Unusual proliferation of the pancreatic endocrine cells in adults, suggestive of islet cell metaplasia

We present two adult autopsy cases with malignancy, in which unusual proliferation of the pancreatic endocrine cells was observed. Histopathological examination revealed extensive proliferation of the pancreatic endocrine cells throughout the pancreata in both cases. The islets of the pancreas were enlarged with irregular contours. An admixture of the islet cells, acinar cells and ductular epithelial cells was also observed. Immunohistochemically, these islets were composed of the endocrine cells of various types, i.e. A-, B-, D- and PP-cells, and they showed a predominance of PP-cells. Clinically, endocrine hyperfunction of the pancreas was not detected in either cases. Although this histological change may be described as endocrine cell hyperplasia or dysplasia, the close connection of the islet cells, acinar cells and ductular epithelial cells might rather suggest metaplastic change of the acinar or ductular cells into the islet cells under unknown stimuli.     

Coincidence between malignant perivascular epithelioid cell tumor arising in the gastric serosa and lung adenocarcinoma

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor(PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary car-cinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease.     

Plasma levels of vascular endothelial growth factor and fibroblast growth factor 2 in patients with major depressive disorders

We investigated the plasma levels of VEGF and FGF-2, important factors for regulation of neuroplasticity such as neurogenesis, in patients in remission from major depressive disorders (MDD). The plasma VEGF levels were significantly higher in the MDD patients than in the matched control subjects, while no significant difference in plasma FGF-2 levels was found. In particular, the MDD patients with family history of psychiatric disorders, but not patients without such a family history, showed significantly higher values of plasma VEGF than the controls. Although this is a preliminary study, altered VEGF levels might be involved in the pathophysiology of MDD.     

Congenital pulmonary lymphangiectasis: Report of an autopsy case masquerading as pulmonary interstitial emphysema

We describe the clinicopathologic features of a case of congenital pulmonary lymphangiectasis (CPL). A male Japanese infant born prematurely at 34 weeks of gestation developed a severe moaning sound, dyspnea, and prominent respiratory acidosis about 10 min after delivery. A chest X-ray film showed bilateral frosted glass-like infiltrates with an air bronchogram and an air leak around the cardiac shadow, suggesting pneumomediastinum. The patient died of hypoxemic respiratory failure 13 h after birth. The death was complicated by bilateral pneumothorax, despite the initiation of artificial ventilation and administration of a surfactant. At autopsy, small cystic lesions were noted in the visceral pleura, interlobular septa, and hilum of both lungs. A histologic examination of the lungs showed diffuse and marked dilation of the lymphatic channels in the subpleural, peribronchial, interlobular, and hilar areas. The channels were lined with flattened endothelium, which was immunohistochemically positive for D2-40. In addition, lymphangiectasis was found around the thymus and intra-abdominal organs, but no cardiovascular anomalies were seen. The findings conformed to a primary form of CPL, Noonan Group 3. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis because of the overlapping clinicopathologic features, a giant cell reaction surrounding the interstitial cystic lesions, a histologic hallmark of PIE, was absent in the present case.     

Kinetics of drug action in disease states. II. Effect of experimental renal dysfunction on phenobarbital concentrations in rats at onset of loss of righting reflect

The purpose of this investigation was to determine if renal dysfunction is associated with an alteration in the concentration-pharmacologic activity relationship of phenobarbital (PB). Adult female rats (congruent to 200 g) were pretreated with uranyl nitate or subjected to bilateral ureteral ligation to produce renal dysfunction. Saline-injected and sham-operated rats, respectively, served as controls. PB (0.824 mg/min) was infused i.v. until the animals lost their righting reflex (LRR). Renal dysfunction reduced the total dose of PB required to produce LRR, the concentrations of total and free (unbound) PB in serum and the concentrations of PB in brain and cerebrospinal fluid at onset of LRR. Results were quantitatively similar in both experimental models of impaired renal function. Concomitant infusion of p-hydroxyphenobarbital (the major metabolite of PB) and PB in rats with uranyl nitrate-induced renal dysfunction had no effect on the PB concentrations at onset of LRR. When PB was infused at different rates (either 0.412, 0.824, 2.04 or 4.12 mg/min), rats with renal dysfunction had increasing concentrations of PB at onset of LRR with increasing infusion rate, not only in serum and brain but also (unlike normal rats) in cerebrospinal fluid. Thus, renal dysfunction is associated with increased sensitivity to PB and with a change in the kinetic relationship between PB in cerebrospinal fluid and in the biophase.     

Serotonin increases glial cell line-derived neurotrophic factor release in rat C6 glioblastoma cells

Antidepressants, which increase monoamine levels, induce glial cell line-derived neurotrophic factor (GDNF) release in C6 cells. Thus, we examined whether monoamines affect on GDNF release in C6 cells. We found that serotonin (5-HT) specifically increased GDNF mRNA expression and GDNF release in a dose- and time-dependent manner. The 5-HT-induced GDNF release was mediated through the MEK/mitogen-activated protein kinase (MAPK) pathway and, at least, 5-HT(2A) receptors. The action of 5-HT on GDNF release may provide important insights into the mechanism of antidepressants.