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Many risk factors for coronary arterial diseases have been reported. Lipoprotein lipase (LPL) mass in serum has been suggested to be a new risk factor, but remains to be proven. The cardio-ankle vascular index (CAVI) was developed as a new arterial stiffness index and is considered to be a surrogate marker of arteriosclerosis. The purpose of this study was to establish the role of LPL mass in arteriosclerosis by examining the relationship between LPL mass and CAVI in patients with arteriosclerotic risk factors. We studied 216 patients who attended our diabetic center with diagnoses of diabetes, hypertension and/or dyslipidemia. CAVI was measured using VaSera1500 (Fukuda Denshi, Tokyo). Serum level of LPL mass was measured by ELISA(Sekisui Co. Ltd.). When the subjects were divided by a CAVI cutoff level of 9.0, the glucose level, glycohemoglobin A1c (HbA1c) level and systolic blood pressure level were significantly higher in the over 9.0 individuals than in the under 9.0 individuals (p0.05). CAVI level was significantly higher in patients with hyperglycemia and hypertension. LPL mass was lower in subjects with higher CAVI than in those with lower CAVI. CAVI level correlated inversely with LPL mass. CAVI adjusted for the age was associated significantly with LPL mass. These results suggest that decreased LPL mass may be a risk marker for arteriosclerosis as indicated by the surrogate marker CAVI.

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

Background: Capillary tube formation is essential for angiogenesis. It was previously thought that capillary tubes are formed through self-division of pre-existing endothelial cells (ECs) or folding of EC-progenitor cells. We found that circulating mononuclear cells that express β-actin (β-MNCs), participate in arteriogenesis, (formation of arterioles and arteries, and their growth) but it remained obscure whether and how they participate in capillary tube formation. Methods: We induced acute myocardial infarction in beagles, and examined the process of capillary tube formation by β-MNCs in the infarcted myocardium. Results: β-MNCs were recruited to coronary vessels, in particular to capillaries, in the border zone of infarcted myocardium. β-MNC nuclei were either round or flat, indicating existence of several species of β-MNCs. They sprouted out from a pre-existing coronary arteriole, capillary or venule into the interstitial space, and adhered to each other in tandem. An intracellular cavity was formed by the loss of granular cytoplasm in each cell. The intercellular junctions which connected cell-to-cell disappeared, and the cavities connected with each other to form a capillary tube. New β-MNCs moved to the distal end of the tube and migrated outside to extend the capillary tube. ECs of the capillary tubes thus formed possessed CD31, a marker for EC, but not β-actin. Their nuclei were either round or flat, indicating existence of two different capillary tubes. Conclusions: Coronary capillary tube formation in the ischemic myocardium is initiated by β-MNCs, not by their folding but by intracellular cavity formation through the loss of their granular cytoplasm and consequent tube formation by cavity-to-cavity connection.

Glistening yellow coronary plaques (GY) seen on angioscopy are considered vulnerable to disruption. Collagen fiber (CF) is the main substance that protects coronary plaques against mechanical stress. Therefore, whether angioscopically defined vulnerable plaques correlate with those defined histologically was investigated.One hundred and thirty-two excised human coronary plaques were classified by angioscopy into 19 GY, 49 non-glistening yellow plaques (non-GY) and 64 white plaques, and their relation to CF density was examined. CF-dense (15/100 µm), CF-loose (5 and15/100 µm), and CF-scanty (5/100 µm) plaques were hypothesized to be stable, relatively stable, and vulnerable, respectively. Histologically the plaques were classified into non-lipid deposition, superficial lipid deposition and diffuse lipid deposition groups; the diffuse lipid deposition group was classified into necrotic core (NC) and non-NC types. Nineteen GY were composed of 4 with superficial lipid deposition, 4 with non-NC type of diffuse lipid deposition, and 11 with NC type. Sixteen (84%) of these were CF scanty. Forty-nine (100%) of non-GY and 57 (89%) of white plaques were CF dense or CF loose The sensitivity, specificity and predictive value of GY in detecting histologically vulnerable plaques were 90%, 97% and 84%, respectively, indicating that GY represented histologically vulnerable plaques.These pathohistological characteristics might indicate that GY, less-protected plaques against mechanical stress, are vulnerable plaques.

Background Although 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. Methods We 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. Results 192 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. Conclusions Our 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.

Primary cardiac synovial sarcoma is a rare disease. A 51-year-old man visited our hospital with the chief complaint of palpitations and shortness of breath while exercising. Copious bloody pericardial effusion and a multicystic intrapericardial tumor were detected. A primary cardiac malignant tumor was suspected, an open-chest tumor resection was performed with the objectives of diagnosis and treatment. Histologically, the tumor cells were uniformly spindle-shaped with an ovoid or oval nucleus, they had proliferated in fascicular fashion. In addition myxoid degeneration, a hemangiopericytomatous vascular pattern and pseudorosette formation were seen in some areas of the tumor. Based on the histopathological and immunohistochemical findings and reverse transcription polymerase chain reaction detection of SS18-SSX1 fusion transcripts, a monophasic fibrous type synovial sarcoma was diagnosed. Postoperative radiation therapy was administered and there had been no recurrence 9 months after the surgery.

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.

Although there are a number of studies on vasospastic angina, the structural changes at the cellular level that occur in the coronary arterial wall during spasm are not well known. Coronary spasm was induced by brushing the coronary adventitia in nine anesthetized beagles, and structural changes in the spastic coronary segments were examined by light and electron microscopy, making comparisons with the adjacent nonspastic segments. The % diameter stenosis of the spastic segments as measured angiographically was 79.4 ± 12% (mean ± SD). Light microscopic changes in the spastic and nonspastic segments were as follows: medial thickness 1,512 vs. 392 μm ( P < 0.0001) and % diameter and % area stenoses of spastic segment 81.0% and 96.5%, respectively, indicating that spasm was induced by medial thickening. Circular smooth muscle cells (SMCs) in the media were arranged in parallel with the internal (IEL) and external (EEL) elastic lamina in nonspastic segments but radially rearranged in spastic segments. SMCs were classified by their patterns of connection to IEL into six types by electron microscopy. Of these, three contracted and pulled the IEL toward the EEL, causing folding of the IEL and waving of EEL resulting in thickening of the media and narrowing of the lumen. We conclude that coronary spasm was elicited by radial rearrangement of the medial SMCs due to their own contraction and resultant medial thickening and folding of IEL, creating a piston effect to narrow the lumen, i.e., spasm.

We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis.

最近我々の経験した肺原発悪性線維性組織球腫 (MFH) 4例について臨床病理学的検討を行った. 全例男性で高喫煙歴があった. 全例赤沈が亢進し, 血清鉄が低値を示した. 腫瘍マーカーでは, フェリチン, 免疫抑制酸性蛋白 (IAP) が高値を示した. 放射線治療を行った症例ではフェリチン, IAPが治療効果と関連して変動を示した. 2症例で白血球増多がみられ, サイトカインとの関連が示唆された. 術前の生検診断に際しては免疫組織化学染色が有用であり3例中2例でMFHと診断し得た. 予後は極めて不良で外科療法, 化学療法, 放射線療法にもかかわらず全例診断後1年以内に死亡した. 剖検では, 全例局所再発もしくは遠隔転移を認めた. 今後の集学的治療の確立が課題であろう.

A case of mucoepidermoid carcinoma of the larynx is reported. The patient was a 63-year-old man who had suffered from sore throat for nine months. By physical examination, swelling in the right epiglottis and arytenoid was noted. Histopathological findings of the specimen showed a mucoepidermoid carcinoma (low grade malignancy). The patient had chemotherapy and radiotherapy. Among malignant tumors of the larynx, mucoepidermoid carcinoma seemed to be extremely rare. Only seven cases of the laryngeal mucoepidermoid carcinoma including this case have been reported in our country. A pertinent literature was reviewed in this paper.

Remnant lipoprotein can be measured by immunoseparation assay and polyacrylamide gel disc electrophoresis; however, these methods have some problems, such as a lack of specificity and being technically complicated. Recently, a new method, the remnant lipoprotein cholesterol homogeneous assay(RemL-C), has been established. In this study, we evaluated the basal performance of RemL-C assay. One hundred and fifty patients with diabetes mellitus were enrolled in this study. RemL-C level was higher in the midband (+) group than in the midband (-) group (p0.01), and a strong correlation was observed between RemL-C level and remnant lipoprotein level measured by conventional method (r=0.89, p0.01). RemL-C level correlated positively with triglyceride(TG) (r=0.94, p0.01) and total cholesterol(TC) (r=0.39, p0.01), negatively with high density lipoprotein(HDL-C) (r=-0.35, p0.01) and positively with apolipoprotein (apo) CII, and apoE (apoCII: r=0.59, p0.01, apoE: r=0.71, p0.01). In particular, RemL-C level correlated strongly with TG and apoE. RemL-C level was significantly higher in patients with combined hyperlipidemia compared to patients with other hyperlipidemias (p0.01). When the serum of a patient with combined hyperlipidemia was separated by sepharose 4B gel filtration, the fraction showing peak RemL-C level was observed between the fraction corresponding to VLDL and the fraction corresponding to LDL. Furthermore, the peak of RemL-C corresponded to the peak of apoE. Moreover RemL-C level correlated negatively with preheparin serum lipoprotein lipase mass that is a marker of metabolic syndrome (r=-0.30, p0.01). These results suggest that the measurement of remnant lipoprotein by RemL-C assay reflects the quantity of intermediate-density lipoprotein. Since RemL-C measurement can be run on an automated clinical analyzer permitting quick and high throughput measurement, RemL-C levels may be useful in the screening of hyperlipidemia.

A rare case of α-fetoprotein (AFP) producing gastric tumor histologially resembling embryonal carcinoma is reported with a review of the literature. A 59-year-old male with an elevated serum AFP level (2651ng/ml) underwent palliative gastrectomy with transverse colectomy for an advanced gastric tumor. Histological examinations revealed that the tumor was largely composed of embryonal carcinoma including yolk sac elements. Production of AFP in the tumor was demonstrated by immunohistochemical technique (peroxidase-antiperoxidase method) and radioimmunoassay. Postoperative combination chemotherapy with cis-platinum, vinblastine and peplomycin resulted in a rapid decrease of serum AFP level but the patient died of severe leukopenia accompanied by intestinal obstruction two months after surgery.

Almost the entire malignant tumors arising in the larynx are the laryngeal carcinoma. Laryngeal carcinosarcoma, in which carcinoma (epithelial malignant tumor) coexists with sarcoma (interstitial malignant tumor) in the same organ, is rarely found.In this report, we described a recent case of carcinosarcoma arising in the epiglottis of a 74-year-old man who visited our hospital with a complaint of nocturnal dyspnea. We discussed the its clinical feature, pathological findings, and the treatment as well as a review of the literature of this disease.The carcinosarcoma in this case was extremely rare and it was comprised of squamous cell carcinoma, adenocarcinoma and sarcoma component which could be confirmed immunohistochemically.This carcinosarcoma was considered to be a true carcinosarcoma.

A 33-year-old male patient with Down syndrome, who stayed in a welfare institution, visited our hospital due to left testicular enlargement. He was diagnosed as having a left testicular tumor and underwent radical inguinal orchiectomy. Preoperatively, serum level of beta-human chorionic gonadotrophin (β-HCG) increased to 0.9 ng/mL (normal range

A 54-year-old male visited a local physician with right dorsolumbar pain as the chief complaint. Ultrasonography revealed a tumor mass 13 cm in diameter at the lower part of the liver, and the patient was referred to our hospital. On abdominal computed tomography, uneven contrast-enhanced effects were recognized in the tumor. On magnetic rescmance imaging studies, T1-weighted images showed a hypoechoic pattern from the kidney and a weak hyperechoic pattern from the muscle. T2-weighted images showed uneven hyperecoic patterns. Uneven contrast-enhanced effects were recognized inside and on the margin of the tumor. A diagnosis of retroperitoneal tumor was made, and surgery was performed. Histopathological examination revealed a fascicular alignment of spindle cells in the area in which the myxoid matrix is seen. On the immunological special test, only vimentin was positive, which led to the diagnosis of fibrosarcoma. Fibrosarcoma originating from retroperitoneal tumor is relatively rare.

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.

Background Leiomyosarcoma occurring as a primary cardiac tumor has been known as an extremely rare condition. Previous studies of leiomyosarcoma with rhabdomyoblastic differentiation have conducted to those arisen from another site, and they indicated a poorer prognosis of this tumor. Case presentation A 69-year-old woman was referred to our hospital for an operation concerning umbilical hernia. Subsequent imaging examinations before an operation indicated the presence of primary cardiac malignant tumor due to its atypical shape. And then, it was surgically removed. Histopathologically, tumor cells consisted of two different types: spindle and polyhedral cells. Immunohistochemically, it is interesting to note that 2.1% of spindle cells and 23.1% of polyhedral cells showed positive reactivity for myogenin. Furthermore, we performed double-immunostaining for alpha-smooth muscle actin (SMA) and myogenin. The rates of alpha-SMA and myogenin double negative, alpha-SMA single positive, myogenin single positive, and alpha-SMA and myogenin double positive in spindle cells were estimated as 69.1%, 28.8%, 1.1% and 1.0%, respectively. In contrast, the rates in polyhedral cells were estimated as 76.9%, 0.0%, 23.1%, and 0.0%, respectively. Conclusion Our immunohistochemical evaluation suggested that rhabdomyoblastic differentiation in leiomyosarcoma might be generated not only by de novo generation from mesenchymal cells. To the best of our knowledge, this is the first case of primary cardiac leiomyosarcoma with partial rhabdomyoblastic differentiation.

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.

Pathological diagnosis, plays a very crucial role in cancer examination. However, because of the shortage of pathologists, increasing working burden has been imposed on pathologists. Aiming to reduce pathologist's burden and improve the reliability of cancer diagnosis, an innovative cancer detection method for pathological images and its extended approach for advanced ability is presented in this paper. The experiments demonstrate the effectiveness of the proposed method in cancer detection and cancer location estimation.

Background Pulmonary 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. Methods Autopsy 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. Results Six 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). Conclusions In 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 Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9204869075191730.