Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases

Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma.     

Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine

Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) in various doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7–10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues; they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner, and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of injury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction. Received: 21 June 1996 Received after revision: 8 October 1996 Accepted: 12 November 1996     

CHARACTERISTICS OF HISTIOCYTIC LESIONS IN THE RETICULOENDOTHELIAL SYSTEM OF NZB MICE

The so-called Potter's lesion, previously described as preneoplastic in the lymph nodes of C58 mice, develops frequently in autoimmune NZB mice. These lesions were characterized in the present study by bands or sheets of palestaining histiocytic cells in the cortex and medulla of the lymph node, and multiple small nodules of the same cells were found in the red pulp of the spleen and the liver. Electron microscopically, the cells had pleomorphic cytoplasm with long processes, electron-dense bodies, abundant mitochondria, and a characteristic labyrinth structure with many C-type viruses. Mac-1 antigen, IgG-Fc receptor, ferritin, and ACPase activity were identified on these cells. Intraperitoneally-injected iron colloids were found in the lesions of the spleen and liver but not in those of the lymph nodes. The lymph node lesions appeared when the mice were about 3 months of age and enlarged until the mice were around 10 months old, after which they gradually receded and were replaced by small vessels and fibroblastic cells. These data indicate that the lesions represent reactive hyperplasia of the macrophage system and may have no direct association with the development of malignant lymphoma in NZB mice.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Establishment and morphologic characterization of a cell line (DMBA-OC-1) from 7,12-dimethylbenz(a)anthracene-induced rat ovarian carcinoma

A new cell line (DMBA-OC-1) from 7,12-dimethylbenz (a) anthracene (DMBA) which induced ovarian carcinoma in rat was established and characterized. DMBA-OC-1 cells showed a paving-stone-like growth pattern at around the 10th to 20th passage, but at the point exceeding the 40th passage the cells showed a spindle form, having strong trends both towards flocculation and piling-up. Furthermore, diastase-resistant PAS-positive and hyaluronidase-digested Alcian blue positive substances were observed in cytoplasms. The cells also showed marked phagocytic activity. These findings suggest that DMBA-OC-1 cells are most likely the site of mesothelial cell origin.     

The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer

Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P<0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP<0.01 andP<0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P<0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P<0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.     

Laparoscopic Findings in Senescent Patients with Primary Biliary Cirrhosis

Abstract: Fifty -two patients with primary biliary cirrhosis (PBC), 10 of whom were 65 years or older at the time of diagnosis, were investigated by laparo-scopy. Laparoscopic findings in these 10 patients were evaluated and compared with those in younger patients. The 10 cases were composed of nine females and one male, and two had been diagnosed as having symptomatic PBC with skin itching, while the remaining eight had asymptomatic PBC. Two, seven and one case were in Scheuer's stage I, II and III, respectively, and eight had chronic non-suppurative destructive cholangitis (CNSDC) on liver biopsy specimens. The majority of senescent PBC patients had typical findings of the early stage of PBC on the liver surface; mild undulations in nine and reddish patches in eight. The laparoscopic findings in senescent PBC were relatively mild.     

A patient with hepatic granuloma formation and angiotensin-converting enzyme production by granuloma cells during clinical relapse of hepatitis A

Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis.     

Alveolar soft part sarcoma of the uterine cervix

A rare case of an alveolar soft part sarcoma of the uterine cervix in an 8 year old girl is presented. The patient was admitted because of genital bleeding lasting for 7 months. A polypoid tumor, 2times1.5 cm in diameter, was found in her external uterine os and was surgically resected. Microscopically, the tumor consisted of a uniform sheet of tumor cells in the cytoplasm which contained granules and which were stained with periodic acid-Schiff, both before and after the diastase digestion. Alveolar arrangement of the tumor cells was manifested with reticulin silver impregnation. Dense, membrane bound granules were evident at an ultrastructural level in the cytoplasm of the tumor cells. An immunohistochemical examination demonstrated a positive reaction for anti-desmin, anti-myoglobin, anti-HHF35 and anti-neuron specific enolase in the cytoplasm.     

Ultrastructural myeloperoxidase activity and expression of myeloid-associated antigens in acute lymphoblastic leukemia

Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL.