Biopsy-proven cerebellar metastasis from a malignant mixed mullerian tumor (MMMT) of the uterus: case report.

Brain metastasis from a malignant mixed Mullerian tumor (MMMT) of the uterus is rare. To our knowledge only three similar cases have been reported in the literature. In this report, the authors present the case of a 57-year-old woman with biopsy-proven cerebellar metastasis from a uterine MMMT. One month after complete resection, the mass showed rapid local recurrence. Attention should be paid to the possibility of unusual brain metastasis from a uterine MMMT, which could have an aggressive clinical course.

Interleukin-8 production in tuberculous pleurisy: role of mesothelial cells stimulated by cytokine network involving tumour necrosis factor-alpha and interleukin-1 beta.

Interleukin-8 (IL-8) plays an important role in the host immune response to Mycobacterium tuberculosis by recruiting inflammatory cells to the site of infection. Here, we investigated the role of pleural macrophages and mesothelial cells in the production of IL-8 in tuberculous pleurisy. Large concentrations of IL-8 were detected in tuberculous pleural effusions, but not in pleural effusions associated with congestive heart failure (CHF). Tuberculous pleural macrophages and M. tuberculosis-infected CHF pleural macrophages produced large concentrations of IL-8. When immunohistochemistry was performed on pleural tissues, antigenic IL-8 was detected in the mesothelial cells lining the tuberculous pleura. Direct stimulation of cultured CHF pleural mesothelial cells with M. tuberculosis induced IL-8 secretion. However, conditioned media from M. tuberculosis-infected pleural macrophages (CoMTB) induced greater mesothelial cell IL-8 secretion. Tumour necrosis factor-alpha (TNF-alpha) and IL-1beta induced mesothelial cell IL-8 mRNA expression, and neutralizing anti-TNF-alpha antibody and IL-1 receptor antagonist nearly completely obliterated CoMTB-induced mesothelial cell IL-8 mRNA expression and protein secretion. These findings demonstrate that both pleural macrophages and mesothelial cells produce IL-8 in tuberculous pleurisy, and cytokines produced by M. tuberculosis-infected macrophages mediate mesothelial cell IL-8 production.

A clinicopathologic study on three cases of constrictive bronchiolitis.

We describe the characteristic clinical and pathologic findings of three cases of constrictive bronchiolitis. All three patients were middle-aged women with chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe obstructive pulmonary dysfunction, relatively normal chest radiographs with occasional peribronchial infiltration, and lack of response to bronchodilators or prednisolone. The patients also had medical diseases such as non-Hodgkin's lymphoma and hyperprolactinemia in case 1 and 3, respectively. None of the patients smoked cigarettes and had clinical evidence of recent viral lower respiratory tract infection. Histologic study by open lung biopsy revealed a spectrum of changes ranging from active cellular bronchiolitis to obliterative peribronchiolar fibrosis. The intervening interstitial and alveolar areas showed no remarkable lesion. Immunohistochemically, the bronchiolar or peribronchiolar inflammatory infiltrates mainly comprised of mixed T- and B-lymphocytes. It may be possible that the active form of constrictive bronchiolitis is initiated by attendant lymphocytic inflammation of the airways, which is followed by fibrous obliteration of bronchioles.

Signet ring cell basal cell carcinoma: a basal cell carcinoma with myoepithelial differentiation.

Basal cell carcinoma (BCC) can show a variety of routes of differentiation, but myoepithelial differentiation has rarely been described. We describe a case of BCC showing histologic and immunohistochemical features of myoepithelial differentiation. Histologically, the lesion showed well-demarcated tumor nodules composed of two different components. One component was typical of BCC, and the other component was composed of tumor cells containing abundant cytoplasm, eccentric nuclei, and no peripheral palisading, with scattered signet ring-shaped cells. Immunohistochemically, the tumor cells in the typical BCC component stained with CKAE1/AE3 and smooth muscle actin (SMA), but not with S-100 protein. They stained weakly with CAM5.2, epithelial membrane antigen, and glial fibrillary acidic protein (GFAP). The tumor cells in the other component stained strongly with CKAE1/AE3 and SMA, moderately with epithelial membrane antigen and GFAP, and weakly with CAM5.2. In a small area, the tumor cells stained with S-100 protein.

Expression of Cyclin-dependent Kinase Inhibitor p21(WAF1/CIP1) in Non-small Cell Lung Carcinomas: Relationship with p53 Status and Proliferative Activity.

PURPOSE: The objectives of this study are to elucidate the level of p21(WAF1/CIP1) expression in non-small cell lung carcinomas (NSCLCs) and to investigate the relationship between the p21(WAF1/CIP1) expression and clinicopathologic features; p53 overexpression; and proliferative activity measured by Ki-67 expression. MATERIALS AND METHODS: The expressions of p21(WAF1/CIP1), p53, and Ki-67 proteins were analyzed by immunohistochemistry in 45 formalin-fixed and paraffin-embedded NSCLC specimens. 43 patients underwent curative resections and 2 patients had bronchoscopic biopsy specimens only. The correlations between p21(WAF1/CIP1) immunoexpression and p53 status; Ki-67 proliferative activity; and clinicopathologic parameters were analyzed statistically by chi-square or Fisher's exact test. RESULTS: p21(WAF1/CIP1) expression in the carcinoma cells was found in 28 (62%) of 45 cases. There was no significant correlation between p21(WAF1/CIP1) expression and abnormal accumulation of p53 protein. In 16 (36%) of 45 cases, p21(WAF1/CIP1) was expressed inde pendently of p53 overexpressions. p21WAF1/CIP1 expression was not associated with patient sex, smoking history, pathological stage, tumor size, histological grade or type. However, p21WAF1/CIP1 immunoreactivity was significantly higher in older individuals over 59 years and tended to occur more intensely in the more highly differentiated portion of the squamous carcinoma. Also, a positive correlation between p21WAF1/CIP1 and Ki-67 expression was observed. CONCLUSION: S: The present findings overall suggest that aberrations in the relationship between p21(WAF1/CIP1) and p53 expressions may be important in the development of NSCLCs; that a p53-independent pathway may be substantially involved in the induction of p21(WAF1/CIP1) expression in NSCLCs; and that the proliferative activity of lung cancers might be dependent on positive control of the cell cycle by p21(WAF1/CIP1).

Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis.

Pathologic findings of scrub typhus have been characterized by vasculitis of the microvasculature of the involved organ resulting from a direct invasion by Orientia tsutsugamushi. We experienced a case of acute respiratory distress syndrome (ARDS) associated with scrub typhus. The case was proven by eschar and high titer of serum IgM antibody (positive at 1:1280). Open lung biopsy showed diffuse alveolar damage (DAD) in the organizing stage without evidence of vasculitis. Immunofluorescent antibody staining and polymerase chain reaction for O. tsutsugamushi failed to demonstrate the organism in the lung tissue. The patient expired due to progressive respiratory failure despite doxycycline therapy. Immunologic mechanism, without direct invasion of the organism, may participate in the pathogenesis of ARDS associated with scrub typhus.

Species, strain and sex differences in susceptibility to gamma radiation combined with diethylnitrosamine.

Our previous data suggested that in Sprague-Dawley (SD) rats, a short-term in vivo radiation carcinogenesis model can be established using glutathione S-transferase placental form (GST-P) positive hepatic foci induced by diethylnitrosamine (DEN) after gamma radiation. In the present study, differences between species, strain and sexes in susceptibility to radiation or radiation combined with DEN were examined. Newborn Fischer 344 (F344) and SD rats, and N:GP(S) mice were irradiated with whole body single 3Gy of gamma rays with or without intraperitoneally-injected DEN (15 mg/kg body weight) within 1 h of irradiation. Three weeks later, 0.05% phenobarbital was given in drinking water as a promoter, and at week 21 after birth, all animals were sacrificed. In both the radiation alone and radiation combined with DEN groups, F344 rats were more susceptible than SD rats to the induction of GST-P+ foci. In F344 rats, no significant difference in foci induction was seen between the sexes in both radiation alone and radiation combined with DEN groups, but in SD rats, female rats were more susceptible than males. In the case of mice, lung tumor incidence was examined, and in the radiation alone group, no differences between the sexes were seen; in the radiation combined with DEN group, however, females were more susceptible than males. These results suggested that susceptibility to radiation carcinogenesis could be potentiated by chemical carcinogens and showed wide variation between species, strains and sexes, of experimental animals.

Short-rib polydactyly syndrome, Beemer-Langer type, with bilateral huge polycystic renal dysplasia: an autopsy case.

Short rib-polydactyly syndrome (SRPS) is a group of lethal skeletal dysplasia of an autosomal recessive inheritance characterized by markedly narrow ribs, micromelia, and multiple anomalies of major organs. We report a case of type IV SRPS with uncommon associations of polydactyly and bilateral polycystic kidneys, in a 28 week old female fetus. She was born dead to a 28 year old mother, showing a hydropic change, narrow thorax, and shortened limbs with postaxial heptasyndactyly of both hands and feet. Radiologic examination revealed short horizontal ribs, curved short tubular limb bones, small ilia and scapula, and a mild vertebral abnormality. Postmortem examination disclosed pulmonary hypoplasia, pancreatic cysts, hepatic fibrosis, and left persistent superior vena cava. In addition this case had bilateral huge polycystic renal dysplasia that was seldom described in any type of SRPS. Histologic sections of the vertebrae disclosed abnormal enchondral ossification with irregular and retarded hypertrophic zone.

Correlation of histopathologic classification with proliferative activity and DNA ploidy in 120 intracranial meningiomas, with special reference to atypical meningioma.

Histologic classification of 120 meningiomas was correlated with their proliferative fraction and DNA ploidy using immunohistochemistry and flow cytometry to differentiate histologically atypical meningiomas from benign ones. Histologically, the 120 meningiomas included 101 benign (43 meningotheliomatous, 40 transitional, 11 fibroblastic, 2 secretory, 2 microcystic, 2 angiomatous, and 1 psammomatous), 15 atypical, and 4 malignant meningiomas. As a histologic spectrum between the benign and malignant meningiomas, atypical meningiomas were defined by the presence of two of the following criteria; high cellularity, focal necrosis, uninterrupted growth pattern, and certain cytologic findings i.e., high nuclear/cytoplasmic ratio, coarse chromatin, and prominent nucleoli. In 56 cases, immunostaining for proliferating cell nuclear antigen showed higher proliferating cell fraction in atypical and malignant meningiomas than that in benign meningiomas (p < 0.05). In the flow cytometric analysis, aneuploidy was more often seen in atypical meningiomas compared to benign meningiomas (p < 0.05). We found that benign, atypical, and malignant meningiomas could be histologically classified and correlated with proliferative activity and DNA ploidy pattern. Therefore, atypical meningiomas should be distinguished from benign meningiomas by histopathologic examination and confirmed by studies on their proliferation fractions and DNA ploidies.

Lipoma of the parotid gland.

We report two cases of lipoma of the parotid gland which present as a non-tender, freely movable and intraparotid mass. Lipomas are common soft tissue neoplasms but found very rarely in the parotid gland, and so are often not considered in the initial differential diagnosis of parotid gland tumor. We believe that these tumors are cured by simple excision, and thus superficial parotidectomy is enough for treatment.

Multicore myopathy--a case report.

Multicore myopathy is a rare congenital myopathy. The multicores consist of numerous small areas of decreased oxidative enzyme activity. The long axis of the lesion is perpendicular or parallel to the long axis of the muscle fiber. These cores are usually smaller than central cores. For this reason they are also called minicores. Although the multicores represent a nonspecific change in that they can be observed in malignant hyperthermia, muscular dystrophy, inflammatory myopathy, etc. Muscular weakness dating from early infancy is combined large proportion of the muscle fibers. In about half of the reported cases the muscular weakness has not been progressive, while in the others a slow progression has occurred. This 9-year-old boy presented with congenital nonprogressive myopathy associated with thoracic scoliosis and bilateral equinovarus deformity. The serum creatine phosphokinase and lactic dehydrogenase levels were normal. Electromyography showed "myopathic" features. The biopsy revealed a marked size variation in myofibers, ranging from 10 microns to 100 microns. A few small angular fibers and slight endomyseal fibrosis were also noted. There was type I fiber predominance. NADH-TR reaction disclosed more well-defined cores with loss of intermyofibrillary mitochondrial activity. These cores were usually located with loss of intermyofibrillary mitochondrial activity. These cores were usually located in the peripheral portions of the myofibers and the core size measured 10-30 microns in diameter. Electron microscopic examination revealed circumscribed areas of disintegrated Z band material and disorganized sarcomeric units near the sarcolemma. A decrease in the number of mitochondria and glycogen particles was noted.

Leigh's disease involving multiple organs.

Leigh's disease is a rare progressive neurological disorder that is characterized light microscopically by focal spongy necrosis in the brain and electron microscopically by mitochondriopathy. We report an autopsy case of Leigh's disease that showed abnormalities in the liver, kidney and skeletal muscle as well as the central nervous system. The patient was an 18-month-old girl who has carried a diagnosis of cerebral palsy ever since her birth to a 20-year-old mother. The baby was generally hypertonic and mentally retarded. She died of severe metabolic acidosis. Postmortem examination showed growth retardation, fatty liver, fatty kidney and soft brain. Brain section showed multifocal softenings in the brainstem, basal ganglia and periventricular areas. Microscopically increased capillaries with endothelial proliferation, vacuolar degeneration and mild gliosis were seen in the brain. The axons were relatively preserved. Liver and kidneys showed microvesicular fatty change. Myofiber degeneration of the skeletal muscle was also noted. Electron microscopic examination showed markedly increased mitochondria in the parenchymal cells of the brain, liver and kidney. The mitochondria showed round to ovoid ballooned appearance including electron-dense core-like structures and pseudoinclusions of glycogen granules.

Central core disease--a case report.

Central core disease is a rare congenital myopathy characterized by the formation of "cores" that consist of abnormal arrangement of myofibrils inside the myofibers. We report a 5-year-old Korean girl who showed a fairly typical clinical course of non-progressive muscle weakness. Electrodiagnostic studies showed low-amplitude polyphasic electromyograph and normal nerve conduction velocity. Gastrocnemius muscle biopsy showed central cores in over 80% of the fibers on H&E section. Histochemistry revealed deficient or absent mitochondrial enzyme in the cores and type I predominance. Ultrastructurally both structured and non-structured cores were found separately or simultaneously in one fiber. This case is the first report in the Korean literature.

Mucin histochemistry by paradoxical concanavalin A staining in early gastric carcinomas.

Phenotypic expression of tumor cells was investigated in 33 early gastric carcinomas by mucin histochemistry using paradoxical concanavalin A staining. This staining method had been developed to differentiate 3 classes of mucins located at various sites of the alimentary tract. Twenty-five (76%) tumors contained mixtures of neutral or acid class II mucin and class III mucin, suggesting the origin of multipotential stem cells. The surface mucous cell expression was more dominant than the pyloric gland or intestinal phenotypes in the well-and poorly differentiated adenocarcinomas. The intestinal properties of the tumor cells were noted not only in the well-differentiated but also in the poorly differentiated or signet ring cell carcinomas, not closely being related to the presence of background intestinal metaplasia. Signet ring cell carcinomas revealed a distinct pattern of mucin histochemistry compared with the other types.

Activities of brush border membrane bound enzymes of the small intestine in Metagonimus yokogawai infection in mice.

The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea.

Effusion cytology of endodermal sinus tumor of the colon. Report of a case.

A three-year-old boy presented with a peritoneal effusion due to an occult endodermal sinus tumor in the ascending colon. Cytologic examination of the ascitic fluid revealed clusters of round plump cells that had large hyperchromatic nuclei, finely stippled chromatin, multiple prominent nucleoli and vacuolated or mucin-containing cytoplasm, features suggesting an adenocarcinoma. The colonic primary was discovered during emergency laparotomy performed due to suspected acute hemoperitoneum. Endodermal sinus tumor should be included in the differential diagnosis when cytologic features reminiscent of adenocarcinoma are encountered in a fluid specimen from a child, especially if there is a history of a gonadal or extragonadal childhood neoplasm.

Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study.

A carcinosarcoma of the stomach in a 66-year-old man is reported. The tumor which had a diameter of 4 cm was an ulcerofungating mass in the posterior wall of the antrum. Histologically it was composed of well-differentiated adenocarcinoma admixed with sarcomatous elements which showed chondrocytic differentiation on light and electron microscopy. The sarcomatous areas were multifocally scattered in the central portion of the tumor and intimately blended with adenocarcinoma cells. CEA immunoreactivity was found not only in the adenocarcinoma but also in the transitional sarcomatous cells, supporting the hypothesis that this tumor might derive from mesenchymal metaplasia of a primarily epithelial neoplasm.

Enhancement of dimethylnitrosamine-induced glutathione S-transferase P-positive hepatic foci by Clonorchis sinensis infestation in F344 rats.

The modifying potential of Clonorchis sinensis (CS) infestation on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis was studied in male F344 rats. The metacercariae of CS were infected, 60 to each animal, by a single intragastric intubation at various times, before, during or after an 8-week period of DMN (25 ppm in drinking water) treatment. Controls were treated with DMN alone or infected with CS without carcinogen. Animals killed at the end of the 40-week experimental period showed a significant enhancing effect of CS on GST-P+ foci induction when CS was infected 4 weeks before DMN treatment, although no such influence was evident with CS infection during or following DMN exposure. The present findings suggest that CS might facilitate the proliferation of DMN-induced preneoplastic lesions of liver in rats.

Abdominal Burkitt's lymphoma diagnosed by fine needle aspiration cytology--a case report.

A case of abdominal Burkitt's lymphoma diagnosed through aspiration cytology is described. This 9-year-old boy presented with abdominal pain and distention for three months accompanied by fever and night sweat during the last month. An abdominal sonography and CT scan showed hepatosplenomegaly and an intrahepatic mass with celiac lymph node enlargement, ascites, and pleural fluid. A peripheral blood smear showed a few blast cells. Aspiration of the abdominal mass revealed very cellular aspirates consisting of diffusely scattered small monotonous round cells. The cells had little cytoplasm, along with round nuclei that showed clear-cut nuclear membrane, coarse chromatin pattern, and multiple small prominent nucleoli. Differential diagnoses considered were small round cell sarcomas such as malignant lymphoma, neuroblastoma, Ewing's sarcoma, and rhabdomyosarcoma. Of these, malignant lymphoma of the small noncleaved cell type was most consistent with the results of several studies including immunohistochemical staining, peripheral blood smear, and bone marrow biopsy. The cells were positive for leukocyte common antigen (LCA) and showed finely vacuolated basophilic cytoplasm in both the peripheral blood smear and bone marrow biopsy, characteristic of Burkitt's lymphoma cells.

The enhancing effect of ethanol on the development of glutatione S-transferase placental form-positive foci induced by diethylnitrosamine in F344 rat.

The effects of ethyl alcohol and pig serum administration on the development of preneoplastic hepatic enzyme-altered foci were examined in an in vivo mid-term assay system. Rats were initially given a single dose (200 mg/Kg) intraperitoneal injection of diethylnitrosamine (DEN). Two weeks later, treatment was started with 10% ethanol + 10% sucrose solution, 10% sucrose solution, or tap water as drinking water for 6 weeks with or without intraperitoneal injection of porcine serum twice a week. All rats were subjected to a two-thirds partial hepatectomy at week 3. The modification potentials were evaluated by comparing the number and area per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the liver of each group. As a result, ethanol significantly enhanced the development of GST-P+ foci. Unfortunately, the porcine serum injection produced no hepatic fibrosis and no significant alteration in GST-P+ foci.