Fhit expression in human gastric adenomas and intramucosal carcinomas: correlation with Mlh1 expression and gastric phenotype.

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P=0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P=0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P=0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.

Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma.

The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple tumour types including colorectal carcinomas. Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated). In addition, we examined whether the Fragile histidine triad and mismatch repair protein expression correlated with p53 expression and clinicopathological findings. Significant loss or reduction of Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately-differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being significantly higher in the latter than that in the former two (P<0.0001). Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile histidine triad and mismatch repair protein expression was not significantly associated with p53 expression. These results suggested that reduced Fragile histidine triad expression might be correlated with mismatch repair expression, but not with p53 expression.

Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no correlation with p53 expression and apoptosis.

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.

Hypoplasia of the left hepatic lobe associated with floating gallbladder: a case report.

Agenesis or hypoplasia of the hepatic lobe and floating gallbladder are both rare. We report an extremely rare case of hypoplasia of the left hepatic lobe accompanied by floating gallbladder. The patient was a 71-year-old woman, with no past history of related symptoms, who was admitted for further evaluation of postprandial epigastralgia, nausea, and diarrhea. Laboratory data on admission showed chronic liver disease with positive anti-hepatitis C virus antibody. Abdominal ultrasonography and computed tomography revealed the absence of the left hepatic lobe and displacement of the gallbladder to the left. On endoscopic retrograde cholangiography, the cystic duct originated from the right side of the bile duct, but the gallbladder was displaced to the left. Poor yolk-induced gallbladder contraction suggested the existence of hypotonic biliary dyskinesia. Angiography demonstrated no middle or left hepatic arteries, indicating congenital hypoplasia of the left hepatic lobe. Open cholecystectomy was carried out, and a diagnosis of hypoplasia of the left hepatic lobe accompanied by floating gallbladder and chronic hepatitis was confirmed. We believe that this is the first reported case of a hypoplasia of the left hepatic lobe coexisting with floating gallbladder.

Histologic examination of two cases of cystosarcoma phylloaes with pulmonary metastases.

BACKGROUND: Cystosarcoma phyllodes (CP) is a rare neoplasm of the breast. Many studies of the histology of CP have been reported. However, few reports have included an evaluation of the histologic appearance of pulmonary metastases, or the change in histologic grade as a function of time in patients with recurrent tumors. METHODS: We treated two patients with pulmonary metastases, CP from 1973 to 1995. One patient died of respiratory failure. The other underwent six operations for CP. We evaluated the histologic characteristics of these metastases and changes in the histologic grade of recurrent tumors. RESULTS: The primary lesions in these two cases were typical high-grade malignant tumors. Case 1 had multiple pulmonary metastases and histologic findings indicated typical malignant CP. Case 2 had a solitary pulmonary metastasis and histologic findings showed low-grade malignant CP, which could be resected. The first patient died of respiratory failure ten months after surgery. The second had no further pulmonary metastases although she had frequent local recurrences, and the histologic features of these tumors became progressively worse. CONCLUSION: We suggest that patients with malignant CP be followed closely and that when pulmonary metastases are detected, they should be resected if possible, because pulmonary metastatic tumors may represent lower-grade malignant CP.

Extrahepatic portal obstruction without hepatopetal pathway associated with congenital arterioportal fistula: a case report.

Extrahepatic portal obstruction is one of the causes of portal hypertension, in which well-developed hepatopetal pathways are commonly recognized. Herein an extremely rare case of extrahepatic portal obstruction without hepatopetal pathway, probably caused by arterioportal fistula, is reported. The patient was a normally matured 16-year-old girl admitted for further evaluation of jaundice, presenting with the clinical manifestations of the portal hypertension associated with hypersplenism and portosystemic venous shunt. Celiac angiography clearly demonstrated an intrahepatic arterial aneurysm fed by the right hepatic artery shunting to the superior mesenteric vein, and portography disclosed complete obstruction of the portal trunk with conspicuous hepatofugal pathway but no hepatopetal collateral veins. The exact mechanism of this phenomenon is not known and whether the extrahepatic portal obstruction was primary or secondary is still obscure. However, this is the first case report in the world literature describing extrahepatic portal obstruction with absence of hepatopetal pathway.

Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases.

AIMS: Four cases of hepatoid adenocarcinoma, three in the stomach, and one in the sigmoid colon, are presented to emphasize venous permeation and mimicry of hepatocellular carcinoma by metastatic liver nodules. METHODS AND RESULTS: Tumour cells in all cases extensively invaded vems, and intravenous tumour thrombi in two cases were grossly observed as anastomosing, worm-like cords up to 10 mm in diameter in the lesser omentum and mesentery in continuity with the primary mucosal lesions. The cytological features and trabecular architecture of the metastatic liver nodules in these subjects mimicked primary hepatocellular carcinoma. In a third case the tumour contained grossly visible bile in a metastatic lung nodule, but there was no evidence of bile production in the primary gastric or metastatic liver lesions. In the fourth case, detailed histopathological study revealed a gastric origin of the hepatoid adenocarcinoma, rather than primary hepatocellular carcinoma metastatic to the stomach, the initial diagnosis. CONCLUSIONS: These cases are reported here to draw attention to this rare variant of gastrointestinal adenocarcinoma, its mimicry of hepatocellular carcinoma when metastatic to the liver and other sites, and its propensity for venous permeation.

Acute necrotizing eosinophilic myocarditis with giant cell infiltration after remission of idiopathic thrombocytopenic purpura.

Acute necrotizing eosinophilic myocarditis is characterized by acute onset, fulminant congestive heart failure, and extensive necrosis of myocytes with striking eosinophilic infiltration. However, multinucleated giant cells sometimes appear in the fulminant phase of severe myocarditis. This is the first case of a patient with a 1 year previous history of idiopathic thrombocytopenic purpura, who presented with acute necrotizing eosinophilic myocarditis with giant cell infiltration.

Epithelial cyst in the cerebellopontine angle.

A 63-year-old male presented with a rare epithelial cyst in the left cerebellopontine angle manifesting as left facial nerve paresis and left cerebellar signs. Computed tomography revealed a well-defined cystic mass of homogeneous low density with no enhancement. Magnetic resonance imaging also demonstrated a cystic mass appearing as low intensity on T1-weighted images and high intensity on T2-weighted images. The cyst content was clear fluid. The cyst wall consisted of nonciliated, columnar epithelial cells, showing a pseudostratified arrangement in focal areas. Positive staining by periodic acid-Schiff, Alcian blue, and carcinoembryonic antigen suggested that the cyst was an enterogenous cyst of endodermal origin. Cysts in this location often cause cranial nerve impairment, but the symptoms are usually resolved by surgical treatment.

Expression of androgen receptors in skin appendage tumors: an immunohistochemical study.

Androgen receptor (AR) expression was examined in normal skin and in 52 cases of various skin appendage tumors using a monoclonal antibody (F39.4.1) raised against the N-terminal domain of human AR. Microwave oven heating in citrate buffer solution followed by immunostaining with the labeled streptavidin biotin (LSAB) method was applied to formalin-fixed paraffin-embedded sections. Immunoreactive AR was restricted to the nuclei. In normal skin, AR was consistently localized in seboblasts and in some differentiated sebocytes, and variable expression was seen in luminal epithelial cells of eccrine and apocrine glands in the secretory portion. Hair follicles and epidermis showed no reactivity. In sweat gland tumors, AR was identified focally in inner layer cells of the tubuloglandular component of ten of thirteen chondroid syringomas but the remaining tumors were nonreactive. In sebaceous gland tumors, benign tumors with mature sebaceous elements (sebaceous nevi and sebaceous adenomas) showed AR expression, but the sebaceous epitheliomas and sebaceous carcinomas lost their expression. No AR expression was observed in hair follicle tumors, except in AR-positive mature sebaceous glands incorporated into the cyst wall of steatocystomas.

Interphase cytogenetics of gastric carcinoma: fluorescence in situ hybridization (FISH) applied to cells obtained from formalin-fixed paraffin-embedded tissues.

The interphase cytogenetics in formalin-fixed and paraffin-embedded gastric cancer tissues were examined by fluorescence in situ hybridization (FISH) with alpha-satellite DNA probes. Two gastric carcinoma cell lines, TMK-1 and MKN-28, were first analyzed cytogenetically. Of 25 TMK-1 cell karyotypes, chromosome 7 showed trisomy and chromosome 17 showed disomy in 18 cells. Most MKN-28 cells showed disomy of both chromosomes 7 and 17. Suspensions of singly isolated TMK-1 and MKN-7 cells were obtained from the cultured cells, and from paraffin-embedded tissue specimens fixed with formalin for 0, 1, 3 and 5 days obtained from xenotransplanted tumors in nude mice. The numbers of chromosomes 7 and 17 analyzed with the karyotypic preparations coincided well with those determined by FISH, even in the paraffin-embedded specimens. The number of tumor cells showing no signals, however, increased in the specimens after 5 days formalin fixation. In 10 surgically removed gastric carcinomas, the predominant signal number for chromosomes 7 and 17 in the cells of paraffin-embedded tissues was two (disomy), except in one papillary carcinoma, which was trisomic for chromosome 7. Large subpopulations (more than 20%) showing trisomy were found in four cases for chromosome 7 and in five cases for chromosome 17. A higher frequency of trisomy was found in well differentiated than in poorly differentiated carcinomas. These findings suggest that the FISH technique is a useful tool for detecting chromosomal aberrations in gastric adenocarcinoma cells, even in paraffin-embedded specimens, as long as the tissues are fixed with formalin for an appropriate time.

T-cell lymphoma of the tonsil with Ki-1 antigen expression.

A 52-year-old woman was admitted to our hospital with a fever and swelling of the tonsils and lymph nodes. A tonsillectomy was performed and she was diagnosed as having non-Hodgkin's lymphoma of T-cell phenotype. Genotypic analysis revealed a rearrangement of the T-cell receptor gene, but not of the immunoglobulin genes. The neoplastic cells of the tonsils also expressed the Ki-1 antigen. The clinical course was aggressive with peripheralization of the neoplastic cells, and the patient died of respiratory failure.

Tenascin expression in normal human adult skin and skin appendage tumours.

The expression and distribution of tenascin, an extracellular matrix glycoprotein, was investigated immunohistochemically using an anti-human tenascin monoclonal antibody (RCB 1) in formalin-fixed paraffin-embedded tissues obtained from 79 patients with skin appendage tumours, and compared with adjacent normal skin. Tissue specimens were pretreated with actinase and processed by the labelled streptavidin-biotin method. In normal skin, tenascin immunoreactivity was consistently found around the ductal portion of the sweat glands, around the lower part of the hair follicle and hair bulbs, and around or within blood vessels. Immunoreactivity was also observed variably around secretory coils of the sweat glands, and below the epidermis. No immunoreactivity was seen around the sebaceous glands. Tumours originating from sweat glands and hair follicles expressed tenascin around the tumour cells nests, while sebaceous gland tumours were immunonegative. Thus, tenascin expression in skin appendage tumours generally resembled that in corresponding normal tissue.

Cytomegalic inclusion disease presenting acute intrahepatic cholestasis.

An 83-year-old man suffering from pulmonary emphysema was admitted to our hospital because of jaundice. He was diagnosed as acute intrahepatic cholestasis but the etiology could not be determined during the treatment period. In spite of treatment, the jaundice worsened progressively without any elevation in serum transaminase, and he died of respiratory failure 58 days later. An autopsy revealed a generalized cytomegalic inclusion disease, predominantly in the biliary tracts, liver and lungs. This is a rare case of cytomegalic inclusion disease presenting acute intrahepatic cholestasis without any elevation of transaminase during the clinical course.

Disseminated carcinomatosis of bone marrow from submucosal carcinoma in adenoma of the rectum.

A 62-year-old man was admitted because of paresis of the legs and a bleeding tendency. He was diagnosed as metastatic bone cancer with disseminated intravascular coagulation (DIC). In spite of treatment, his general condition progressively deteriorated and he died of respiratory failure 13 days later. Autopsy revealed a carcinoma in adenoma in the rectum. Although the depth of cancer invasion was confined to the submucosal layer, disseminated carcinomatosis of the bone marrow and tumor emboli in blood vessels of the lung were present.

Spontaneous epidural hematoma from a hepatocellular carcinoma metastasis to the skull--case report.

A rare case of acute epidural hematoma originating from a hepatocellular carcinoma metastasis to the skull in a 52-year-old male is reported. The skull metastasis and epidural hematoma were completely removed, but he died of large liver tumor. Histological examination of the removed tumor showed many sinusoid-like blood vessels, which probably lead to hemorrhage and formation of epidural hematoma.

[A case of abdominal actinomycosis following foreign body in the stomach wall].

Recently abdominal actinomycosis is rare. Its diagnosis is difficult because it resembles malignant diseases. We reported a case of abdominal actinomycosis considered to be of the stomach origin and attempted to correlate the radiological findings with the pathological features referring to the previous reports.

Preoperative radiotherapy and intra-abdominal metastasis of the lymph node in the surgical treatment of carcinoma of the thoracic esophagus.

Esophagectomy was performed upon 84 patients treated surgically for squamous cell carcinoma of the thoracic esophagus from 1965 to 1985 at the Tottori School of Medicine. Forty-four of these patients received preoperatively a total of 30 to 40 grays of cobalt 60 (2 grays per day) to the primary lesions, and 40 patients did not receive preoperative radiation therapy. A decreased tendency in the occurrence of metastasis to the intrathoracic lymph nodes was observed histologically in the group exposed preoperatively to radiation. A significant decrease in the occurrence of metastasis to the intrathoracic regional nodes in patients with carcinoma of the middle part of the thoracic esophagus was observed (p less than 0.02). A significant increase in the occurrence of metastasis to the intra-abdominal lymph nodes was observed in the patients receiving radiation therapy (p less than 0.01). The results indicate that preoperative radiotherapy for carcinoma of the thoracic esophagus may increase the risk of metastasis to the intra-abdominal lymph nodes.

Esophageal cancer developed after gastrectomy.

Between 1965 and 1983 we treated 129 patients with primary esophageal squamous cell carcinoma. Of these patients, 12 (9.3%) had previously undergone partial gastrectomy and six manifested tumors in the lower thoracic esophagus. Esophagitis of the noncancerous esophageal mucosa surrounding the cancer was confirmed in three of five patients who underwent esophagectomy. We also retrospectively evaluated 130 patients with esophageal cancer who had undergone gastrectomy, including our 12 patients, reported in the Japanese literature between the same period. Between patients with esophageal cancer who had undergone gastrectomy and those who had not there was no age difference; there were more men in the first group. Cancer developed in the lower thoracic esophagus with relatively high frequency in patients who had undergone gastrectomy compared with those who had not. The possibility of an association between gastrectomy and the subsequent development of esophageal cancer, especially lower thoracic esophageal cancer, cannot be ruled out. Further studies are necessary to clarify a possible association.