基本情報
- 所属
- 自治医科大学 医学部 病理学講座・附属病院病理診断部 教授 (部長)(兼任)病理診断科 診療科長
- 学位
- 医学博士(東京大学)
- J-GLOBAL ID
- 201401077459790889
- researchmap会員ID
- B000237516
- 外部リンク
・平成2年 宮崎医科大学卒業
・平成2年 NTT関東逓信病院
臨床研修医(消化器内科・外科・画像診断・病理)・専修医(病理診断科)
・平成7年 国立がんセンター研究所支所 臨床腫瘍病理部 リサーチ・レジデント
・平成9年 国立がんセンター中央病院 臨床検査部 医員
・平成13年 ジョンズ・ホプキンス大学医学部 病理部 研究員
・平成16年 東京医科大学 病理診断学講座 講師
・平成17年 東京大学大学院医学系研究科 病理学講座 講師
・平成18年 東京大学大学院医学系研究科 病理学講座 准教授
東京大学病院病理部 副部長
・平成21年 自治医科大学医学部病理学講座 教授
自治医科大学附属病院 病理診断部 部長
(平成26年~自治医科大学附属病院 病理診断科 科長)
・平成2年 NTT関東逓信病院
臨床研修医(消化器内科・外科・画像診断・病理)・専修医(病理診断科)
・平成7年 国立がんセンター研究所支所 臨床腫瘍病理部 リサーチ・レジデント
・平成9年 国立がんセンター中央病院 臨床検査部 医員
・平成13年 ジョンズ・ホプキンス大学医学部 病理部 研究員
・平成16年 東京医科大学 病理診断学講座 講師
・平成17年 東京大学大学院医学系研究科 病理学講座 講師
・平成18年 東京大学大学院医学系研究科 病理学講座 准教授
東京大学病院病理部 副部長
・平成21年 自治医科大学医学部病理学講座 教授
自治医科大学附属病院 病理診断部 部長
(平成26年~自治医科大学附属病院 病理診断科 科長)
研究分野
1経歴
2-
2009年9月 - 現在
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2014年
論文
418-
Clinical case reports 9(5) e04118 2021年5月Long-acting somatostatin analogs, including lanreotide slow release (LAN-SR) and octreotide long-acting release (OCT-LAR), can improve hypoglycemia in insulinoma. LAN-SR may be more beneficial in some patients with insulinoma than OCT-LAR.
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胆と膵 42(5) 393-400 2021年5月胆膵領域に発生する腫瘍は、しばしば画像診断に難渋する。画像診断精度を向上させるためには、術前画像で異常所見を拾い上げる所見のための根拠を病理組織学的に検証していくことが重要である。当施設では、詳細な術前画像と病理像の対比のために、臨床医と病理医が協力して「検体造影検査」に加え「術後検体超音波検査」を行っている。とくに、「術後検体超音波検査」は、簡便で、病理像・画像対比に適した病理組織標本を作ることができ、画像所見へのフィードバックや診療科横断的なコミュニケーションツールとしても有意義な検査である。(著者抄録)
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Scientific reports 11(1) 8454-8454 2021年4月19日Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.
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Brain tumor pathology 38(3) 250-256 2021年4月9日Rosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in DNTs, but was diagnosed as RGNT because of the presence of neurocytic rosettes. Genetic analysis detected fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain, which was previously reported to be specific for DNT. RGNTs with FGFR1-ITD may show atypical clinical presentation and pathological features.
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Surgery today 51(10) 1713-1719 2021年3月20日PURPOSE: The aim of this study was to evaluate both the intestinal mucosa staple line integrity and anastomotic leak pressure after healing in a porcine survival model. METHODS: We used two suture models using two different size staples (incomplete mucosal closure model: group G [staple height 0.75 mm], complete mucosal closure model: group B [staple height 1.5 mm]) in the porcine ileum. Five staple lines were created in each group made in the ileum for each model, and the staple sites harvested on days 0, 2, and 7. The leak pressure at the staple site was measured at each time point. RESULTS: On day 0, the leak pressure for group G (79.5 mmHg) was significantly lower than that for group B (182.3 mmHg) (p < 0.01). On days 2 and 7, there was no significant difference between groups G and B (171 mmHg and 175.5 mmHg on day 2, 175.5 mmHg and 175.5 mmHg on day 7, p > 0.05). The histological findings in both groups showed similar healing at postoperative days 2 and 7. CONCLUSION: The integrity of the mucosal staple lines was associated with the postoperative leak pressure on day 0. However, there was no association with the leak pressure at two days or more postoperatively in a porcine model.
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Medicine 100(2) e24011 2021年1月15日RATIONALE: Salivary duct carcinoma (SDC) is a rare and highly aggressive cancer with a poor prognosis. SDC demonstrates a potential for invasive growth with early regional and distant metastasis to organs, such as bone, lung, liver, and brain. Because, adrenal gland metastasis from SDC is rare, its treatment options are not well established. Herein, we report a case of SDC metastasis from the parotid gland to the adrenal gland, which was successfully treated by surgery. PATIENT CONCERNS: The patient had an abnormal but painless lump on the right parotid gland. The size of the mass had increased over a period of 3 years. The patient underwent complete removal of the right parotid gland and radical neck dissection followed by adjuvant radiotherapy and chemotherapy. Two years later, a mass was identified in the left adrenal gland by computed tomography. As no local recurrence or metastasis to other organs was observed, the patient underwent adrenalectomy. DIAGNOSES: Metastasis of SDC in the adrenal gland was confirmed by histopathological examination of the adrenalectomized specimen. INTERVENTIONS: After adrenalectomy, the patient was followed-up without adjuvant therapy. OUTCOMES: The patient was well and alive during the 13-month postoperative follow-up period without any complications. LESSONS: Surgical resection of solitary metastatic lesion may show a survival benefit with metastatic SDC.
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Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 34(1) 4-12 2021年1月Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.
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The American journal of surgical pathology 44(12) 1712-1724 2020年12月Switch/sucrose nonfermenting complex subunits, such as BRG1, INI1, and ARID1B, are inactivated in a subset of endometrial undifferentiated carcinoma and dedifferentiated carcinoma (DC). Limited information is currently available on their prevalence in other subtypes or the nosological status of endometrial carcinoma with their deficiencies. This study immunohistochemically examined the expression status of BRG1, INI1, and ARID1B using 570 archived cases of endometrial carcinoma and carcinosarcoma resected at a single institution. We identified 1 BRG1-deficient undifferentiated carcinoma, 8 BRG1/INI1/ARID1B-deficient DC, and 3 BRG1-deficient clear-cell carcinomas. None of the cases of endometrioid and serous carcinomas or carcinosarcoma showed deficiencies of these subunits. We then compared 8 BRG1/INI1/ARID1B-deficient DC with 6 BRG1/INI1/ARID1B-intact DC and 28 carcinosarcomas, the latter of which was often confused with DC. Histologically, BRG1/INI1/ARID1B-intact and BRG1/INI1/ARID1B-deficient DC shared a monotonous solid appearance with rhabdoid and epithelioid cells and a myxoid stroma; however, abrupt keratinization and cell spindling was absent in BRG1/INI1/ARID1B-deficient tumors. The median overall survival of patients with BRG1/INI1/ARID1B-deficient DC was 3.8 months, which was worse than those with BRG1/INI1/ARID1B-intact DC (P=0.008) and with carcinosarcoma (P=0.004). BRG1/INI1/ARID1B-deficient DC may be a separate entity with an aggressive behavior to be distinguished from BRG1/INI1/ARID1B-intact DC and carcinosarcoma. Regarding clear-cell carcinoma (n=12), BRG1 deficiency appeared to be mutually exclusive with abnormal ARID1A, BRM, and p53 expression. Further studies are needed to clarify whether BRG1 deficiency plays a role in the pathogenesis of clear-cell carcinoma.
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Pathology international 70(11) 857-864 2020年11月Extrahepatic bile duct (EHBD) cancer is a devastating cancer, and more common in Asian countries than in Western countries. Histological grading continues to be a highly relevant factor in prognosis and management of many kinds of cancer, however no uniform histological grading system exists for EHBD cancer. Histological heterogeneity within tumors is a problem in the evaluation of EHBD cancer. We developed an EHBD histological grading scheme to evaluate tumor differentiation pattern, and statistically analyzed its relationship with prognosis. In the present study, 257 surgically resected EHBD cancers were reviewed and their histological glandular differentiation (HGD) pattern was scored, and then we summed up the most and second most predominant scores. These scores were statistically analyzed for their relationship with patient prognosis. Patients showed a trend of shortening recurrence-free survival (RFS) and overall survival (OS) in association with higher HGD scores. In multivariate analyses, HGD score was determined to be an influential factor in RFS (P = 0.00041) and OS (P < 0.0001). In addition, combining HGD score and lymph node status correctly stratified patient prognosis in RFS. In conclusion, this new HGD scoring system is highly practical and has powerful prognostic value for EHBD cancer.
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Medicine 99(42) e22665 2020年10月16日INTRODUCTION: Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME. PATIENT CONCERNS: A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed. DIAGNOSIS: The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ. OUTCOMES: The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation. CONCLUSION: HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.
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Pathology international 70(10) 699-711 2020年10月 査読有りThe biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.
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Journal of hepato-biliary-pancreatic sciences 27(9) 581-597 2020年9月 査読有りBACKGROUND: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location. METHODS: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated. RESULTS: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups. CONCLUSION: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.
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Medical molecular morphology 53(3) 177-182 2020年9月 査読有りWe herein report a variant case of desmoplastic small round cell tumor (DSRCT) showing limited desmoplasia and confusing immunohistochemical findings. A 26-year-old male was referred for multiple abdominal masses. Laparoscopic biopsy showed only the solid proliferation of small round cells, and he was initially diagnosed with small cell carcinoma. At autopsy, the tumor spread diffusely throughout the abdominal and pelvic cavities. Although the tumor was composed of a predominantly solid pattern of small round cells, multiple samples revealed a fibrous stroma in limited areas only. While immunohistochemistry showed the diffuse expression of desmin, CD99, and bcl-2, epithelial differentiation was unclear with few cytokeratin-positive cells and no staining for the epithelial membrane antigen. Although fluorescence in situ hybridization analysis indicated the EWSR1 gene rearrangement, we were unable to exclude Ewing sarcoma considering the morphological and immunohistochemical findings. The diagnosis of DSRCT was confirmed with a reverse transcription-polymerase chain reaction for EWSR1-WT1 fusion transcripts. DSRCT must be included in a differential diagnosis of small round cell tumors even if desmoplasia is not immediately detected, and thorough sampling and a molecular analysis are mandatory.
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Surgical case reports 6(1) 128-128 2020年6月5日 査読有りBACKGROUND: Aspergillus endocarditis (AE) is a rare and lethal cardiac infection with a high rate of mortality. AE most commonly presents in immunocompromised patients and is associated with various co-morbidities. Herein, we present a case of AE associated with lung, brain, and cervical abscesses after chemotherapy for malignant lymphoma that was successfully treated by a combination of antifungal and surgical therapy. CASE PRESENTATION: A 29-year-old man was admitted to our hospital with an unidentified fever. He was diagnosed with malignant lymphoma (extra-nodal NK/T cell lymphoma nasal type), and chemotherapy was administered. After chemotherapy, nodular lung shadows along with new brain, cervical, and myocardial abscesses appeared, despite anti-bacterial/fungal therapy. Gene analysis of the cervical abscess biopsy revealed the presence of Aspergillus fumigatus species, and the transesophageal echocardiogram showed a mobile mural vegetation in the left ventricle (22 × 8 mm). He underwent surgical resection of this mural vegetation. His postoperative course was uneventful. He remains healthy at 28 months after surgery with continued oral antifungal therapy. CONCLUSION: Although AE associated with immunosuppression is a fatal clinical presentation, combined treatment with surgical resection and antifungal therapy was effective.
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Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33(3) 456-467 2020年3月 査読有り
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Pathology international 70(2) 123-125 2020年2月 査読有り
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自治医科大学臨床検査技師年報 (42) 52-55 2019年12月症例は60歳代女性で、2週間程度で亜急性進行性の多発脳神経障害と錐体路・小脳・全感覚路の障害を認めた。頭部MRI所見より中枢神経系原発悪性リンパ腫(PCNSL)と考えられたが、脳幹部位であったため生検による組織診断が不可能で、脳脊髄液細胞診においても確定には至らなかった。ステロイド治療により病変の縮小と造影効果の消失を認めたが、約半年後に症状の急速な悪化がみられた。MRIで病変の広がりを認め、鎖骨上窩や腹腔内リンパ節の腫大、右腎周囲・脾・膵・腸管周囲の腫瘤、胸腹水貯留がみられ、再発/浸潤が疑われた。その後の治療で寛解になっている。当院の過去10年間において脳生検または手術を施行したPCNSLは34例で、全脳腫瘍に対して4.9%と少なく、全例においてDLBCLであった。さらに脳脊髄液細胞診を行い、悪性リンパ腫が疑われた症例は2例であった。脳生検または手術を施行しなかったPCNSLの症例は今回の症例のみで、他臓器転移があった症例は他に1例みられた。
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自治医科大学臨床検査技師年報 (42) 56-63 2019年12月当院では開院当初(1974年)からの旧病理解剖室と2016年にリニューアル移転した現在の新病理解剖室において、ホルマリン濃度が0.1ppm以下の第1管理区分を目標とした環境改善対策を旧剖検室で1回、新剖検室で3回、合わせて4回実施した。本稿では、対策前後の作業環境改善結果について報告した。当院の旧剖検室はホルマリン環境対策を一切行っていなかった。旧倉庫は病理レポートの保管棚と同じスペースにあり、切り出し台、ホルマリン原液ストック場と床に直置きした臓器保管用ホルマリンバケツ置き場が混在していた。2013年に旧解剖室と旧倉庫のホルマリン対策を初めて行い、それを参考に2016年に新解剖室・臓器保管倉庫のリニューアルが実施され、1階の旧剖検室から地下1階の新剖検室に場所を移した。リニューアル移転時のホルマリン環境測定結果は、第1管理区分に至らなかった。新解剖室では切り出し臓器時にホルマリン吸収シートを使用したり、新倉庫で保管容器のビニール袋使用による二重密閉・パッキン付き容器への変更・ホルマリン吸着ビーズを使用したりと工夫を重ね、最終的には何とか第1管理区分を達成できた。旧剖検室では、ホルマリン臭がするのが当たり前との意識で剖検業務をこなしていた。現在の新剖検室は旧剖検室に比べてホルマリン臭はかなり軽減されてはいる。しかし現在第1管理区分を達成していても、ホルマリン臭がきつくなる場面も多々あり、ホルマリン濃度の低減への根本的な解決にはなっていないと思われる。
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The American journal of surgical pathology 43(11) 1526-1535 2019年11月 査読有りAtypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.
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Journal of medical case reports 13(1) 289-289 2019年9月6日 査読有りBACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.
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Medicine 98(32) e16643 2019年8月 査読有りRATIONALE: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication. PATIENT CONCERNS: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure. DIAGNOSES: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy. INTERVENTIONS: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma. OUTCOMES: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery. LESSONS: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.
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Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 19(5) 793-793 2019年7月 査読有り
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Rheumatology international 39(5) 901-909 2019年5月 査読有りThe objective was to investigate the clinical and histological features of liver dysfunction in patients with polymyositis (PM) or dermatomyositis (DM).A total of 115 patients (38 with PM and 77 with DM), who were admitted to our hospital between 2001 and 2012, were retrospectively reviewed. Liver dysfunction was defined as an alanine transaminase (ALT) level ≥ 60 U/l and a disproportionate ALT elevation relative to the creatine kinase level. The histological findings from liver biopsies were also assessed.The frequencies of liver dysfunction were 3% and 17% in the patients with PM and DM, respectively. Liver dysfunction was not observed in the patients who had malignancies. Among the patients with DM with no malignancies (n = 50), 20% had liver dysfunction, and all of the patients with liver dysfunction were positive for the anti-melanoma differentiation-associated gene 5 (MDA5) antibody. Compared with those in the patients who did not have liver dysfunction, the ALT, alkaline phosphatase, γ-glutamyl transferase, and KL-6 levels were significantly elevated in the patients who had liver dysfunction. Six patients, comprising four with DM and two with PM, underwent liver biopsies, and the common histological findings associated with DM were steatosis, hepatocyte ballooning, increases in the pigmented macrophage numbers, and glycogenated nuclei. Hemophagocytosis was detected in two of three patients with DM who underwent liver biopsies and bone marrow aspirations. In conclusion, Liver dysfunction might be an extramuscular manifestation in patients with DM who are anti-MDA5 antibody-positive. Steatosis and hepatocyte ballooning could be common histological features.
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Pancreas 48(4) 480-487 2019年4月 査読有りOBJECTIVE: The grading and typing of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are challenging for pathologists. We aimed to clarify the points of consistency and disagreement in assessing the grades and types of IPMNs. METHODS: Digital slide images of 20 IPMNs were independently assessed by 10 Japanese pathologists, who then held a consensus meeting to discuss the points of disagreement and develop a consensus and recommendations. RESULTS: The average agreement rates for grade and type were 83.5% (range, 100%-40%) and 82.5% (range, 100%-50%) and the Fleiss' κ values were 0.567 and 0.636, respectively. CONCLUSIONS: The disagreement points and recommendations were as follows: destructed ductal walls with desquamated neoplastic epithelia or mucin lakes partially lined with neoplastic cells could be invasion; intraductal stromal invasion could be dismissed unless vascular or lymphatic invasion existed; elastica staining may help visualize ducts in colloidal nodules; high-grade can be distinguished from low/intermediate grade by marked nuclear disarrangements and complex architecture in the intestinal papillae; oncocytic papillae are characterized by eosinophilic cells with round disoriented nuclei; high-grade gastric papillae can be distinguished from pancreatobiliary papillae by relatively low but complex architecture; and the most dysplastic papillae should be used to assess type in mixed papillae types.
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MODERN PATHOLOGY 32 2019年3月 査読有り
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LABORATORY INVESTIGATION 99 2019年3月 査読有り
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Pathology international 69(2) 86-93 2019年2月 査読有りBile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.
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Medicine 98(4) e14211 2019年1月 査読有りRATIONALE: Liver heterotopia associated with congenital diaphragmatic hernia (CDH) is a rare condition; to the best of our knowledge, only 17 cases have been reported to date. The histogenesis and clinicopathological features are largely unknown. We herein report 2 cases of liver heterotopia associated with CDH along with 17 cases described in the literature to shed light on their clinicopathological characteristics. PATIENT CONCERNS: Case 1 was a vaginally delivered male newborn who presented with respiratory distress immediately after birth. Case 2 was a female fetus who was found to have left-sided CDH during gestation. DIAGNOSIS: In case 1, a chest X-ray revealed left-sided CDH. In case 2, magnetic resonance imaging performed at 33 weeks of gestation revealed left-sided CDH. INTERVENTIONS: Case 1 underwent diaphragmatic patch repair surgery 3 days after birth. Histopathological examination following surgery in case 1 revealed the presence of ectopic liver tissue in the hernia sac. Case 2 was delivered by Cesarean section, and diaphragmatic patch surgery was performed 3 days after birth. During surgery, an isolated nodule was identified on the peritoneal side of the border of the defective foramen of the diaphragm. Histopathological examination following surgery in case 2 confirmed the presence of an epidermal cyst in the hernia sac. In addition, the isolated nodule was histopathologically found to be ectopic liver tissue. OUTCOMES: In Case 1, CDH recurred at 6 months after surgery, and a second patch repair surgery was performed. The surgically removed hernia sac was found to contain microscopic ectopic liver tissue on histopathology. Case 1 recovered well after surgery, and there was no critical change during the 10-month postoperative period. Case 2 recovered well after surgery, and there was no critical change during the 20-month postoperative period. LESSONS: There were no secondary pathological conditions associated with the presence of ectopic liver in CDH, such as torsion, infarction, rupture, intra-abdominal bleeding, or tumorization. Our observations suggest that liver heterotopia is a rare but asymptomatic condition in patients with CDH.
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BMC cancer 18(1) 1249-1249 2018年12月13日 査読有りBACKGROUND: Thymomas are typically slow-growing tumors and AB type thymomas are considered no/low risk tumors with a better prognosis. Extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis from a thymoma has been reported. We report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after thymectomy. CASE PRESENTATION: The patient is a 78-year-old man. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma. Five years after thymectomy, a nodule appeared in the spleen, and the lesion enlarged gradually for three years thereafter. The patient was referred for further examination and treatment. Computed tomography scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous lesion in the spleen. On T2-weighted images on Magnetic Resonance Imaging, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and showed a low-signal spoke-wheel sign in the margin, enhanced gradually in the dynamic study. Positron emission tomography-CT scan, showed relatively low accumulation. Surgical resection was undertaken, and pathological examination showed metastatic thymoma. The patient is without recurrence and has no other symptoms three years after splenectomy. CONCLUSIONS: This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.
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DIAGNOSTIC CYTOPATHOLOGY 46(12) 1077-1080 2018年12月 査読有り
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Medicine 97(49) e13466 2018年12月 査読有りLittle is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.
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Pancreas 47(8) 1019-1026 2018年9月 査読有りOBJECTIVE: The aim of this study was to evaluate the clinicopathological features of solid pseudopapillary neoplasms (SPNs). METHODS: In this retrospective study, 288 SPNs were analyzed. RESULTS: Overall, 214 patients (74%) were female. Distant metastases occurred in 4 patients, and splenic vein tumor thrombus occurred in 1 patient. Although imaging findings showed large (>2.0 cm) SPNs with clear, regular border, and heterogeneous internal structure, small SPNs appeared as almost entirely solid. Surgical resection was performed in 278 cases. The 5-year survival rate was 98.8%. Six patients had tumor recurrence after the initial resection. The detection rate in typical pathological findings was low for small SPNs. Tumor extension to the pancreatic parenchyma was detected in greater than 70% of the cases. Tumor invasion to adjacent organs was detected in 13 cases. One was given a diagnosis of apparent high-grade malignant transformation. CONCLUSIONS: The proportion of male cases was higher than that in previous studies, and there were statistically significant differences in the onset age and tumor diameter between male and female patients. Therefore, women seemed to have an early occurrence of SPNs, suggesting a difference in the developmental stage between men and women. Images and pathological findings of SPNs varied according to tumor size. Our findings indicated that SPN patients have excellent survival after margin-negative surgical resection.
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AMERICAN JOURNAL OF SURGICAL PATHOLOGY 42(7) 891-897 2018年7月 査読有りPancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.
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NEURO-ONCOLOGY 20 146-146 2018年6月 査読有り
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Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 18(4) 407-412 2018年6月 査読有りBACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. MATERIALS AND METHODS: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. RESULTS: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. CONCLUSIONS: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN.
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Pathology international 2018年4月17日 査読有り
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MODERN PATHOLOGY 31 681-682 2018年3月 査読有り
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Journal of hepato-biliary-pancreatic sciences 25(3) 181-187 2018年3月 査読有りIntraductal papillary neoplasm of bile duct (IPNB) was described as a preinvasive neoplastic lesion of the biliary tract in the 2010 World Health Organization (WHO) classification. Although a number of studies have since been conducted on IPNBs, controversy remains, particularly regarding the standardization of its definition. Meetings by Japanese and Korean expert pathologists were held twice to resolve the pathological diagnostic aspects of IPNB. Through round-table discussions and histological reviews, we reached the common understanding that IPNBs diagnosed according to the criteria of WHO 2010 are characterized by intraductal predominant papillary or villous biliary neoplasms covering delicate fibrovascular stalks and are classified into two types pathologically. One type (type 1 IPNB) is histologically similar to intraductal papillary mucinous neoplasms of pancreas, and typically develops in the intrahepatic bile ducts, while the other (type 2 IPNB) has a more complex histological architecture with irregular papillary branching or with foci of solid-tubular components and typically involves the extrahepatic bile ducts. This report states the diagnostic pathologic features of IPNB proposed by WHO 2010. Since currently, the concept of IPNB is still confusing, the proposed diagnostic pathologic features stated here will be of use for future clinicopathological and molecular analyses toward consensus building of IPNB.
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INTERNAL MEDICINE 57(6) 835-839 2018年 査読有りThe diagnosis of cardiac sarcoidosis (CS) has become easier due to advances in imaging modalities, but we sometimes encounter difficult-to-diagnose patients. We herein report the case of a 60-year-old Japanese woman who was diagnosed with isolated CS, although she also met the diagnostic criteria of arrhythmogenic right ventricular cardiomyopathy (ARVC). A histological examination by an endomyocardial biopsy of the right ventricle revealed the typical findings of granulomatous change for CS. Although she did not show any characteristics of systemic sarcoidosis, oral prednisolone treatment was introduced, and she achieved a good response. This case shows that the characteristics of CS can overlap with the diagnostic criteria of ARVC, and that a histological examination is essential for the correct diagnosis of CS.
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ENDOSCOPY INTERNATIONAL OPEN 5(9) E913-E917 2017年9月 査読有りBackground and study aims Tumor seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is rare. A 53-year-old man underwent transesophageal EUS-FNA for diagnosis of a 6-cm mass in the mediastinum as seen by computed tomography (CT). Four weeks later, repeat CT scan revealed a mass in the esophageal wall. Upper gastrointestinal endoscopy confirmed a lesion in the mid-esophagus, which was biopsied and found to be consistent with needle tract seeding after EUS-FNA. Tumor seeding in the gastrointestinal wall or peritoneum after EUS-FNA is rare, but may adversely affect the prognosis. Indications for EUS-FNA must be carefully considered.
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INTERNATIONAL SURGERY 102(5-6) 210-215 2017年5月 査読有りEosinophilic granulomatosis with polyangiitis (EGPA) is a vascular disorder of unknown etiology characterized by severe asthma, eosinophilia, and granulomatous vasculitis. It is sometimes associated with gastrointestinal lesions, although perforations are uncommon. Corticosteroids are commonly used in the treatment of patients with EGPA; however, they may impair tissue repair and induce fibrotic changes in the vascular intima, which can lead to vascular occlusion, ischemia, and perforation. The anti-inflammatory properties of corticosteroids may mask symptoms of gastroduodenal ulcers or other intra-abdominal conditions, which can lead to a delay in diagnosis. From January 1, 2001 to December 31, 2014, 71 patients underwent surgery for small intestinal perforations. Of these, 4 operations were performed on 3 patients with EGPA who were receiving corticosteroids. We retrospectively reviewed the clinical and pathologic features of these patients. All 3 patients with EGPA were men, with a mean age of 56 years. The length of resected intestine ranged from 10 to 60 cm. Histopathologic examination revealed ulcers and perforations of the small intestine associated with vasculitis, compatible with EGPA. All patients had an uneventful postoperative course. Patients with EGPA presenting with abdominal pain must be carefully evaluated for possible intestinal perforation, especially those receiving corticosteroid therapy.
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PATHOLOGY INTERNATIONAL 67(4) 214-221 2017年4月 査読有りUnilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.
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ONCOLOGY LETTERS 13(3) 1731-1740 2017年3月 査読有りPathological complete response (pCR) is considered to be a useful prognostic marker for neoadjuvant chemotherapy to improve the survival rate of patients with operable breast cancer. In the present study, we identified differentially expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab. Expression profiles were examined by miRNA microarrays using total RNA extracted from formalin-fixed, paraffin-embedded tissues from pretreatment biopsy specimens. Significant differences were observed in miRNAs associated with pCR between the luminal B-like (HER2-positive) and HER2posi-tive (nonluminal) subtypes, which were further classified according to their estrogen receptor (ER) status. Prediction models constructed with differentially expressed miRNAs performed well. In conclusion, the combination of miRNA profiles and ER status may improve the accuracy of pCR prediction in patients with HER2-positive breast cancer and enable the development of personalized treatment regimens.
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LABORATORY INVESTIGATION 97 447A-447A 2017年2月 査読有り
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MODERN PATHOLOGY 30 447A-448A 2017年2月 査読有り
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MODERN PATHOLOGY 30 447A-447A 2017年2月 査読有り
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LABORATORY INVESTIGATION 97 447A-448A 2017年2月 査読有り
MISC
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胆と膵 44(10) 975-979 2023年10月改訂された膵癌取扱い規約第8版において,膵癌に対する薬物・放射線治療後の組織学的効果判定基準については,前版で提示した「生存し得ると判断される癌細胞の残存率を目安に行う」独自の分類システムを継承しつつ,国際動向もにらみCAP(College of American Pathologists)システムの併記を推奨した。両システムの違いは,規約システムが,残存した腫瘍量の割合を評価の軸にした「相対的評価」であるのに対し,CAPシステムでは,残存腫瘍にフォーカスした「絶対的評価」に近いシステムであるということにある。それぞれに課題はあるが,国際動向を踏まえれば,CAPシステムへの変更という選択肢もあった。ただし,国内では規約システムでのデータが蓄積されてきていること,CAPシステムも今後の改訂が予想されることなどから,現状では,規約システムとCAPシステムでの評価の併記を推奨することで,国内の現状,国際的動向にも沿うものになったと考える。(著者抄録)
書籍等出版物
25共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2018年4月 - 2021年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2017年4月 - 2020年3月