Metastatic bronchogenic carcinoma with human chorionic gonadotropin production manifesting as cerebellar hemorrhage--case report.

A 58-year-old male presented with a rare case of brain metastatic bronchogenic carcinoma with human chorionic gonadotropin (hCG) production causing cerebellar hemorrhage with symptoms of nausea, vomiting, and headache. Bronchogenic carcinoma manifesting as gynecomastia had been resected a few months previously. Neurological examination revealed left cerebellar ataxia. Neuroimaging showed multiple cerebellar metastases with cerebellar hemorrhage adjacent to the tentorium. Angiography demonstrated tumor staining fed by the hemispheric branch of the left posterior inferior cerebellar artery. Suboccipital craniectomy was performed. The left cerebellar hematoma was evacuated and the tumor was partially removed to prevent massive intraoperative hemorrhage and avoid brain stem injury. Histological examination showed the resected tumor was large cell carcinoma. hCG was detected in the cerebrospinal fluid and was identified by immunohistochemical staining in tumor cells. The primary lesion of bronchogenic carcinoma showed choriocarcinomatous change because the tumor could produce hCG. The choriocarcinomatous cells with higher metastatic potential formed lesions in the brain, and finally intratumoral hemorrhage occurred producing the rapid development of symptoms.

Association of p53 gene mutation and telomerase activity in resectable non-small cell lung cancer.

PURPOSE: Mutation of the p53 gene and deregulation of telomerase may be essential for canceration in some malignant diseases. However, relationships between these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). METHODS: Frozen sections of 40 surgically resected NSCLC specimens were used. DNA extracted from fresh tumor specimens was analyzed with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts on SSCP were reamplified, and the PCR products were directly sequenced. In addition, the telomerase activity of the same specimens was analyzed quantitatively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and pathologic parameters were evaluated using a statistical analysis system. RESULTS: Mutations of the p53 gene relevant to an altered protein were confirmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene mutation was significantly higher than that of the 21 specimens negative for p53 gene mutation. Furthermore, the degree of cell differentiation was significantly correlated with both p53 gene mutation and high telomerase activity. CONCLUSIONS: p53 gene mutation and high telomerase activity cooperate to induce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occurrence of p53 gene mutation and high telomerase activity may be relevant to the grade of malignancy in NSCLC.

Parosteal fasciitis of the clavicle.

A rare case of parosteal fasciitis arising from the periosteum of the left clavicle in a 27-year-old woman is reported. Magnetic resonance imaging demonstrated the lesion surrounding the periosteum of the clavicle. The lesion was iso-intense with muscle on T(1)-weighted images and hyperintense on T(2)-weighted images. At surgery, the lesion was discovered to be densely adherent with the periosteum, and excised along with the periosteum. Histopathological examination revealed the proliferation of myofibroblasts in a vague storiform or short fascicular pattern. A large amount of extravasated erythrocytes, and a few lymphocytes were present in the matrix. There were some foci of abundant myxoid materials. Immunohistochemical study showed the cells to be positive for vimentin, alpha-smooth muscle actin and HHF35, but negative for desmin. There was no local recurrence at a 6 months postoperative follow up.

Aortic root dilatation among young competitive athletes: echocardiographic screening of 1929 athletes between 15 and 34 years of age.

BACKGROUND: Aortic dilatation can be lethal for young competitive athletes. The prevalence among athletes is not known, however, and thus a reasonable approach to early recognition remains uncertain. METHODS AND RESULTS: Echocardiograms of 1929 normotensive athletes 15 to 34 years of age were analyzed. Five (0.26%) athletes had aortic dilatation; 4 of the 5 played basketball. This made the prevalence of aortic dilatation 0.96% (4 of 415) among basketball and volleyball players, who represented a population of especially tall athletes. Tallness aside, only 2 of the 5 athletes had features of Marfan syndrome. Among the athletes without aortic dilatation, the relation between body surface area and aortic root dimension was nonlinear and best described with a quadratic regression model. Athletes with aortic dilatation fell well outside the 95% confidence interval. CONCLUSION: Because a higher incidence of aortic dilatation is to be anticipated among very tall athletes, inclusion of echocardiography in screening before participation in certain sports should be considered.

[Multicentric Castleman's disease with lymphoid interstitial pneumonia and polyneuropathy].

A 51-year-old woman was admitted to a local hospital because of pneumonia, and received a diagnosis of cervical lymphadenopathy, anemia, and hyperimmunoglobulinemia with suspected multicentric Castleman's disease (MCD). At the age of 53 she was transferred to our hospital because of numbness and muscle weakness. Polyclonal hyperimmunoglobulinemia was observed, and biopsy specimens of lymph node tissue revealed infiltration of plasma cells in the interfollicular areas, thus leading to a diagnosis of MCD. A chest computed tomography scan revealed diffuse nodular shadows in all lung fields, and a transbronchial lung biopsy disclosed infiltration of plasma cells in the alveolar septa. Together, these findings indicated lymphoid interstitial pneumonia (LIP). Polyneuropathy was diagnosed by neurological examination and nerve conduction studies. Treatment with prednisolone and cyclophosphamide was ineffective against LIP probably because the patient had coexising pulmonary fibrosis. Since pulmonary complications of MCD determine its prognosis, their early detection and treatment are essential.

Ovarian strumal carcinoid with markedly high serum levels of tumor markers.

We report a 54-year-old woman with ovarian strumal carcinoid in association with dermoid cyst and mucinous cystadenoma in the same ovary and who had markedly high serum levels of CEA (202 ng/ml), CA125 (710 U/ml), and CA19-9 (11,500 U/ml). These tumor markers were not found in the thyroid tissue or carcinoid by immunohistochemical methods, but their serum levels decreased to below the cutoff levels after surgery. In our case, the change of serum levels of these tumor markers may be useful for the follow-up after surgery.

Thymoma: tumour type related to expression of epidermal growth factor (EGF), EGF-receptor, p53, v-erb B and ras p21.

As clinicopathological features may not be sufficient to predict the progression of thymoma, we have carried out what we believe to be the first immunohistochemical study describing the relationship between the different types of thymoma and the tumour stage, on the one hand, and the expression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v-erb B and ras p21, on the other. The positive rates versus histological types and Masaoka's clinical stages in the 47 cases were as follows: p53 (non-invasive thymoma: 41.7%; malignant thymoma category I: 82.4%; malignant thymoma category II: 83.3%), EGF (non-invasive thymoma: 4.2%; malignant thymoma category I: 11.8%; malignant thymoma category II: 33.3%) and EGFR (non-invasive thymoma: 8.3%; malignant thymoma category I: 35.3%; malignant thymoma category II: 66.7%); p53 (stages I and II: 51.7%; stages III and IV: 77.8%), EGF (stages I and II: 3.4%; stages III and IV: 22.2%) and EGFR (stages I and II: 13.8%; stages III and IV: 44.4%). These data suggest that p53 may be implicated in the initial stages of tumorigenesis and that increased expression of EGF and EGFR may play a role in thymoma progression.

Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues.

Immunohistochemical studies were performed to clarify the significance of the expression or overexpression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v-erb B, ras p21 in 23 cases each of tubular adenoma and adenocarcinoma. The expression of EGF, EGFR, p53, v-erb B, and ras p21 in paraffin-embedded tissues, from 46 patients with colorectal tumors (adenoma: 23 cases; 14 mild dysplasia, six moderate dysplasia, three severe dysplasia, adenocarcinoma: 23 cases; 17 well differentiated, two moderately differentiated, three poorly differentiated, one mucinous carcinoma was analyzed immunohistochemically using anti-EGF, EGFR, p53, v-erb B and ras p21 antibodies. The EGF and ras p21 tended to express more strongly in carcinoma cases than in the adenoma cases, and in severe and moderate dysplasia than in mild dysplasia (EGF: stained positive in five adenomas [21.74%] and 17 adenocarcinomas [73.91%]; ras p21: stained positive in six adenomas [26.09%] and 14 adenocarcinomas [60.87%]. The EGFR stained positive in two adenomas (8.70%) and two adenocarcinomas (8.70%). The p53 and v-erb B showed positive staining only in the carcinoma cases (p53: stained positive in four cases [17.39%]; v-erb B: stained positive in eight cases [34.78%]). This study suggests that these factors seem to have some role in the progression of colon neoplasms. It suggests that genetic alteration is not always equal to the overexpression of protein products, but that it reflects them well, and that the staining makes some contribution to differential diagnosis in colorectal neoplasms.

MR detection of degenerating uterine leiomyomas.

OBJECTIVE: Gonadotropin-releasing hormone (GnRH) analogues have been advocated for the conservative management of uterine leiomyoma. These drugs induce a hypoestrogenic state and affect undegenerated myoma cells. Therefore, we evaluated the usefulness of MRI for distinguishing undegenerated and degenerated leiomyomas. MATERIALS AND METHODS: Twenty lesions were studied in 16 patients with surgically resected leiomyoma. A 1.5 T unit was used to obtain T1- and T2-weighted images and Gd-DTPA-enhanced T1-weighted images. Signal intensity maps were made for each pulse sequence, and detailed histological maps were also made in the same plane as the MR images. Then the MR maps were compared with the histological maps of the resected specimens. RESULTS: Interstitial edema, the initial sign of degeneration, was detected as a high signal intensity region on T2-weighted images and showed enhancement with Gd-DTPA. Hyaline degeneration could not be distinguished from smooth muscle whorls on T1- and T2-weighted images. However, undegenerated leiomyoma could be distinguished from hyaline degeneration, because the former was slightly enhanced by Gd-DTPA but the latter was not. CONCLUSION: These findings showed that Gd-DTPA-enhanced MRI can distinguish undegenerated leiomyomas from degenerated leiomyomas and suggest that MRI may be useful for predicting the response of this tumor to GnRH analogue therapy.

Infantile neuroaxonal dystrophy--immunohistochemical and ultrastructural studies on the central and peripheral nervous systems in infantile neuroaxonal dystrophy.

We performed pathological studies on the central and peripheral nervous systems of cases with infantile neuroaxonal dystrophy (INAD). Numerous spheroid bodies in the central and peripheral nervous systems, were seen and divided into large spheroid bodies (LSB) and small spheroid bodies (SSB) photo-microscopically. LSB had a relation to some specific neurons with weak expression of neuron specific enolase, neurofilament and chromogranin using PAP method. SSB showed a relation to the axon without immunohistochemical expression of neuron specific enolase, neurofilament, glial fibrillary acidic protein, myelin basic protein, chromogranin, S 100 protein or antitrypsin. LSB were prominent in the posterior column, gracile nucleus, cuneate nucleus, and the tegmentum of the midbrain and the pons associated with neuronal loss and gliosis. SSB were observed in the thalamus, basal ganglia and the cerebral cortex. The cerebellum was sclerotic with few microtubule-like structures disposed in a dense network in association with degenerated mitochondria. Similar changes were observed in the sural nerves, autonomic nerve endings in the skin, and the nerve plexus of the digestive tract. Although INAD is a generalized neurodegenerative disease, it is suggested that the primary disorder might occur in the neurons and axons of the sensory tracts.

Pathological findings in dicephalus dipus dibrachius: implications for mechanisms in two pairs of lateral conjoined twins.

The anatomical and pathological features of two pairs of dicephalic conjoined twins (case 1 and 2) are described. Both twins showed duplicitas lateralis representing diprosopus dipus dibrachius. There were two complete heads on two necks, one thorax, one abdomen and externally normal two arms and two legs. Case 1 showed dicephalus with anencephaly, two vertebral columns and two spinal cords, which converged from the thoracic region distally. The esophagus, stomachs and partial small intestines were duplicated, which fused at yolk sac (with Meckel's diverticulum). The heart was incompletely fused. The lungs and trachea were doubled. Two spinal cords were fused from the thoracic region caudally and showed myelomeningocele and Arnold-Chiari malformation in case 2. Two larynxes and two thracheas connected with the incompletely fused three lobes of lungs. The conjoined lungs were hypoplastic. The heart was single, showing ventral septal defect, transposition of great arteries, two cuspid aortic valves and preductal aortic coarctation. The duplicated esophagi were conjoined in Y-shape and single stomach, duodenum, intestine and colon were found. There were pairs of kidneys, adrenal glands and ureters and single female genitalia in both cases. These findings indicate that the craniocaudal paleoaxes were separated in the cranial region and converted or fused under the thoracic region like a Y-shape. Further development defects and deformations might be important factors to form malformations in these case.

[A study of the utility of the MR image for the diagnosis of thymic tumors--imaging and pathologic correlation].

MR imaging was performed in 25 patients with thymic tumors (five with non-invasive thymomas, 15 with invasive thymomas, and five with thymic carcinomas), and the MR imaging appearance was compared with the pathological findings. Non-invasive thymomas showed generally oval or round masses with well-defined margins and homogeneous intensity on T1- and T2-weighted images. Invasive thymomas showed a multinodular appearance in 79% (11/15) of cases, and an internodular difference in signal intensity (IDSI) in 64% (7/11) on T2-weighted images. It was considered that the IDSI on T2-weighted images correlated pathologically with the hemorrhagic and/or necrotic areas and hyalinization. The IDSI seemed to be a characteristic finding of invasive thymomas. The histological findings and MR imaging appearance of thymomas were compared. The predominantly epithelial type showed a low incidence of nodular appearance but showed marked IDSI on T2-weighted images. Therefore, it is more likely that the predominantly epithelial type induced more varied intratumoral changes than other types. Extension of thymic carcinomas was similar to that of invasive thymomas on MR imaging, but thymic carcinomas showed no definite nodular appearance. In conclusion, MR images in thymic tumors were useful for not only determining the morphology of the tumor but also the tissue characteristics. Therefore, MR imaging can be a useful modality to correlate with the histological findings and biological behavior of thymic tumors.

Magnetic resonance imaging of Krukenberg tumor from gastric cancer.

The magnetic resonance imaging (MRI) findings in a 42-year-old woman with a giant Krukenberg tumor from gastric cancer are reported. The macroscopic features of the Krukenberg tumor resulting from gastric cancer were clearly and precisely shown on MRI. Furthermore, MRI was more useful than ultrasonography or CT for determining the origin and further tissue characterization of the tumor. These findings suggest that MRI can be especially useful in the evaluation of giant ovarian tumors as in the present case.

[Effect of lactulose on ammonia metabolism during exercise].

In seven athletes, the effects of lactulose on ammonia metabolism during dynamic exercise were studied with a cycle ergometer. Each subject performed a graded incremental test with increases in work rate of 300 kpm/3 min until exhaustion set in, on two separate days, one without lactulose and one with 20 mg/day lactulose for 3 days. Without lactulose, maximal heart rate and peak oxygen uptake (VO2) were 193 beats/min and 4280 ml/min, respectively. LA was unchanged early in exercise, but elevated rapidly at work rates of 900 kpm (54% peak VO2) and thereafter. AMM increased even at rates as low as 600 kpm (40% peak VO2) and continued to rise attaining peak value at the termination of exercise. After exercise, AMM decreased rapidly. On the other hand, LA was still significantly above the basal level after 30 min of recovery. After lactulose, heart rate, duration of exercise or LA was not significantly different from the value without lactulose at the same work rate, however, AMM at low work rate was lower and VO2 at 1500 kpm was higher. Lactulose had small but significant effects on some parameters of graded exercise.