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A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

A 68-year-old man with a history of diabetes mellitus was admitted to our hospital with a diagnosis of acute pancreatitis. Abdominal computed tomography revealed a suspicious tumor in the body of the pancreas, along with a dilated main pancreatic duct and edema of the pancreatic tail. Endoscopic retrograde pancreatography was performed after treating the patient's pancreatitis. When a cannula tip was advanced beyond the stenosis, deep into the distal pancreatic duct, thick white pus was evacuated. A bacteriological examination of the aspirated pancreatic juice revealed Enterobacter cloacae, and a cytological examination revealed adenocarcinoma. The diagnosis was acute obstructive suppurative pancreatic ductitis associated with pancreatic carcinoma.

A 71-year-old woman with idiopathic thrombocytopenic purpura (ITP), who had been treated with steroid and cyclosporine, was admitted in an emergency with fever and dyspnea. The diagnosis was mitral regurgitation due ton infective endocarditis. Although she received treatments for infection and cardiac failure, the cardiac failure could not be controlled. After high-dose γ-globulin therapy, an emergency operation was performed during the active phase of infective endocarditis. Rapid platelet transfusion was administered after weaning from extracorporeal circulation. She recovered and was discharged without postoperative bleeding and re-infection.The treatment course of elective cardiac surgery complicated with ITP has been established, but the course of emergency surgery has not been established because of the small number of cases reported. Since few patients have undergone emergency surgery for active infective endocarditis, we had difficulty in deciding the time of surgery and treatment for increasing the number of platelets before surgery, it was considered that the case provided us with useful suggestion for the future treatment for urgent surgery complicated with ITP.

d Kanifukuoka-Kyodo Clinic, Fujimino, Japan Abstract Helicobacter pylori infection has been reported to be inversely associated with allergic disorders. We by chance experienced a patient with atrophic gastritis who presented marked elevations of both nonspecific serum immunoglobulin E and eosinophil counts after H. pylori eradication. A 49-year-old Japanese man received eradication of H. pylori using lansoprazole 60 mg/day, amoxicillin 1,500 mg/day, and clarithromycin 400 mg/day for 7 days. Serum immunoglobulin E increased to more than four times its pretreatment level, 306 ) 485 ) 1,325 U/ml, and peripheral eosinophil counts increased to more than three times, 99 ) 139 ) 298 per μl. Deducing from the current case, H. pylori eradication might develop allergic disorders in some patients.

A 63-year-old man revealed a four-month history of muscle weakness of the lower limbs, hypoesthesia of the L5 and S1 area and ischuria. On MRI, the spinal cord was compressed by an encircled mass, which showed hypointensity on T1- and T2-weighted images with gadolinium enhancement at the Th11 to Th12 vertebra. Because of the rapid progression of myelopathy, posterior decompression was performed and idiopathic hypertrophic spinal pachymeningitis (HSP) was finally diagnosed. The patient's neurological signs markedly improved with postoperative corticosteroid treatment. Idiopathic HSP is a clinical emergency and early surgical intervention is essential to prevent irreversible damage to the nervous system.

Purpose: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult ­tissues. However, survivin expression has been detected in various human cancers and ­correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expres­sion in osteosarcoma tissues and clinicopathological parameters. Methods: There were 22 osteosarcoma patients in our hospital with paraffin-embedded ­tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. Results: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p

Acinic cell carcinoma is a rare and low-grade malignant tumor of the parotid gland. We treated two acinic cell carcinomas of the parotid gland, each occurring in a young man (18 and 30 years old, respectively). Based on preoperative examination and MRI findings, we expected to find benign tumors, but they were revealed to be acinic cell carcinomas by the permanent pathological specimens. We performed partial parotidectomy in one case, and subtotal parotidectomy in the other, and preserved the facial nerve in both. There has been no metastasis or recurrence for two years after the operations, but we need to follow both patients for a long time.

Immunostaining of proliferating cell nuclear antigen (PCNA), which can be applied to routinely processed tissue sections, has extended the applications of cell kinetic studies. PCNA immunostaining intensity of cells varies among individual nuclei in tissue sections. To determine the changes in PCNA expression level during carcinogenesis, we employed an image analyzer to evaluate PCNA staining intensity in diisopropanolnitrosamine (DIPN) -induced neoplastic lesions of rat thyroid glands.In the normal thyroid gland, only small numbers of cells showed weak PCNA expression. The percentage of PCNA-positive cells increased during carcinogenesis, i. e. hyperplasia, adenoma, and then carcinoma. Analysis of PCNA staining intensity histograms revealed that the population of cells with stronger intensity increased during carcinogenesis, i. e. from adenoma to carcinoma. However, the percentage of cells with weak PCNA staining increased in hyperplasia, and did not change in intensity during further carcinogenic sequelae. These differences in PCNA expression level recognized by immunostaining intensity may reflect different cell kinetics between the process of hyperplasia and that of differentiation from adenoma to carcinoma.

To elucidate the nature and significance of calcium oxalate crystals in the pathologic thyroid, we used polarized light microscopy to review 357 thyroid lesions. Under polarized light, calcium oxalate crystals had brilliant birefringence, and they were invariably identified within the colloid of follicles. The highest prevalence of crystals (87.9%) was in nodular goiters; they were also found in 60.0% of follicular adenomas and 33.3% of follicular carcinomas. The prevalence of crystals in papillary carcinomas was very low (5.4%). Therefore, the overall prevalence was 69.4% in benign nodules and 7.6% in malignant nodules. A heavy deposit of crystals was seen only in benign nodules except for one case of follicular carcinoma. Graves' disease, focal thyroiditis, and subacute thyroiditis showed low prevalence: 25.0, 46.9, and 40.0%, respectively. In cases of toxic nodules, the crystals were sparsely identified within nodules, but abundantly observed in surrounding inactive tissues. Immunohistochemistry for thyroid hormones confirmed that the crystals tended to appear in inactive follicles. On tissue x-ray film, the crystals appeared as microcalcifications. As a result of these findings, we suggest that examinations of crystals are likely to be useful in the differential diagnosis of thyroid diseases and in possible estimations of the functional state of lesions.

Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 10⁹/l by 5-6 months, 1 year, 2 years and 3 years or more (from 24.2+/-5.6 to 23.1+/-5.0, 23.0+/-5.0, 22.1+/-4.5, 22.4+/-5.6, and 21.6+/-5.3 × 10⁹/l: p =0.0001,0.0001, 0.0001, 0.0052, and0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 10⁹/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.

A case of extraskeletal myxoid chondrosarcoma (ESMC), which developed in the right thigh of a middle-aged Japanese woman, was studied using immunohistochemistry, conventional electron microscopy, and the quick-freezing and deep-etching (QF-DE) method. In addition to typical light microscopic findings of ESMC, conventional electron microscopy indicated that the tumor cells had features of chondrocytes. Immunohistochemically, the tumor cells showed a positive immunoreaction for S100 protein. A diagnosis of ESMC was made. An interesting observation was the ultrastructural features of collagen fibrils in the myxoid matrix highlighted by the QF-DE method. These collagen fibrils consisted of relatively thin collagen (20-35 nm) with pleated surface structures. The surface striation at 65 nm was obscure. We consider that such a finding of collagen fibrils identified by the QF-DE method is one of the characteristics of the myxoid matrix of ESMC, and this is useful for the differential diagnosis of myxoid soft tissue tumors.

We herein describe the first reported case of duodenal stenosis caused by cystic dystrophy in heterotopic pancreas (CDHP) in Asia. A 63-year-old man was admitted to the hospital presenting with nausea and vomiting of 2 days' duration. Laboratory examinations showed an elevation in both the serum amylase level (275 IU/l) and white blood cell count (13 600/microl). A 3-cm-diameter tumor close against the duodenum was pointed out from the results of computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP); the tumor contained a cystic and solid component. Endoscopic examinations and an upper gastrointestinal series showed stenosis of the second portion of the duodenum without any mucosal change. The tumor was considered to be located at the submucosal layer of the second duodenum. The biopsy specimen of the duodenum revealed no malignancy. We strongly doubted the presence of a malignant submucosal tumor in the duodenum based on the findings of diagnostic imaging, and a pancreaticoduodenectomy was thus performed. Histopathologically, the lesion was diagnosed to be CDHP. The postoperative course was uneventful. The patient was symptomatic but was free of any symptoms after surgery. He continues to be regularly followed up on an outpatient basis and has had no recurrence of symptoms. This case demonstrates the need to consider CDHP in the differential diagnosis as a rare cause of duodenal stenosis.

A middle-aged Japanese woman visited the Orthopedics Department of Nihon University Nerima Hikarigaoka Hospital complaining of pain in the left hip joint that had started approximately 8 months earlier. Following several examinations, including imaging diagnoses, an incisional biopsy demonstrated a malignant acetabular bone tumor, which was removed and examined by a quick-freezing and deep-etching (QF-DE) method, conventional electron microscopy, and light microscopy. Histologically, the tumor was a chondrosarcoma with marked myxoid changes. An interesting extracellular matrix was observed by the QF-DE method. The myxoid area consisted of a fine meshwork of proteoglycans (PG) without obvious aggrecans, which resembled that of PG usually present in the pericellular matrix of normal cartilage. Thin collagen fibrils with pleated surface structures of regular periodicity were also seen, which were sparsely distributed in wide areas except for the pericellular matrix. These collagen fibrils were of the type that are mainly located in the pericellular side of the territorial matrix in normal cartilage. A myxoid matrix consisting of thin collagen fibrils on the background of pericellular type PG suggested that the myxoid matrix in the chondrosarcoma resembled those of the pericellular and pericellular sides of the territorial matrices in normal cartilage.

Purpose.Giant cell tumour of bone with pulmonary metastases is rare. However, some patients die of pulmonary metastases, and histological examination cannot distinguish between benign tumour and malignant metastases. In this study, we present clinical and immunohistochemical findings associated with giant cell tumour of bone with pulmonary metastases.Methods.Five patients with benign giant cell tumour of bone with pulmonary metastases (one man and 4 women) were studied. Patients' ages ranged between 20 and 23 years (mean age, 21.8 years). Tumours were in the distal femur in 2 cases, and in the proximal tibia, distal tibia, and lumbar spine in one case each. The tissue specimens from primary tumours, recurrent tumours, and pulmonary metastases were studied using immunohistochemical techniques.Results.Three of the 5 primary tumours were of the spontaneous regression or growth cessation type, or the continuously slow-growing type, showing 4.2% to 6.2% of positive cells for Ki-67 after immunohistochemical staining. However, 2 patients with the rapid-growing type of disease died of pulmonary metastases; their primary, recurrent, and metastatic tumour specimens contained 9.0% to 11.5% of positive cells for Ki-67.Conclusion.Three of the 5 primary tumours had a benign clinical pattern and immunohistochemistry. Two of the 5 patients died of pulmonary metastases, which had an aggressive clinical pattern and a high prevalence of positive cells in Ki-67. Examination of Ki-67 should be carried out for aggressive type of giant cell tumour.

The aim of the present work was to assess osteopontin (OPN) expression in the colon tissues of ulcerative colitis (UC), Crohn's disease (CD), and diverticulitis (Div) patients.This study included three groups: the UC group, CD group, and Div group. Immunohistochemical staining was performed, using an immunoperoxidase method.Regarding OPN expression in intestinal epithelial cells, no difference was noted among the three groups. However, in the submucosa of the UC group, the ratio of two types of large cells (oval and spindle-shaped) expressing OPN was 61.2 +/- 14.4% (mean +/- SD), which was significantly higher than that in the CD group (14.9 +/- 7.0%; P0.05) and that in the Div group (11.2 +/- 6.1%; P0.05). In addition, in the UC group, the ratio of these cells in the subserosa (50.1 +/- 15.0%; mean +/- SD) was significantly higher than that in the CD group (16.9 +/- 6.2%; P0.05) and that in the Div group (12.6 +/- 5.7%; P0.05). In a serial section study, the oval-shaped cells were stained for anti-CD 68, while the spindle-shaped cells were stained for anti-vimentin.OPN in two types of large colon-infiltrating cells is possibly related to one of the pathogenic factors of UC.

A squamous cell carcinoma (SCC) with sarcomatous features (so-called carcinosarcoma) of stomach is reported in a 72-year-old man. The gastric submucosal tumor (12 x 11 x 6 cm) consisted of carcinoma cells and sarcomatous spindle cells, which were immunohistochemically recognized to contain high molecular weight cytokeratin. These histological and immunohistochemical results indicated that carcinoma cells and spindle tumor cells had cytokeratin similar to that of stratified squamous epithelium. These features were consistent with so-called carcinosarcoma of esophagus. A combined type of tumor consisting of polypoid and shallow ulcerative lesions (5.5 cm in diameter) was demonstrated by the biopsy to have SCC on the polypoid surface area. Therefore, the gastric tumor was thought to have metastasized from the esophageal tumor. The quick-freezing and deep-etching (QF-DE) method demonstrated that many spindle tumor cells in the gastric tumor had abundant intermediate filaments, which were evenly distributed in more peripheral cytoplasm along the cell membrane. This feature was similar to that of the control SCC. Intramembranous protein particles in the cell membrane of the tumor cells were markedly decreased as compared with those of control SCC. These ultrastructures by QF-DE method could be used for the pathological diagnosis of so-called carcinosarcomas of esophagus.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is an angiogenic factor that plays important roles in tumor growth. Angiogenesis studies on VEGF deal with various types of malignant tumors, but very little is known about the role or significance of VEGF in human thyroid neoplasms. Therefore, in the current study, we determined whether VEGF is found in normal and neoplastic thyroids and whether its expression is altered in different histological types of thyroid neoplasms. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that all specimens of thyroid tumors expressed bands corresponding to 121-, 165-, and 189-amino acid forms of VEGF. Northern blot analysis showed an increase in VEGF mRNA levels in neoplastic tissues in comparison with normal thyroid samples. By nonisotopic in situ hybridization, most of the tumor cells in follicular adenomas expressed VEGF mRNA, whereas VEGF mRNA expression was identified only in epithelium of isolated follicles in normal thyroid tissues. In papillary thyroid carcinomas, an intense labeling with VEGF probe was often found in overlying tumor cells of neoplastic papillae. VEGF expression was distinctly intensified in undifferentiated carcinoma cells that were immediately adjacent to necrotic foci. The immunohistochemical localizations of VEGF protein were comparable to the localization of VEGF mRNA. In conclusion, our results suggest that the histological types of thyroid tumor may determine the vascular pattern through a paracrine mechanism involving VEGF.

A 57-year-old woman had a bronchial carcinoid tumor. Tc-99m MIBI SPECT showed accumulation both on early and delayed images, but there was no activity in the tumor on delayed Tl-201 SPECT. Histopathology and electron microscopy showed carcinoid tumor without oncocytic features. Early uptake and retention of sestamibi in the tumor might be related to the vascularity as well as increased mitochondrial potential.

To increase our understanding of the basic biological mechanisms of thyroid diseases, growth activity (GA) in 232 thyroid lesions was determined by immunohistochemistry using monoclonal antibody MIB-1. The GA tended to be higher in hyperplastic lesions, adenomatous goiter (MIB-1-positive cell rate, 0.73%), and Graves' disease (1.68%) than in normal tissue (0.19%). The GA for differentiated thyroid carcinomas (2.00%) was much lower than for adenocarcinomas of other organs, such as breast, lung, stomach and colon (44.67%). Of the thyroid carcinomas, the highest GA was observed in undifferentiated carcinomas (32.67%), and follicular carcinomas (3.18%) showed a higher GA than papillary carcinomas (1.83%). There was no significant difference between the GA of follicular carcinomas and solid/trabecular adenomas, although widely invasive follicular carcinomas showed a higher GA than minimally invasive carcinomas. No significant correlations between GA and patient age, sex, and tumor diameter, metastasis, or histological features were observed in papillary carcinomas. Familial medullary carcinomas showed a higher GA than sporadic tumors. All latent papillary carcinomas had a very low GA. Our findings suggest that immunohistochemical investigation using the antibody MIB-1 contributes to the understanding of growth characteristics and biological activities in thyroid diseases.

Basement membrane (BM) alteration in thyroid diseases was examined by immunohistochemistry using antibodies for the three major BM proteins: type IV collagen, laminin and heparan sulphate proteoglycan. Linear epithelial BMs surrounding follicles accompanied by vascular BMs forming loops, similar to those seen in the normal thyroid, were observed in Graves' disease and adenomatous goitre. Hashimoto's thyroiditis showed scant epithelial BMs as a result of follicle destruction. In follicular adenomas, development of epithelial BMs seemed to be related to follicle formation; well-developed epithelial BMs were frequently seen in normo- or large-follicular type, whereas trabecular or solid types revealed scant or poorly developed epithelial BMs. Lumpy accumulation of BM proteins was detected in hyalinizing trabecular adenomas. Papillary carcinomas revealed two different types of papillae; one type contained both epithelial and vascular BMs, and the other had only vascular BMs. Epithelial BMs in invasive areas of papillary carcinoma were distributed in an irregular, interrupted manner, and were completely absent in many foci. Anaplastic carcinomas showed scant or a total loss of epithelial BMs. These results suggest that alterations of BM in thyroid diseases clearly reflect their architectural variations, presumably in connection with their function and/or biological behaviour.

Malignant pleomorphic adenoma arising in the trachea has not been reported in the literature. We report here a case of malignant pleomorphic adenoma (malignant mixed tumor) occurring in the trachea of a 65-year-old woman. The tumor metastasized to the lung and the chest wall 11 years after complete resection of the primary tumor, which was a polypoid submucosal tumor, 1.3 cm in diameter. Light microscopic examination of the primary and metastatic tumors showed the presence of epithelial and stromal elements, consisting of grandular structures, foci of squamous metaplasia and a myxochondroid stroma. Many tumor cells showed myoepithelial cell features by electron microscopy, and immunoreactivity for S-100 protein and GFAP was also seen in many of them. These findings were consistent with those of pleomorphic adenoma. However, the epithelial elements were cytologically atypical with prominent mitotic figures. Infiltration of the tumor cells into the surrounding soft tissue was also seen. No foci of benign pleomorphic adenoma were found in the primary tumor. These findings indicate that this tumor was not a carcinoma ex pleomorphic adenoma, but a true malignant pleomorphic adenoma (true malignant mixed tumor) of the trachea.