Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

BACKGROUND: Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor. CASE PRESENTATION: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein-Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C-X-C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein-Barr virus type 2 infection. CONCLUSIONS: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein-Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein-Barr virus-associated gastric cancer.

Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma.

BACKGROUND: Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear. OBJECTIVE: To correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma. METHODS: Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion. RESULTS: Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (P = 0.033 for lymph node, P = 0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (P = 0.015) and the presence of vascular invasion (P = 0.017). On further evaluation of MAGL-positive primary lesions, staining intensity of MAGL tended to be higher in deeper areas of the tumour mass. CONCLUSIONS: The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression.

Upregulation of integrin ß4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and often lethal malignant tumor. Several studies have shown that epithelial-mesenchymal transition (EMT) is frequently observed in clinical samples of PDA and is related to high metastatic rates and poor outcomes. To identify candidate molecules regulating EMT in PDA, we previously used cDNA microarray analysis and identified integrin ß4 (ITGB4) as one of the genes upregulated in high-EMT xenografts derived from PDA patients. The aim of the current study was to clarify the clinicopathological and functional significance of ITGB4 overexpression in PDA. ITGB4 upregulation in high-EMT xenografts was confirmed by immunohistochemistry. Immunohistochemical analyses of 134 surgically resected PDA cases revealed intratumoral heterogeneity with respect to ITGB4 expression and showed that cancer cells undergoing EMT often display strong diffuse ITGB4 expression. High levels of ITGB4 expression were significantly correlated with the hallmarks of EMT (solitary cell infiltration, reduced E-cadherin expression, and increased vimentin expression), with high tumor grade, and with the presence of lymph node metastasis, and showed an independent prognostic effect. Immunocytochemical analyses of PDA cell lines revealed that localization of ITGB4 changed from regions of cell-cell contact to diffuse cytoplasm and cell edges with occasional localization in filopodia during EMT. Knockdown of ITGB4 reduced the migratory and invasive ability of PDA cells. Overexpression of ITGB4 promoted cell scattering and cell motility in combination with downregulation of E-cadherin and upregulation of vimentin expression. In conclusion, we elucidated the prognostic and clinicopathological significance of ITGB4 overexpression in PDA and also the potential role for ITGB4 in the regulation of cancer invasion and EMT.

Increased plasma levels of high mobility group box 1 in patients with acute liver failure.

BACKGROUND: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF). PATIENTS AND METHODS: We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1. RESULTS: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 ± 0.3 in HVs, 4.0 ± 2.0 in LC, 5.2 ± 2.6 in CH, 8.6 ± 4.8 in severe AH, 7.8 ± 2.7 in FH with a history of PE, and 12.5 ± 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 ± 116 in FH vs. 874 ± 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH. CONCLUSION: We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue.

A case report of post-thymectomy myasthenia gravis with residual thymoma.

A forty-nine-year-old female patient, complaining of swallowing difficulties and general fatigue, was admitted to the first hospital of Nippon Medical School. At the age of 32, she was operated on for the removal of a well encapsulated non-invasive thymoma. Since then, she had been well till the age of 46, when chest X-ray films showed a recurrent thymoma which was excised together with the complete thymic tissues. One year later, she developed myasthenia gravis (MG) with a ptotic right upper eyelid and general fatigue. Subsequently, she was placed on medication. After 21 months, however, she died of myasthenic crisis in spite of vigorous respiratory and nutritional support. The autopsy revealed a small residual thymoma on the left lung, and systemic atrophy of the skeletal muscles. In this paper, the mechanism of post-thymectomy MG and the recurrence of non-invasive thymoma are discussed.

Calcification in human osteoblasts cultured in medium conditioned by the prostatic cancer cell line PC-3 and prostatic acid phosphatase.

A medium that had been conditioned by PC-3 cells stimulated the calcification of a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The calcification of the osteoblasts was stimulated maximally at a 25% concentration of the conditioned medium. Calcification activity was markedly enhanced by the addition of both prostatic acid phosphatase (PAP) and its substrate, alpha-glycerophosphate, to the medium; however, PAP added alone did not enhance this activity. These results suggest that human prostatic carcinoma cells produce a factor that stimulates the calcification of the human osteoblasts. Results have also suggested that PAP is a requisite for osteogenesis provided that its substrates are abundant in the medium.

Effect of dextrans of various molecular weights on mesangial transport in ddY mice pretreated with sheep anti-type IV collagen serum.

The authors' previous report concluded that increased mesangial IgA deposition seen in ddY mice pretreated with mesangiotropic anti-type IV collagen serum might be due to a dysfunction of mesangial transport of macromolecules such as polymeric autologous IgA. In the present study we examined the effect of macromolecules upon mesangial transport in similarly treated ddY mice, using intravenously administered FITC-labeled dextrans of various molecular weights as tracers. The intensity of each resulting mesangial dextran deposit inspected directly by immunofluorescence was measured periodically and compared with the deposition of autologous mouse IgA examined using rhodamine-labeled rabbit anti-mouse IgA. High-molecular-weight dextran of 2,000 kDa showed prolonged mesangial deposition which paralleled the intensity and distribution of the autologous mouse IgA deposition. In contrast, medium- and low-molecular-weight dextrans of 500 and 150 kDa, respectively, disappeared earlier from the mesangium, unlike the autologous IgA deposition which persisted. Based on these results, it was concluded that the macromolecularity of certain substances and a transport dysfunction of the mesangium may both be major factors in prolonged mesangial deposition. These findings may provide some clues to help clarify the pathogenesis of human IgA nephritis.

Role of elastic fiber degradation in emphysema-like lesions of pulmonary lymphangiomyomatosis.

To study the pulmonary structural remodeling in pulmonary lymphangiomyomatosis, electron microscopy and light and electron microscopic immunohistochemical observations for elastin and alpha 1-antitrypsin were performed on five open lung biopsy samples. Lung specimens showed emphysema-like changes in areas of abnormally accumulated smooth muscle cells. In the alveolar walls having accumulated smooth muscle cells, elastic fibers were decreased in number, disrupted, granular, and occasionally accumulated. Ultrastructurally, elastic fibers in areas of smooth muscle cell accumulation showed poorly outlined amorphous components and a few microfibrils, and occasionally showed electron-dense granular deposits in and around the amorphous components. Spiraling collagen fibrils were frequently found associated with these abnormal elastic fibers. Immunohistochemistry for elastin showed even staining of amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. alpha 1-Antitrypsin was also detected evenly in amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. It is proposed that the emphysema-like lesions of lymphangiomyomatosis are mediated by the degradation of elastic fibers, and these degraded elastic fibers are related to an imbalance of the elastase/alpha 1-antitrypsin system similar to the probable pathogenesis of emphysema.

Intraluminal fibrosis and elastic fiber degradation lead to lung remodeling in pulmonary Langerhans cell granulomatosis (histiocytosis X).

To evaluate the morphogenesis of lung remodeling in pulmonary Langerhans cell granulomatosis (LCG; previously called histiocytosis X or eosinophilic granuloma), lung tissues obtained by open biopsy from 62 patients with pulmonary LCG were studied by light and electron microscopy. Tissues from 20 patients were also studied by immunohistochemical methods for the detection of fibronectin, elastin, and S-100 protein, and samples from six patients were studied using OKT6 monoclonal antibody. In early stages of pulmonary LCG, the epithelial lining cells were detached and Langerhans cells, inflammatory cells, and myofibroblasts migrated into intraluminal spaces through gaps in the epithelial basement membranes in and around the granulomatous lesions. In late stages, intraluminal fibrosis led to obstruction of alveolar spaces and airways and to coalescence of alveolar walls in and around the granulomatous lesions. Adjacent to these lesions, irregularly dilated alveoli were found with degraded and disrupted elastic fibers. Together, these observations suggest that intraluminal fibrosis and elastic fiber degradation are important processes of lung remodeling in pulmonary LCG.

[Healing of the operative cardiac wound in postinfarction ventricular septal perforation].

We studied the healing processes of operative cardiac wound around the patch on 8 patients (5 males, 3 females), who survived 6 to 147 days postoperatively for postinfarction ventricular septal perforation. The perforation was repaired either with a Dacron patch or with a Teflon-backed glutaraldehyde-preserved equine pericardium (Xenomedica). The patients with the Xenomedica patch had no perioperative bleeding or residual shunting across the patch. However, our long-term observations show that the patch is not covered with neoendocardium after 5 months and thus may pose a greater risk for thrombus formation, embolisms or infections; For instances, one case with mural thrombus formation and two cases of infection around the patch were observed. Therefore, while the Xenomedica patch may provide advantages in the immediate postoperative period, long term results indicate that this patch is inferior to the Dacron patch. We have also observed that the progress of healing was different on the patch between the right and left surface. Neoendocardium was observed on the 30th postoperative day on the right sided surface of the Darcron patch, while only pseudoneointima (mostly fibrinous membrane) with a few endothelial cells were found on the left side. The healing of infarcted myocardium was slower in these patients with patch than in patients with myocardial infarction without operation. Even after 62nd postoperative day, scarring was still incomplete, only granulation tissue was observed. Certainly, the operative trauma including the effect of extracorporeal circulation and postoperative low output syndrome may contribute to this finding. Suture insufficiency occurred in 4 cases, which may be associated with the delayed wound healing.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of Takayasu's arteritis associated with membranoproliferative glomerulonephritis and nephrotic syndrome.

We describe a 57-year-old Japanese female who had Takayasu's arteritis associated with nephrotic syndrome due to membranoproliferative glomerulonephritis. Although a focal and segmental mesangial proliferative glomerulonephritis associated with Takayasu's arteritis has been described, membranoproliferative glomerulonephritis has not been reported previously in this condition.

In situ localization of pepsinogens I and II mRNA in human gastric mucosa.

Localization of pepsinogens I and II mRNA in the human gastric mucosa was investigated by an in situ hybridization method using digoxigenin-labeled cDNA probes. Gastric fundic mucosa from healthy volunteers, which was stained with digoxigenin-labeled pepsinogens I and II cDNA probes, showed positive staining in the cytoplasm of both chief cells and mucous neck cells. In contrast, gastric antral mucosa stained with the pepsinogen I cDNA probe showed no positive reaction in the surface mucous cells or pyloric glands. On the other hand, the pyloric glands were stained positively with the pepsinogen II cDNA probe and the staining appeared to be identical to that obtained with the antipepsinogens I and II monoclonal antibodies using the avidin-biotin-peroxidase complex technique. These results are consistent with those of previous studies that have employed immunochemical and immunohistochemical techniques.

[A case of renal leiomyoma with extensive cystic degeneration].

An extremely rare case of renal leiomyoma presenting as a cystic mass, involving the upper pole of the right kidney in a 59-year-old woman, complaining of right flank pain is reported. Some discussion regarding pathogenesis of leiomyoma with cystic change, diagnostic feature, malignant potential of leiomyoma and others was done. Since 1948, 19 cases including our own case of renal leiomyoma have been reported in the Japanese literature.

Morphogenesis of abnormal elastic fibers in lungs of patients with panacinar and centriacinar emphysema.

Pulmonary elastic fibers in a patient with panacinar emphysema due to alpha-1-antitrypsin deficiency and three patients with centriacinar emphysema related to anthracosis were studied by electron microscopy and by light and electron microscopic immunohistochemistry for elastin. Four types of abnormal elastic fibers were found: (1) finely disrupted fibers, (2) fibers with vacuolar changes and deposits of electron-dense granular material, (3) accumulations of small, rounded amorphous components of elastic fibers near bundles of microfibrils, and (4) large, confluent masses consisting mainly of aggregates of irregularly and compactly arranged, small-sized amorphous components. The amorphous components in these four types of abnormal elastic fibers tended to stain evenly with antielastin antibody. This is attributed to greater penetration of antielastin antibody into fibers that were incompletely polymerized because of immaturity or hydrolytic damage. Finely disrupted fibers were frequently found in the patient with panacinar emphysema and were presumed to have been damaged by elastase. The other three types of elastic fibers were frequently found in the patients with centriacinar emphysema. The vacuoles and electron-dense deposits in elastic fibers probably represented the consequence of damage to elastic fibers. The small round amorphous components in elastic fibers might be formed from abnormal elastogenesis. The large, confluent elastic masses were thought to be formed by the aggregation of elastic fibers in areas of coalescence of alveolar walls undergoing structural remodeling.

Evidence of delayed mesangial transport of human IgA in glomeruli of ddY mice pretreated with sheep anti-type IV collagen serum.

In order to investigate whether mesangial transport by glomeruli is delayed in ddY mice pretreated with sheep anti-type IV collagen serum, the mice were administered an overload of human IgA myeloma serum. Non-pretreated ddY mice used as controls and both experimental and control BALB/c mice were also processed in a similar manner. The intensities of mesangial deposition of human IgA were examined periodically and were found to correlate well with deposition of mouse IgA. Both mouse and human IgAs showed a gradual increase for up to 8 experimental weeks. In the control young ddY mice, however, the overloaded mesangial human IgA quickly disappeared, presenting no appreciable mesangial deposition of autologous IgA. In sharp contrast, both the experimental and control BALB/c mice showed an initially prolonged and rather heavy mesangial deposition of human IgA, followed by a gradual decrease and somewhat light mesangial deposition of autologous mouse IgA. These results obtained using experimental ddY mice appear to confirm the possibility that non-immunological local trapping, due to retardation of mesangial transport function, causes mesangial deposition of autologous mouse IgA in this particular strain.

Pepsinogens I and II in gastric cancer: an immunohistochemical study using monoclonal antibodies.

Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II-positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Histologically, there were 54 intestinal-type and 53 diffuse-type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II-positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded-type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.

Suppression of glomerular IgA deposition in ddY mice through periodic injections of lipopolysaccharides.

We investigated the role of lipopolysaccharides (LPS) in glomerular IgA deposition of ddY mice. The incidence of IgA deposition was lower in the LPS-injected mice at 10 and 13 months of age as compared with that of their age-matched controls (10 months, LPS 20% vs control 60%; 13 months, LPS 14% vs control 100%). Serum levels of IgA were lower in the LPS-injected mice than in the control mice. There were no appreciable differences in the percentage value of Thy-1+ cells, the ratio of Lyt-1+/Lyt-2+ cells, mitogenic responses, or IL-1 activities between the LPS-injected and the control mice. On the other hand, the IgA responses of spleen and Peyer's patch cells in the LPS-injected mice were lower than those observed in the control mice. These results suggest that the persistent use of LPS directly suppresses gut-associated lymphoreticular tissue (GALT), and that the lower IgA response in GALT induced by LPS causes suppression of glomerular IgA deposition in ddY mice.

[Two autopsy cases of primary pituitary carcinoma].

We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)