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Article ; Online: Immunohistochemical and ultrastructural review of six cases previously diagnosed as null cell PitNETs.

Inoshita, Naoko / Yoshimoto, Toyoki / Takazawa, Yutaka / Fukuhara, Noriaki / Okada, Mitsuo / Nishioka, Hiroshi / Yamada, Shozo

Brain tumor pathology

2023 Volume 40, Issue 3, Page(s) 158–162

Abstract: Pituitary neuroendocrine tumors (PitNETs) lacking lineage affiliation are termed "null cell" PitNETs (NCTs). NCTs are characterized as being immunonegative for pituitary hormones as well as transcription factors. We analyzed the ultrastructure and ... ...

Abstract	Pituitary neuroendocrine tumors (PitNETs) lacking lineage affiliation are termed "null cell" PitNETs (NCTs). NCTs are characterized as being immunonegative for pituitary hormones as well as transcription factors. We analyzed the ultrastructure and immunohistochemistry of six hormone-negative and transcription factor (TPIT, PIT1, SF1)-negative PitNETs, with less than 1% immunoreactive cells. Histologically, three cases presented a perivascular pattern and pseudorosettes; the other three showed a solid pattern with oncocytic changes. Electron microscopic examination revealed poorly differentiated tumor cells with sparsely scattered secretory granules and intracellular organelles in all null cell tumors when compared with hormone-positive PitNETs. Two cases harbored a honeycomb Golgi (HG) structure, and three oncocytic tumors showed mitochondrial accumulation. The two HG cases were immunopositive for newly obtained TPIT (CL6251) and showed some adrenocorticotropic hormone-positive cells, while the remaining four were diffusely immunopositive for GATA3, with two SF1-positive cases identified in subsequent immunostaining. Thus, these six cases may be classified as two sparsely granulated corticotroph PitNETs, two gonadotroph PitNETs with SF1 re-staining, and two likely gonadotroph PitNETs with GATA3 immunostaining. No "true NCT" was detected among 1071 PitNETs, demonstrating the importance of precise diagnosis following the most recent criteria to improve therapeutic success.
MeSH term(s)	Humans ; Pituitary Neoplasms/diagnosis ; Pituitary Neoplasms/pathology ; Transcription Factors ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/pathology ; Hormones
Chemical Substances	Transcription Factors ; Hormones
Language	English
Publishing date	2023-04-18
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1193775-0
ISSN	1861-387X ; 1433-7398 ; 0914-8108
ISSN (online)	1861-387X
ISSN	1433-7398 ; 0914-8108
DOI	10.1007/s10014-023-00462-9
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Article ; Online: A double-edged sword: The world according to Capicua in cancer.

Tanaka, Miwa / Yoshimoto, Toyoki / Nakamura, Takuro

Cancer science

2017 Volume 108, Issue 12, Page(s) 2319–2325

Abstract: CIC/Capicua is an HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes, such as PEA3 family genes. The receptor tyrosine kinase/RAS/MAPK signals downregulate CIC ...

Abstract	CIC/Capicua is an HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes, such as PEA3 family genes. The receptor tyrosine kinase/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity; CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma. CIC is also involved in chromosomal translocation-associated gene fusions in highly aggressive small round cell sarcoma that is biologically and clinically distinct from Ewing sarcoma. In these mutations, PEA3 family genes and other important target genes are upregulated, inducing malignant phenotypes. Downregulation of CIC abrogates the effect of MAPK inhibitors, suggesting its potential role as an important modifier of molecular target therapies for cancer. These data reveal the importance of CIC as a key molecule in signal transduction, carcinogenesis, and developing novel therapies.
MeSH term(s)	Animals ; Humans ; Neoplasms/genetics ; Repressor Proteins/genetics
Chemical Substances	CIC protein, human ; Repressor Proteins
Language	English
Publishing date	2017-10-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.13413
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Article ; Online: CIC-DUX4

Yoshimoto, Toyoki / Tanaka, Miwa / Homme, Mizuki / Yamazaki, Yukari / Takazawa, Yutaka / Antonescu, Cristina R / Nakamura, Takuro

Cancer research

2017 Volume 77, Issue 11, Page(s) 2927–2937

Abstract: ... CIC- ... ...

Abstract	CIC-DUX4
MeSH term(s)	Animals ; Biomarkers, Tumor/genetics ; Bone Neoplasms/genetics ; Disease Models, Animal ; Humans ; Mice ; Microarray Analysis ; Oncogene Proteins, Fusion/genetics ; Sarcoma, Ewing/genetics
Chemical Substances	Biomarkers, Tumor ; CIC-DUX4 fusion protein, human ; Oncogene Proteins, Fusion
Language	English
Publishing date	2017-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-16-3351
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Article: Rapid detection of papillary thyroid carcinoma by fluorescence imaging using a γ-glutamyltranspeptidase-specific probe: a pilot study.

Hino, Rumi / Inoshita, Naoko / Yoshimoto, Toyoki / Ogawa, Makiko / Miura, Daishu / Watanabe, Ryoko / Watanabe, Kenta / Kamiya, Mako / Urano, Yasteru

Thyroid research

2018 Volume 11, Page(s) 16

Abstract: Background: Nodular lesions of the thyroid gland, including papillary thyroid carcinoma (PTC), may be difficult to diagnose by imaging, such as in ultrasonic echo testing, or by needle biopsy. Definitive diagnosis is made by pathological examination but ...

Abstract	Background: Nodular lesions of the thyroid gland, including papillary thyroid carcinoma (PTC), may be difficult to diagnose by imaging, such as in ultrasonic echo testing, or by needle biopsy. Definitive diagnosis is made by pathological examination but takes several days. A more rapid and simple method to clarify whether thyroid nodular lesions are benign or malignant is needed. Fluorescence imaging with γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) uses γ-glutamyltranspeptidase (GGT), a cell-surface enzyme, to hydrolyze the γ-glutamyl peptide and transfer the γ-glutamyl group. GGT is overexpressed in several cancers, such as breast, lung, and liver cancers. This imaging method is rapid and useful for detecting such cancers. In this study, we tried to develop a rapid fluorescence detection method for clinical samples of thyroid cancer, especially papillary carcinoma. Methods: Fluorescence imaging with gGlu-HMRG was performed to detect PTC using 23 surgically resected clinical samples. A portable imaging device conveniently captured white-light images and fluorescence images with blue excitation light. Hematoxylin-eosin (HE) staining was used to evaluate which fluorescent regions coincided with cancer, and immunohistochemical examination was used to detect GGT expression. Results: All 16 PTC samples exhibited fluorescence after topical application of gGlu-HMRG, whereas the normal sections of each sample showed no fluorescence. HE staining revealed that each fluorescent region corresponded to a region with carcinoma. The PTC samples also exhibited GGT expression, as confirmed by immunohistochemistry. Conclusions: All PTC samples were detected by fluorescence imaging with gGlu-HMRG. Thus, fluorescence imaging with gGlu-HMRG is a rapid, simple, and powerful detection tool for PTC.
Language	English
Publishing date	2018-11-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2454440-1
ISSN	1756-6614
ISSN	1756-6614
DOI	10.1186/s13044-018-0060-y
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Article ; Online: TTF-1-positive oncocytic sellar tumor with follicle formation/ependymal differentiation: non-adenomatous tumor capable of two different interpretations as a pituicytoma or a spindle cell oncocytoma.

Yoshimoto, Toyoki / Takahashi-Fujigasaki, Junko / Inoshita, Naoko / Fukuhara, Noriaki / Nishioka, Hiroshi / Yamada, Shozo

Brain tumor pathology

2015 Volume 32, Issue 3, Page(s) 221–227

Abstract: We describe herein the unique case of a 70-year-old male with a TTF-1-positive non-adenomatous sellar tumor that has unusual morphological and immunohistochemical features. MRI examination detected a 2-cm sellar mass that was enhanced heterogeneously. By ...

Abstract	We describe herein the unique case of a 70-year-old male with a TTF-1-positive non-adenomatous sellar tumor that has unusual morphological and immunohistochemical features. MRI examination detected a 2-cm sellar mass that was enhanced heterogeneously. By histology, the tumor was composed of epithelioid and oncocytic cells arranged in a trabecular pattern with occasional luminal structures. The lesion was diffusely immunopositive for thyroid transcription factor-1 (TTF-1) and vimentin but negative for S100 protein and GFAP. Immunoreactivity for epithelial membrane antigen, low molecular weight cytokeratin (CAM 5.2), and neuronal markers was also observed in the tumor cells. By electron microscopy, the tumor cells were filled with abundant mitochondria and extended microvillous projections into small extracellular and intracellular lumens. TTF-1 is considered to be an excellent marker of pituicytes, specialized glia of the neurohypophysis. This case can be regarded as a variant of pituicytoma, showing both ependymal differentiation and oncocytic changes. However, the immunoprofile was not completely consistent with a pituicyte lineage; the epithelial features suggested a possibility of folliculostellate cell origin. TTF-1-positive sellar neoplasms might therefore have variable morphological and immunohistochemical profiles. For suitable classification of TTF-1 positive sellar neoplasms, their histological features should be carefully re-evaluated.
MeSH term(s)	Adenoma, Oxyphilic/diagnosis ; Adenoma, Oxyphilic/genetics ; Adenoma, Oxyphilic/pathology ; Adenoma, Oxyphilic/ultrastructure ; Aged ; Biomarkers, Tumor/analysis ; Cell Transformation, Neoplastic ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Male ; Microscopy, Electrochemical, Scanning ; Microvilli/ultrastructure ; Mitochondria/ultrastructure ; Nuclear Proteins/analysis ; Pituitary Neoplasms/diagnosis ; Pituitary Neoplasms/genetics ; Pituitary Neoplasms/pathology ; Pituitary Neoplasms/ultrastructure ; Thyroid Nuclear Factor 1 ; Transcription Factors/analysis
Chemical Substances	Biomarkers, Tumor ; NKX2-1 protein, human ; Nuclear Proteins ; Thyroid Nuclear Factor 1 ; Transcription Factors
Language	English
Publishing date	2015-07
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	1193775-0
ISSN	1861-387X ; 1433-7398 ; 0914-8108
ISSN (online)	1861-387X
ISSN	1433-7398 ; 0914-8108
DOI	10.1007/s10014-015-0219-3
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Article ; Online: Pulmonary Carcinoids and Low-Grade Gastrointestinal Neuroendocrine Tumors Show Common MicroRNA Expression Profiles, Different from Adenocarcinomas and Small Cell Carcinomas.

Yoshimoto, Toyoki / Motoi, Noriko / Yamamoto, Noriko / Nagano, Hiroko / Ushijima, Masaru / Matsuura, Masaaki / Okumura, Sakae / Yamaguchi, Toshiharu / Fukayama, Masashi / Ishikawa, Yuichi

Neuroendocrinology

2017 Volume 106, Issue 1, Page(s) 47–57

Abstract: Background: It is still uncertain whether small cell lung carcinomas (SCLCs), pulmonary carcinoids, and the gastrointestinal neuroendocrine tumors (GI-NETs) have a common origin. MicroRNA (miRNA) expression may clarify their genetic relationships and ... ...

Abstract	Background: It is still uncertain whether small cell lung carcinomas (SCLCs), pulmonary carcinoids, and the gastrointestinal neuroendocrine tumors (GI-NETs) have a common origin. MicroRNA (miRNA) expression may clarify their genetic relationships and origin. Methods: First, we compared the miRNA expression signature of formalin-fixed paraffin-embedded (FFPE) samples with frozen samples to verify the applicability of microarray analysis. Second, we compared the comprehensive miRNA expression patterns of pulmonary carcinoids and GI-NETs as well as other types of tumors and normal tissues from each organ using FFPE samples. These data were analyzed by hierarchical clustering and consensus clustering with nonnegative matrix factorization. Results: We confirmed that FFPE samples retained the miRNA signatures. In the first hierarchical clustering comparing carcinoids/NETs with adenocarcinomas and normal tissues, most of the carcinoids (48/50) formed 1 major cluster with loose subpartitioning into each organ type, while all the adenocarcinomas (9/9) and normal tissues (15/15) formed another major cluster. The nonnegative matrix factorization approach largely matched the classification of the hierarchical clustering. In the additional cluster analysis comparing carcinoids/NETs with SCLCs, most carcinoids/NETs (17/22) formed a major cluster, while SCLCs (9/9) grouped together with pulmonary adenocarcinomas (3/3) and normal tissues (6/6) in another major cluster. Furthermore, a subset of miRNAs was successfully identified that exhibited significant expression in carcinoids/NETs. Conclusion: Carcinoids/NETs had a characteristic pattern of miRNA expression, suggesting a common origin for pulmonary carcinoids and GI-NETs. The expression profiles of pulmonary carcinoids and SCLCs were quite different, indicating the distinct histogenesis of these neuroendocrine neoplasms.
MeSH term(s)	Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Carcinoid Tumor/metabolism ; Carcinoid Tumor/pathology ; Carcinoma, Small Cell/metabolism ; Carcinoma, Small Cell/pathology ; Cluster Analysis ; Female ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; MicroRNAs/metabolism ; Microarray Analysis ; Middle Aged ; Neoplasm Grading ; Neuroendocrine Tumors/metabolism ; Neuroendocrine Tumors/pathology ; Young Adult
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2017-02-17
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000461582
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Article ; Online: Recurrent pericardial effusion after treatment for primary effusion lymphoma-like lymphoma: an autopsied case.

Kagoya, Yuki / Takahashi, Tsuyoshi / Yoshimoto, Toyoki / Ichikawa, Motoshi / Hangaishi, Akira / Fukayama, Masashi / Kurokawa, Mineo

Annals of hematology

2011 Volume 90, Issue 2, Page(s) 219–220

MeSH term(s)	Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autopsy ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Fatal Outcome ; Humans ; Lymphoma/drug therapy ; Lymphoma/physiopathology ; Lymphoma, Primary Effusion/drug therapy ; Lymphoma, Primary Effusion/physiopathology ; Male ; Pericardial Effusion/drug therapy ; Pericardial Effusion/physiopathology ; Prednisone/therapeutic use ; Recurrence ; Rituximab ; Vincristine/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Agents ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2011-02
Publishing country	Germany
Document type	Case Reports ; Letter
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-010-0975-4
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Article ; Online: Hepatoid tenosynovial giant cell tumor - a rare morphologic variant case report.

Yoshimoto, Toyoki / Motoi, Noriko / Kanda, Hiroaki / Tanizawa, Taisuke / Shimoji, Takashi / Matsumoto, Seiichi / Mukai, Hiroyuki / Ishikawa, Yuichi / Machinami, Rikuo

Pathology, research and practice

2014 Volume 210, Issue 10, Page(s) 694–697

Abstract: We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and ...

Abstract	We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and extra-osseous region of the right distal femur. Histologically, the tumor consisted of epithelioid mononuclear cells and they looked like to have abundant eosinophilic cytoplasm reminiscent of hepatic tissues. In some areas, however, typical histologic features of TSGCT were observed. Electron microscopy revealed that the eosinophilic cytoplasm-like substance was intercellular fibrinous material surrounding the mononuclear tumor cells. Immunohistochemically, mononuclear tumor cells and multinucleate giant cells were positive for CD68 (Kp1) and some of the mononuclear tumor cells were also positive for desmin. Finally, we made the diagnosis of hepatoid TSGCT.
MeSH term(s)	Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biopsy/methods ; Giant Cell Tumors/diagnosis ; Giant Cell Tumors/pathology ; Humans ; Male ; Microscopy, Electron/methods ; Middle Aged ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/pathology ; Synovial Membrane/ultrastructure
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD68 antigen, human
Language	English
Publishing date	2014-10
Publishing country	Germany
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2014.05.012
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Article: Pulmonary Carcinoids and Low-Grade Gastrointestinal Neuroendocrine Tumors Show Common MicroRNA Expression Profiles, Different from Adenocarcinomas and Small Cell Carcinomas

Yoshimoto, Toyoki / Motoi, Noriko / Yamamoto, Noriko / Nagano, Hiroko / Ushijima, Masaru / Matsuura, Masaaki / Okumura, Sakae / Yamaguchi, Toshiharu / Fukayama, Masashi / Ishikawa, Yuichi

Neuroendocrinology

2017 Volume 106, Issue 1, Page(s) 47–57

Institution	Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR Genome Center, The Cancer Institute, JFCR Department of Chest Surgery, The Cancer Institute Hospital, JFCR Department of Digestive Surgery, The Cancer Institute Hospital, JFCR, Koto-ku, and Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Abstract	Background: It is still uncertain whether small cell lung carcinomas (SCLCs), pulmonary carcinoids, and the gastrointestinal neuroendocrine tumors (GI-NETs) have a common origin. MicroRNA (miRNA) expression may clarify their genetic relationships and origin. Methods: First, we compared the miRNA expression signature of formalin-fixed paraffin-embedded (FFPE) samples with frozen samples to verify the applicability of microarray analysis. Second, we compared the comprehensive miRNA expression patterns of pulmonary carcinoids and GI-NETs as well as other types of tumors and normal tissues from each organ using FFPE samples. These data were analyzed by hierarchical clustering and consensus clustering with nonnegative matrix factorization. Results: We confirmed that FFPE samples retained the miRNA signatures. In the first hierarchical clustering comparing carcinoids/NETs with adenocarcinomas and normal tissues, most of the carcinoids (48/50) formed 1 major cluster with loose subpartitioning into each organ type, while all the adenocarcinomas (9/9) and normal tissues (15/15) formed another major cluster. The nonnegative matrix factorization approach largely matched the classification of the hierarchical clustering. In the additional cluster analysis comparing carcinoids/NETs with SCLCs, most carcinoids/NETs (17/22) formed a major cluster, while SCLCs (9/9) grouped together with pulmonary adenocarcinomas (3/3) and normal tissues (6/6) in another major cluster. Furthermore, a subset of miRNAs was successfully identified that exhibited significant expression in carcinoids/NETs. Conclusion: Carcinoids/NETs had a characteristic pattern of miRNA expression, suggesting a common origin for pulmonary carcinoids and GI-NETs. The expression profiles of pulmonary carcinoids and SCLCs were quite different, indicating the distinct histogenesis of these neuroendocrine neoplasms.
Keywords	Carcinoids (carcinoid tumors) ; MicroRNA ; Microarray analysis ; Hierarchical clustering ; Consensus clustering with nonnegative matrix factorization
Language	English
Publishing date	2017-02-17
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000461582
Database	Karger publisher's database

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