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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.

Pineal anlage tumor (PAT) is a rare subtype of pineoblastoma (PB), which shows a poor prognosis. We report a case of a 5-year-old boy with PB with a rhabdomyoblastic component. He presented at a local clinic with vomiting and was transferred to our hospital following discovery of a pineal mass. An endoscopic biopsy was performed and was diagnosed as a PB with a rhabdomyoblastic component. Histopathology of PAT is characterized by both neuroectodermal and ectomesenchymal differentiation, and only a few confirmed cases have been reported. Although the histopathological features of the reported case resembled that of PAT, the ectomesenchymal component in the presented case was only a rhabdomyoblastic one. Therefore, we have diagnosed this case as PB with a rhabdomyoblastic component. As PAT is a rare pineal tumor, clinical, histopathological and genetic evaluation of additional cases is needed to define the characteristics of PAT as one of the pineal gland tumors.

The present study aimed to examine the changes induced in proximal tubules by renal congestion using the in vivo cryotechnique (IVCT). Twelve male Wistar rats were divided into four equal groups: group 1 (the control); groups 2 and 3, which were subjected to 2 and 5 min of congestion, respectively; and group 4, which was subjected to 5 min of congestion followed by 10 min of recirculation. Under anesthesia, renal congestion was induced in the bilateral kidneys by ligating the inferior vena cava just above the branching renal veins. The left kidneys, which were subjected to the IVCT, were then compared with the right kidneys, which underwent a conventional fixation method. Among the left kidneys, the proximal tubules in group 1 consisted of cuboidal cells and had open lumina. In the congestive groups, the diameters of the proximal tubules were increased, and their lumina were obstructed by swollen cells and ischemia-associated cell debris. In group 4, the proximal tubules were still dilated, as seen in the congestive groups; however, the swollen cells had recovered their cuboidal form, and the cell debris had disappeared from the tubules' lumina. The present study demonstrated the in vivo morphology of proximal tubules in living rats subjected to congestion, which was unclear using conventional fixation methods.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. To identify potential effective therapeutic drugs for PDAC, we established a screening system based on spheroid formation using 170#3 mouse PDAC cells with or without fibroblasts. We found that indirubin 3′-oxime (Indox) and 5-methoxyindirubin 3′-oxime (5MeOIndox) inhibited PDAC cell proliferation. Furthermore, PDAC xenograft growth was also inhibited in BALB/c nu/nu mice after administration of Indox and 5MeOIndox. Both phosphorylated CDK1 and cyclin B1 levels in 170#3 cells were significantly reduced by treatment with Indox and 5MeOIndox in vitro and in vivo. Cell cycle analysis revealed that 5MeOIndox, but not Indox, induced G2/M arrest. Annexin V–propidium iodide double-staining analysis demonstrated that Indox induced abundant non-apoptotic cell death of 170#3 cells, while 5MeOIndox predominantly induced early apoptosis, indicating that the cytotoxicity of 5MeOIndox is lower than that of Indox. These results suggest that one mechanism of 5MeOIndox is to induce G2/M arrest of PDAC cells via inhibition of CDK1/cyclin B1 levels, thereby leading to apoptosis. Our findings suggest 5MeOIndox as a potential useful anticancer agent in PDAC.

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.

The "in vivo cryotechnique" (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and "cryobiopsy" (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi-IIc at the BBM, being controlled by a different mechanism. In this method, the PTH-induced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level.

71歳，男性．平成6年6月に直腸癌のため腹会陰式直腸切断術を受けている．術後再発徴候は無く，定期検診を続けていた．平成17年7月頃より人工肛門部からの出血が度々認められ，平成18年4月には，同部位に顆粒状の粘膜異常を伴う1.5cm大の粘膜下腫瘤を認めるようになったため，平成18年5月に腫瘍摘出術を施行した．病理組織学的診断では粘膜下に高度の炎症細胞浸潤を認め，結節状の腫瘤を形成していた．腫瘍性変化は認めず，炎症性偽腫瘍と診断した．直腸癌術後から隔日で洗腸を続けていたことが，炎症性偽腫瘍の原因になったと推察された．大腸原発の炎症性偽腫瘍では稀であり，人工肛門部での発症例はこれまでに報告がない．

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.

A poorly differentiated leiomyosarcoma of the stomach in a 41-year-old woman is reported. The diagnosis was confirmed by the diffuse immunohistochemical reaction to HHF35, and the presence of focal density and caveolas in some of the tumour cells by conventional electron microscopy. Immunohistochemically, most tumour cells had an undifferentiated nature, in which negative immunostaining for desmin, alpha-smooth muscle actin, and type IV collagen, and positive immunostaining for vimentin were observed. By the quick-freezing and deep-etching (QF-DE) method, these tumour cells revealed the loss of bundled actin and myosin filaments, which constitute desmin associated structures (focal densities and dense patchy areas). Their cytoplasm had many mitochondria and other cell organelles. The intermediate filaments (IFs), which were determined to be vimentin by immunohistochemistry, were observed in the inter-organellar spaces, and connected with these cell organelles. Actin filaments formed a meshwork structure and were distributed mainly in subplasmalemmal regions. Although a basal lamina was not detected by conventional electron microscopy, basal lamina-like structures, an association between the extracellular matrices and the cell membrane, were observed. Using the QF-DE method, three dimensional ultrastructural alterations of the cytoskeleton and extracellular matrix of the leiomyosarcoma were observed.

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.

Invasive pulmonary aspergillosis (IPA) is an important and fatal complication in the patients with neutropenic or immunosuppressed condition. In spite of intensive treatment with anti-fungal drugs, the prognosis of the patients who have been suffered from IPA is extremely poor. This case was an 85-year-old Japanese man who was diagnosed as idiopathic thrombocytopenic purpura (ITP). He underwent high-dose corticosteroids and gamma-globulin therapy. During the hospitalization, he complained respiratory symptoms, and the abnormal shadow suggesting pulmonary infiltration and cavitation was pointed out on chest imaging. He was diagnosed as IPA because of high level of serum beta-D-glucan and positive for aspergillus antigen. Although he underwent intensive care with anti-fungal drug administration and artificial respiration, he died of respiratory distress on the 68th hospitalization. Postmortem examination disclosed severe bronchopneumonia, cavitation and pulmonary arterial thrombi in both lungs. Histological examination showed widely distributed epitheloid cell granulomata with central necrosis containing aspergillus hyphae, and vasodestructive growth of fungus with occasional organized thrombi.

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.

Cytokeratin distribution in the collecting tubules (CTs) of the rat kidney was studied by immunohistochemistry and scanning electron microscopy (SEM). After preparation of sections from formalin-fixed, paraffin-embedded tissue for immunohistochemistry, the remaining tissue was prepared for SEM. The cut surfaces of the tissue were examined by SEM and compared with sections stained with anti cytokeratin antibody. The immunostained sections revealed positive staining along the entire CTs. However, in addition to diffusely stained cells, unstained and partially stained cells were seen. The latter were not distributed in inner medullary CTs, whereas the diffusely stained cells were observed in cortical, outer medullary and inner medullary CTs. This immunohistochemical heterogeneity of cytokeratin reactivity was prominent in the outer medullary and cortical CTs. From this comparative study of immunostained sections and SEM specimens, it was concluded that the hetero-geneously stained cells correspond to intercalated cells, whereas the diffusely stained cells represent most principal cells. These results suggest that the difference in cytokeratin density among CT cells may represent different functional states, at least in intercalated cells.

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.

The adequate treatment for patients with thrombocytopenia, encephalopathy, ascites and esophagogastric varices due to portal hypertension are very important. This review explains the relations between heavy drinkers and symptoms of portal hypertension, especially with regard to the form of esophageal varices. Between heavy drinker and non-heavy drinker, there was no significant differences for form, color and red color sign of varices. In heavy drinker, the ratio of strong red color sign might be higher than non-heavy drinker. Value of portal pressure in heavy drinker might be higher. These results can bring sudden variceal bleeding in heavy drinkers.

Hepatic resection is the first choice of treatment for hepatocellular carcinoma (HCC), and has the best results among the therapeutic options. Preoperative evaluation of liver function in patients and perioperative management for patients, to prevent postoperative complications, are very important. Postoperative pulmonary complications, including pneumonia and atelectasis, were frequently shown in patients who had past history of heavy alcohol-intake. Postoperative pulmonary complications in heavy drinkers were associated with their habit of smoking. Temperance and non-smoking should be required, when hepatectomy will be performed for heavy drinker.

A case of elastofibroma in a middle-aged Japanese woman was examined by the quick-freezing and deep-etching (QF-DE) method, as well as by immunohistochemistry and conventional electron microscopy. The slowly growing tumor developed at the right scapular region and was composed of fibrous connective tissue with unique elastic materials called elastofibroma fibers. A normal elastic fiber consists of a central core and peripheral zone, in which the latter has small aggregates of 10 nm microfibrils. By the QF-DE method, globular structures consisting of numerous fibrils (5-20 nm in width) were observed between the collagen bundles. We could confirm that they were microfibril-rich peripheral zones of elastofibroma fibers by comparing the replica membrane and conventional electron microscopy. One of the characteristics of elastofibroma fibers is that they are assumed to contain numerous microfibrils. Immunohistochemically, spindle tumor cells showed positive immunoreaction for vimentin, whereas alpha-smooth muscle actin, desmin, S-100 protein and CD34 showed negative immunoreaction. By conventional electron microscopy, the tumor cell had thin cytoplasmic processes, pinocytotic vesicles and prominent rough endoplasmic reticulum. Abundant intracytoplasmic filaments were observed in some tumor cells. Thick lamina-like structures along with their inner nuclear membrane were often observed in the tumor cell nuclei. The whole image of the tumor cell was considered to be a periosteal-derived cell, which would produce numerous microfibrils in the peripheral zone of elastofibroma fibers. This study indicated that the QF-DE method could be applied to the pathological diagnosis and analysis of pathomechanism, even for surgical specimens obtained from a patient.

Small liver metastasis of rectal carcinoma is mostly solid and rarely accompanied by necrosis. Microscopic invasion of the hepatic vein is rare in colorectal metastasis. A 53-year-old man, 2 years after rectal carcinoma resection, was noted to have a 15-mm liver tumor. On imaging, it was difficult to determine if the mass was hepatic abscess, cyst, solitary necrotic nodule, or liver metastasis. The resected tumor was metastatic liver cancer, the center of which had mostly atheromatous necrosis. Also, a microscopic tumor embolism was detected in the hepatic vein around the tumor. Liver tumors that grow should be suspected of being malignant and be resected.

Hepatectomy for hepatocellular carcinoma remains associated with significant morbidity and mortality, despite improved surgical techniques and perioperative management. The relationship between the extent of liver fibrosis and postoperative complications is controversial.We studied 50 patients in whom hepatectomy for Child-Pugh grade A or B had been indicated. Surgical procedures were determined by the indocyanine green retention rate after 15 minutes (ICGR15). The extent of liver fibrosis was graded according to the Desmet classification. The frequency and grade of severity of postoperative complications were evaluated.Postoperative complications occurred in 24 patients (48%), the frequency being significantly higher among those with liver cirrhosis. However, no significant difference in the incidence of major complications was observed between cirrhotic and non-cirrhotic patients (p=0.311). There was no association between grade of severity of postoperative complications and extent of fibrosis.When the surgical indication and procedure were selected based on the Child-Pugh classification and ICGR15 value, respectively, the extent of liver fibrosis did not influence the incidence of major postoperative complications. In particular, there was no significant difference in the incidence of life-threatening postoperative complications between cirrhotic and non-cirrhotic patients.

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.

The patient was a 50-year-old female with peritoneal metastasis of Type 4 gastric cancer. She underwent a relative curative resection with total gastrectomy and peritonectomy. Postoperative chemotherapy with 5'-DFUR following 5-FU and CDDP was performed. Thirteen months after surgery, cancer recurrence was suspected due to elevated levels of the serum tumor markers carcinoembryonic antigen (8.9 ng/ml) and alpha fetoprotein (85.8 ng/ml). She was additionally treated with UFT 300 mg/day and Lentinan 2 mg/week. The serum tumor markers decreased gradually returned to normal levels. At 5 years and 8 months after surgery, she is alive without any sign of recurrence.

Our previous study of a gastrointestinal autonomic nerve tumor with skeinoid fibers (SF) using the quick-freezing and deep-etching method, suggested that the distance between one radix and a neighboring radix (DRNR) in pre-existing meshwork structures around the tumor cells is consistent with the periodicity of the SF. Therefore, measurement of the DRNR in the meshwork could clarify the significance of the pericellular matrix for SF development. In the present study, we analyzed the meshwork in three cases of gastrointestinal stromal tumor (GIST), which showed different immunohistochemical stainings, but confirmed to have smooth muscle differentiation (SMD) by immunohistochemistry and/or electron microscopy. The DRNR from the three cases of GIST showed similar histogram patterns (a peak of 20-30 nm, mean values of 28.02, 25.74 and 26.45 nm), which were significantly shorter than the periodicity of SF (a peak of 40-45 nm, mean value of 42.14). Although we need further studies with additional GIST cases, we speculate that the pericellular matrix of GIST with SMD is not suitable for SF development.

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 case of gastrointestinal autonomic nerve tumour with skeinoid fibres (SFs) of the jejunum in a 79-year-old Japanese man, was examined by the quick-freezing and deep-etching (QF-DE) method. The tumour consisted of spindle cells with immunohistochemical reactions for vimentin, NSE and CD34. Electron microscopically, features of the neural cells of the myenteric plexus were observed. The QF-DE method demonstrated intercellular meshwork structures, consisting of thin filaments (7–15 nm), with granular deposits. Fully developed parts of the deposits formed nodular aggregates composed of irregularly surfaced thick fibrils (30–48 nm) with a tendency to linear arrangement (SFs). We detected many interconnecting thin filaments (ICTFs) between the SFs, which were pre-existing components in the meshwork, avoiding the granular deposits. The focal thickening formed by the connection between SFs and ICTFs revealed a periodicity typical of SFs (33–45 nm). We conclude that SFs are formed by decoration of the granular deposits along pre-existing intercellular meshwork structures.

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.

The relationship between cell differentiation and ultrastructural changes of intermediate filaments (IF) was studied in columnar cells of large intestinal mucosa of rats by confocal laser scanning microscopy and quick-freezing and deep-etching method. A feature of the IF in immature columnar cells was minibundle formation with prominent branching, which organized the meshwork structures. The minibundles, which appeared to be formed by the attachment of two or more IF in side-to-side fashion, were loosely distributed throughout the cytoplasm. In contrast, in mature columnar cells, the IF were densely distributed under the terminal web in the cytoplasm and beneath the upper part of the lateral membrane regions, whereas the other areas of the cytoplasm contained only a small number of IF. Minibundle formation was not observed, and the branching was rarely identified. The changes in the distribution and density of IF, which are expressed in specific areas of mature columnar cells, apparently represent a characteristic of intracellular differentiation. It is suggested that the dissociation of minibundled IF, which was often observed in the immature columnar cells, is an important step in the acquisition of functional polarity in cells of this type.

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.

To elucidate the significance and nature of calcium oxalate crystals in the thyroid, we studied these crystals clinicopathologically and immunohistochemically in 182 normal thyroids from patients autopsied within 5 h of death. Under polarized light, calcium oxalate crystals showed brilliant birefringence and were invariably found within the colloid. The crystals were found in 73.1% of all cases but were more prevalent and denser in older individuals, with the highest prevalence (85.2%) being observed in those over 70 years of age. No crystals were seen in those under 10 years of age. Although underlying diseases seemed to have little influence, post-mortem delay apparently affected the prevalence and density of occurrence since the crystals tended to disappear with hours after death. An immunohistochemical study using anti-thyroid hormone antibodies revealed that the crystals were within negatively or weakly stained colloid and were not common in strongly stained colloid. These findings support the hypothesis that the occurrence of calcium oxalate crystals in normal human thyroid is associated with a low functional state of the thyroid follicles.

In order to assess the expression of different cytokeratins in the collecting duct cells (CDCs) of the human kidney, three consecutive sections were stained with periodic acid-Schiff, CAM 5.2, and AE-1 (CAM 5.2 recognizes cytokeratins #19,18,8 and AE 1 #19,16,15,14,10 of Moll's catalog.), respectively. By comparing these sections, it was found that most CDCs in the inner medulla were both CAM 5.2 and AE 1 positive, whereas in the outer medulla and cortex, 77% of the CDCs were both CAM 5.2 and AE 1 positive, 15% CAM 5.2 positive and AE 1 negative, 8% both CAM 5.2 and AE-1-negative, and 0.4% CAM 5.2 negative and AE 1 positive. Recent studies have shown that most CDCs express low-molecular weight cytokeratins #7,8,18 and 19(17,18,19,20). Of these cytokeratins, CAM 5.2 recognizes cytokeratins #8,18,19 and AE-1 recognizes cytokeratin #19. Therefore, most CDCs belong to one of the following three major types; 1. Those positive for cytokeratins #8,18 and 19 (CAM 5.2 and AE 1 positive), 2. Those positive for cytokeratins #8 and 18 and negative for #19 (CAM 5.2-positive and AE 1 -negative) and 3. Those negative for cytokeratins #8,18 and 19 (CAM 5.2 and AE 1 negative). A few CAM 5.2 negative and AE 1 positive cells were thought to express high molecular weight cytokeratins. The significance of these various cytokeratin expressions is discussed. Acta Pathol Jpn 41: 516 520, 1991.