Ikuo Matsuda

Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

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Publications (16)21.87 Total impact

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    ABSTRACT: We report a case of a 49-year-old Japanese man, who was admitted to our hospital because of severe dyspnea. He was found to have severely low serum folate and megaloblastic anemia, which was at first suspected to cause his dyspnea. It was assumed that severely low serum folate might be related to his malnutrition, probably caused by habitual alcohol consumption. He died in several days because of acute respiratory distress syndrome. Autopsy revealed diffuse alveolar damage (DAD) in the lungs and systemic lymph node swelling by EBV-positive diffuse large B-cell lymphoma, in addition to megaloblastic anemia in the bone marrow. Together with histological hemophagocytosis and high level of serum iron and ferritin, DAD was considered to be caused by hypercytokinemia triggered by the presence of EBV-positive diffuse large B-cell lymphoma. On the other hand, pathological findings suggestive of habitual alcohol consumption were not apparent. We considered that low serum folate in this case was not by the low intake but by increased consumption of folate by rapid progression of the lymphoma.
    International journal of clinical and experimental pathology 01/2014; 7(4):1742-7. · 2.24 Impact Factor
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    ABSTRACT: Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.
    International journal of clinical and experimental pathology. 01/2014; 7(10):7020-7.
  • Ikuo Matsuda, Yukihiro Imai, Seiichi Hirota
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    ABSTRACT: Lymphomas are malignant neoplasms composed of lymphoid cells at various developmental stages and lineages. Recent advances in comprehensive genomic analyses in acute myeloid leukemia have revealed prevalent mutations in regulators of epigenetic phenomena including global DNA methylation status. The examples include mutations in isocitrate dehydrogenase 1 (IDH1), IDH2, and ten-eleven translocation 2. These mutations are proposed to inhibit conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), leading to global accumulation of 5 mC. These changes in global DNA methylation status can be visualized immunohistochemically using specific antibodies against 5 mC and 5 hmC. We examined the global DNA methylation status of B-cell lymphomas and that of their normal counterparts by immunohistochemistry for 5 mC and 5 hmC. Non-tumor lymphoid cells inside germinal centers (GC) in reactive lymphoid hyperplasia (RLH) were stained positive for 5 mC, but they were negative for 5 hmC. Similarly, follicular lymphomas, whose postulated normal counterparts are centrocytes in GCs, were 5 mC-positive but 5 hmC-negative by immunohistochemistry. This immunostaining pattern was also observed in Burkitt lymphoma. In contrast, non-tumor lymphoid cells in mantle zones were stained positive for 5 mC as well as for 5 hmC. Likewise, most mantle cell lymphomas, whose postulated normal counterparts are mantle zone B cells in RLH, were stained positive for 5 mC as well as for 5 hmC. This immunostaining pattern was also observed in chronic lymphocytic leukemia/small lymphocytic lymphoma. These results suggest that, in terms of 5 mC/5 hmC immunohistochemistry, B-cell lymphomas with different histological subtypes are associated with distinct global DNA methylation statuses that resemble those of their postulated normal counterparts. [J Clin Exp Hematop 54(1): 67-73, 2014].
    Journal of Clinical and Experimental Hematopathology 01/2014; 54(1):67-73.
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    ABSTRACT: Primary malignant lymphoma of the urinary bladder is a rare disease constituting less than 1% of neoplasms of the urinary bladder. The most prevalent histological subtype is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). It is frequently associated with chronic cystitis and predominantly occurs in females. On the other hand, malakoplakia is thought to be a reactive granulomatous lesion occurring most prevalently in the genitourinary tracts. It is frequently found in females and often associated with bacterial infection in immunosuppressive status. Here we report a rare case of concurrent primary MALT lymphoma and malakoplakia in the urinary bladder in a 78-year-old Japanese female. Presumably, both lymphoma and malakoplakia are considered to be involved in the antecedent cystitis and might contribute to the development of the urinary bladder tumor of the patient, leading to the occlusion of the right ureter with subsequent hydronephrosis.
    International journal of clinical and experimental pathology. 01/2014; 7(8):5280-4.
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    ABSTRACT: Nodal follicular lymphoma (FL) is typically composed of follicular or nodular proliferation of small cleaved lymphoid cells, presumably derived from germinal center (GC) B cells. The hallmark of FL is t(14;18)(q32;q21) chromosomal translocation, which juxtaposes anti-apoptotic gene BCL2 to immunoglobulin heavy chain (IGH) promoter. Reflecting this background, FL cells are immunohistochemically positive for BCL2 as well as GC B cell markers CD10 and BCL6. It is known that low grade B-cell lymphomas, including FL, chronic lymphocytic leukemia/small lymphocytic lymphoma, and marginal zone lymphoma, are sometimes associated with marginal zone differentiation or plasmacytic differentiation. The marginal zone differentiation obscures the morphological differences among these, providing diagnostic challenges for histopathologists. In this paper, we present a case of FL, originally mimicking marginal zone lymphoma in the axillary lymph node. Subsequent bone marrow biopsy showed paratrabecular infiltration of small to medium-sized lymphoid cells. Immunohistochemical analysis of the bone marrow biopsy together with histopathology and flow cytometry of the axillary lymph node led to a final diagnosis of FL with marginal zone differentiation in the axillary lymph node and its bone marrow infiltration. Our case illustrates and reconfirms the importance of clinicopathological correlation which leads to a correct diagnosis.
    International journal of clinical and experimental pathology. 01/2014; 7(10):7076-81.
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    ABSTRACT: Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma was incidentally found in an enlarged spleen resected palliatively to alleviate symptomatic pancytopenia of the patient. The main characteristic of our case is an incidental finding of a rare situation brought by careful pathological examination. Our case illustrates the importance to recognize a possibility of co-occurrence of chronic liver disease and extrahepatic lymphoma.
    International journal of clinical and experimental pathology. 01/2014; 7(7):4484-8.
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    ABSTRACT: BACKGROUND: Recently it has been revealed that lung adenocarcinomas with distinct gene mutations or fusions are associated with particular histopathological entities. For example, epidermal growth factor receptor (EGFR) gene mutations are often associated with well differentiated adenocarcinoma of the lung with bronchioloalveolar pattern. On the other hand, Echinoderm microtubule associated protein-like 4 (EML4)-Anaplastic large cell lymphoma kinase (ALK) fusion gene in a subset of lung adenocarcinoma is related to mucinous cribriform histology. CASE PRESENTATION: Reported herein is a case of synchronous EML4-ALK positive lung adenocarcinoma and adenocarcinoma in situ in the bilateral lungs of a 55-year-old Japanese woman. The woman had EML4-ALK positive lung adenocarcinoma in the right lower lung while adenocarcinoma in situ in the left upper lung, which was EML4-ALK negative. CONCLUSION: To our knowledge, this is the first report of synchronous, bilateral lung adenocarcinomas composed of EML4-ALK positive and negative ones.
    BMC Pulmonary Medicine 04/2013; 13(1):25. · 2.76 Impact Factor
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    ABSTRACT: The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene, which encodes KIT receptor tyrosine kinase. Most of the mutations are located at exon 11, but some are at exon 9 or at other exons. Mutation types at exon 11 vary, while most mutations at exon 9 are a particular duplication of Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently a duplication of Ser501Ala502 (KIT-Dup-Ser501Ala502) at exon 9 has been reported in two cases of pediatric mastocytosis and one case of adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not been reported in GISTs, we found two GIST cases possessing the mutation in 45 GIST cases with exon 9 c-kit gene mutations, among a total of approximately 500 GIST cases examined. In this report, we briefly summarize clinicopathological findings of the two cases, and characterize the biology of the mutation. When autophosphorylation of KIT-Dup-Ser501Ala502 was examined by transient transfection of c-kit cDNA with Dup-Ser501Ala502 into CHO-K1 cells, KIT-Dup-Ser501Ala502 was ligand-independently activating. The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation of KIT-Dup-Ser501Ala502 at a concentration of 0.1 μM, whereas it inhibited that of KIT-Dup-Ala502Tyr503 at a concentration of 10 μM. Constitutive activation of KIT-Dup-Ser502Ala503 was not inhibited by nilotinib even at a concentration of 10 μM but that of KIT-Dup-Ala501Tyr502 was almost completely inhibited at a concentration of 1 μM. The results suggest that imatinib and nilotinib could be more effective on GISTs with KIT-Dup-Ser501Ala502 than those with KIT-Dup-Ala502Tyr503. In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503.Laboratory Investigation advance online publication, 4 March 2013; doi:10.1038/labinvest.2013.43.
    Laboratory Investigation 03/2013; · 3.96 Impact Factor
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    ABSTRACT: Myxoid/round cell liposarcomas are rare mesenchymal neoplasms. They preferentially occur in the lower extremity, and most of them have type 1 or type 2 DDIT3-FUS fusion gene. We report here a very rare case of myxoid/round cell liposarcoma of the paratesticular region with type 3 DDIT3-FUS fusion gene. A 46-year-old Japanese man noticed a gradually enlarged intrascrotal mass without pain. Surgical resection of 3.4cm×2.1cm oval mass was carried out, and it was located in the right paratesticular region apart from the spermatic cord and epididymis. Histological examination of the tumor revealed ovoid cell proliferation with anastomosing vascular network and scattered lipoblasts. Genetic analysis elucidated that the tumor had a chromosomal translocation, type 3 DDIT3-FUS chimeric gene. The tumor was definitely diagnosed as myxoid/round cell liposarcoma of the paratesticular region.
    Pathology - Research and Practice 12/2012; · 1.21 Impact Factor
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    ABSTRACT: The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.
    Oncology letters 11/2012; 4(5):910-914. · 0.24 Impact Factor
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    ABSTRACT: BACKGROUND: Colorectal metastasis of lobular carcinoma of the breast is a diagnostic challenge. It may macroscopically simulate primary colon cancer or inflammatory bowel disease. In some cases, the interval between the primary breast cancer and metastatic colorectal lesions is so long that the critical records for diagnosis including history might be lost or missed. CASE PRESENTATION: Reported herein is a case of metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer developed in a 62-year-old Japanese woman. The case initially presented as a circumferential rectal lesion, and information on the patient's history of breast cancer was not noted. As the result of endoscopic biopsy, diagnosis of poorly differentiated rectal adenocarcinoma was made. The lesion was surgically resected after chemo-radiotherapy. Histopathological examination of the resected specimen with hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical analysis revealed an immunophenotype consistent with lobular carcinoma of the breast. Because further review of the patient's history revealed an occurrence of 'poorly differentiated adenocarcinoma of the breast', which she had experienced 24 years earlier, the final diagnosis of the lesion was made as rectal metastasis from lobular breast carcinoma. CONCLUSIONS: Poorly differentiated adenocarcinoma of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer of the colorectum is also rarer than that of the stomach. A lesson from the present case is that before we conclude a linitis plastica-type cancer of poorly differentiated type as a primary colorectal cancer, it is critical to exclude a possibility of metastatic colorectal cancer.
    World Journal of Surgical Oncology 10/2012; 10(1):231. · 1.09 Impact Factor
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    ABSTRACT: Primary carcinoid tumor of the urinary bladder is a very rare neoplasm. We report here a case of primary carcinoid tumor of the urinary bladder with an unusual cytological feature in a 72-year-old Japanese man. A bladder polypoid mass was incidentally found by ultrasonography during the follow-up of a benign prostate hyperplasia. Histological examination of the transurethrally resected tissue revealed that the upper part of the mass was a tumor showing tubuloglandular anastomosing structures. Most of the tumor cells had peculiar subnuclear eosinophilic granules. The features of the granules were reminiscent of those observed in neuroendocrine cells of the intestine. The tumor cells were immunohistochemically positive for chromogranin A and synaptophysin. The tumor was diagnosed as carcinoid tumor of pure form of the urinary bladder. The lower part of the mass showed the findings of glandular cystitis, as its coexistence with carcinoid tumors of the bladder has often been described in previous reports.
    Pathology - Research and Practice 11/2011; 208(2):109-12. · 1.21 Impact Factor
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    ABSTRACT: Procedure of endoscopic submucosal dissection (ESD) has been introduced widely for treatment of early gastric cancers. For such specimens, accurate pathological diagnosis, especially concerning depth of the invasion and exposure to margins, is essential to decide on the necessity of additional treatment. Therefore, easy and reliable tissue-processing method for multiple cut specimens is needed. The authors report here a new double embedding technique for specimens of ESD. Formalin-fixed whole specimen was superficially wrapped by agarose (the first embedding), and the tissue-agarose block was cut at 2-3 mm intervals. Each cut specimen was laid down with 90° rotation. This procedure permitted 'on edge' embedding of thin tissues in paraffin (the second embedding) and subsequent preparation of perpendicular section to the tissue surface. The authors compared the handleability and stainability among several media including various types of agar, agarose and gelatin for first embedding. A survey by questionnaire was carried out on handleability and/or impression on various tissue-processing steps from pathology technicians. Among the media examined, agarose showed the best solubility in water and the best transparency on several representative stainings. According to the survey, pathology technicians seemed to feel that the present method was better than the usual tissue processing method, especially in shortened time consumption and accuracy of alignment of multiple tissues for ESD specimens. The present new double embedding technique using agarose provides not only an easy and reliable embedding procedure for technicians but also accurate and exact diagnosis for pathologists.
    Journal of clinical pathology 10/2010; 63(10):904-9. · 2.43 Impact Factor
  • Ikuo Matsuda, Yukihiro Imai, Seiichi Hirota
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    ABSTRACT: The identification of cell type is essential in diagnostic tumor histopathology. We hypothesized that some patterns of global histone modification are specific to both particular cell types of non-neoplastic tissues and their neoplastic counterparts. To examine the hypothesis in lymphoid cells, global histone modification patterns of germinal center and mantle zone B cells in reactive lymphoid hyperplasia (RLH) were compared with those of follicular lymphoma (FL) and mantle cell lymphoma (MTL) cells by immunohistochemistry. We revealed that FL cells and MTL cells exhibited the similar histone modification pattern to that of germinal center B lymphocytes and mantle zone B lymphocytes in RLH, respectively. These results indicate that global histone modification profiles specific to non-neoplastic germinal center B lymphocytes and mantle zone B lymphocytes are well conserved in corresponding neoplastic lymphoma cells, and suggest that they will be indicative of tumor cell type at least in B cell lymphoma.
    Pathology & Oncology Research 12/2009; 16(3):447-51. · 1.56 Impact Factor
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    ABSTRACT: Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic tumor primarily affecting women in their twenties. It is characterized by a well-demarcated or encapsulated mass, indolent behavior and favorable prognosis. Capsular or punctate calcification is occasionally observed. Reported herein is a case of SPN of the pancreas with massive calcification in a 76-year-old Japanese man. Macroscopically, the pancreatic tumor appeared to be a simple calcified nodule, but histological examination revealed that it was an epithelioid tumor with massive calcification. The tumor cells, forming nests and cords, had eosinophilic cytoplasm and small eccentric nuclei. They were immunohistochemically positive for vimentin, CD56 and neuron-specific enolase. Nuclear accumulation of beta-catenin protein and a point mutation of the beta-catenin gene by genomic DNA sequencing confirmed that the tumor was SPN. This is a very rare case of pancreatic SPN with massive calcification in an old man.
    Pathology - Research and Practice 09/2009; 206(6):372-5. · 1.21 Impact Factor
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    ABSTRACT: Two families with a germline Asp820Tyr mutation at exon 17 of the c-kit gene and multiple gastrointestinal stromal tumors (GISTs) have been reported. Recently, we generated a knock-in mouse model of the family, and mice with KIT-Asp818Tyr corresponding to human KIT-Asp820Tyr showed a cecal GIST-like tumor. In this report, we examined the in vivo effect of imatinib on tumor progression in knock-in mice. Imatinib of 100 microg/g body weight was administered to heterozygous (KIT-Asp818Tyr/+) mice orally for 7, 14 and 28 days, and cecal tumors were dissected. Both macroscopic size and the measured volume of cecal tumors were not significantly reduced after a 7-, 14- and 28-day administration of imatinib when compared with those before imatinib administration. Cell proliferation was assessed by Ki-67 immunohistochemistry and the labeling index significantly decreased after imatinib administration, but the value of the index after imatinib was only about half compared with that before imatinib. Western blotting and real-time PCR revealed that KIT expression was almost equivalent, but KIT phosphorylation was significantly but not completely inhibited in tumor tissues after 7, 14 and 28 days of imatinib administration when compared with that before imatinib administration. Phosphorylation of Akt and Stat1 was accordingly inhibited after imatinib administration. Thus, imatinib seemed to inhibit in vivo tumor proliferation but not decrease tumor volume on this mouse model, probably because of an insufficient inhibition of phosphorylation of KIT and its downstream signaling molecules. These results suggested that progression of multiple GISTs in patients with germline Asp820Tyr might be partially controlled by imatinib and that model mice provide an opportunity to examine the effect of various other targeted drugs on in vivo tumor progression.
    Laboratory Investigation 08/2009; 89(10):1161-8. · 3.96 Impact Factor