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Annual Report 2018

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, Kuniko Sunami, Taiki Hashimoto

Introduction

 The practice, education, and research on diagnostic and anatomic pathology are carried out in the Pathology Division. Diagnostic pathology practice comprises all issues concerning the processing of cell and tissue specimens obtained from patients, preparation of tissue blocks and pathology slides, and histological and cytopathological diagnoses of diseases. Anatomic pathology practice, by contrast, comprises the autopsy and post-mortem systemic gross and microscopic examinations of patients. Case conferences with each clinical division are held periodically, and residents and trainees are accepted for training in diagnostic pathology on a rotating basis. To provide more accurate and informative diagnoses in the future, the staff members conduct basic, clinical, or translational research by themselves or in collaboration with other divisions or 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 this department have acquired ISO 15189 accreditation, which certifies the quality and competency of a medical laboratory with regard to the quality management and technique, as established by the International Organization for Standardization's Technical Committee 212 (ISO/ TC 212). The staff of the Clinical Laboratories Division is continuously striving to maintain the quality and quantity of laboratory services through this system.

The Team and What We Do

Pathology Division:

 In 2018, 12 staff pathologists, seven residents, and 14 medical technologists, including 12 cytotechnologists, cooperatively performed routine histological and cytopathological diagnoses of specimens obtained from patients at the National Cancer Center Hospital (NCCH) and educated residents. We accepted a total of 25,502 histological specimens, including 20,806 biopsy and 4,696 surgically resected specimens and 12,731 cytological specimens (Table 1). These included 1,969 intraoperative frozen sections and 342 intraoperative cytological diagnoses. We also provided a total of 192 pathological diagnoses to the outpatient clinic for pathology consultation (second opinion).

Clinical Laboratories Division:

 A total of 56 full-time and 13 part-time medical technologists, two photographers, and five assistants provide services in this division. 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 in the Screening Center. Sections 1) to 5) are 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, Masahiko Fukasawa, Go Omura, Kenya Kobayashi, Satoko Matsumura and Atsuo Ikeda (Head and Neck Oncology); and 9) by the doctors in the Pathology Division. The bacteriology staff are members of the Infection Control Team and participate in infection management. The actual number of laboratory tests performed in this division in 2018 is shown in Table 2.

Table 1. Numbers of Histopathological and Cytopathological Specimens Diagnosed in and of Autopsies Performed in the Department of Pathology in 2018
Table 1. Numbers of Histopathological and Cytopathological Specimens Diagnosed in and of Autopsies Performed in the Department of Pathology in 2018

Table 1. Numbers of Histopathological and Cytopathological Specimens Diagnosed in and of Autopsies Performed in the Department of Pathology in 2018
Table 1. Numbers of Histopathological and Cytopathological Specimens Diagnosed in and of Autopsies Performed in the Department of Pathology in 2018(Full Size)

Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2018
Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2018

Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2018
Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2018(Full Size)

Research activities

1. Hepato-biliary pancreatic pathology

 We reported that the intrapancreatic neural density is reduced in pancreatic cancer tissues and an independent prognosticator. The frequency of HER2 positivity was found to differ among the organs in the biliary tract, and the HER2 protein expression was usually heterogenous.

2.  Gastrointestinal pathology

 We demonstrated the frequent presence of RHOA mutations in intestinal-type adenocarcinoma with anastomosing glands of the stomach, suggesting this is a genetically distinct subtype. Our analysis of precursor polyp-associated traditional serrated adenomas (TSAs) revealed the role of the WNT pathway gene mutation in the development of TSA. We proposed superficially serrated adenoma as a novel subtype of colorectal serrated lesion. An analysis of a large number of sessile serrated adenoma/polyps revealed a degree of genetic heterogeneity of this entity.

3. Thoracic pathology

 We conducted clinicopathological, morphological, and genetic analyses to identify predictive factors of a prognostic or therapeutic response in cases of lung and other thoracic malignancies. We reported the clinicopathological significance of a histopathological assessment of invasive mucinous adenocarcinoma (a rare variant of lung cancer) related to the outcome, a clinicopathological comparison study between lung and mediastinal neuroendocrine tumor, and a feasibility study of lung cytology specimens for biomarker tests. We also contributed to several collaboration studies, including a study of the SP gene mutation in idiopathic pulmonary fibrosisassociated non-small cell carcinoma and a study on the clinical use of cytology specimens for biomarker tests.

4. Bone and soft tissue pathology

 We revisited the utility of MDM2 and H3K27me3 in differentiating malignant peripheral nerve sheath tumor and dedifferentiated liposarcoma. The MDM2 and H3K27me3 status was also examined in extraskeletal osteosarcoma to evaluate the disease heterogeneity. We showed that INSM1 is often expressed in extraskeletal myxoid chondrosarcoma, which may have potential diagnostic utility. We compared the utility of NKX2-2 and PAX7 in the diagnosis of Ewing sarcoma and discovered that a subset of dedifferentiated chondrosarcoma is deficient in H3K27me3, and this group is associated with characteristic clinicopathological features. We contributed to the comprehensive genetic and epigenetic analyses of myxofibrosarcoma and an international project to identify the fusioncreating mechanism in Ewing sarcoma.

5. Breast pathology

 We reported our experience with two cases of endosalpingiosis in axillary SLNs, which we confirmed using immunohistochemistry. We also reported biomarker discordance between primary breast cancer and bone or bone marrow metastases.

6. Gynecological pathology

 We reported positive pelvic cytology as a prognostic factor for stage I-II uterine serous carcinoma. We also showed that synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC) patients had unique prognostic features, indicating that SEO-EC patients with tumors localized to the uterine body and adnexa lesions had a low risk for recurrence and might not require adjuvant therapy. We reported the prevalence of lymphangioleiomyomatosis in lymph nodes sampled in gynecological surgery and discussed the risk of subsequent pulmonary LAM. We reported a case of endometrial cancer among patients with Cornelia de Lange syndrome and a case of endometrial cancer showing a unique morphology and tumor extension in a patient with Cowden syndrome. We and the researchers of NCCRI have collaborated on several research projects and reported targets of synthetic lethality in ovarian clear cell carcinoma with an ARID1A mutation.

7. Head and neck/ophthalmic pathology

 We reported that the CyclinD1 expression in thyroid nodules is a novel marker for both the sensitivity and specificity and that a screening system using CyclinD1 is also useful for cytopathology. We analyzed p53 protein expression and all TP53 exon sequences in 317 head and neck squamous cell carcinomas. We classified two risk categories as "p53 adverse function" and "p53 favorable function" based on TP53 mutation status and p53 protein phenotype. The "p53 adverse function" was an independent poor predictor of overall survival, local control, and distant metastasis-free survival.

8. Brain tumor pathology

 We developed a novel FISH probe set to improve the diagnostic accuracy of 1p/19q codeleted glioma in collaboration with the Division of Brain Tumor Translational Research. The utility of H3K27me3 immunohistochemistry for dividing posterior fossa ependymomas into PFA and PFB groups was confirmed. We showed that IDH1 (R132H) mutation-specific antibody often provides false-negative results in frozen section control slides.

9. Skin pathology

 We reported the frequent presence of transforming YAP1 fusions (YAP1-MAML2, YAP1-NUTM1, WWTR1-NUTM1) in poromas and porocarcinoma. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. These findings suggest that YAP1/TEAD-dependent transcription is a candidate therapeutic target for porocarcinoma.

10. Clinical laboratories

 In order to facilitate the implementation of cancer genome medicine, wherein gene mutation profiles in cancer tissues are used to select ideal treatment options, we performed Advanced Medical Care B clinical research using the NCC Oncopanel System. Several medical technologists obtained interesting findings in their routine practice and made presentations at several domestic medical conferences. In the cytogenetics section, the FISH technique using the Metafer system to evaluate the gene amplification of HER2; the gene rearrangement of DDIT3, EWSR1 and SS18 for musculoskeletal/soft tissue tumors; and the formation of IGH-MYC and IGH-BCL2 for malignant lymphoma provided useful data for not only clinical practices but also research activities of doctors in the NCCH and NCCRI. In addition, an in-hospital bio-bank system has been maintained in order to aid in clinical research being conducted by various researchers in the NCCH and NCCRI. More than 600,000 postclinical-test serum samples have been stored at -20°C as of the end of March 2019.

List of papers published in 2018

Journal

 1. Nakano Y, Tomiyama A, Kohno T, Yoshida A, Yamasaki K, Ozawa T, Fukuoka K, Fukushima H, Inoue T, Hara J, Sakamoto H, Ichimura K. Identification of a novel KLC1-ROS1 fusion in a case of pediatric low-grade localized glioma. Brain Tumor Pathol, 36:14-19, 2019

 2. Asano N, Matsuzaki J, Ichikawa M, Kawauchi J, Takizawa S, Aoki Y, Sakamoto H, Yoshida A, Kobayashi E, Tanzawa Y, Nakayama R, Morioka H, Matsumoto M, Nakamura M, Kondo T, Kato K, Tsuchiya N, Kawai A, Ochiya T. A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes. Nat Commun, 10:1299, 2019

 3. Hashimoto T, Ogawa R, Tang TY, Yoshida H, Taniguchi H, Katai H, Oda I, Sekine S. RHOA mutations and CLDN18-ARHGAP fusions in intestinal-type adenocarcinoma with anastomosing glands of the stomach. Mod Pathol, 32:568-575, 2019

 4. Hashimoto T, Ogawa R, Yoshida H, Taniguchi H, Kojima M, Saito Y, Sekine S. Acquisition of WNT Pathway Gene Alterations Coincides With the Transition From Precursor Polyps to Traditional Serrated Adenomas. Am J Surg Pathol, 43:132-139, 2019

 5. Hironaka-Mitsuhashi A, Tsuda H, Yoshida M, Shimizu C, Asaga S, Hojo T, Tamura K, Kinoshita T, Ushijima T, Hiraoka N, Fujiwara Y. Invasive breast cancers in adolescent and young adult women show more aggressive immunohistochemical and clinical features than those in women aged 40-44 years. Breast Cancer, 26:386-396, 2019

 6. Ino Y, Oguro S, Yamazaki-Itoh R, Hori S, Shimada K, Hiraoka N. Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies. Oncotarget, 10:1149-1159, 2019

 7. Jain D, Nambirajan A, Borczuk A, Chen G, Minami Y, Moreira AL, Motoi N, Papotti M, Rekhtman N, Russell PA, Savic Prince S, Yatabe Y, Bubendorf L. Immunocytochemistry for predictive biomarker testing in lung cancer cytology. Cancer Cytopathol, 127:325-339, 2019

 8. Kawai H, Matsushita H, Kawakami S, Furuya D, Shiraiwa-Hara S, Ichiki A, Hara R, Aoyama Y, Ogiya D, Suzuki R, Machida S, Onizuka M, Shirasugi Y, Ogawa Y, Kawada H, Nakamura N, Ando K. A Case of Composite Lymphoma with Extranodal NK/T-cell Lymphoma, Nasal-type and Diffuse Large B-cell Lymphoma. J Clin Exp Hematop, 59:34-39, 2019

 9. Kobayashi K, Yoshimoto S, Matsumoto F, Ando M, Murakami N, Omura G, Fukasawa M, Matsumoto Y, Matsumura S, Akamatsu M, Hiraoka N, Eigitsu R, Mori T. All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma. Ann Surg Oncol, 26:2294-2303, 2019

10. Kojima N, Yoshida H, Uehara T, Ushigusa T, Asami Y, Shiraishi K, Kato T. Primary Clear Cell Adenocarcinoma of the Vulva: A Case Study With Mutation Analysis and Literature Review. Int J Surg Pathol, 1066896919848823, 2019.

11. Kuno I, Tate K, Yoshida H, Takahashi K, Kato T. Endometrial Endometrioid Carcinoma With Ovarian Metastasis Showing Morula-like Features in a Patient With Cowden Syndrome: A Case Report. Int J Gynecol Pathol, 2019

12. Kuno I, Yoshida H, Kohno T, Ochiai A, Kato T. Endometrial cancer arising after complete remission of uterine malignant lymphoma: A case report and mutation analysis. Gynecol Oncol Rep, 28:50- 53, 2019

13. Makise N, Sekimizu M, Konishi E, Motoi T, Kubo T, Ikoma H, Watanabe SI, Okuma T, Hiraoka N, Fukayama M, Kawai A, Ichikawa H, Yoshida A. H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features. Mod Pathol, 32:435-445, 2019

14. Nakai T, Matsumoto Y, Sasada S, Tanaka M, Tsuchida T, Ohe Y, Motoi N. Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology. Jpn J Clin Oncol, 49:559-566, 2019

15. Nakamura Y, Shida D, Shibayama T, Yoshida A, Matsui Y, Shinoda Y, Iwata S, Kanemitsu Y. Giant multilocular prostatic cystadenoma. World J Surg Oncol, 17:42, 2019

16. Ogasawara A, Matsushita H, Tanaka Y, Shirasugi Y, Ando K, Asai S, Miyachi H. A simple screening method for the diagnosis of chronic myeloid leukemia using the parameters of a complete blood count and differentials. Clin Chim Acta, 489:249-253, 2019

17. Ogiwara H, Takahashi K, Sasaki M, Kuroda T, Yoshida H, Watanabe R, Maruyama A, Makinoshima H, Chiwaki F, Sasaki H, Kato T, Okamoto A, Kohno T. Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Cancers. Cancer Cell, 35:177-190.e8, 2019

18. Ohashi-Nakatani K, Shibuki Y, Fujima M, Watanabe R, Yoshida A, Yoshida H, Matsumoto Y, Tsuchida T, Watanabe SI, Motoi N. Primary pulmonary meningioma: A rare case report of aspiration cytological features and immunohistochemical assessment. Diagn Cytopathol, 47:330-333, 2019

19. Oyama R, Kito F, Qiao Z, Sakumoto M, Shiozawa K, Toki S, Yoshida A, Kawai A, Kondo T. Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1. In Vitro Cell Dev Biol Anim, 55:62-73, 2019

20. Sato J, Shimoi T, Shimomura A, Noguchi E, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Fujiwara Y, Yoshida M, Tamura K. The Incidence of Nonmalignant Diseases among Patients with Suspected Carcinoma of Unknown Primary Site. Intern Med, 58:1423-1428, 2019

21. Sekimizu M, Yoshida A, Mitani S, Asano N, Hirata M, Kubo T, Yamazaki F, Sakamoto H, Kato M, Makise N, Mori T, Yamazaki N, Sekine S, Oda I, Watanabe SI, Hiraga H, Yonemoto T, Kawamoto T, Naka N, Funauchi Y, Nishida Y, Honoki K, Kawano H, Tsuchiya H, Kunisada T, Matsuda K, Inagaki K, Kawai A, Ichikawa H. Frequent mutations of genes encoding vacuolar H+ -ATPase components in granular cell tumors. Genes Chromosomes Cancer, 58:373-380, 2019

22. Shiino S, Yoshida M, Jimbo K, Asaga S, Takayama S, Maeshima A, Tsuda H, Kinoshita T, Hiraoka N. Two rare cases of endosalpingiosis in the axillary sentinel lymph nodes: evaluation of immunohistochemical staining and one-step nucleic acid amplification (OSNA) assay in patients with breast cancer. Virchows Arch, 474:633-638, 2019

23. Tate K, Yoshida H, Ishikawa M, Shimizu H, Uehara T, Kato T. Endometrial Carcinoma With an Unusual Morphology in a Patient With Cornelia de Lange Syndrome: A Case Study. Int J Gynecol Pathol, 38:340-345, 2019

24. Teshima M, Tokita K, Ryo E, Matsumoto F, Kondo M, Ikegami Y, Shinomiya H, Otsuki N, Hiraoka N, Nibu KI, Yoshimoto S, Mori T. Clinical impact of a cytological screening system using cyclin D1 immunostaining and genomic analysis for the diagnosis of thyroid nodules. BMC Cancer, 19:245, 2019

25. Tozawa K, Ono-Uruga Y, Yazawa M, Mori T, Murata M, Okamoto S, Ikeda Y, Matsubara Y. Megakaryocytes and platelets from a novel human adipose tissue-derived mesenchymal stem cell line. Blood, 133:633-643, 2019

26. Uehara T, Yoshida H, Tate K, Kato T. Metachronous occurrence of two different histological subtypes of endometriosis-related neoplasms. Gynecol Oncol Rep, 27:42-45, 2019

27. Yatabe Y, Dacic S, Borczuk AC, Warth A, Russell PA, Lantuejoul S, Beasley MB, Thunnissen E, Pelosi G, Rekhtman N, Bubendorf L, Mino-Kenudson M, Yoshida A, Geisinger KR, Noguchi M, Chirieac LR, Bolting J, Chung JH, Chou TY, Chen G, Poleri C, Lopez-Rios F, Papotti M, Sholl LM, Roden AC, Travis WD, Hirsch FR, Kerr KM, Tsao MS, Nicholson AG, Wistuba I, Moreira AL. Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer. J Thorac Oncol, 14:377-407, 2019

28. Yoneoka Y, Yoshida H, Ishikawa M, Shimizu H, Uehara T, Murakami T, Kato T. Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma. J Gynecol Oncol, 30:e7, 2019

29. Yoshida A, Satomi K, Ohno M, Matsushita Y, Takahashi M, Miyakita Y, Hiraoka N, Narita Y, Ichimura K. Frequent false-negative immunohistochemical staining with IDH1 (R132H)-specific H09 antibody on frozen section control slides: a potential pitfall in glioma diagnosis. Histopathology, 74:350-354, 2019

30. Yuda S, Shimizu C, Yoshida M, Shiino S, Kinoshita T, Maeshima AM, Tamura K. Biomarker discordance between primary breast cancer and bone or bone marrow metastases. Jpn J Clin Oncol, 49:426-430, 2019

31. Sunami K, Ichikawa H, Kubo T, Kato M, Fujiwara Y, Shimomura A, Koyama T, Kakishima H, Kitami M, Matsushita H, Furukawa E, Narushima D, Nagai M, Taniguchi H, Motoi N, Sekine S, Maeshima A, Mori T, Watanabe R, Yoshida M, Yoshida A, Yoshida H, Satomi K, Sukeda A, Hashimoto T, Shimizu T, Iwasa S, Yonemori K, Kato K, Morizane C, Ogawa C, Tanabe N, Sugano K, Hiraoka N, Tamura K, Yoshida T, Fujiwara Y, Ochiai A, Yamamoto N, Kohno T. Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: A hospital-based study. Cancer Sci, 110:1480-1490, 2019

32. Shiino S, Matsuzaki J, Shimomura A, Kawauchi J, Takizawa S, Sakamoto H, Aoki Y, Yoshida M, Tamura K, Kato K, Kinoshita T, Kitagawa Y, Ochiya T. Serum miRNA-based Prediction of Axillary Lymph Node Metastasis in Breast Cancer. Clin Cancer Res, 25:1817-1827, 2019

33. Kato M, Nakamura H, Nagai M, Kubo T, Elzawahry A, Totoki Y, Tanabe Y, Furukawa E, Miyamoto J, Sakamoto H, Matsumoto S, Sunami K, Arai Y, Suzuki Y, Yoshida T, Tsuchihara K, Tamura K, Yamamoto N, Ichikawa H, Kohno T, Shibata T. A computational tool to detect DNA alterations tailored to formalin-fixed paraffin-embedded samples in cancer clinical sequencing. Genome Med, 10:44, 2018

34. Ohara K, Arai E, Takahashi Y, Fukamachi Y, Ito N, Maeshima AM, Fujimoto H, Yoshida T, Kanai Y. Feasibility of methylome analysis using small amounts of genomic DNA from formalin-fixed paraffin-embedded tissue. Pathol Int, 68:633-635, 2018

35. Anderson ND, de Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, Hajjar S, Layeghifard M, Novokmet A, Kowalski PE, Anaka M, Davidson S, Zarrei M, Id Said B, Schreiner LC, Marchand R, Sitter J, Gokgoz N, Brunga L, Graham GT, Fullam A, Pillay N, Toretsky JA, Yoshida A, Shibata T, Metzler M, Somers GR, Scherer SW, Flanagan AM, Campbell PJ, Schiffman JD, Shago M, Alexandrov LB, Wunder JS, Andrulis IL, Malkin D, Behjati S, Shlien A. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors. Science, 361:2018

36. Ando Y, Maeshima AM, Fukuhara S, Makita S, Munakata W, Suzuki T, Maruyama D, Taniguchi H, Izutsu K. CD3+ CD56+ EBER1+ atypical extraosseous plasmacytoma of the nasal cavity. Int J Hematol, 108:344-347, 2018

37. Cho H, Hashimoto T, Yoshida H, Taniguchi H, Ogawa R, Mori T, Hiraoka N, Saito Y, Sekine S. Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp. Histopathology, 73:672-680, 2018

38. Ebata T, Shimoi T, Bun S, Miyake M, Yoshida A, Shimomura A, Noguchi E, Yonemori K, Shimizu C, Fujiwara Y, Narita Y, Tamura K. Efficacy and Safety of Pazopanib for Recurrent or Metastatic Solitary Fibrous Tumor. Oncology, 94:340-344, 2018

39. Frezza AM, Jones RL, Lo Vullo S, Asano N, Lucibello F, Ben-Ami E, Ratan R, Teterycz P, Boye K, Brahmi M, Palmerini E, Fedenko A, Vincenzi B, Brunello A, Desar IME, Benjamin RS, Blay JY, Broto JM, Casali PG, Gelderblom H, Grignani G, Gronchi A, Hall KS, Mir O, Rutkowski P, Wagner AJ, Anurova O, Collini P, Dei Tos AP, Flucke U, Hornick JL, Lobmaier I, Philippe T, Picci P, Ranchere D, Renne SL, Sbaraglia M, Thway K, Wagrodzki M, Wang WL, Yoshida A, Mariani L, Kawai A, Stacchiotti S. Anthracycline, Gemcitabine, and Pazopanib in Epithelioid Sarcoma: A Multi-institutional Case Series. JAMA Oncol, 4:e180219, 2018

40. Hama N, Totoki Y, Miura F, Tatsuno K, Saito-Adachi M, Nakamura H, Arai Y, Hosoda F, Urushidate T, Ohashi S, Mukai W, Hiraoka N, Aburatani H, Ito T, Shibata T. Epigenetic landscape influences the liver cancer genome architecture. Nat Commun, 9:1643, 2018

41. Ito Y, Makita S, Maeshima AM, Hatta S, Suzuki T, Yuda S, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Izutsu K. Paraneoplastic Pemphigus Associated with B-cell Chronic Lymphocytic Leukemia Treated with Ibrutinib and Rituximab. Intern Med, 57:2395-2398, 2018

42. Karakawa A, Taoka K, Kaburaki T, Tanaka R, Shinozaki-Ushiku A, Hayashi H, Miyagi-Maeshima A, Nishimura Y, Uekusa T, Kojima Y, Fukayama M, Kurokawa M, Aihara M. Clinical features and outcomes of secondary intraocular lymphoma. Br J Haematol, 183:668-671, 2018

43. Kawai H, Matsushita H, Aoyama Y, Matsui K, Onizuka M, Ando K. Dysplastic features seen in a patient with acute myeloid leukemia harboring the KMT2A-TET1 fusion gene. Int J Hematol, 108:1-2, 2018

44. Kishi Y, Nara S, Esaki M, Hiraoka N, Shimada K. Extent of lymph node dissection in patients with gallbladder cancer. Br J Surg, 105:1658-1664, 2018

45. Kito F, Oyama R, Sakumoto M, Takahashi M, Shiozawa K, Qiao Z, Sakamoto H, Hirose T, Setsu N, Yoshida A, Kawai A, Kondo T. Establishment and characterization of novel patient-derived osteosarcoma xenograft and cell line. In Vitro Cell Dev Biol Anim, 54:528-536, 2018

46. Kuno I, Yoshida H, Shimizu H, Uehara T, Uno M, Ishikawa M, Kato T. Incidental lymphangioleiomyomatosis in the lymph nodes of gynecologic surgical specimens. Eur J Obstet Gynecol Reprod Biol, 231:93-97, 2018

47. Machado I, Yoshida A, Morales MGN, Abrahao-Machado LF, Navarro S, Cruz J, Lavernia J, Parafioriti A, Picci P, Llombart-Bosch A. Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, "undifferentiated small round cell tumors". A clinicopathologic, immunophenotypic and molecular analysis. Ann Diagn Pathol, 34:1-12, 2018

48. Makise N, Sekimizu M, Kubo T, Wakai S, Watanabe SI, Kato T, Kinoshita T, Hiraoka N, Fukayama M, Kawai A, Ichikawa H, Yoshida A. Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity. Histopathology, 73:147-156, 2018

49. Makita S, Maeshima AM, Maruyama D, Izutsu K, Tobinai K. Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review. Onco Targets Ther, 11:2287-2293, 2018

50. Masai K, Motoi N. Response to Letter to the Editor Titled "Comments on Prognostic Impact of Margin Distance and Tumor Spread through Air Spaces in Limited Resection for Primary Lung Cancer". J Thorac Oncol, 13:e58-e59, 2018

51. Matsuo K, Takazawa Y, Ross MS, Elishaev E, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Baba T, Satoh S, Shida M, Ikeda Y, Adachi S, Yokoyama T, Takekuma M, Yanai S, Takeuchi S, Nishimura M, Iwasaki K, Johnson MS, Yoshida M, Hakam A, Machida H, Mhawech-Fauceglia P, Ueda Y, Yoshino K, Kajiwara H, Hasegawa K, Yasuda M, Miyake TM, Moriya T, Yuba Y, Morgan T, Fukagawa T, Pejovic T, Nagano T, Sasaki T, Richmond AM, Post MD, Shahzad MMK, Im DD, Yoshida H, Enomoto T, Omatsu K, Ueland FR, Kelley JL, Karabakhtsian RG, Roman LD. Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma. Ann Surg Oncol, 25:3676-3684, 2018

52. Matsuo K, Takazawa Y, Ross MS, Elishaev E, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Baba T, Satoh S, Shida M, Ikeda Y, Adachi S, Yokoyama T, Takekuma M, Yanai S, Takeuchi S, Nishimura M, Iwasaki K, Johnson MS, Yoshida M, Hakam A, Machida H, Mhawech-Fauceglia P, Ueda Y, Yoshino K, Kajiwara H, Hasegawa K, Yasuda M, Miyake TM, Moriya T, Yuba Y, Morgan T, Fukagawa T, Pejovic T, Nagano T, Sasaki T, Richmond AM, Post MD, Shahzad MMK, Im DD, Yoshida H, Enomoto T, Omatsu K, Ueland FR, Kelley JL, Karabakhtsian RG, Roman LD. Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma. Ann Surg Oncol, 25:2756-2766, 2018

53. Miura A, Mori T, Yoshida A, Watanabe Y, Sunami K, Watanabe S, Kohno T, Tsuta K. Primary adenocarcinoma of the trachea revealing a mucinous bronchial gland cell origin. Pathol Res Pract, 214:796-799, 2018

54. Nagumo Y, Maejima A, Toyoshima Y, Komiyama M, Yonemori K, Yoshida A, Fujimoto H. Neoadjuvant crizotinib in ALK-rearranged inflammatory myofibroblastic tumor of the urinary bladder: A case report. Int J Surg Case Rep, 48:1-4, 2018

55. Nomura T, Maki D, Matsumoto F, Mori T, Yoshimoto S. A rare case of coexisting lacrimal sac adenocarcinoma and transitional cell carcinoma. Ear Nose Throat J, 97:E32-E35, 2018

56. Ogura K, Hosoda F, Arai Y, Nakamura H, Hama N, Totoki Y, Yoshida A, Nagai M, Kato M, Arakawa E, Mukai W, Rokutan H, Kawai A, Tanaka S, Shibata T. Integrated genetic and epigenetic analysis of myxofibrosarcoma. Nat Commun, 9:2765, 2018

57. Oyama R, Kito F, Qiao Z, Sakumoto M, Noguchi R, Takahashi M, Toki S, Tanzawa Y, Yoshida A, Kawai A, Kondo T. Establishment of a novel patient-derived Ewing's sarcoma cell line, NCCES1-C1. In Vitro Cell Dev Biol Anim, 54:770-778, 2018

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