Faculty Profiles - YAMAMOTO HIDETAKA

Papers - YAMAMOTO HIDETAKA

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Hypoxemia due to pulmonary tumor microembolisms from a hepatocellular carcinoma: a case report

YAMASHITA Nobuyuki, TANIMOTO Hironori, YAMAMOTO Hidetaka, NISHIURA Saburo, NOMURA Hideyuki

Nippon Shokakibyo Gakkai Zasshi 112 ( 6 ) 1060 - 1066 2015

Language：Japanese Publisher：The Japanese Society of Gastroenterology

We report a case of pulmonary tumor embolism due to hepatocellular carcinoma (HCC). A woman in her 60s was treated with sorafenib 800 mg daily for HCC with lymph node metastasis. Approximately 50 days after taking sorafenib, she experienced dyspnea and was admitted to the hospital on account of hypoxia. Although her oxygen saturation levels deteriorated, we could find no obvious cause for the hypoxia; despite artificial respiration and oxygenation, she died of respiratory failure on the fourth day of admission. Tissue samples revealed that the HCC cells had infiltrated her lung arterioles; therefore, we concluded that multiple tumor microembolisms from the HCC to the lungs had caused death via respiratory failure. Cases of hypoxia caused by multiple invisible embolisms from HCCs are rarely reported. We believe that infiltration into the lymphatic system may have been related to the development of pulmonary tumor microembolisms.

DOI： 10.11405/nisshoshi.112.1060

Other Link： http://search.jamas.or.jp/link/ui/2015259396

Complete remission of anaplastic thyroid carcinoma after concomitant treatment with docetaxel and radiotherapy. Reviewed International journal

Ichiro Abe, Satoko Karasaki, Yayoi Matsuda, Shohei Sakamoto, Torahiko Nakashima, Hidetaka Yamamoto, Hisaya Kawate, Keizo Ohnaka, Hisashi Nakashima, Kunihisa Kobayashi, Yoshinao Oda, Masatoshi Nomura, Ryoichi Takayanagi

Case reports in endocrinology 2015 726085 - 726085 2015

Language：English Publishing type：Research paper (scientific journal)

Anaplastic thyroid carcinoma (ATC) although rare is the most lethal form of thyroid cancer. The mortality rate for ATC is very high, with a median survival time of only 5 months; the survival rate at 1 year after diagnosis is <20%. Management of ATC is extremely difficult and rife with uncertainties. Herein, we describe a 75-year-old woman who presented with ATC and was successfully treated using concomitant treatment with docetaxel and high-dose radiotherapy. This case appears to be the first to have been reported in the literature involving complete remission of ATC confirmed by autopsy, suggesting the therapeutic potential of this combination.

DOI： 10.1155/2015/726085

Close correlation between CXCR4 and VEGF expression and frequent CXCR7 expression in rhabdomyosarcoma. Reviewed International journal

Kina Miyoshi, Kenichi Kohashi, Fumiyoshi Fushimi, Hidetaka Yamamoto, Junji Kishimoto, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda

Human pathology 45 ( 9 ) 1900 - 9 2014.9

Language：English Publishing type：Research paper (scientific journal)

CXC chemokine receptor 4 (CXCR4) expression is reportedly correlated with both vascular endothelial growth factor (VEGF) expression and poor prognosis in a variety of cancers. Its relation to CXC chemokine receptor 7 (CXCR7) is also noted in several malignancies, including rhabdomyosarcoma (RMS) cell lines. However, the correlations between these chemokine receptors and angiogenic factors have not yet been adequately investigated in RMS clinical specimens. By immunohistochemistry, we assessed CXCR4, CXCR7, CC chemokine receptor 6, CC chemokine receptor 7, VEGF expression, microvessel density, and MIB-1 labeling index in 82 formalin-fixed RMS specimens, including 34 primary alveolar RMS and 44 primary embryonal RMS (ERMS). Twenty-six frozen samples were available for investigation by quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression levels of these molecules. We also evaluated their significance with respect to clinicopathological factors and patient survival rates. Primary RMS showed high expression of CXCR7 (83.1%) regardless of the histologic subtype. High cytoplasmic CXCR4 and high VEGF expression revealed significant correlations in both ERMS and alveolar RMS (P = .0051 and P = .0003, respectively). By univariate analysis of ERMS cases, the tumors with high VEGF expression showed significantly poor prognoses (P = .0017). High VEGF expression also was the independent adverse prognostic factor for ERMS. Because CXCR4, CXCR7, and VEGF are widely expressed in RMS, the combination of these antagonists may provide a potential target for molecular therapy.

DOI： 10.1016/j.humpath.2014.05.012

Differentiation between benign phyllodes tumors and fibroadenomas of the breast on MR imaging. Reviewed International journal

Takeshi Kamitani, Yoshio Matsuo, Hidetake Yabuuchi, Nobuhiro Fujita, Michinobu Nagao, Satoshi Kawanami, Masato Yonezawa, Yuzo Yamasaki, Eriko Tokunaga, Makoto Kubo, Hidetaka Yamamoto, Hiroshi Honda

European journal of radiology 83 ( 8 ) 1344 - 9 2014.8

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The purpose of this study was to determine the factors that contribute to the differentiation between phyllodes tumors (PTs) and fibroadenomas (FAs) on MR imaging. MATERIALS AND METHODS: This retrospective study included 19 PTs and 18 FAs with ≥ 2 cm diameter. The presence or absence of a capsule and internal septum, the extent of lobulation, and the apparent diffusion coefficient (ADC) values were determined. The presence or absence of a cystic component, the time-intensity curve, and the signal intensity on delayed-phase contrast-enhanced T1WI were also evaluated in 31 patients (16 PTs and 17 FAs) who underwent a contrast-enhanced study. RESULTS: Cystic components were seen in 10 of the 16 PTs (63%) and in 4 of the 17 FAs (24%; P=0.03). The PTs showed strong lobulation more frequently compared to the FAs (14/19 [74%] vs. 7/18 [39%], respectively; P=0.04). Though there was no significant difference, PT tended to be heterogeneous more frequently on the delayed phase of the contrast-enhanced T1WI compared to the FA (11/16 [69%] vs. 7/17 [41%], respectively). No significant difference was found in the other findings. CONCLUSIONS: Although PTs and FAs show similar MR findings, the presence of a cystic component, strong lobulation, and heterogeneity on delayed-phase contrast-enhanced T1WI suggests a PT.

DOI： 10.1016/j.ejrad.2014.04.031

A case of gastric plexiform fibromyxoma: radiological and pathological findings. Reviewed

Katsumi Sakamoto, Masakazu Hirakawa, Kazushige Atsumi, Koshi Mimori, Kohei Shibata, Taro Tobo, Hidetaka Yamamoto, Hiroshi Honda

Japanese journal of radiology 32 ( 7 ) 431 - 6 2014.7

Language：English Publishing type：Research paper (scientific journal)

Plexiform fibromyxoma is a relatively new pathological category that consists of a rare group of non-gastrointestinal stromal tumors with a peculiar plexiform growth pattern. We report a case of gastric plexiform fibromyxoma in a 60-year-old man. Gastroscopic examination revealed a gastric submucosal tumor in the antrum. Magnetic resonance imaging (MRI) showed a nodule with distinct signal hyperintensity on T2-weighted images, with strong enhancement peripherally in the early phase to the entire lesion in the delayed phase. Endoscopic ultrasound-guided fine-needle aspiration cytology was performed, and the cytological diagnosis was spindle cell tumor, so partial gastrectomy was performed under a preoperative diagnosis of GIST. The resected tumor demonstrated plexiform architecture, myxoid stroma, prominent vasculature, and spindle cells, reflecting the characteristic findings on MRI. This is the first report to describe radiological findings for gastric plexiform fibromyxoma.

DOI： 10.1007/s11604-014-0315-z

Differential microRNA expression profiles between malignant rhabdoid tumor and epithelioid sarcoma: miR193a-5p is suggested to downregulate SMARCB1 mRNA expression. Reviewed International journal

Kenichi Kohashi, Hidetaka Yamamoto, Reiko Kumagai, Yuichi Yamada, Yuka Hotokebuchi, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 ( 6 ) 832 - 9 2014.6

Language：English Publishing type：Research paper (scientific journal)

Malignant rhabdoid tumor and epithelioid sarcoma are classified as tumors of uncertain differentiation. However, it is controversial whether these tumors are distinct entities because they share similar histological and immunohistochemical features such as the existence of rhabdoid cells or complete loss of SMARCB1 protein expression. MicroRNAs are small non-coding RNAs, and it is suggested that knowledge of microRNA expression profiles in cancer may have substantial value for diagnostics. We first analyzed microRNA expression profiles in 13 frozen materials (five malignant rhabdoid tumors, two proximal type epithelioid sarcomas, and six conventional type epithelioid sarcomas) and subsequently examined the specific microRNA expressions in 29 paraffin-embedded materials (8 malignant rhabdoid tumors, 13 proximal type epithelioid sarcomas, and 8 conventional type epithelioid sarcomas) and 13 previously described frozen materials by quantitative RT-PCR. According to the unsupervised hierarchical clustering of microRNA, proximal type epithelioid sarcoma and conventional type epithelioid sarcoma were classified into the same category, whereas malignant rhabdoid tumor was a distinct category from both types of epithelioid sarcoma. In addition, when malignant rhabdoid tumor with SMARCB1 gene alterations and proximal type and conventional type epithelioid sarcoma with no SMARCB1 gene alterations were compared, 56 microRNAs were isolated as being significantly different (ANOVA, P<0.05). Among them, quantitative RT-PCR using frozen and paraffin-embedded materials demonstrated that expression levels of miR193a-5p (P=0.002), which has been suggested to downregulate SMARCB1 mRNA expression, showed statistically different expression levels between malignant rhabdoid tumor and epithelioid sarcoma with no SMARCB1 gene alterations. These results suggest that epithelioid sarcoma, especially proximal type epithelioid sarcoma, and malignant rhabdoid tumor are distinct tumors with respect to the microRNA expression profiles and that miR193a-5p may have an important role in the inhibition of SMARCB1 mRNA expression.

DOI： 10.1038/modpathol.2013.213

Solitary fibrous tumor of the thyroid gland. Reviewed

Yusuke Mizuuchi, Hidetaka Yamamoto, Katsuya Nakamura, Kengo Shirahane, Masae Souzaki, Masao Tanaka, Yoshinao Oda

Medical molecular morphology 47 ( 2 ) 117 - 22 2014.6

Language：English Publishing type：Research paper (scientific journal)

Solitary fibrous tumor is a spindle cell neoplasm rarely arising in the thyroid gland. We present a 78-year-old man with the diagnosis of solitary fibrous tumor of the thyroid gland resected by subtotal thyroidectomy. Fine needle aspiration cytology via ultrasound guidance demonstrated a hypocellular aspirate that revealed follicular epithelial cells with mild nuclear atypia and scattered spindle cells with bland nuclei. Histologically, the patternless proliferation of spindle cells was seen among collagenous bundles, accompanied by hemangiopericytomatous vessels, and variously dilated follicles with mild atypical cells having slightly enlarged nuclei, indicating adenomatous goiter. The neoplastic spindle cells showed diffuse immunoreactivity to CD34, bcl-2, CD99 and vimentin, but were negative for cytokeratins, calcitonin, TTF-1 and CD5. Although solitary fibrous tumor arising in thyroid gland is rare, this tumor should be included in the differential diagnosis of thyroid spindle cell tumors and also that of adenomatous.

DOI： 10.1007/s00795-013-0056-6

Inflammatory pseudotumor in head and neck. Reviewed International journal

Yuichi Segawa, Ryuji Yasumatsu, Hideki Shiratsuchi, Akihiro Tamae, Teppei Noda, Hidetaka Yamamoto, Shizuo Komune

Auris, nasus, larynx 41 ( 3 ) 321 - 4 2014.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease. CASE SUMMARY: We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40% of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease. DISCUSSION: IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.

DOI： 10.1016/j.anl.2013.11.002

Activation of the Akt/mammalian target of rapamycin pathway in myxofibrosarcomas. Reviewed International journal

Yusuke Takahashi, Kenichi Kohashi, Yuichi Yamada, Makoto Endo, Nokitaka Setsu, Takeaki Ishii, Hidetaka Yamamoto, Yukihide Iwamoto, Yoshinao Oda

Human pathology 45 ( 5 ) 984 - 93 2014.5

Language：English Publishing type：Research paper (scientific journal)

The Akt/mammalian target of rapamycin (mTOR) pathway plays important roles in modulating cellular function in response to extracellular signals such as growth factors and cytokines. The Akt/mTOR signaling pathway is activated in certain kinds of sarcomas. Myxofibrosarcoma is a soft tissue sarcoma, characterized by abundant myxoid stroma and frequent local recurrence. Here, we conducted a large-scale examination of the clinicopathological and activation statuses of the Akt/mTOR pathways in myxofibrosarcoma. The phosphorylation status of Akt, mTOR, S6 ribosomal protein, and the eukaryotic translation initiation factor 4E-binding protein, and mitogen-activated protein kinase were assessed by immunohistochemistry in 101 formalin-fixed, paraffin-embedded samples, including 68 primary tumors in myxofibrosarcoma. Immunohistochemical expressions were confirmed by Western blotting with 20 frozen samples, which were paired with normal tissue samples. PIK3CA and AKT1 gene mutations were also analyzed using 12 primary tumor frozen samples. Immunohistochemically, phosphorylations of Akt, mTOR, S6 ribosomal protein, 4E-binding protein, and mitogen-activated protein kinase 1/2 were observed in 64.7%, 45.6%, 42.6%, 63.2%, and 64.7% of samples. Phosphorylated Akt/mTOR pathway proteins were correlated with one another and were also correlated with the phosphorylation of these proteins in the concordant recurrent tumors. Immunoblotting showed a high degree of phosphorylation in tumor samples, compared with that in normal tissue samples. Activation of the Akt/mTOR pathway was correlated with histologic grade and tumor progression. Mutational analysis failed to reveal any PIK3CA or AKT1 mutations around the hot spots. Activation of the Akt/mTOR pathway was associated with histologic malignancy and tumor progression in primary and recurrent myxofibrosarcoma.

DOI： 10.1016/j.humpath.2013.12.012

Successful chemoradiotherapy for undifferentiated malignant neoplasm arising from the left pulmonary artery. Reviewed International journal

Hozumi Kumagai, Kenta Nio, Yuta Okumura, Masato Komoda, Tsuyoshi Shirakawa, Hitoshi Kusaba, Shioto Yasuda, Keita Odashiro, Shuji Arita, Hiroshi Ariyama, Yuichi Yamada, Hidetaka Yamamoto, Yoshinao Oda, Katsumasa Nakamura, Koichi Akashi, Eishi Baba

Case reports in oncology 7 ( 2 ) 484 - 90 2014.5

Language：English

Undifferentiated malignant neoplasms, which occur primarily in the pulmonary artery, are extremely rare and associated with poor outcomes as there is no effective therapy. A 67-year-old woman visited our hospital with complaints of dry cough and dyspnea on exertion. A contrast-enhanced chest computed tomography revealed an intravascular tumor obstructing the left pulmonary artery and a pedunculated lesion extending to the main and right pulmonary artery. Multiple metastases in the lung, bones and bilateral adrenal glands were identified by fluorodeoxyglucose-positron emission tomography. A small sample was obtained by catheter aspiration biopsy of the intravascular tumor, and examination revealed undifferentiated small atypical cells. The tumor was diagnosed as an undifferentiated neoplasm arising from the pulmonary artery based on immunohistochemical findings, including the absence of expressions of organ-specific markers. Systemic chemotherapy (paclitaxel and carboplatin) and concurrent radiation were performed as treatment for the primary tumor. Marked shrinkage of the intravascular tumor was achieved, and no serious adverse events were observed during therapy. Chemotherapy was continued for 5 months, but the patient died because of tumor progression 9 months after the initial diagnosis. Chemoradiotherapy has efficacy against undifferentiated neoplasm of the pulmonary artery.

DOI： 10.1159/000365387

Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome. Reviewed International journal

Yasunari Sakai, Ryota Souzaki, Hidetaka Yamamoto, Yuki Matsushita, Hazumu Nagata, Yoshito Ishizaki, Hiroyuki Torisu, Yoshinao Oda, Tomoaki Taguchi, Chad A Shaw, Toshiro Hara

BMC medical genomics 7 19 - 19 2014.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: 2q37 deletion syndrome is a rare congenital disorder that is characterized by facial dysmorphism, obesity, vascular and skeletal malformations, and a variable degree of intellectual disability. To date, common but variable phenotypes, such as skeletal or digit malformations and obesity, have been associated with the deleted size or affected genes at chromosome 2q37. However, it remains elusive whether 2q37 deletion per se or other genetic factors, such as copy number variations (CNVs), may confer the risk for the tumorigenic condition. CASE PRESENTATION: We report a two-year-old Japanese boy with 2q37 deletion syndrome who exhibited the typical facial appearance, coarctation of the aorta, and a global developmental delay, while lacking the symptoms of brachydactyly and obesity. He developed a sex cord-stromal tumor of the right testis at three months of age. The array comparative genome hybridization analysis identified an 8.2-Mb deletion at 2q37.1 (chr2:234,275,216-242,674,807) and it further revealed two additional CNVs: duplications at 1p36.33-p36.32 (chr1:834,101-2,567,832) and 20p12.3 (chr20:5,425,762-5,593,096). The quantitative PCRs confirmed the heterozygous deletion of HDAC4 at 2q37.3 and duplications of DVL1 at 1q36 and GPCPD1 at 20p12.3. CONCLUSION: This study describes the unique phenotypes in a boy with 2q37 deletion and additional CNVs at 1p36.33-p36.32 and 20p12.3. The data provide evidence that the phenotypic variations and unusual complications of 2q37 deletion syndrome are not simply explained by the deleted size or genes located at 2q37, but that external CNVs may account at least in part for their variant phenotypes. Accumulating the CNV data for chromosomal disorders will be beneficial for understanding the genetic effects of concurrent CNVs on the syndromic phenotypes and rare complications.

DOI： 10.1186/1755-8794-7-19

Activation of the Akt-mTOR pathway and receptor tyrosine kinase in patients with solitary fibrous tumors. Reviewed International journal

Yuichi Yamada, Kenichi Kohashi, Fumiyoshi Fushimi, Yusuke Takahashi, Nokitaka Setsu, Makoto Endo, Hidetaka Yamamoto, Shoji Tokunaga, Yukihide Iwamoto, Yoshinao Oda

Cancer 120 ( 6 ) 864 - 76 2014.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Solitary fibrous tumors (SFTs) are soft tissue tumors of intermediate malignancy that rarely metastasize. Although unresectable SFTs are reported to have a poor prognosis, to the authors' knowledge there is currently no effective therapy. Molecular target therapy is a promising approach for patients with unresectable tumors, but knowledge of the molecular biology of SFTs is currently insufficient to support such therapy. The current study investigated the activation of receptor tyrosine kinases (RTKs) and the Akt-mammalian target of rapamycin (Akt-mTOR) pathway in SFTs as therapeutic targets. METHODS: The phosphorylation statuses of Akt-mTOR pathway proteins (p-Akt, p-mTOR, phosphorylated 4E-binding protein [p-4EBP1], and phosphorylated S6 ribosomal protein [p-S6RP]) and RTKs (phosphorylated platelet-derived growth factor receptor-α [p-PDGFRα], p-PDGFRβ, p-c-met, and phosphorylated insulin-like growth factor-1 receptor-β [p-IGF-1Rβ]) were assessed by immunohistochemistry in 66 samples of SFTs, and the data were compared with clinicopathological and histopathological findings. The expression of phosphorylated proteins was assessed by Western blot analysis in 6 frozen samples. RESULTS: The immunohistochemical results were as follows: p-Akt, 56.0% (nuclear and cytoplasmic staining); p-mTOR, 69.6% (nuclear and cytoplasmic staining); p-4EBP1, 80.3% (nuclear and cytoplasmic staining); p-S6RP, 69.6% (cytoplasmic staining); p-PDGFRα, 39.0% (cytoplasmic staining); p-PDGFRβ, 52.0% (cytoplasmic staining); p-c-met, 37.8% (nuclear staining) and 19.6% (cytoplasmic staining); and p-IGF-1Rβ, 16.6% (nuclear staining). Phosphorylation of the Akt-mTOR pathway proteins was correlated with one another except for p-Akt with S6RP. p-PDGFRβ and p-IGF-1Rβ were correlated with p-Akt. Moreover, significant relationships were noted between disease-free survival or overall survival and the presence of hypoglycemia, necrosis, cystic and myxoid degeneration, and atypical findings. CONCLUSIONS: The Akt/mTOR pathway was activated in approximately 50% of the cases of SFTs and was associated with RTKs, which were phosphorylated at different rates. Thus, the Akt-mTOR pathway may be involved in the tumorigenesis of SFTs.

DOI： 10.1002/cncr.28506

Insulin-like growth factor II messenger RNA-binding protein 3 expression in gastrointestinal mesenchymal tumors. Reviewed International journal

Hidetaka Yamamoto, Katsumi Arakaki, Katsuya Morimatsu, Yoko Zaitsu, Aya Fujita, Kenichi Kohashi, Minako Hirahashi, Junichi Motoshita, Yumi Oshiro, Yoshinao Oda

Human pathology 45 ( 3 ) 481 - 7 2014.3

Language：English Publishing type：Research paper (scientific journal)

Insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) is a recently identified biomarker demonstrated to be useful in diagnosis and prognostic prediction for several kinds of malignant tumors. However, the clinicopathologic and diagnostic value of IMP3 in mesenchymal tumors of the gastrointestinal tract is not clear. In this study, we examined the immunohistochemical expression of IMP3 in gastrointestinal stromal tumor (GIST) (n = 150), malignant melanoma (n = 17), malignant mesothelioma (n = 6), leiomyosarcoma (n = 6), inflammatory myofibroblastic tumor (IMT) (n = 12), desmoid fibromatosis (n = 8), leiomyoma (n = 20), and schwannoma (n = 20). Focal (≥10%) or diffuse (≥50%) expression with strong staining for IMP3 was judged as positive. We found that malignant melanomas (16/17 cases, 94.1%), malignant mesotheliomas (5/6 cases, 83.3%), IMTs (7/12 cases, 58.3%), and leiomyosarcomas (2/6 cases, 33.3%) were positive for IMP3. Among IMTs and leiomyosarcomas, IMP3-positive cases were histologically and/or clinically aggressive subtypes. Other kinds of tumors, including GIST, desmoid fibromatosis, leiomyoma and schwannoma, were essentially negative for IMP3. Our results suggest that IMP3 may be an ancillary tool in identifying aggressive abdominal mesenchymal tumors other than GIST.

DOI： 10.1016/j.humpath.2013.10.010

Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature. Reviewed International journal

Eriko Tokunaga, Shinji Okano, Yuichiro Nakashima, Nami Yamashita, Kimihiro Tanaka, Sauri Akiyoshi, Kenji Taketani, Mitsunori Shirouzu, Hidetaka Yamamoto, Masaru Morita, Yoshihiko Maehara

International journal of clinical and experimental pathology 7 ( 7 ) 4371 - 80 2014

Language：English Publishing type：Research paper (scientific journal)

Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon. However, the mechanism remains to be elucidated. We herein report a case of the SR of breast cancer at both the primary site and metastatic axillary lymph node with spontaneously-induced T cell-mediated immunological responses. A 52-year-old female with a lump in the left axilla was diagnosed to have a small breast carcinoma with a distinct axillary lymph node metastasis. During the preoperative systemic examination, she was diagnosed to have severe type 2 diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized after one month. Surgery for left breast cancer was then performed. The postoperative histopathological examination revealed the SR of breast cancer at both the primary site and metastatic axillary lymph node. Immunohistochemical studies revealed that estrogen receptor positive, AE1/AE3-positive ductal carcinoma completely underwent necrosis associated with extensive infiltration of CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary ductal carcinoma cells also underwent single cell necrosis with infiltration of T cells with lymph follicle-like organization of B cells in the mammary gland. The features were suggestive that the tumor eradication in the metastatic lymph node and regression of the primary ductal carcinoma could be due to host T cell response to the ductal carcinoma. As far as we know it is the first report that shows the spontaneous regression of breast cancer, probably due to the spontaneously-induced T cell response.

IgG4-related disease of the ileocecal region mimicking malignancy: A case report. Reviewed International journal

Yukiharu Hiyoshi, Eiji Oki, Yoko Zaitsu, Koji Ando, Shuhei Ito, Hiroshi Saeki, Masaru Morita, Hidetaka Yamamoto, Hideo Baba, Yoshihiko Maehara

International journal of surgery case reports 5 ( 10 ) 669 - 72 2014

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease characterized by chronic fibrosing inflammation with abundant IgG4-positive plasma cells, and responds well to steroids. Previous reports of IgG4-RD have focused on pancreatic and extrapancreatic including the gastrointestinal tract, however, the colonic IgG4-RD is rare. PRESENTATION OF CASE: We herein report the case of a 74-year-old female with edematous wall thickening of the terminal ileum to the lower ascending colon confirmed by several preoperative imaging studies, who underwent right hemi-colectomy for suspected malignant lymphoma. The resected specimen showed an irregular wall thickness with subserosal sclerosis, and the lesion was 10cm in length from the terminal ileum to the ascending colon. The patient was diagnosed with IgG4-RD by pathological examinations, which demonstrated an increased number of IgG4-positive plasma cells (150/HPF), and an elevated IgG4/IgG ratio (50%). DISCUSSION: Gastrointestinal IgG4-RD appears to be difficult to diagnose prior to surgical resection because of its rarity, and the similarity of its features to malignancy. The measurement of the serum IgG4 levels, immunohistochemical examination of biopsy specimens and use of several imaging modalities might help us to diagnose the disease without surgical resection, and this disease can generally be treated with steroid therapy. However, surgical resection for IgG4-RD may still be also necessary for patients with concerns regarding malignancy or with intractable gastrointestinal obstruction caused by this disease. CONCLUSION: Gastrointestinal IgG4-RD often mimics malignancy, and we should therefore consider this disease in the differential diagnosis of colonic lesions in order to optimize the treatment.

DOI： 10.1016/j.ijscr.2014.08.003

Conventional spindle cell-type malignant peripheral nerve sheath tumor arising in a sporadic schwannoma. Reviewed International journal

Makoto Endo, Hidetaka Yamamoto, Katsumi Harimaya, Kenichi Kohashi, Takeaki Ishii, Nokitaka Setsu, Yukihide Iwamoto, Yoshinao Oda

Human pathology 44 ( 12 ) 2845 - 8 2013.12

Language：English Publishing type：Research paper (scientific journal)

Malignant peripheral nerve sheath tumor is a malignant tumor showing nerve sheath differentiation. Approximately one-half of malignant peripheral nerve sheath tumors arise from a benign peripheral nerve sheath tumor, which is commonly a neurofibroma in patients with neurofibromatosis type 1. Malignant peripheral nerve sheath tumor arising in a sporadic schwannoma of soft tissue is extremely rare. In this condition, malignant cells usually show epithelioid morphology, meeting the diagnostic criteria for epithelioid malignant peripheral nerve sheath tumor. Here, we present an extraordinary case of spindle cell-type malignant peripheral nerve sheath tumor arising in a schwannoma on the back of a 58-year-old woman without neurofibromatosis. The malignant component showed hypercellular spindle cell proliferation with high mitotic activities; in contrast, the benign component showed hypocellular spindle cell proliferation in a palisading pattern and with Verocay bodies. Immunohistochemical S-100 protein staining showed a clear contrast between the malignant (negative) and benign (positive) components, which was useful for differentiating cellular schwannoma. Recognizing this rare condition is helpful in the pathologic diagnosis of schwannoma showing cellular proliferation in part.

DOI： 10.1016/j.humpath.2013.05.021

Ossifying fibromyxoid tumor presenting EP400-PHF1 fusion gene. Reviewed International journal

Makoto Endo, Kenichi Kohashi, Hidetaka Yamamoto, Takeaki Ishii, Tatsuya Yoshida, Tomoya Matsunobu, Yukihide Iwamoto, Yoshinao Oda

Human pathology 44 ( 11 ) 2603 - 8 2013.11

Language：English Publishing type：Research paper (scientific journal)

Ossifying fibromyxoid tumor is a rare soft tissue tumor of borderline malignancy and uncertain differentiation. Recently, a novel fusion gene, EP400-PHF1, was discovered in ossifying fibromyxoid tumor; however, its relation to this type of tumor has been uncertain because the EP400-PHF1 fusion gene has been successfully detected in only 1 case. We present an ossifying fibromyxoid tumor case with the EP400-PHF1 fusion gene detected by reverse transcriptase polymerase chain reaction, along with compatible cytogenetic data showing a t(6;12)(p21;q24.3) translocation. Our results suggest that the EP400-PHF1 fusion gene is a reproducible finding in ossifying fibromyxoid tumor.

DOI： 10.1016/j.humpath.2013.04.003

Prognostic impact of the activation status of the Akt/mTOR pathway in synovial sarcoma. Reviewed International journal

Nokitaka Setsu, Kenichi Kohashi, Fumiyoshi Fushimi, Makoto Endo, Hidetaka Yamamoto, Yusuke Takahashi, Yuichi Yamada, Takeaki Ishii, Koichirou Yokoyama, Yukihide Iwamoto, Yoshinao Oda

Cancer 119 ( 19 ) 3504 - 13 2013.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The Akt/mammalian target of rapamycin (mTOR) pathway, downstream from phosphatidylinositol 3-kinase (PI3K), mediates cell survival and proliferation. Although this pathway reportedly contributes to the progression of synovial sarcoma, its prognostic impact has not been clarified. METHODS: The authors analyzed clinicopathologic data and phosphorylation status of Akt (a serine/threonine kinase also known as protein kinase B), mTOR, the eukaryotic translation initiation factor 4E binding protein (4E-BP1), and the S6 ribosomal protein by immunohistochemical analysis of 120 formalin-fixed, paraffin-embedded samples and by Western blot analysis of 24 frozen samples from 112 patients with synovial sarcoma. RESULTS: Akt, mTOR, 4E-BP1, and S6 were activated in 76.5%, 67.6%, 59.6%, and 42.6% of samples, respectively. Immunohistochemically positive phosphorylated (p) mTOR (pmTOR) and p4E-BP1 results were correlated with higher mitotic activity, and positive p4E-BP1 results were correlated with greater necrosis. No mutations around the hot spots in the PI3K catalytic subunit α (PI3KCA) and Akt1 genes were observed. In multivariate analysis of clinicopathologic parameters, frequent mitosis was a risk factor for shorter overall survival; and male sex, visceral location, larger tumor size, and frequent mitosis were identified as risk factors for shorter event-free survival. Positive pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival, and positive p4E-BP1 results were correlated with shorter event-free survival in univariate analysis. Positive pAkt results were associated significantly with shorter event-free survival in multivariate analysis. CONCLUSIONS: In this study, the Akt/mTOR pathway was activated and was associated with worse clinical and pathologic behavior in patients with synovial sarcoma. The authors propose that this pathway may have potential as a therapeutic target.

DOI： 10.1002/cncr.28255

Insulin-like growth factor II messenger RNA-binding protein-3 is a valuable diagnostic and prognostic marker of intraductal papillary mucinous neoplasm. Reviewed International journal

Katsuya Morimatsu, Shinichi Aishima, Hidetaka Yamamoto, Akifumi Hayashi, Kohei Nakata, Yasunori Oda, Koji Shindo, Minoru Fujino, Masao Tanaka, Yoshinao Oda

Human pathology 44 ( 9 ) 1714 - 21 2013.9

Language：English Publishing type：Research paper (scientific journal)

Recently, various studies have shown that insulin-like growth factor II messenger RNA-binding protein-3 (IMP3) is a useful diagnostic marker for malignant lesions and a prognostic marker for poor survival in several kinds of tumors. However, the value of IMP3 as a diagnostic and prognostic marker in intraductal papillary mucinous neoplasm (IPMN) of pancreas has been unclear until now. In this study, we examined IMP3 immunohistochemical expression in 190 resection samples and 15 biopsy samples of IPMN and analyzed the value of IMP3 as a diagnostic and prognostic marker. IMP3 expression was recognized in 71.8% (28/39) of IPMNs with high-grade dysplasia and in 81.3% (26/32) of IPMNs with an associated invasive carcinoma (IPMN-IC), but it was not found in any IPMNs with low-grade dysplasia or in IPMNs with intermediate dysplasia. IMP3 expression was significantly higher in cancerous lesions (IPMN with high-grade dysplasia and IPMN-IC) than in noncancerous lesions (IPMN with low-grade dysplasia and IPMN with intermediate-grade dysplasia), with a sensitivity of 76.1% and a specificity of 100% (P < .001). We also identified a significant difference in IMP3 expression between cancerous lesions and noncancerous lesions in biopsy specimens (P = .027). In IPMN-IC, disease-specific survival was significantly shorter in the high-expression group (>50% tumor staining) than in the low-expression group (≤50% tumor staining; P = .0069). In conclusion, our findings show that IMP3 is a useful diagnostic marker for distinguishing between noncancerous and cancerous lesions and is a valuable prognostic biomarker in IPMN.

DOI： 10.1016/j.humpath.2012.12.020

HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status. Reviewed International journal

Takafumi Nakano, Hidetaka Yamamoto, Kazuki Hashimoto, Sadafumi Tamiya, Hideki Shiratsuchi, Torahiko Nakashima, Ken-ichi Nishiyama, Yuichiro Higaki, Shizuo Komune, Yoshinao Oda

Histopathology 63 ( 3 ) 378 - 92 2013.9

Language：English Publishing type：Research paper (scientific journal)

AIMS: In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). METHODS AND RESULTS: In 31 cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC. CONCLUSIONS: These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status.

DOI： 10.1111/his.12183

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