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Annual Report 2017

Department of Pathology and Clinical Laboratories

Nobuyoshi Hiraoka, Shigeki Sekine, Hiromichi Matsushita, Noriko Motoi, Akiko Maeshima, Taisuke Mori, Hirokazu Taniguchi, Reiko Watanabe, Masayuki Yoshida, Akihiko Yoshida, Hiroshi Yoshida, Kaishi Satomi, Aoi Sukeda, Kuniko Sunami, Taiki Hashimoto, Kenichi Yoshida, Michiko Sugiyama, Hiroki Tanaka, Yuki Nishimura, Naohiro Makise

Introduction

 The Department of Pathology and Clinical Laboratories is composed of two divisions as follows: the Pathology Division and the Clinical Laboratories Division. In the Pathology Division, the practice, education, and research of diagnostic and anatomic pathology were carried out. Diagnostic pathology practice comprises all issues on the processing of cell and tissue specimens obtained from patients, preparation of tissue blocks and pathology slides, and histological and cytopathological diagnoses of diseases. The practice of anatomic pathology consists of the autopsy, post-mortem systemic gross, and microscopic examination of patients. Case conferences with each clinical department were held periodically. Residents and trainees were accepted for training of diagnostic pathology on a rotating basis. To provide more accurate and informative diagnosis in future, staff members conduct basic, clinical, or translational research by themselves or in collaboration with other clinical departments of the National Cancer Center Hospital (NCCH), the NCC Research Institute (NCCRI), or external institutions.

 The Clinical Laboratories Division provides an important service as an in-hospital diagnostic unit by examining laboratory specimens and screening for disorders. All laboratory data are provided for clinicians under strict internal and external quality control. The laboratories in the Department of Pathologyand Clinical Laboratories have acquired the accreditation of ISO 15189, which certifies the quality and competence of a medical laboratory with regard to quality management and techniques, developed by the International Organization for Standardization's Technical Committee 212 (ISO/TC 212). In order to start a genome medicine where gene mutation profiles occurring in cancer tissues can contribute to select a treatment option, a new genetic analyzing laboratory is established for performing comprehensive gene mutation analysis to clinical cancer samples using new-generation-sequencers under accreditation of semi- Clinical Laboratory Improvement Amendments (CLIA). The staff of the Clinical Laboratories Division will continuously work to improve the quality and quantity of laboratory services.

Our team and what we do

Pathology Division:

 In 2017, a total of 14 board-certified pathologists, five residents and 14 medical technologists, including 12 cytotechnologists, cooperatively performed routine histological and cytopathological diagnosis of specimens obtained from patients at the NCCH, and education of the residents. Sixteen pathologists working exclusively in the NCCH also shared management of this Pathology Division. We provided a total of 30,966 histological diagnoses consisting of 25,408 biopsy specimens including 2,372 intraoperative frozen sections and 5,558 surgically resected specimens, a total of cytopathological diagnoses of 16,402 patients including 451 for intraoperative diagnosis, and a total of 37 autopsies. We also provided a total of 262 pathological diagnoses for an outpatient clinic for pathology consultation (second opinion).

Clinical Laboratories Division:

 Fifty-four full-time and 13 part-time medical technologists, two photographers, and five assistants provide services. These staff work in the sections of 1) general laboratory medicine and hematology, 2) biochemistry, 3) endocrinology, immunology, and tumor markers, 4) bacteriology, 5) genetic diagnostics, 6) transfusion, 7) phlebotomy, 8) physiological examination, and 9) pathology in the NCCH, and in the sections of phlebotomy and physiological examination of the Cancer Screening Center of the NCCH. The sections of 1) to 5) are to be supervised by Drs. Hiromichi Matsushita and Kuniko Sunami, 6) and 7) by Dr. Saiko Kurosawa (Transfusion Therapy), 8) by Dr. Yasunori Mizuguchi (Diagnostic Radiology), Drs. Masaaki Shoji and Takeshi Iwasa (General Internal Medicine), and Dr. Eriko Iwamoto (Breast Surgery), Drs. Fumihiko Matsumoto, Kenya Kobayashi and Masahiko Fukasawa (Head and Neck Oncology), and 9) by doctors in the Pathology Division. The bacteriology staffs are members of the Infection Control Team and participate in the activities of infection management. The actual number of laboratory tests performed in this division in 2017 is shown in Table 2.

Research activities

1. Hepatobiliary pancreatic pathology

 We reported how to measure tumor-infiltrating immune cells in small biopsied pancreatic cancer tissues. The reliable results were obtained by qRT-PCR methods not by immuno-histochemistry. Infrequent mismatch repair protein loss was found in gallbladder cancer in Japanese patients.

2. Gastrointestinal pathology

 Our mutational analyses revealed critical roles of WNT pathway gene mutations in the development of dysplasia in sessile serrated adenoma/polyps. Molecular and histological characterization of Lynch syndrome-associated colorectal adenomas suggested that, in contrast to the current understanding, mismatch repair deficiency commonly precedes adenoma formation. Automated histological classification of gastric and colorectal biopsy specimens indicated potential utility of this technology in the clinical settings.

3. Hematopathology

 We reported differences of clinicopathologic characteristics of gastric follicular lymphomas and duodenal follicular lymphoma, and distribution of malignant lymphomas in the anterior mediastinum: A single-institution study of 76 cases in Japan, 1997-2016.

4. Thoracic pathology

 We studied clinicopathological, morphological and genetic analysis on prognostic and/or therapeutic response predictive factors of lung and other thoracic malignancies. We reported clinicopathological significance on primary adenocarcinoma's invasion factors, including spread through air space and invasion size of large lepidic adenocarcinoma related to outcome. Systematic review and clinical validated studies on PD-L1 and other new biomarkers for developing targetable gene mutated lung cancer were reported. Also, we contributed several collaboration studies including SP-gene mutation on idiopathic pulmonary fibrosis associated non-small cell carcinomas.

5. Bone and soft tissue pathology

 We reported a series of dedifferentiated liposarcoma with epithelioid/epithelial features. The utility of H3K27me3 immunohistochemistry for the diagnosis of malignant peripheral nerve sheath tumor was validated. We characterized 12 cases of SMARCA4-deficient thoracic sarcoma and clarified their nosologic position. We showed that a subset of CIC-rearranged sarcomas was associated with false-negative results by CIC break-apart FISH assay.

6. Breast pathology

 We reported the clinicopathological features of triple-negative breast cancers that showed progressive disease during neoadjuvant chemotherapy. The combinations of high proliferation, metaplastic features, and immunohistochemical statuses of some EMT and basal-like markers and androgen receptor appeared to be able to characterize the TNBCs that showed cPD after NAC. We also reported the prognostic significance of progesterone receptor expression in estrogen receptor positive, HER2-negative, node-negative invasive breast cancer with a low Ki-67 labeling index.

7. Gynecological pathology

 We reported clinicopathologic association and prognostic impact of microcystic, elongated, and fragmented (MELF) pattern in endometrial endometrioid carcinoma. We showed tumor-associated CD204(+) M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. We reviewed and reported clinicopathological features of uterine adenosarcoma in Japan. We examined predictors of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer. We participated in the collaborative study and elucidated gene aberration profile of tumors of adolescent and young adult females.

8. Head and Neck/ Ophthalmic pathology

 We analyzed the pigmented ciliary adenoma / adenocarcinoma, a black tumor of the eye, and found that the BRAF mutation is negative SOX10 at the protein level. As a result, it was clarified that GNAQ / GNA11 mutation and SOX10 positive uvelal melanoma can be diagnosed as distinguished.

9. Brain tumour pathology

 We are developing a novel FISH probe set to improve diagnostic accuracy of 1p/19q codeleted glioma in collaboration with the Division of Brain Tumor Translational Research, the NCCRI.

10. Skin pathology

 A case of rapidly developed BRAF inhibitor-induced verrucous keratosis was reported.

11. Clinical Laboratories

 An in-hospital bio-bank has been maintained for use by various researchers, and more than 650,000 post-clinical-test blood samples have been stored at -20 °C as of the end of March 2018. Three sections of hematology, biochemistry and endocrinology, immunology and tumor markers, participated in the external quality control program endorsed by the Japanese Society of Laboratory Medicine. Some medical technologists found interesting findings in their routine practice and made presentations at several domestic medical assemblies. At the molecular diagnostic section, the mutation analyses of EGFR, and the chimeric gene detection of BCR-ABL1, RUNX1-RUNX1T1 and CBFB-MYH11 were provided as routine tests. At the cytogenetics section, using the Metafer system (an automated image analysis-assisted fluorescence in situ hybridization [FISH] system), the technique to evaluate the FISH imaging of the gene amplification of HER2 and the gene rearrangement of DDIT3, EWSR1 and SS18 were established and maintained. These two sections provided data not only for clinical practices but also for research activities of doctors in the NCCH and/or the NCCRI.

Table 1. Numbers of histopathological and cytopathological specimens diagnosed in and of autopsies performed in the Pathology Division in 2017
Table 1. Numbers of histopathological and cytopathological specimens diagnosed in and of autopsies                 performed in the Pathology Division in 2017

Table 1. Numbers of histopathological and cytopathological specimens diagnosed in and of autopsies performed in the Pathology Division in 2017
Table 1. Numbers of histopathological and cytopathological specimens diagnosed in and of autopsies
                performed in the Pathology Division in 2017(Full Size)


Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2017
Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2017

Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2017
Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2017(Full Size)

List of papers published in January 2017 - March 2018

Journal

 1. Ebata T, Yunokawa M, Yoshida H, Bun S, Shimoi T, Shimomura A, Kodaira M, Yonemori K, Shimizu C, Fujiwara Y, Kato T, Tamura K. The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma. Int J Gynecol Cancer, 27:1850-1855, 2017

 2. Yamashita A, Saito T, Akaike K, Arakawa A, Yoshida A, Kikuchi K, Sugitani M, Yao T. Mast cell sarcoma of the sternum, clonally related to an antecedent germ cell tumor with a novel D579del KIT mutation. Virchows Arch, 470:583-588, 2017

 3. Buttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, Lopez-Rios F, Penault-Llorca F, Viale G, Wotherspoon AC, Kerr KM, Tsao MS. Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer. J Clin Oncol, 35:3867-3876, 2017

 4. Mori T, Sukeda A, Sekine S, Shibata S, Ryo E, Okano H, Suzuki S, Hiraoka N. SOX10 Expression as Well as BRAF and GNAQ/11 Mutations Distinguish Pigmented Ciliary Epithelium Neoplasms From Uveal Melanomas. Invest Ophthalmol Vis Sci, 58:5445-5451, 2017

 5. Yoshida A, Kobayashi E, Kubo T, Kodaira M, Motoi T, Motoi N, Yonemori K, Ohe Y, Watanabe SI, Kawai A, Kohno T, Kishimoto H, Ichikawa H, Hiraoka N. Clinicopathological and molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol, 30:797-809, 2017

 6. Asano N, Yoshida A, Ichikawa H, Mori T, Nakamura M, Kawai A, Hiraoka N. Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours. Histopathology, 70:385-393, 2017

 7. Nagasato M, Rin Y, Yamamoto Y, Henmi M, Hiraoka N, Chiwaki F, Matsusaki K, Tagawa M, Sasaki H, Aoki K. A Tumor-targeting Adenovirus with High Gene-transduction Efficiency for Primary Pancreatic Cancer and Ascites Cells. Anticancer Res, 37:3599-3605, 2017

 8. Yoshida H, Ikeda S, Tsukada T, Watanabe R, Hiraoka N, Kato T. Methods for Measuring and Staging a Uterine Cervical Adenocarcinoma Showing Intracystic Papillary Growth: A Case Report. Int J Gynecol Pathol, 2017

 9. Kojima M, Shimazaki H, Iwaya K, Nakamura T, Kawachi H, Ichikawa K, Sekine S, Ishiguro S, Shimoda T, Kushima R, Yao T, Fujimori T, Hase K, Watanabe T, Sugihara K, Lauwers GY, Ochiai A. Intramucosal colorectal carcinoma with invasion of the lamina propria: a study by the Japanese Society for Cancer of the Colon and Rectum. Hum Pathol, 66:230-237, 2017

10. Makise N, Yoshida A, Komiyama M, Nakatani F, Yonemori K, Kawai A, Fukayama M, Hiraoka N. Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features. Am J Surg Pathol, 41:1523-1531, 2017

11. Yoshida H, Shimada K, Hiraoka N. Infrequent mismatch repair protein loss in gallbladder cancer patients in Japan. Virchows Arch, 470:109-112, 2017

12. Nakamura Y, Mori T, Takae Y, Tsutsumida A, Takahashi A, Namikawa K, Hirai I, Yamazaki N. Rapidly developed BRAF inhibitor-induced verrucous keratosis. J Dermatol, 44:e274-e275, 2017

13. Maki D, Mori T, Teshima M, Kobayashi K, Matsumoto F, Sakai A, Okami K, Yoshimoto S. Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy. Auris Nasus Larynx, 44:629-634, 2017

14. Ono M, Tsuda H, Yoshida M, Shimizu C, Kinoshita T, Tamura K. Prognostic Significance of Progesterone Receptor Expression in Estrogen-Receptor Positive, HER2-Negative, Node-Negative Invasive Breast Cancer With a Low Ki-67 Labeling Index. Clin Breast Cancer, 17:41-47, 2017

15. Fujiwara T, Uotani K, Yoshida A, Morita T, Nezu Y, Kobayashi E, Uehara T, Omori T, Sugiu K, Komatsubara T, Takeda K, Kunisada T, Kawamura M, Kawai A, Ochiya T, Ozaki T. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. Oncotarget, 8:33375-33392, 2017

16. Kuji S, Watanabe R, Sato Y, Iwata T, Hirashima Y, Takekuma M, Ito I, Abe M, Nagashio R, Omae K, Aoki D, Kameya T. A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases. Gynecol Oncol, 144:384-390, 2017

17. Kitano A, Ono M, Yoshida M, Noguchi E, Shimomura A, Shimoi T, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Kinoshita T, Fujiwara Y, Tsuda H, Tamura K. Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer. ESMO open, 2:e000150, 2017

18. Sasada S, Kurihara H, Kinoshita T, Yoshida M, Honda N, Shimoi T, Shimomura A, Yonemori K, Shimizu C, Hamada A, Kanayama Y, Watanabe Y, Fujiwara Y, Tamura K. Visualization of HER2-specific breast cancer intratumoral heterogeneity using 64Cu-DOTA-trastuzumab PET. Eur J Nucl Med Mol Imaging, 44:2146-2147, 2017

19. Mori S, Motoi N, Ninomiya H, Matsuura Y, Nakao M, Mun M, Okumura S, Nishio M, Morikawa T, Ishikawa Y. High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild-type epidermal growth-factor receptor cases. Pathol Int, 67:37-44, 2017

20. Li J, Motoi N, Kanda H, Sugiura Y, Nagano H, Yonese J, Okumura S, Matsumoto S, Machinami R, Ishikawa Y. A newly emerged osteosarcomatous dedifferentiation of liposarcoma in lung metastasis - a potential diagnostic pitfall. Pathol Int, 67:50-52, 2017

21. Kawai H, Matsushita H, Kawada H, Ogawa Y, Ando K. The Successful Prevention of Thromboembolism Using Rivaroxaban in a Patient with Antithrombin Deficiency during the Perioperative Period. Intern Med, 56:2339-2342, 2017

22. Shimada Y, Kohno T, Ueno H, Ino Y, Hayashi H, Nakaoku T, Sakamoto Y, Kondo S, Morizane C, Shimada K, Okusaka T, Hiraoka N. An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma. Oncologist, 22:158-164, 2017

23. Hara R, Onizuka M, Matsusita E, Kikkawa E, Nakamura Y, Matsushita H, Ohgiya D, Murayama H, Machida S, Ohmachi K, Shirasugi Y, Ogawa Y, Kawada H, Ando K. NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib. Int J Hematol, 106:666-674, 2017

24. Thunnissen E, Borczuk AC, Flieder DB, Witte B, Beasley MB, Chung JH, Dacic S, Lantuejoul S, Russell PA, den Bakker M, Botling J, Brambilla E, de Cuba E, Geisinger KR, Hiroshima K, Marchevsky AM, Minami Y, Moreira A, Nicholson AG, Yoshida A, Tsao MS, Warth A, Duhig E, Chen G, Matsuno Y, Travis WD, Butnor K, Cooper W, Mino-Kenudson M, Motoi N, Poleri C, Pelosi G, Kerr K, Aisner SC, Ishikawa Y, Buettner RH, Keino N, Yatabe Y, Noguchi M. The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases. J Thorac Oncol, 12:334-346, 2017

25. Matsuzawa H, Matsushita H, Yahata T, Tanaka M, Ando K. Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells between Humans and a Humanized Xenograft Model. Tokai J Exp Clin Med, 42:41-51, 2017

26. Okuma HS, Horinouchi H, Kitahara S, Asao T, Sunami K, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Ohe Y. Comparison of Amrubicin and Weekly Cisplatin/Etoposide/Irinotecan in Patients With Relapsed Small-cell Lung Cancer. Clin Lung Cancer, 18:234-240 e232, 2017

27. Makita S, Munakata W, Watabe D, Maeshima AM, Taniguchi H, Toyoda K, Yamauchi N, Fukuhara S, Maruyama D, Kobayashi Y, Tobinai K. Azacitidine-induced acute lung injury in a patient with therapy-related myelodysplastic syndrome. J Int Med Res, 45:886-893, 2017

28. Kihara A, Yoshida H, Watanabe R, Takahashi K, Kato T, Ino Y, Kitagawa M, Hiraoka N. Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma. Am J Surg Pathol, 41:896-905, 2017

29. Hayashi H, Kohno T, Ueno H, Hiraoka N, Kondo S, Saito M, Shimada Y, Ichikawa H, Kato M, Shibata T, Morizane C, Sakamoto Y, Shimada K, Komatsu Y, Sakamoto N, Okusaka T. Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer. Pancreas, 46:335-340, 2017

30. Kitahara H, Maruyama D, Maeshima AM, Makita S, Miyamoto K, Fukuhara S, Munakata W, Suzuki T, Kobayashi Y, Tajima K, Terauchi T, Kurihara H, Taniguchi H, Komatsu N, Tobinai K. Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment. Ann Hematol, 96:411-420, 2017

31. Tsuneki M, Kinjo T, Mori T, Yoshida A, Kuyama K, Ohira A, Miyagi T, Takahashi K, Kawai A, Chuman H, Yamazaki N, Masuzawa M, Arakawa H. Survivin: A novel marker and potential therapeutic target for human angiosarcoma. Cancer Sci, 108:2295-2305, 2017

32. Matsumoto F, Mori T, Matsumura S, Matsumoto Y, Fukasawa M, Teshima M, Kobayashi K, Yoshimoto S. Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients. Jpn J Clin Oncol, 47:699-704, 2017

33. Kikuta K, Nakayama R, Yoshida A, Sasaki A, Kameyama K, Chuman H, Kawai A, Nakamura M, Matsumoto M, Morioka H. A histological positive margin after surgery is correlated with high local re-recurrence rate in patients with recurrent myxofibrosarcoma. Jpn J Clin Oncol, 47:334-341, 2017

34. Araki Y, Yoshida A, Chuman H, Tanzawa Y, Endo M, Kawai A, Kobayashi E. Angioleiomyoma mimicking pes anserinus bursitis: A case report. J Dermatol, 44:e194-e195, 2017

35. Sekine S, Ogawa R, Saito S, Ushiama M, Shida D, Nakajima T, Taniguchi H, Hiraoka N, Yoshida T, Sugano K. Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion. Histopathology, 70:664-669, 2017

36. Yamada M, Saito Y, Takamaru H, Sasaki H, Yokota T, Matsuyama Y, Sato Y, Sakamoto T, Nakajima T, Taniguchi H, Sekine S, Matsuda T. Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study. Endoscopy, 49:233-242, 2017

37. Machado I, Yoshida A, Lopez-Guerrero JA, Nieto MG, Navarro S, Picci P, Llombart-Bosch A. Immunohistochemical analysis of NKX2.2, ETV4, and BCOR in a large series of genetically confirmed Ewing sarcoma family of tumors. Pathol Res Pract, 213:1048-1053, 2017

38. Nakamura K, Nonaka S, Nakajima T, Yachida T, Abe S, Sakamoto T, Suzuki H, Yoshinaga S, Oda I, Matsuda T, Sekine S, Kanemitsu Y, Katai H, Saito Y, Hirota S. Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis. Endosc Int Open, 5:E137-E145, 2017

39. Yamashita R, Watanabe R, Ito I, Shinsaka H, Nakamura M, Matsuzaki M, Niwakawa M. Risk factors for intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma. Int Urol Nephrol, 49:425-430, 2017

40. Matsuyama A, Shiba E, Umekita Y, Nosaka K, Kamio T, Yanai H, Miyasaka C, Watanabe R, Ito I, Tamaki T, Hayashi S, Hisaoka M. Clinicopathologic Diversity of Undifferentiated Sarcoma With BCOR-CCNB3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for BCOR and CCNB3. Am J Surg Pathol, 41:1713-1721, 2017

41. Ueno H, Kanemitsu Y, Sekine S, Ishiguro M, Ito E, Hashiguchi Y, Kondo F, Shimazaki H, Mochizuki S, Kajiwara Y, Shinto E, Yamamoto J. Desmoplastic Pattern at the Tumor Front Defines Poor-prognosis Subtypes of Colorectal Cancer. Am J Surg Pathol, 41:1506-1512, 2017

42. Masai K, Sakurai H, Sukeda A, Suzuki S, Asakura K, Nakagawa K, Asamura H, Watanabe SI, Motoi N, Hiraoka N. Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer. J Thorac Oncol, 12:1788-1797, 2017

43. Shiokawa D, Sato A, Ohata H, Mutoh M, Sekine S, Kato M, Shibata T, Nakagama H, Okamoto K. The Induction of Selected Wnt Target Genes by Tcf1 Mediates Generation of Tumorigenic Colon Stem Cells. Cell Rep, 19:981-994, 2017

44. Kobayashi K, Mori T, Matsumoto F, Murakami N, Teshima M, Fukasawa M, Matsumoto Y, Matsumura S, Itami J, Asai M, Yoshimoto S. Impact of microscopic orbital periosteum invasion in orbital preservation surgery. Jpn J Clin Oncol, 47:321-327, 2017

45. Ito Y, Maeda D, Yoshida M, Yoshida A, Kudo-Asabe Y, Nanjyo H, Izumi C, Yamamoto F, Inoue M, Shibata H, Katoh H, Ishikawa S, Nakamura H, Totoki Y, Shibata T, Yachida S, Goto A. Cardiac intimal sarcoma with PDGFRbeta mutation and co-amplification of PDGFRalpha and MDM2: an autopsy case analyzed by whole-exome sequencing. Virchows Arch, 471:423-428, 2017

46. Tabe Y, Yamamoto S, Saitoh K, Sekihara K, Monma N, Ikeo K, Mogushi K, Shikami M, Ruvolo V, Ishizawa J, Hail N Jr, Kazuno S, Igarashi M, Matsushita H, Yamanaka Y, Arai H, Nagaoka I, Miida T, Hayashizaki Y, Konopleva M, Andreeff M. Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells. Cancer Res, 77:1453-1464, 2017

47. Tanabe Y, Tsuda H, Yoshida M, Yunokawa M, Yonemori K, Shimizu C, Yamamoto S, Kinoshita T, Fujiwara Y, Tamura K. Pathological features of triple-negative breast cancers that showed progressive disease during neoadjuvant chemotherapy. Cancer Sci, 108:1520-1529, 2017

48. Sakakibara R, Inamura K, Tambo Y, Ninomiya H, Kitazono S, Yanagitani N, Horiike A, Ohyanagi F, Matsuura Y, Nakao M, Mun M, Okumura S, Inase N, Nishio M, Motoi N, Ishikawa Y. EBUS-TBNA as a Promising Method for the Evaluation of Tumor PD-L1 Expression in Lung Cancer. Clin Lung Cancer, 18:527-534.e1, 2017

49. Fuji S, Maeshima AM, Kim SW, Fukuda T. Significant nutrient deposition in the liver after allogeneic hematopoietic stem cell transplantation: pathological analysis of 25 autopsy cases. Bone Marrow Transplant, 52:781-782, 2017

50. Mayumi Kobayashi HY, Reiko Watanabe, Tomoyasu Kato. Ovarian metastasis of gastrointestinal stromal tumor: A case report and review of the literatures. J Case Rep Images Gynecol Obstet, 2:9-12, 2017

51. Saito K, Kobayashi E, Yoshida A, Araki Y, Kubota D, Tanzawa Y, Kawai A, Yanagawa T, Takagishi K, Chuman H. Angiomatoid fibrous histiocytoma: a series of seven cases including genetically confirmed aggressive cases and a literature review. BMC Musculoskelet Disord, 18:31, 2017

52. Yoshida A, Arai Y, Kobayashi E, Yonemori K, Ogura K, Hama N, Mukai W, Motoi T, Kawai A, Shibata T, Hiraoka N. CIC break-apart fluorescence in-situ hybridization misses a subset of CIC-DUX4 sarcomas: a clinicopathological and molecular study. Histopathology, 71:461-469, 2017

53. Maeshima AM, Taniguchi H, Suzuki T, Yuda S, Toyoda K, Yamauchi N, Makita S, Fukuhara S, Munakata W, Maruyama D, Kobayashi Y, Tobinai K. Distribution of malignant lymphomas in the anterior mediastinum: a single-institution study of 76 cases in Japan, 1997-2016. Int J Hematol, 106:675-680, 2017

54. Maeshima AM, Taniguchi H, Suzuki T, Yuda S, Toyoda K, Yamauchi N, Makita S, Fukuhara S, Munakata W, Maruyama D, Kobayashi Y, Saito Y, Tobinai K. Comparison of clinicopathologic characteristics of gastric follicular lymphomas and duodenal follicular lymphomas. Hum Pathol, 65:201-208, 2017

55. Hironaka-Mitsuhashi A, Matsuzaki J, Takahashi RU, Yoshida M, Nezu Y, Yamamoto Y, Shiino S, Kinoshita T, Ushijima T, Hiraoka N, Shimizu C, Tamura K, Ochiya T. A tissue microRNA signature that predicts the prognosis of breast cancer in young women. PLoS One, 12:e0187638, 2017

56. Hashimoto T, Yamashita S, Yoshida H, Taniguchi H, Ushijima T, Yamada T, Saito Y, Ochiai A, Sekine S, Hiraoka N. WNT Pathway Gene Mutations Are Associated With the Presence of Dysplasia in Colorectal Sessile Serrated Adenoma/Polyps. Am J Surg Pathol, 41:1188-1197, 2017

57. Ohmoto A, Fuji S, Miyagi-Maeshima A, Kim SW, Tajima K, Tanaka T, Okinaka K, Kurosawa S, Inamoto Y, Taniguchi H, Fukuda T. Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection. Bone Marrow Transplant, 52:1201-1203, 2017

58. Yamada M, Oda I, Tanaka H, Abe S, Nonaka S, Suzuki H, Yoshinaga S, Kuchiba A, Koyanagi K, Igaki H, Taniguchi H, Sekine S, Saito Y, Tachimori Y. Tumor location is a risk factor for lymph node metastasis in superficial Barrett's adenocarcinoma. Endoscopy international open, 5:E868-E874, 2017

59. Sasada S, Kurihara H, Kinoshita T, Yoshida M, Honda N, Shimoi T, Shimomura A, Yunokawa M, Yonemori K, Shimizu C, Hamada A, Kanayama Y, Watanabe Y, Fujiwara Y, Tamura K. 64Cu-DOTA-trastuzumab PET imaging for HER2-specific primary lesions of breast cancer. Ann Oncol, 28:2028-2029, 2017

60. Furukawa D, Chijiwa T, Matsuyama M, Mukai M, Matsuo EI, Nishimura O, Kawai K, Suemizu H, Nakagohri T, Ozawa S, Shimada K, Hiraoka N, Nakamura M. Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma. Oncology letters, 14:3633-3640, 2017

61. Sugawara M, Kobayashi E, Asano N, Yoshida A, Kawai A. Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported by Complete Immunohistochemical Loss of H3K27me3. Int J Surg Pathol, 25:629-634, 2017

62. Yamamoto Y, Nagasato M, Rin Y, Henmi M, Ino Y, Yachida S, Ohki R, Hiraoka N, Tagawa M, Aoki K. Strong antitumor efficacy of a pancreatic tumor-targeting oncolytic adenovirus for neuroendocrine tumors. Cancer Med, 6:2385-2397, 2017

63. Kasahara N, Wakuda K, Omori S, Nakashima K, Ono A, Taira T, Kenmotsu H, Naito T, Murakami H, Mori K, Watanabe R, Endo M, Nakajima T, Yamada M, Takahashi T. Amrubicin monotherapy may be an effective second-line treatment for patients with large-cell neuroendocrine carcinoma or high-grade non-small-cell neuroendocrine carcinoma. Molecular and clinical oncology, 6:718-722, 2017

64. Sakumoto M, Takahashi M, Oyama R, Takai Y, Kito F, Shiozawa K, Qiao Z, Yoshida A, Endo M, Kawai A, Kondo T. Establishment and proteomic characterization of NCC-LMS1-C1, a novel cell line of primary leiomyosarcoma of the bone. Jpn J Clin Oncol, 47:954-961, 2017

65. Kikuta K, Kubota D, Yoshida A, Qiao Z, Morioka H, Nakamura M, Matsumoto M, Chuman H, Kawai A, Kondo T. Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling. Biochim Biophys Acta, 1865:1160-1166, 2017

66. Oyama R, Takahashi M, Yoshida A, Sakumoto M, Takai Y, Kito F, Shiozawa K, Qiao Z, Arai Y, Shibata T, Araki Y, Endo M, Kawai A, Kondo T. Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines. Sci Rep, 7:4712, 2017

67. Yunokawa M, Yoshida H, Watanabe R, Noguchi E, Shimomura A, Shimoi T, Yonemori K, Shimizu C, Fujiwara Y, Tamura K. Allred score is a promising predictor of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer. Cancer Chemother Pharmacol, 80:127-134, 2017

68. Asano N, Yoshida A, Mitani S, Kobayashi E, Shiotani B, Komiyama M, Fujimoto H, Chuman H, Morioka H, Matsumoto M, Nakamura M, Kubo T, Kato M, Kohno T, Kawai A, Kondo T, Ichikawa H. Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Oncotarget, 8:12941-12952, 2017

69. Sekine S, Ogawa R, Hashimoto T, Motohiro K, Yoshida H, Taniguchi H, Saito Y, Yasuhiro O, Ochiai A, Hiraoka N. Comprehensive characterization of RSPO fusions in colorectal traditional serrated adenomas. Histopathology, 71:601-609, 2017

70. Ogura K, Hosoda F, Nakamura H, Hama N, Totoki Y, Yoshida A, Ohashi S, Rokutan H, Takai E, Yachida S, Kawai A, Tanaka S, Shibata T. Highly recurrent H3F3A mutations with additional epigenetic regulator alterations in giant cell tumor of bone. Genes Chromosomes Cancer, 56:711-718, 2017

71. Sekine S, Mori T, Ogawa R, Tanaka M, Yoshida H, Taniguchi H, Nakajima T, Sugano K, Yoshida T, Kato M, Furukawa E, Ochiai A, Hiraoka N. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis. Mod Pathol, 30:1144-1151, 2017

72. Kodaira M, Yonemori K, Shimoi T, Yoshida A, Yoshida M, Kitano A, Shimomura A, Yunokawa M, Shimizu C, Takiguchi Y, Fujiwara Y, Tamura K. Prognostic impact of presumed breast or ovarian cancer among patients with unfavorable-subset cancer of unknown primary site. BMC Cancer, 18:176, 2018

73. Tate K, Watanabe R, Yoshida H, Shimizu H, Uehara T, Ishikawa M, Ikeda SI, Hiraoka N, Kato T. Uterine adenosarcoma in Japan: Clinicopathologic features, diagnosis and management. Asia Pac J Clin Oncol, 2018

74. Kanke Y, Shimomura A, Saito M, Honda T, Shiraishi K, Shimada Y, Watanabe R, Yoshida H, Yoshida M, Shimizu C, Takahashi K, Totsuka H, Ogiwara H, Hirose S, Kono K, Tamura K, Okamoto A, Kinoshita T, Kato T, Kohno T. Gene aberration profile of tumors of adolescent and young adult females. Oncotarget, 9:6228-6237, 2018

75. Araki Y, Yoshida A, Tanzawa Y, Endo M, Kobayashi E, Kawai A. Reconstruction of the Shoulder Joint with a Custom-Made Ceramic Implant After a Total Scapulectomy: A Case Report. JBJS Case Connect, 8:e12, 2018

76. Yoshida H, Shimazu T, Kiyuna T, Marugame A, Yamashita Y, Cosatto E, Taniguchi H, Sekine S, Ochiai A. Automated histological classification of whole-slide images of gastric biopsy specimens. Gastric Cancer, 21:249-257, 2018

77. Shimoi T, Yoshida M, Kitamura Y, Yoshino T, Kawachi A, Shimomura A, Noguchi E, Yunokawa M, Yonemori K, Shimizu C, Kinoshita T, Ichimura K, Fukuda T, Fujiwara Y, Tamura K. TERT promoter hotspot mutations in breast cancer. Breast Cancer, 25:292-296, 2018

78. Fukuhara S, Nomoto J, Kim SW, Taniguchi H, Miyagi Maeshima A, Tobinai K, Kobayashi Y. Partial deletion of the ALK gene in ALK-positive anaplastic large cell lymphoma. Hematol Oncol, 36:150-158, 2018

79. Cho H, Sekine S, Sekiguchi M. Adenocarcinoma of the colon presenting as a submucosal tumor. Dig Endosc, 30:114-115, 2018

80. Kito M, Munakata W, Ono K, Maeshima AM, Matsushita H. The infiltration of classical Hodgkin lymphoma cells into pleural effusion. Int J Hematol, 107:1-2, 2018

81. Kanke Y, Shimomura A, Saito M, Honda T, Shiraishi K, Shimada Y, Watanabe R, Yoshida H, Yoshida M, Shimizu C, Takahashi K, Totsuka H, Ogiwara H, Hirose S, Kono K, Tamura K, Okamoto A, Kinoshita T, Kato T, Kohno T. Gene aberration profile of tumors of adolescent and young adult females. Oncotarget, 9:6228-6237, 2018

82. Aruga Y, Arakawa A, Ono K, Ogawa C, Matsushita H. Pseudo-Chediak-Higashi granules and Auer rods in mixed phenotype acute leukaemia, T/myeloid, not otherwise specified. Br J Haematol, 180:175, 2018

83. Kawashima I, Inamoto Y, Maeshima AM, Nomoto J, Tajima K, Honda T, Shichijo T, Kawajiri A, Takemura T, Onishi A, Ito A, Tanaka T, Fuji S, Kurosawa S, Kim SW, Maruyama D, Tobinai K, Kobayashi Y, Fukuda T. Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant, 24:294-300, 2018

84. Inagaki C, Shimoi T, Okuma H, Kitano A, Shimomura A, Noguchi E, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Yoshida A, Fujiwara Y, Tamura K. A case of heavily pretreated metastatic cardiac angiosarcoma treated successfully using eribulin. Anticancer Drugs, 29:97-101, 2018

85. Sakumoto M, Oyama R, Takahashi M, Takai Y, Kito F, Shiozawa K, Qiao Z, Endo M, Yoshida A, Kawai A, Kondo T. Establishment and proteomic characterization of patient-derived clear cell sarcoma xenografts and cell lines. In Vitro Cell Dev Biol Anim, 54:163-176, 2018

86. Udagawa C, Nakamura H, Ohnishi H, Tamura K, Shimoi T, Yoshida M, Yoshida T, Totoki Y, Shibata T, Zembutsu H. Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity. Cancer Sci, 109:446-452, 2018

87. Sugiura Y, Kanda H, Motoi N, Nomura K, Inamura K, Okada E, Matsumoto H, Shimoji T, Matsumoto S, Nakayama J, Takazawa Y, Ishikawa Y, Machinami R. Osteosarcoma arising in fibrous dysplasia, confirmed by mutational analysis of GNAS gene. Pathol Res Pract, 214:318-324, 2018

88. Kawachi A, Yoshida H, Kitano S, Ino Y, Kato T, Hiraoka N. Tumor-associated CD204+ M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci, 109:863-870, 2018

89. Higashiyama RI, Makita S, Maeshima AM, Maruyama D. Atypical radiological presentation of pulmonary invasion of diffuse large B-cell lymphoma mimicking Pneumocystis jiroveci pneumonia. Jpn J Clin Oncol, 48:298-299, 2018

90. Yoshida H, Shimazu T, Kiyuna T, Marugame A, Yamashita Y, Cosatto E, Taniguchi H, Sekine S, Ochiai A. Automated histological classification of whole-slide images of gastric biopsy specimens. Gastric cancer, 21:249-257, 2018

91. Yoshimoto T, Motoi N, Yamamoto N, Nagano H, Ushijima M, Matsuura M, Okumura S, Yamaguchi T, Fukayama M, Ishikawa Y. Pulmonary Carcinoids and Low-Grade Gastrointestinal Neuroendocrine Tumors Show Common MicroRNA Expression Profiles, Different from Adenocarcinomas and Small Cell Carcinomas. Neuroendocrinology, 106:47-57, 2018

92. Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, Motomura K, Ohka F, Shiina S, Yamamoto T, Nagata Y, Yoshizato T, Mizoguchi M, Abe T, Momii Y, Muragaki Y, Watanabe R, Ito I, Sanada M, Yajima H, Morita N, Takeuchi I, Miyano S, Wakabayashi T, Ogawa S, Natsume A. Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro Oncol, 20:66-77, 2018

93. Oyama R, Kito F, Sakumoto M, Shiozawa K, Toki S, Yoshida A, Kawai A, Kondo T. Establishment and proteomic characterization of a novel cell line, NCC-UPS2-C1, derived from a patient with undifferentiated pleomorphic sarcoma. In Vitro Cell Dev Biol Anim, 54:257-263, 2018

94. Hino R, Motoi N, Toda K, Ebina A, Yamada K, Higuchi M, Hirokawa M, Ishikawa Y. Stromal tiny black dots, like "sugar-coated", of von Kossa stain is a diagnostic clue to hyalinizing trabecular tumor of the thyroid gland. Pathol Int, 68:176-182, 2018