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Biomedical subjects

Masao Matsutani

Publications and source records attributed to Masao Matsutani.

14 recordsLinked to original sources

Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma.

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.

Biomarkers, Tumor↗

Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression.

Podoplanin (aggrus) is a mucin-like transmembrane sialoglycoprotein that is expressed on lymphatic endothelial cells. Podoplanin is putatively involved in cancer cell migration, invasion, metastasis, and malignant progression and may be involved in platelet aggregation. Previously, we showed upregulated expression of podoplanin in central nervous system (CNS) germinomas, but not in non-germinomatous germ cell tumors, except for parts of immature teratomas in limited numbers. However, little information exists about its role in CNS astrocytic tumors. In this study, 188 astrocytic tumors (30 diffuse astrocytomas, 43 anaplastic astrocytomas, and 115 glioblastomas) were investigated using immunohistochemistry with an anti-podoplanin antibody, YM-1. In 11 of 43 anaplastic astrocytomas (25.6%) and in 54 of 115 glioblastomas (47.0%), podoplanin was expressed on the surface of anaplastic astrocytoma cells and glioblastoma cells, especially around necrotic areas and proliferating endothelial cells. However, the surrounding brain parenchyma was not stained by YM-1. On the other hand, podoplanin expression was not observed in diffuse astrocytoma (0/30: 0%). Furthermore, we investigated the expression of podoplanin using quantitative real-time PCR and Western blot analysis in 54 frozen astrocytic tumors (6 diffuse astrocytomas, 14 anaplastic astrocytomas, and 34 glioblastomas). Podoplanin mRNA and protein expression were markedly higher in glioblastomas than in anaplastic astrocytomas. These data suggest that podoplanin expression might be associated with malignancy of astrocytic tumors.

Astrocytoma↗

Papillary glioneuronal tumor with minigemistocytic components and increased proliferative activity.

Papillary glioneuronal tumor (PGNT) is a rare and new type of glioneuronal neoplasm of the central nervous system. It is characterized by pseudopapillary structures composed of hyalinized vessels rimmed by cuboidal glial cells and the proliferation of neuronal cells. We report a peculiar PGNT arising in the parietal lobe of a 67-year-old man, which was characterized by proliferation of minigemistocytic cells as well as typical components. The minigemistocytic cells had eccentric nuclei and plump eosinophilic cytoplasm that was filled with glial filaments. The Ki-67 labeling index was as high as 10% in the minigemistocytic areas. Recently, the presence of oligodendroglial-like component was suggested in PGNT. Considering that oligodendroglioma sometimes accompanies minigemistocytic components, the minigemistocytic cells in PGNT were suggested to be a part of oligodendroglial differentiation. Although PGNT is defined as an indolent glioneuronal tumor, the presence of minigemistocytic components with the high Ki-67 labeling index may indicate more aggressive nature.

Aged↗

[Efficacy and safety of monotherapy with temozolomide in patients with anaplastic astrocytoma at first relapse--a phase II clinical study].

The efficacy and safety of temozolomide were evaluated in 32 patients with anaplastic astrocytoma at first relapse. Temozolomide was administered orally once daily for the first five days of a 28-day cycle, at a dose of 150 or 200 mg/m(2)/day. The response rate determined by independent central review of MRI was 34% (95% confidence interval: 18.6%-53.2%), with 3 complete response and 8 partial response. The rate of "no change or better" was 91% (95% confidence interval: 75.0%-98.0%). Progression-free survival (PFS) at 6 months was 40.6%, and the median PFS was 4.1 months. The incidence of constipation (50%) and nausea (25%) was high,but these events were all mild or moderate in severity except in one subject with constipation,and could be managed with standard laxatives and antiemetics. The main laboratory test abnormalities (total incidence and incidence of grade 3/4 change) were lymphocytopenia (50%, 25%), neutropenia (47%, 6%), leukopenia (38%, 3%), thrombocytopenia (31%, 9%), and increased GPT (25%, 3%). Temozolomide was shown to have good efficacy and tolerability in patients with anaplastic astrocytoma at first relapse.

Adult↗

Mixed neuronal-glial tumor of the fourth ventricle and successful treatment of postoperative mutism with bromocriptine: case report.

BACKGROUND: Tumors composed of both neurocytic and astrocytic cells are uncommon and poorly understood. We describe the clinicopathologic features of a very rare rosette-forming glioneuronal tumor of the fourth ventricle and propose bromocriptine as a useful therapeutic agent for cerebellar mutism after posterior fossa surgery. CASE DESCRIPTION: A fourth ventricle tumor was incidentally discovered in an 18-year-old woman. Magnetic resonance imaging revealed ventriculomegaly and a solid tumor with low-intensity signals on T1-weighted images and high-intensity signals on T2-weighted images. There was slight gadolinium enhancement. The tumor was subtotally resected. Although its lower half was well circumscribed, its upper half manifested invasive growth. Histologically, 2 components were identified, synaptophysin-positive neurocytic cells forming perivascular pseudorosettes and glial fibrillary acidic protein-positive astrocytic cells with Rosenthal fibers. Overall, cellular atypia was minimal and the MIB-1 labeling index was low. On the basis of these histologic findings, the tumor bore striking similarity to the recently described rosette-forming glioneuronal tumors of the fourth ventricle. Postoperatively, the patient manifested cerebellar mutism. The administration of bromocriptine improved her neurological status dramatically. CONCLUSION: The natural history of rosette-forming glioneuronal tumors of the fourth ventricle is not yet fully understood. Therefore, careful and long-term follow-up monitoring of the tumor hosts is necessary. Bromocriptine therapy may promote recovery from mutism after posterior fossa surgery.

Adolescent↗

Immunohistochemical analysis of the mutant epidermal growth factor, deltaEGFR, in glioblastoma.

The naturally occurring mutated form of the epidermal growth factor receptor, deltaEGFR (also named EGFRvIII and de2-7EGFR), greatly enhances glioblastoma (GBM) cell growth in vivo through several activities, such as down-regulating p27 and up-regulating BclX(L) while increasing signaling through the RAS-MAPK and PI3-K cascades. More than half of GBMs, especially of the de novo type, overexpress EGFR, and 50%-70% of these express deltaEGFR. However, little is known about the distribution of deltaEGFR-expressing tumor cells within surgical specimens. In order to address this clinically important issue, we performed immunohistochemical analyses of 53 GBMs obtained during surgery using the anti- deltaEGFR monoclonal antibody, DH8.3. We also simultaneously analyzed wild-type EGFR expression in these tissues using the anti-EGFR monoclonal antibody, EGFR.113. deltaEGFR and wild-type EGFR expression were observed in 20/53 (38%) and 29/53 (55%), respectively. Nineteen (95%) of the deltaEGFR-positive tumors also expressed wild-type EGFR; one case was deltaEGFR-positive but wild-type EGFR-negative. In 13/20 (65%) of the deltaEGFR-positive tumors, tumor cells were scattered diffusely within the tumors, 6/20 showed geographical distribution of deltaEGFR-positive tumor cells, and one case showed homogeneous staining. In the wild-type EGFR-positive cases, almost all tumor cells expressed EGFR. The differential distribution of cells expressing the two receptors observed here may suggest either that deltaEGFR arises at a low frequency from wild-type EGFR-expressing cells, perhaps during the process of gene amplification, or that there is a paracrine-type of interaction between them.

Blotting, Western↗

Chemoradiotherapy for brain tumors: current status and perspectives.

Brain tumors growing in the parenchyma of the brain infiltrate diffusely, and the role of surgery is restricted to maximal tumor-bulk removal. Residual tumor cells beyond the surgical margin are not killed by conventional radiation therapy with 60 'Gy. Many clinical trials delivering chemotherapy during radiation therapy and after radiation therapy have been performed, but the results remain poor. Here the author reviews the current treatments of gliomas, malignant lymphomas, medulloblastomas, and germ cell tumors, and their results.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical management of primary central nervous system germ cell tumors.

Despite excellent long-term results for patients with germinoma treated with radiation therapy, the potential for late effects makes the treatment controversial. On the other hand, most patients with non-germinomatous tumors treated by conventional treatment with surgery and radiation therapy fail to survive longer than 3 years. After combination chemotherapy with cisplatin was confirmed to be effective in gonadal germ cell tumors, germ cell tumors of the brain became candidates for chemotherapy. The author reviews several prospective phase II studies that are being investigated to assess the effect of combination chemotherapy and radiation therapy for germ cell tumors. The aim of these studies is to reduce the volume and dose of radiation therapy for germinoma and prolong the survival of patients of non-germinomatous tumors. For germinoma, a trial with chemotherapy alone failed, with a high rate of recurrence, but Japanese and European trials with reduced-dose chemotherapy and a smaller volume of radiation therapy have resulted in high event-free survival (EFS) rates. Ongoing phase II studies with combined chemotherapy and radiation therapy for non-germinomatous tumors will result in a 5-year survival rate of greater than 50%, which is better than that achieved by radiation therapy alone.

Central Nervous System Neoplasms↗

Hypomethylated X chromosome gain and rare isochromosome 12p in diverse intracranial germ cell tumors.

Twenty-five primary intracranial germ cell tumors (11 germinomas, 5 teratomas, 5 mixed teratomas-germinomas. 1 mixed choriocarcinoma-teratoma, 1 yolk sac tumor, 1 mixed yolk sac tumor-teratoma, and 1embryonal carcinoma; from 24 males and 1 female) were studied by fluorescence in situ hybridization with probes to the X and Y chromosomes, chromosome 12p, the CDKN2A/p16 gene, and chromosome 13q-loci previously noted to be altered in either intracranial or systemic germ cell tumors. An increased number of X chromosomes, typically 1 extra copy, was observed in 23 of 25 cases (92%), with methylation-sensitive PCR demonstrating that the additional X chromosomes were hypomethylated in 13 of 16 (81%) studied tumors. Five cases (20%) had increased copy numbers of 12p (including tumors with isochromosome 12p), and 3 (12%) had 13q loss. No tumors had CDKN2A/p16 deletion or mutation, and 16 of 25 (64%) were positive for p16 expression by immunohistochemistry. Genetic alterations such as isochromosome 12p, 13q loss and CDKN2A/p16 are therefore not common in intracranial germ cell tumors. However, gains of hypomethylated, active X chromosomes occur in nearly all intracranial germ cell tumors, regardless of histological subtype. Along with the observed male predominance of intracranial germ cell tumors and the predisposition in Klinefelter syndrome patients for these lesions, the data argue strongly that sex chromosome aberrations, rather than isochromosome 12p, are integral to intracranial germ cell tumorigenesis

Adolescent↗

Synchronous optic and pineal pilocytic astrocytomas in a paediatric patient with neurofibromatosis type 1.

A 12-year-old girl with neurofibromatosis type 1 presented with headache, visual acuity and visual field disturbance. Computed tomography and magnetic resonance imaging revealed an enhanced solid mass involving her right optic nerve and optic chiasm, and a cystic lesion in the pineal region that had resulted in obstructive hydrocephalus. An open biopsy of the right optic nerve tumour was performed, and it was histologically identified as a pilocytic astrocytoma. Local irradiation of 50 Gy to the optic pathway tumour was performed, and the tumour has remained stable for more than 29 months. On the contrary, the pineal cystic mass that was also histologically identified as a pilocytic astrocytoma showed marked enlargement within 5 months after a subtotal resection. Chemotherapy with cisplatin and vincristine was performed after a second surgery, and the pineal tumour has not re-grown in 18 months. To our knowledge, this is the first case report to describe synchronous optic and pineal pilocytic astrocytomas associated with neurofibromatosis type 1.

Astrocytoma↗

Giant invasive pituitary adenoma extending into the sphenoid sinus and nasopharynx: report of a case with intraoperative cytologic diagnosis.

BACKGROUND: Invasive pituitary adenomas involving the skull base are difficult to distinguish from other, more aggressive tumors. Intraoperaive diagnoses are crucial for deciding the course of treatment. CASE: A large mass extending from the sella turcica to the sphenoid sinus and nasopharynx was identified in a 42-year-old male. Because of the lack of endocrine abnormalities and lack of an apparent rise in pituitary hormones, preoperative diagnoses included chordoma, chondrosarcoma, meningioma and pituitary adenoma. Tumor fragments were easily squeezed into a thin layer of cells for cytologic specimens. Uniform, round tumor cells were arranged in minimally cohesive cell sheets and possessed regular, ovoid nuclei with a fine chromatin pattern and granular cytoplasm with prominent Golgi areas. The cytologic features indicated a probable diagnosis of pituitary adenoma and excluded other possibilities. Immunohistochemical demonstration of prolactin and ultrastructural features established the final diagnosis of prolactinoma. With the administration of bromocriptine, a large reduction in tumor size occurred. As compared to frozen sections, cytologic preparations are more effective for the intraoperative diagnosis of pituitary adenomas. Such neoplasms should always be included in the differential diagnosis of tumors involving the skull base.

Adult↗

Cytologic features of chordoid meningioma. A case report.

BACKGROUND: Chordoid meningioma is a rare subtype of meningioma characterized by myxoid matrices deposited among epithelioid or vacuolated tumor cells and infiltrates of inflammatory cells, and its cytologic features have rarely been reported. CASE: A 57-year-old man with a history of headache and visual disturbance presented with a tumor in the suprasellar region. Intraoperative touch smear cytology of the tumor disclosed a cord-like arrangement of polygonal tumor cells occasionally containing intranuclear inclusions. Furthermore, periodic acid-Schiff-positive, mucinous matrices were deposited among the tumor cells. Also, infiltrates of lymphocytes and plasma cells were noted. Histologic, immunohistochemical and ultrastructural examination confirmed the diagnosis of chordoid meningioma. CONCLUSION: Intraoperative smear cytology in a case of chordoid meningioma showed distinctive cytologic features suggestive of the histologic patterns. The cytologic features, together with a histologic examination, are useful for its diagnosis.

Choroid Neoplasms↗