Nobuyuki Hiruta

Malignant glomus tumor: a case report and review of the literature.

This report concerns a malignant glomus tumor, a rare soft tissue tumor that was examined immunohistochemically and ultrastructurally. It occurred in a 44-year-old male patient who had suffered from dull pain and stiffness in the right thigh for 10 months. Radiographic examination revealed a well-defined osteolytic lesion in the diaphysis of the right femur. Hypervascularity of the tumor was observed angiographically. Computed tomographic and magnetic resonance examinations showed an intramuscular mass invading the marrow space of the femur. Wide resection was performed after open biopsy. Histologically, round to polygonal tumor cells revealed a uniform appearance of round to ovoid nuclei with single large nucleoli and slightly eosinophilic cytoplasm, forming solid sheets of cells interrupted by vessels of varying size. A few mitotic figures and vascular invasion were observed. Immunohistochemically, vimentin and alpha-smooth muscle actin were stained intensely, and muscle actin was positive for tumor cells of the perivascular area. Tumor cells were negative for desmin, factor VIII-related antigen, S-100 protein, neurofilament, cytokeratin, and epithelial membrane antigen. Ultrastructurally, tumor cells were characterized by many cytoplasmic processes, pinocytotic vesicles, plasmalemmal dense plaques, and scattered microfilaments in the cytoplasm. Few cell junctions and focal basement membrane-like structures were observed. No recurrence or metastasis was noted 57 months after operation. This case was considered to be a malignant glomus tumor, that is, a glomangiosarcoma arising de novo.

Literature survey on epidemiology and pathology of gangliocytic paraganglioma

BackgroundAlthough gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications.MethodsWe searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case.Results192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors.ConclusionsOur literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.

Pulmonary tumor thrombotic microangiopathy induced by gastric carcinoma: Morphometric and immunohistochemical analysis of six autopsy cases

BackgroundPulmonary tumor thrombotic microangiopathy (PTTM) has been known as a rare and serious cancer-related pulmonary complication. However, the pathogenesis and pathophysiology of this debilitating condition still remains obscure and no effective management was recommended. The present study aims to elucidate the pathophysiology of PTTM.MethodsAutopsy records were searched to extract cases of pulmonary tumor embolism induced by metastasis of gastric carcinoma in the Toho University Omori Medical Center from 2000 to 2006. And then, tissue sections of extracted cases were prepared for not only light microscopic observation but morphometric analysis with the use of selected PTTM cases.ResultsSix autopsies involved PTTM and clinicopathological data of them were summarized. There was a significant negative association between pulmonary arterial diameter and stenosis rate in four cases. Although all cases showed an increase of stenosis rate to some degree, the degree of stenosis rate varied from case to case. Significant differences were found for average stenosis rate between the under 100 micrometer group or the 100 to 300 micrometer group and the 300 micrometer group in four cases. However, no significant differences were found for average stenosis rate between the under 100 micrometer group and the 100 to 300 micrometer group in all cases. Meanwhile, all cases showed positive reactivity for tissue factor (TF), five showed positive reactivity for vascular endothelial growth factor (VEGF), and three showed positive reactivity for osteopontin (OPN).ConclusionsIn the present study, we revealed that the degree of luminal narrowing of the pulmonary arteries varied from case to case, and our results suggested that pulmonary hypertension in PTTM occurs in selected cases which have a widespread pulmonary lesion with severe luminal narrowing in the smaller arteries. Furthermore, our immunohistochemical examination indicated that gastric carcinoma indicating PTTM shows a higher TF-positive rate than typical gastric carcinoma. However, it remains still obscuring whether gastric carcinoma indicating PTTM shows a higher VEGF or OPN-positive rate as determined by immunohistochemistry.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9204869075191730.

True Malignant Mixed Tumor of the Submandibular Gland

A case of true malignant mixed tumor of the submandibular gland is reported. The submandibular tumor, occurring in a 52‐year‐old man, started to grow rapidly after a long history without any change in size. Surgical resection was carried out and the resected tumor measured 5.5 cm with a cut surface showing mixed solid structures. Microscopically, the tumor had both carcinomatous and sarcomatous elements, the former consisting of poorly differentiated adenocarcinoma with squamous cell differentiation and the latter consisting of osteosarcoma with chondrosarcomatous and fibrosarcomatous elements. A remnant of benign pleomorphic adenoma could also be identified. Immunohistochemical study demonstrated keratin and epithelial membrane antigen in the carcinoma cells and vimentin in all elements of the osteosarcoma. It is assumed from these clinical and histological findings that the tumor had transformed from a pre‐existing benign pleomorphic adenoma. Acta Pathol Jpn 40: 137–142, 1990.

Kawasaki Disease as a Systemic Vasculitis in Childhood

Kawasaki disease is a disease of unknown etiology that most frequently affects infants and children under 5 years of age. Inflammation occurs in medium-sized muscular arteries throughout the body including the coronary artery, being classified as a systemic vasculitis syndrome. Histopathological investigations of Kawasaki disease have mainly focused on the coronary artery because it is directly associated with the cause of death. However, to identify the cause and pathology of Kawasaki disease, it is necessary to investigate lesions of whole organs. Thus, we attempted to review lesions in organs other than the heart and hypotheses of pathogenesis recently attracting attention.

Localization of Oxidized Low-Density Lipoprotein and Its Relation to Plaque Morphology in Human Coronary Artery

Objectives Oxidized low-density lipoprotein (oxLDL) plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. Methods Evans blue dye (EB) elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM) using EB as a biomarker. Results (1) By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05) higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2) By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. Conclusion Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

Identification of Fusarium Species in Formalin-Fixed and Paraffin-Embedded Sections by In Situ Hybridization Using Peptide Nucleic Acid Probes

ABSTRACT Fusarium has recently emerged as an opportunistic pathogen of humans, but the histological differentiation of Fusarium from Aspergillus and Scedosporium is particularly difficult because these fungi may induce similar clinical features and exhibit filamentous development in host tissues. Thus, there is a need to establish rapid and reliable methods that are applicable to pathological diagnoses. The aim of this study was to evaluate and establish in situ hybridization (ISH) using peptide nucleic acid (PNA) probes targeting the 28S rRNA to identify Fusarium species in tissue sections. This technique was validated using both formalin-fixed and paraffin-embedded pulmonary tissues from mice infected with seven different species of fungi and cell blocks from fungal cultures of 30 strains. As a result, strong positive signals were observed within fungal organisms present in tissues of the lung from mice infected with Fusarium solani. Furthermore, this probe reacted strongly with both F. solani and Fusarium oxysporum in sections from cell blocks. Although some cross-reactivity occurred with the Pseudallescheria boydii in sections from cell blocks, the signal intensity was low and most hyphae were not reactive. In conclusion, it was confirmed that ISH with PNA probes is accurate and is a valuable tool for identifying Fusarium spp. among organisms that have identical morphological features in formalin-fixed and paraffin-embedded sections.

Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma

The human glycine-N-acyltransferase (hGLYAT) gene and two related-genes (GLYATL1 and GLYATL2) were isolated. Human GLYAT, GLYATL1, and GLYATL2 cDNAs were isolated and shown to encode polypeptides of 295, 302, and 294 amino acids, respectively. GLYAT catalyzes glycine-N-acyltransfer reaction with benzoyl-CoA acting as a typical aralkyl transferase, while GLYATL1 catalyzed glutamine-N-acyltransfer reaction with phenylacetyl-CoA as an arylacetyl transferase. GLYAT was shown to be expressed specifically in the liver and kidney, and the cellular localization of GLYAT protein was restricted to the mitochondria. Interestingly, labeling using highly affinity purified anti-GLYAT antibody revealed that GLYAT expression was suppressed in all hepatocellular carcinomas, but not in other liver diseases. hGLYAT repression in cancerous cells in the liver was controlled at the transcriptional level. hGLYAT is a good candidate as a novel marker of hepatocellular carcinoma and may be a key molecule in the transition between differentiation and carcinogenesis of liver cells.

Molecular Imaging of Low-density Lipoprotein in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy

Objectives Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall. Methods (1) The fluorescence characteristic of LDL was investigated by color fluorescent microscopy (CFM) with excitation at 470-nm and emission at 515-nm using Nile blue dye (NB) as a biomarker. (2) Native LDL in 40 normal segments, 42 white plaques and 35 yellow plaques (20 with necrotic core) of human coronary arteries was investigated by color fluorescent angioscopy (CFA) and CFM. Results (1) NB elicited a brown, golden and red fluorescence characteristic of LDL, apolipoprotein B-100, and lysophosphatidylcholine/triglyceride, respectively. (2) The % incidence of LDL in normal segments, white, and yellow plaques was 25, 38 and 14 by CFA and 42, 42 and 14 by CFM scan of their luminal surface, respectively, indicating lower incidence (p<0.05) of LDL in yellow plaques than white plaques, and no significant differences in detection sensitivity between CFA and CFM. By CFM transected surface scan, LDL deposited more frequently and more diffusely in white plaques and yellow plaques without necrotic core (NC) than normal segments and yellow plaques with NC. LDL was localized to fibrous cap in yellow plaques with NC. Co-deposition of LDL with other lipid components was observed frequently in white plaques and yellow plaques without NC. Conclusions (1) Taken into consideration of the well-known process of coronary plaque growth, the results of the present study suggest that LDL begins to deposit before plaque formation; increasingly deposits with plaque growth, often co-depositing with other lipid components; and disappears after necrotic core formation. (2) CFA is feasible for visualization of LDL in human coronary artery wall.

Primary leiomyosarcoma of bone. A case report and review of the literature.

A 62‐year‐old female with primary leiomyosarcoma of the left femur is reported with a review of 21 cases reported in the literature. The resected specimen showed that the tumor extended from the femoral head to the diaphysis for 13cm in length. The tumor showed mainly intramedullary proliferation, but extraosseous growth was also noted at the great trochanter. Microscopic examination revealed well differentiated leiomyosarcoma characterized by interlacing bundles of fusiform cells with eosinophilic cytoplasm and rod‐shaped hyperchromatic nuclei. PAP stain of actin on the tumor cells was positive. On electron microscopy, microfilament of 6–8 nm in diameter, dense bodies, plnocytotic vesicles, marginal attachment plate, and basal lamina were noted. The patient died with pulmonary metastasis, 1 year and 7 months after the operation. An autopsy showed metastases in the right pelvic cavity and bilateral lungs, and confirmed the primary site to be the left femur.