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Biomedical subjects

M Hirokawa

Publications and source records attributed to M Hirokawa.

At least 37 records · Page 2Linked to original sources

Intranodal benign thyroid tissue: significance of HBME-1 in differentiation from metastatic papillary thyroid carcinoma.

The aim of this study was to determine the significance of HBME-1 immunostaining in the differentiation between intranodal benign thyroid tissue and metastatic papillary thyroid carcinoma in the lymph node. Immunohistochemically we examined normal-appearing intranodal thyroid tissue in four patients who did not show evidence of papillary carcinoma histologically or clinically. We also examined follicular-pattern-predominant papillary carcinoma with metastatic foci in the lymph nodes. Normal-appearing intranodal thyroid tissue and normal thyroid showed no immunopositivity for HBME-1. In contrast, all papillary carcinomas in both the lymph nodes and thyroid demonstrated strong positivity for HBME-1. HBME-1 was predominantly positive for the luminal surface of the tumor cells. The immunopositivity of the cuboidal and low columnar carcinoma cells was more intensive than that of the flat-shaped cells in the lymph nodes and thyroid. The results probably indicate that HBME-1 immunostaining is helpful in distinguishing between intranodal benign thyroid tissue and metastatic papillary carcinoma in lymph nodes. We emphasize that the HBME-1 reactivity should be evaluated in connection with the histological findings, and that positive and negative controls stained in parallel are necessary.

Aged↗

Abnormal venous structures in salivary gland tumors: vasculature characteristics of pleomorphic adenoma.

To clarify the diagnostic significance of abnormal venous structures present in salivary gland tumors, we examined 21 pleomorphic adenomas, 14 Warthin tumors, 1 oncocytic adenoma, 3 myoepitheliomas, 7 basal cell adenomas, 5 mucoepidermoid carcinomas, and 6 adenoid cystic carcinomas. Verhoeffvan Gieson staining was carried out and the morphology of the veins within the tumors was observed microscopically. Branching veins, thickened intima of the veins, discontinuous elastic membrane and multilayered elastic membrane were seen in 71.4%, 76.2%, 47.6% and 85.7% of pleomorphic adenomas, respectively, and were abundant and easily found in most cases. The abnormal venous structures were also found in other salivary gland tumors examined, but they were few in number and lacked variety. Elastic fibers extending radially into the surrounding stroma were seen in 66.7% of pleomorphic adenomas, and were not seen in other salivary gland tumors. Our results showed that a variety of abnormal venous structures are more abundant and more easily found in pleomorphic adenoma compared with other salivary gland tumors, and, in particular, that perivascular radiating elastic fibers are characteristic of pleomorphic adenoma. We emphasize that the presence of perivascular radiating elastic fibers may be helpful in diagnosing pleomorphic adenoma in small biopsy specimens.

Adenoma, Pleomorphic↗

Endolymphatic sac tumor associated with a von Hippel-Lindau disease patient: an immunohistochemical study.

The authors report a case of endolymphatic sac tumor (ELST) associated with Von Hippel-Lindau disease (VHL). A 20-year-old female VHL patient received a resection of a cerebellar hemangioblastoma 3 years ago and she had a co-existing of left petrous tumor. The petrous tumor showed a remarkable progression in 3 years and was resected subtotally. Histologically, the resected petrous tumor showed a papillary structure containing cuboidal or columnar cells with fibrous stroma and numerous microvessels and destructed temporal bone, all of which are consistent with ELST. We studied the expression of various kinds of cytokeratins (CKs) immunohistochemically and found distinct expression of CKs (CAM 5.2, 34betaE-12, CK7, CK8 and CK19), but not for CK10/13 or CK20. Vascular endothelial growth factor and neuron specific enolase showed strong immunoreactivity in the tumor cells. CD34 also had weak expression. Ki-67 antigen (MIB-1) immunoreactivity was found in focal areas, and the labeling index in the highest-density area was 48.9%. These findings suggest that vascular endothelial growth factor overexpression is an important factor for angiogenesis in ELST, much like other VHL-associated tumors, and that ELST may have a more highly aggressive component than the low-grade malignancy noted in previous reports.

Adult↗

Extensive clonal expansion of T lymphocytes causes contracted diversity of complementarity-determining region 3 and skewed T cell receptor repertoires after allogeneic hematopoietic cell transplantation.

We previously described skewed repertoires of the T cell receptor-beta chain variable region (TCRBV) and the TCR-alpha chain variable region (TCRAV) soon after allogeneic hematopoietic cell transplantation. To determine the characteristics of skewed TCRBV after transplantation, we examined the clonality of T lymphocytes carrying skewed TCRBV subfamilies and determined the CDR3 sequences of expanded T cell clones. In all 11 recipients examined, TCR repertoires were skewed, with an increase of certain TCRBV subfamilies that differed among individuals. In nine of 11 patients, clonal/oligoclonal T cell expansion was observed, although the expanded T cells were not necessarily oligoclonal. The extent of expansion after transplantation appeared to predict clonality. The arginine (R)-X-X-glycine (G) sequence was identified in clonally expanded T cells from four of five recipients examined, and glutamic acid (E), aspartic acid (D) and alanine (A) were frequently inserted between R and G. These results suggest that T lymphocyte expansion may result from the response to antigens widely existing in humans, and that the extensive clonal expansion of a limited number of T cells leads to contracted CDR3 diversity and post-transplant skewed TCR repertoires.

Clone Cells↗

Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(-) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire.

We have previously reported that skewed repertoires of T cell receptor-beta chain variable region (TCRBV) and TCR-alpha chain variable region (TCRAV) are observed at an early period after allogeneic hematopoietic cell transplantation. Furthermore, we found that T lymphocytes using TCRBV24S1 were increased in 28% of the recipients of allogeneic grafts and an increase of TCRBV24S1 usage was shown to result from clonal expansions. Interestingly, the arginine residue was frequently present at the 3' terminal of BV24S1 segment and was followed by an acidic amino acid residue within the CDR3 region. These results suggest that these clonally expanded T cells are not randomly selected, but are expanded by stimulation with specific antigens. This study was undertaken to elucidate the mechanisms of the post-transplant skewing of TCR repertoires. Since the CD8(+)CD28(-)CD57(+) T cell subset has been reported to expand in the peripheral blood of patients receiving allogeneic hematopoietic cell grafts, we examined the TCRAV and TCRBV repertoires of the CD8(+)CD28(-) T cell and CD8(+)CD28(+) T cell subsets, and also determined the clonality of both T cell populations. In all three recipients examined, the CD8(+)CD28(-) T cell subset appeared to define the post-transplant TCR repertoire of circulating blood T cells. Moreover, the CDR3 length of TCRBV imposed constraints in both CD8(+)CD28(-) T cell and CD8(+)CD28(+) T cell subsets. The DNA sequences of the CDR3 region were determined, and the same clones were identified within both CD8(+)CD28(-) and CD8(+)CD28(+) T cell subsets in the same individuals. These results suggest that the clonally expanded CD8(+)CD28(-) T cells after allogeneic hematopoietic cell transplantation derive from the CD8(+)CD28(+) T cell subset, possibly by an antigen-driven mechanism, resulting in the skewed TCR repertoire.

Amino Acid Sequence↗

Oligoclonal expansion of CD4(+)CD28(-) T lymphocytes in recipients of allogeneic hematopoietic cell grafts and identification of the same T cell clones within both CD4(+)CD28(+) and CD4(+)CD28(-) T cell subsets.

Recipients of allogeneic bone marrow grafts have clonally expanded CD8(+)CD28(-) T lymphocytes during the early period after transplantation, which leads to skewing of T cell receptor (TCR) repertoires. Here, we have addressed the question of whether clonal expansion of CD28(-) T cells is also observed in CD4(+) T lymphocytes after human allogeneic hematopoietic cell transplantation. We found that the fraction of T cells lacking CD28 expression in the CD4(+) subset was increased after transplantation, and expanded CD4(+)CD28(-) T lymphocytes carrying certain TCRBV subfamilies showed limited TCR diversity. In order to further study the ontogeny of CD4(+)CD28(-) T cells, we analyzed the complementarity-determining region 3 (CDR3) of the TCR-beta chain of CD4(+)CD28(+) and CD4(+)CD28(-) cells. We identified the same T cell clones within both CD4(+)CD28(-) and CD4(+)CD28(+) T cell subsets. These results suggest that both subsets are phenotypic variants of the same T cell lineage.

Amino Acid Sequence↗

Fatty acids enhance GRO/CINC-1 and interleukin-6 production in rat intestinal epithelial cells.

Intestinal mucosal immunity is modulated by cytokine release from intestinal cells, but little is known about the relation between nutrient absorption and cytokine release. In this study, we examined how exposure to fatty acids affects the production of growth-regulated oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) and interleukin (IL)-6 in rat intestinal epithelial cells (IEC). The long-chain fatty acids, oleic, linoleic and arachidonic acids, and the middle-chain fatty acid octanoic acid were administered to subconfluent cultures of IEC-6 cells alone, or in combination with IL-1beta and transforming growth factor (TGF)-beta. The GRO/CINC-1 and IL-6 concentrations in culture media were determined by sandwich enzyme immunoassay. In epithelial cells, GRO/CINC-1 and IL-6 mRNA expression were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and mitogen-activated protein kinase (MAPK) activities determined by immunoblotting. Administration of long-chain fatty acids significantly increased the GRO/CINC-1 and IL-6 secretion into culture media, and this secretion was markedly increased (P < 0.05) in the presence of IL-1beta or TGF-beta. Octanoic acid had no effect on GRO/CINC-1 or IL-6 production. Furthermore, treatment with long-chain fatty acids significantly enhanced the GRO/CINC-1 and IL-6 expression that was induced by IL-1beta or TGF-beta. MAPK activity was significantly enhanced by treatment with long-chain fatty acids. Inhibitors of phospholipase C, protein kinase C or MAPK significantly reduced the fatty acid-induced increase in GRO/CINC-1 secretion, whereas a calcium/calmodulin inhibitor did not attenuate the secretion. These results suggest that long-chain fatty acids enhance cytokine release under conditions of inflammatory stimulation in the intestinal mucosa.

Animals↗

Nuclear findings of ovarian surface epithelial tumors.

While cytoplasmic features of ovarian surface epithelial tumors are well-known, the nuclear findings have received little attention. We reviewed imprint cytology materials of the ovary which were collected at the Kawasaki Medical School Hospital between January 1989-July 1999, and identified 15 mucinous cystadenomas, 3 borderline mucinous tumors, 4 mucinous cystadenocarcinomas, 4 serous cystadenomas, 4 borderline serous tumors, 7 serous cystadenocarcinomas, 6 endometrioid carcinomas, and 2 clear-cell adenocarcinomas. We microscopically observed nuclear findings of the 45 cases. Coffee-bean nuclei were observed in 15.0%, 15.8%, and 10.1% of the tumor cells in mucinous adenomas, borderline mucinous tumors, and borderline serous tumors, respectively. The frequencies of the coffee-bean nuclei in the three tumors were higher than in the remaining tumors (P < 0.001). Intranuclear cytoplasmic inclusions were observed in 2.1% of the tumor cells in mucinous cystadenoma, and their frequency was significantly higher than that in cases of other surface epithelial ovarian tumors (P < 0.001). Semilunar-shaped nuclei were seen in all cases of mucinous cystadenomas and borderline mucinous tumors, and in 3 of 4 mucinous adenocarcinomas. The remaining surface epithelial tumors did not reveal the semilunar-shaped nuclei. In the cytology of the ovary, the semilunar nuclei are characteristic of mucinous tumors, and the intranuclear cytoplasmic inclusion may be a diagnostic clue to mucinous cystadenoma, when it is conspicuous. The coffee-bean nuclei can be seen in mucinous cystadenoma, borderline mucinous tumors, and borderline serous tumors.

Cell Nucleus↗

Hypersegmentation of inflammatory cells in Langerhans cell granulomatosis.

Langerhans cell granulomatosis (LCG) is characterized by a mixture of Langerhans cells and eosinophils in varying proportions. The characteristic morphology of Langerhans cells have already been described in many articles, but little attention has been paid to inflammatory cells. We examined six cases of Langerhans cell granulomatosis, which had originally been diagnosed as eosinophilic granuloma. Inflammatory cells present in LCG showed hypersegmentation. Twenty percent to 70% of eosinophils had three or more segmented nuclei, and 10-25% of neutrophils had five or more segmented nuclei. Such findings have never been described, and we believe hypersegmentation to be a feature of LCG. Furthermore, we emphasize that eosinophils in LCG mimic neutrophils in ethanol-fixed preparations, and thus may be a pitfall in making a diagnosis in cytology and intraoperative consultation.

Adult↗

Gastrointestinal stromal tumor with skeinoid fibers of the ileum.

Gastrointestinal stromal tumor (GIST) is not uncommon among gastrointestinal nonepithelial tumors, but there are few reports describing the cytologic findings. We report a case of GIST with skeinoid fibers in scrape cytology preparation. The patient was a 53-year-old man with a tumor in the small intestine. Scrape preparations from the cut surface of the resected tumor revealed cellular material composed of spindle cells showing loose clusters or single cells. The nuclei were spindled, elongated or cigar-shaped, and relatively uniform. The cytoplasm was fragile and demonstrated a finely fibrillar material. Dense hyaline materials with irregular outline were observed within the loose clusters composed of the tumor cells. The hyaline materials were also observed in the background. Histologic preparation showed spindle cells arranged in a fascicular or storiform pattern. Most eosinophilic globules were distributed between the tumor cells. The globules were positive in periodic acid-Schiff reaction, and were stained blue with Masson's trichrome stain. Immunohistochemically, the tumor cells were strongly and diffusely positive for c-kit, focally and weakly positive for alpha-smooth muscle actin, and negative for CD34 and S-100 protein. We emphasize that skeinoid fibers are characteristic of GIST arising in the small intestine, and their presence predicts a good prognosis, even in malignant GIST.

Gastrointestinal Neoplasms↗

Cytology of microcystic meningioma in crush preparation.

Microcystic meningioma is a rare variant of meningioma, showing microcystic formations throughout the tumor. To the best of our knowledge, there have been no reports describing cytologic findings of microcystic meningioma. Our case was a 66-yr-old woman with a tumor mass adhered to the dura matter. The crush preparations of a small tissue fragment resected from the mass showed medium- to large-sized, well-cohesive clusters or sheets of uniform tumor cells. The tumor cells did not show a feathering-off pattern. Various-sized cystic spaces were observed within the clusters and sheets. The cytoplasm was relatively abundant, and the nuclear:cytoplasmic ratio was lower than that of classic meningioma. We believe that the cystic spaces within the cell clusters or sheets are characteristic of microcystic meningioma. The cytology of microcystic meningioma seen in our case was similar to that of metastatic adenocarcinoma, but relatively monotonous bland cells, smooth nuclear outline, and inconspicuous nucleoli led us to the diagnosis of meningioma rather than adenocarcinoma.

Aged↗

Dilated rough endoplasmic reticulum corresponding to septate cytoplasmic vacuoles in papillary thyroid carcinoma.

Septate cytoplasmic vacuoles, which are one of the cytologic findings characteristic of papillary thyroid carcinoma, are small, uniform, and well-defined vacuoles, with defined strands of cytoplasm separating them. We report on a case with histologic and ultrastructural findings corresponding to septate cytoplasmic vacuoles, which have not been previously described. The patient was a 51-yr-old man with a mass in the left anterior of the neck, measuring 4.0 x 3.5 cm in diameter. Aspiration cytology smears revealed findings typical of papillary thyroid carcinoma, including papillary tissue fragments, intranuclear inclusions, nuclear grooves, powdery chromatin, and psammoma bodies. The tumor cells which were located at the periphery of small three-dimensional clusters, and others which showed a sheet-like arrangement, demonstrated uniform, small vacuoles in relatively abundant, dense cytoplasm. Histologically, a small number of papillary thyroid carcinoma cells with multiple vacuoles were observed, which were limited to the hobnail-shaped cells located at papillary configurations or floating tumor cells within the papillary lumen. Ultrastructurally, the hobnail-shaped tumor cells demonstrated various-sized dilated rough endoplasmic reticulum and rich heterochromatin. We emphasize that septate cytoplasmic vacuoles correspond to dilated rough endoplasmic vacuoles and are probably related to degenerative changes.

Carcinoma, Papillary↗

Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma.

OBJECTIVE: We attempted to prospectively determine the role of magnetic resonance imaging (MRI) in very early cervical cancer. STUDY DESIGN: T2-weighted and T1-dynamic enhanced images from patients with invasive or noninvasive lesions of the cervix were reviewed by two radiologists who had no clinical information on these patients. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. RESULTS: Seventy-nine cases were entered into the study and 75 were evaluable. Accuracy of T2 MR images for invasive and noninvasive disease by Radiologist 1 and Radiologist 2 was 0.8533 and 0.7733, respectively. Accuracy was greater (0.9867 and 0.9467, respectively) for the detection of noninvasive plus microinvasive lesions </=5 mm vs invasive lesions >5 mm. Dynamic technique provided only limited additional value in the detection of microinvasive cervical carcinoma. CONCLUSION: Simple T2 MRI is useful in differentiating noninvasive or microinvasive cervical lesions from invasive cervical carcinoma of the cervix >5 mm.

Adult↗

Well-differentiated adenocarcinoma of the gallbladder mimicking minimal deviation adenocarcinoma of the cervix.

We report a case of well-differentiated adenocarcinoma of the gallbladder, histologically mimicking minimal deviation adenocarcinoma (MDA) of the cervix. A 71-year-old Japanese male underwent cholecystectomy because of the suggestion of gallbladder carcinoma. The resected gallbladder showed a localized thickening of the gallbladder wall with a polypoid lesion measuring 12x7 mm in diameter. Microscopically, the polypoid lesion proved to be a well-differentiated adenocarcinoma composed of columnar cells with a clear cytoplasm. In the thickened gallbladder wall, well-formed glands were extensively distributed; they were surrounded by a slightly desmoplastic reaction instead of lamina propria, or were directly in contact with smooth muscle cells. The diagnostic criteria for cervical MDA may be useful in distinguishing well-differentiated adenocarcinoma of the gallbladder from benign conditions, such as Rokitansky-Aschoff sinus and adenomyomatosis. It is remarkable that the tumor cells of the present case expressed gastric type mucin which is characteristic of mucinous type cervical MDA.

Adenocarcinoma↗

Vasitis nodosa: immunohistochemical findings--case report.

We report the immunohistochemical features of vasitis nodosa and discuss the differential diagnosis. The patient was a 42-year-old Japanese man with bilateral small indurations of the vas deferens at the site of a previous vasectomy. Microscopically, small-sized ducts proliferated within the muscular wall of the vas deferens, and focally in the surrounding connective tissue. Immunohistochemically, most proliferating glandular cells were strongly positive for cytokeratins 7, 19, and 34betaE12, and vimentin. Epithelial membrane antigen and Leu-M1 reacted against the luminal surface of the cells. Focally, glandular cells were also positive for CA125. Cytokeratin 20, carcinoembryonic antigen, and prostate-specific antigen were negative. We discuss the immunohistochemical differentiation of vasitis nodosa from prostatic adenocarcinoma, adenocarcinoma of the rete testis, and adenomatoid tumor.

Adult↗

Teratocarcinosarcoma of the nasal cavity. Report of a case showing favorable prognosis.

We report a very rare case of teratocarcinosarcoma of the nasal cavity showing a favorable prognosis. The patient was a 66-year-old man with a mass completely obstructing the right nasal cavity. Subsequently, extirpation of the mass and Denker-Watsuji operation were performed, and the patient was treated with a combination of radiation therapy and chemotherapy. Neither recurrence nor distant metastasis was observed during follow-up lasting 30 months. Histologic examination of the resected mass revealed several tissue elements including columnar and squamous epithelia with atypia, smooth muscle cells with rare mitotic activity, and neuroectodermal tissue. The glandular epithelium and smooth muscle cells were reminiscent of a primitive intestinal organoid structure, suggestive of teratomatous tumorigenesis. Our case and a review of the literature indicate that the absence of invasiveness to the stroma or surrounding tissue is closely related to a favorable prognosis.

Aged↗