

病理と臨床 38 巻 ( 臨増 ) 頁： 84 - 93 2020年4月

唾液腺導管癌におけるEZH2蛋白発現の臨床病理学的意義

平井秀明, 多田雄一郎, 川北大介, 中黒匡人, 三枝奈津季, 長尾俊孝

日本病理学会会誌 109 巻 ( 1 ) 頁： 290 - 290 2020年3月

唾液腺導管癌におけるEZH2蛋白発現の臨床病理学的意義

平井秀明, 多田雄一郎, 川北大介, 中黒匡人, 三枝奈津季, 長尾俊孝

日本病理学会会誌 109 巻 ( 1 ) 頁： 290 - 290 2020年3月

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry 査読有り国際誌

Kohno, K; Sakakibara, A; Iwakoshi, A; Hasegawa, M; Adachi, S; Ishikawa, E; Suzuki, Y; Shimada, S; Nakaguro, M; Shimoyama, Y; Takahara, T; Takahashi, E; Ohashi, A; Satou, A; Kato, S; Asano, N; Nakamura, S

PATHOLOGY INTERNATIONAL 70 巻 ( 2 ) 頁： 108 - 115 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Pathology International

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein–Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed–Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing ‘confluent’ sheets in the diagnostic workup for SV-CHL.

DOI： 10.1111/pin.12888

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm 査読有り国際誌

Nakaguro, M; Urano, M; Ogawa, I; Hirai, H; Yamamoto, Y; Yamaguchi, H; Tanigawa, M; Matsubayashi, J; Hirano, H; Shibahara, J; Tada, Y; Tsuzuki, T; Okada, Y; Sato, Y; Ikeda, K; Sukeda, A; Honda, Y; Mikami, Y; Nagao, T

HISTOPATHOLOGY 76 巻 ( 3 ) 頁： 411 - 422 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Histopathology

Aims: Minor salivary gland tumours showing a predominant papillary–cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). Methods and results: We retrieved 28 papillary–cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. Conclusion: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary–cystic tumours.

DOI： 10.1111/his.13990