Nobukazu Miyoshi

Endocrine cell carcinoma (carcinoid) of the gallbladder.

We report two cases of endocrine cell carcinoma of the gallbladder associated with adenocarcinoma. The patients were women with numerous gallstones. Histologically, the tumors consisted of adenocarcinoma and endocrine cell carcinoma. An apparent transition was noted between the two types. Tumor cells of both the endocrine cell carcinoma and the adenocarcinoma were argyrophilic. In one case the tumor was surrounded by metaplastic mucosa; in the other case, it was surrounded by dysplastic and metaplastic mucosa. The nonneoplastic mucosae also contained argyrophil cells in varying number. These findings suggest that endocrine cell carcinoma of the gallbladder is derived from metaplastic epithelium of the gallbladder.

PTEN expression is maintained in sporadic colorectal tumours

Loss of PTEN (phosphatase and tensin homologue deleted from chromosome 10) function has been implicated in the progression of several types of cancer. Allele loss close to the PTEN locus occurs in sporadic colon cancer and germline PTEN mutations cause Cowden disease, an inherited cancer syndrome characterized by an increased incidence of gastrointestinal tract lesions that can progress to colorectal carcinoma. However, although PTEN is a good candidate for involvement in the pathogenesis of sporadic colon cancer, previous analyses have not revealed a high frequency of somatic mutations in colorectal tumours. Alternative mechanisms which could lead to a loss of PTEN expression in colon cancer have not been investigated. This study monitored PTEN mRNA and protein levels in a panel of 50 tumour tissues obtained from 35 patients with sporadic colon cancer. RT‐PCR and immunohistochemistry were used to evaluate the expression of mRNA and protein, respectively, in normal, adenoma and adenocarcinoma colorectal tissues as well as in metastatic lesions. To overcome the problem of heterogeneity and normal stromal cell contamination in homogenized tissue specimens, specific cell types were isolated by microdissection prior to PCR analysis. No loss of PTEN expression was evident in any of the colon tissues examined. PTEN protein was localized exclusively in the cytoplasm of normal and tumour cells and no correlation of immunostaining intensity and tumour stage or grade was revealed. As with previous deletion and mutation analyses, the present study suggests that loss of PTEN expression is not prevalent in sporadic colon cancer. Copyright

Carcinosarcomas of the esophagus

Two cases of carcinosarcoma of the esophagus are reported. Both were polypoid tumors occurring in the middle of the intrathoracic esophagus. The tumors were predominantly composed of spindle‐shaped sarcoma cells with some squamous cell carcinomas (SCC). One tumor showed many bizarre giant cells with filamentous materials in the cytoplasm. Microscopical examination of both tumors revealed transition from SCC to sarcoma cells. Immunohistochemi‐cally, the spindle‐shaped sarcoma cells in both tumors displayed a strongly positive immunoreaction to alpha‐smooth muscle actin, as did the bizarre giant cells of one tumor to sarcomeric actin. SCC and a few spindle‐shaped sarcoma cells near the SCC showed a positive immunoreaction to cytokeratin. Electron microscopy revealed that the spindle‐shaped cells had many myofilaments with dense bodies and that the bizarre giant cells had sarcomere structures with 2‐bands in their cytoplasm. These findings indicate that both tumors were carcinosarcomas of SCC and myogenic sarcoma. We considered that sarcoma cells might originate in SCC, representing its metaplastic differentiation, or that both SCC and sarcoma might originate in a pluripotent stem cell.

Comparison of proliferative activities and metastases between two subtypes classified at the deeply infiltrating sites of colorectal moderately differentiated adenocarcinomas

Twenty‐eight moderately differentiated adenocarcinomas invading beyond the muscularis propria of the colorectum were subclassified as 13 moderate‐ and 15 poor‐subtype tumors based on the histology at the deeply infiltrating sites. Moderately differentiated cancer cells were correlated with liver metastasis and p53 immunoreactivity. Poorly differentiated cancer cells were correlated with lymph node metastases but not to p53 immunoreactivity. The proliferative cell nuclear antigen (PCNA) labeling index (LI), Ki‐67 LI and agyrophilic nuclear organizer regions (AgNOR) values determined for the poorly differentiated cancer cells in the poor‐subtype tumors were significantly lower than those of moderately differentiated cancer cells in the moderate‐subtype tumors. In cells from tumors classified as poor‐subtype, poor differentiation was associated with decreased PCNA LI levels, but with unchanged Ki‐67 LI and AgNOR values. These results Indicate that colorectal adenocarclnoma cells that are histologically subclassified as moderately differentiated have different proliferative and metastatic activities from cancer cells that are poorly differentiated. Moderately differentiated cancer cells are associated with hematogen‐ous metastasis to liver and high proliferative activity, and loss of tubular formation of cancer cells may be fundamentally related to lymph node metastasis and infittrative growth.

Changes in blood catecholamine levels and ultrastructure of dog adrenal medullary cells during hemorrhagic shock.

SummaryBlood catecholamine levels and ultrastructural changes in adrenal medullary cells were followed during the course of oligemic and normovolemic shock in dogs. Blood adrenaline concentration rose promptly after hemorrhage, reaching a maximum that was 10-fold greater than normal during the early period of hemorrhagic hypotension. Thereafter, adrenaline levels gradually declined until the end of the critical stage of hemorrhagic shock when the blood concentration rose to a level 8-fold that of normal. Following the critical stage, and throughout the irreversible stages of shock, adrenaline levels remained near normal. Noradrenaline, which was initially undetectable, first appeared in the impending stage of hemorrhagic hypotension and showed little change during the course of severe hemorrhagic hypotension.Ultrastructural studies demonstrated A-cell degranulation as early as 5 min after initiation of hemorrhage. Degranulation continued throughout the impending stage of hemorrhagic hypotension and was associated with an increasing number of autophagic vacuoles containing empty vesicles. At the end of the critical stage, all A cells showed complete degranulation and degenerative hydropic change. Progression to necrosis rather than arrest or reversal of hydropic change was observed after reinfusion of blood. In contrast to the marked alterations in A cells, most N cells were morphologically unchanged.

ENDOCRINE CELL CARCINOMA OF EXTRAHEPATIC BILE DUCT

An endocrine cell carcinoma of the extrahepatic bile duct in a 79‐year‐old man is described. The patient had complaints of jaundice and epigastric pain due to a small tumor located at the confluence of the common hepatic duct with the cystic duct. Microscopically, the tumor showed a well differentiated tubular adenocarcinoma and was confined to the mucosa. Numerous tumor cells showed argyrophil and/or argentaffin reactions. Immunoperoxidase staining revealed that the tumor tissue contained somatostatin‐, gaastrin‐and serotonin‐ immunoreactive cells. From these findings the tumor was diagnosed as endocrine cell carcinoma. Four years later he remains well without any evidence of recurrence or metastasis. The histogenesis of endocrine cells in the biliary tract is briefly discussed.