Shoji Tokuoka

Duodenal gangliocytic paraganglioma with lymph node metastasis in a 17-year-old boy

A case of duodenal gangliocytic paraganglioma (DGP) in a 17‐year‐old boy is presented. In this case a lymph node in the peripancreatic region was involved by a metastatic tumor. A review of the literature on DGP indicates that this case represents the youngest patient and is the second case of DGP with metastasis. Immunohistochemical staining for neuron‐specific enolase (NSE), neurofilament (NF), pancreatic polypeptide, and somatostatin showed positive results for epithelioid and ganglion‐like cells, whereas spindle cells showed immunoreactivities for S‐100 protein, NSE, and NF. The histogenesis of DGP is discussed.

Hepatocellular Tumorigenicity of Butylated Hydroxytoluene Administered Orally to B6C3F1 Mice

Butylated hydroxytoluene (BHT), a preservative widely found in food as a food additive, was orally administered at concentrations of 1% and 2% of the diet to B6C3F1 mice for 104 consecutive weeks. Treated animals underwent a 16‐week recovery period prior to pathological examination. In male mice administered BHT, the incidence of mice with either a hepatocellular adenoma or a focus of cellular alteration in the liver was increased in a clear dose‐response relationship. The incidences of male mice with other tumors and the incidences of female mice with any tumor were not significantly increased as a consequence of BHT administration. The results of this study indicate BHT to be tumorigenic to the liver of the B6C3F1 male mouse.

EARLY CANCER AND RELATED LESIONS IN THE BRONCHIAL EPITHELIUM IN FORMER WORKERS OF MUSTARD GAS FACTORY

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex‐workers with lung cancer, 17 MG ex‐workers with non‐lung cancer, 10 non‐MG lung cancer cases, and 20 non‐MG non‐lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2, 226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non‐lung cancer cases resembled that found in lung cancer cases of both MG and non‐MG exposed. Seven CIS lesions were detected from among all MG‐exposed cases and one CIS was found in a non‐MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi‐variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.

Tumorigenicity study of butyl and isobutyl p-hydroxybenzoates administered orally to mice

Butyl p-hydroxybenzoate (n-BHB) and isobutyl p-hydroxybenzoate (i-BHB) were administered orally to ICR/Jcl mice at concentrations of 0.6 (maximum tolerated dose), 0.3 or 0.15% in the diet for up to 102 wk. Tumours were observed at various sites including the haematopoietic system, the lung and the soft tissue. However, at none of the sites did the tumour incidence or the time to death with tumours differ significantly from that in the untreated control group.

Tumorigenicity study of disodium glycyrrhizinate administered orally to mice

Disodium glycyrrhizinate (DG) was administered at concentrations of 0.15 (maximum tolerated dose), 0.08, 0.04 or 0% in the drinking-water to groups of 50, 70, 60 and 60 male B6C3F1 mice, respectively. Female groups, each consisting of 50 mice, were given DG in the drinking-water at concentrations of 0.3 (maximum tolerated dose), 0.15, 0.08 or 0%. Treatment was continued for 96 wk and the experiment was terminated at wk 110. There was no difference between treated and control groups in tumour incidence, in the latent period before tumours appeared or in the distribution of different types of tumour. Thus the long-term oral administration of DG to mice did not yield any evidence of chronic toxicity or tumorigenicity.

Findings of myoepithelial cells in human breast cancer. Ultrastructural and immunohistochemical study by means of anti-myosin antibody.

Detailed light and electron microscopic, and immunohistochemical observations were made on the distribution and morphological characteristics of myoepithelial cells in the 53 cases of breast cancer. In non‐invasive carcinoma, myoepithelial cells in the normal duct were found to be remaining at the outer margin of the cancer nests, but neoplastic myoepithelial cells were not detected in the carcinoma tissue. In invasive carcinoma, a small number of fluorescence‐weakly‐positive cells could be observed in more than 50% of medullary‐tubular carcinoma, in all cases of papillary‐tubular carcinoma, and two of three cases of invasive lobular carcinoma. Almost all of these cells were ultrastructurally intermediate cells which have the morphological characteristics of both epithelial cell and myoepithelial cell. Fluorescence‐positive cells were observed in all cases of scirrhous carcinoma. Moreover, these cells showed a stronger fluorescence than that of other types of carcinoma and were ultrastructurally more similar to normal myoepithelial cell. The tumor cells having myoepithelial characteristics in invasive carcinoma showed a stronger tendency for arranging at the margin of carcinoma nests in contact with the stroma. The results of the present study indicate that in invasive carcinoma of the breast, neoplastic myoepithelial cells could be demonstrated together with ductal epithelial cells and as to its histogenesis, there is a possibility that breast cancer develops from common stem cells which have the ability of differentiating into both epthelial and myoepithelial cell because of the presence of intermediate cells. ACTA PATHOL. JPN. 34: 537–552, 1984.

Response of the uterine smooth muscle cell to estrogen stimulation;An electron microscopic and autoradiographic study

A study of the myometrial smooth muscle cells of the rat and mouse uteri following estrogen administration was undertaken in order to correlate known chemical changes in the estrogen‐stimulated uterus, to possible morphological and/or functional alterations in the myometrial smooth muscle cells.

Lack of Tumorigenicity of Aminopyrine Orally Administered to B6C3F1 Mice

To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1, mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study.

An ultrastructural study on precancerous and cancerous lesions of the glandular stomach in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine.

Electron microscopic study was made on precancerous and cancerous lesions in glandular stomach of rats induced by MNNG. Three types of lesions, were found; regenerative glandular hyperplasia, adenomatous hyperplasia and adenocarcinoma. These were compared with the fine structure of similar lesions produced by X‐irradiation in the glandular stomach of mice. The precancerous lesion in the present study demonstrated formation of adenomatous hyperplasia by epithelial cells which included mucoid cells characterized by sparce surface microvilli, a few erratic terminal webs, small number of mucous granules, many small mitochondria, and a bizarre nucleus. The development of these mucoid cells seems to be related with the growth of gastric carcinoma. The ultrastructure of adenocarcinomas revealed many structural variations or abnormalities of cellular differentiation. They were classified into 1) surface and pit mucous cell type, 2) pyloric gland cell type, 3) goblet cell type, 4) paneth cell type, 5) intestinal epithelial cell type, 6) endocrine cell type, 7) oncocyte type, 8) filament‐rich cell type, and 9) anaplastic cell type involving intracellular microcyst cells. Filament‐rich cells were found in poorly differentiated adenocarcinoma or scirrhous carcinoma and may be derived from metaplasia of tumor cell.

An altered lectin binding to mucus glycoprotein in goblet cells of human tracheobronchial epithelium among former mustard-gas workers.

Lectins, which are well known to have an ability to bind with specific carbohydrate residues of glycoprotein, have been used to examine cellular changes associated with malignant transformation. For the analysis of mucus glycoprotein of goblet cells in the tracheobronchial epithelium, 192 paraffin‐embedded sections from 54 autopsy cases including the cases with a history of mustard‐gas (MG) exposure were stained with seven plant lectins using PAP method. PNA binding with no neuraminidase treatment as well as BSA‐1 binding was observed most frequently in MG‐exposed lung cancer cases. The proportion of cases positive for SBA binding in MG‐exposed and/or lung cancer cases had a statistical difference from non‐MG‐exposed non‐lung cancer cases. These observations may indicate a large heterogeneity in oligosaccharide chains of mucus glycoprotein and suggest its incomplete or abnormal synthesis, which is most likely to be due to previous exposure to carcinogen, such as MG. ACTA PATHOL. JPN. 37:537–548, 1987.