Serial histologic observation of endometrial adenocarcinoma treated with high-dose progestin until complete disappearance of carcinomatous foci--review of more than 25 biopsies from five patients.

This study aimed to document chronologic histologic changes of endometrial biopsies from patients with endometrial adenocarcinoma on high-dose progestin therapy. Seven patients with presumptive FIGO stage IA endometrial adenocarcinoma treated with medroxyprogesterone acetate 600 mg/day were investigated retrospectively. Good response was defined as complete disappearance of carcinoma foci within 16 weeks of treatment and poor response as the presence of residual foci at 16 weeks. Two patients were poor responders and were excluded from the study, while five good responders were analyzed. Hematoxylin and eosin (H&E)-stained slides were reviewed and analyzed based on nine histologic features to describe the histology observed commonly in good responders. All the five good responders showed relatively uniform morphologic changes during the high-dose progestin therapy and the common histology was described as follows. The first change was swelling of the neoplastic glandular epithelial cells with pale vacuolated cytoplasm and round to oval nuclei. Mitotic arrest was also observed. Next, the epithelia were disrupted by lymphoplasmocytic infiltration and replaced by low cuboidal epithelium with or without squamous or morular metaplasia. The stromal area increased with predecidual changes. The final morphology was small atrophic glands scattered in predecidual stroma with dilated vessels. Therefore, the morphologic change of the endometrial biopsy observed in earlier stage of treatment might be able to predict good response to high-dose progestin therapy.

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Mitotic index and ki-67 nuclear antigen labeling index as predictors of chemotherapy response in uterine cervical carcinoma.

OBJECTIVE: The aim of this study was to determine if the mitotic index (MI) and the Ki-67 nuclear antigen labeling index (Ki67LI) obtained from biopsy specimens could be used as predictors of chemotherapy response in uterine cervical carcinomas. METHODS: Six patients with squamous cell carcinoma who received neoadjuvant chemotherapy before radical surgery were entered into the study. The MI and the Ki67LI were evaluated using hematoxylin and eosin (H&E)-stained and immunostained slides before and after chemotherapy. Tumor size was measured three-dimensionally by magnetic resonance imaging. We compared the values of MI and Ki67LI with changes in tumor size. RESULTS: The cases were classified according to the percentage reduction in tumor mass: one case showed a marked response (98%), four showed a moderate response (53-78%), and one showed a slight response (approximately 0%). In the case with a marked response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 15, 2, and 0, respectively. The corresponding Ki67LI values were 51, 16, and 0, respectively. In the moderate response cases, the corresponding MI values before and 3 and 7 days after chemotherapy were 3.9-13.6, 0.8-1.6, and 1.6-4.0, respectively. The Ki67LI was 21.8-44.2 before chemotherapy, with two cases increasing and two decreasing at 7 days after chemotherapy. In the case showing a slight response, the MI values before chemotherapy and 3 and 7 days after chemotherapy were 0.5, 0.8, and 1.0, respectively. The Ki67LI was 4.0 before chemotherapy and increased slightly to 6.0 at 7 days after chemotherapy. CONCLUSIONS: In six cases examined, high MI and Ki67LI values before chemotherapy and a marked decrease in MI shortly after chemotherapy appeared to be predictors of good neoadjuvant chemotherapy response in uterine cervical carcinomas.

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium.

To determine whether pulmonary alveolar capillaries manifest ultrastructural remodeling at areas of neoplastic invasion of primary lung adenocarcinomas, we examined 17 well-differentiated adenocarcinomas of lung (2 bronchioloalveolar and 15 papillary adenocarcinomas) by electron microscopy. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was demonstrated by immunohistochemical stainings. VEGF messenger RNA (mRNA) isoforms were detected by reverse-transcription polymerase chain reaction (RT-PCR) in alveolar walls microdissected from normal and tumor-associated tissues. Cytoplasm of neoplastic cells expressed VEGF protein in all patients. Endothelial cell nuclei of alveolar capillaries showed positive reaction for PCNA. Alveolar capillary lumina were distended like venules, and some intercellular junctions remained open. The cytoplasm of the capillary endothelial cells was enlarged and developed numerous organelles such as Weibel-Palade bodies and vesiculovacuolar organelles, in contrast to marked attenuation in their normal counterpart. Capillary sprouting occurred from proper alveolar capillaries in 2 patients. Cytoplasmic segments became extremely attenuated and developed diaphragm-like fenestrae in 65% of the patients. A relatively higher expression of diffusable isoforms of VEGF mRNA was seen in the tumor-bearing alveolar walls than in normal walls. Expression of KDR (one of the VEGF receptors) mRNA in tumor exceeded that in normal tissues. These results suggest that diffusable isoforms of VEGF mRNA released from the neoplastic cells are deeply involved in the induction of growth activity of alveolar capillary endothelial cells as much as in the characterization of tumor-associated microvessels in primary lung adenocarcinomas.

Gastrointestinal stromal tumor of the stomach diagnosed preoperatively.

A case of gastrointestinal stromal tumor (GIST) of the stomach is reported. GIST has been applied to gastrointestinal submucosal tumors mainly composed of spindle shaped cells that represent neither typical features of myogenic nor neurogenic tumors, and immunohistochemical studies are necessary for the diagnosis of GIST. The patient was a 39-year-old man and was successfully diagnosed to be GIST (uncommitted type) preoperatively by immunohistochemical studies of biopsy specimens from an ulcerative submucosal tumor with bridging folds in the fundus, approximately 3.0 cm in size. Local excision of the stomach was performed. This is the 3rd case of GIST with a preoperative diagnosis to appear in the literature in Japan. For gastroenterological surgeons, it is critical to select the most suitable surgical procedure. In the present, because the number of papers reporting GIST of the stomach is small, it is impossible to review GIST clinicopathologically. We reviewed the surgical procedure for gastric leiomyosarcomas, because of including many cases with GIST in them. Therefore, we performed 54 cases of gastric GIST in the literature, compared with 92 cases of gastric leiomyosarcoma. As a result, it was thought that local excision for gastric GIST should be preferred.

MRI findings of a case of uterine tumor resembling ovarian sex-cord tumors coexisting with endometrial adenoacanthoma.

A case of uterine tumor resembling ovarian sex-cord tumors is reported. MRI was performed for the staging of the endometrial adenoacanthoma diagnosed by biopsy. A well-defined, slightly hyperintense mass with central hypointensity was noted in the myometrium on T2-weighted images. Pathological diagnosis of the myometrial mass was uterine tumor resembling ovarian sex-cord tumors. The central hypointense area was a leiomyomatous component. Adenoacanthoma was also confirmed. These features of coexisting tumors correlated well with the MRI findings.

Spontaneous regression of a germinoma in the pineal body after placement of a ventriculoperitoneal shunt.

The authors report a case in which a germinoma in the pineal body displayed spontaneous regression after placement of a ventriculoperitoneal (VP) shunt. Spontaneous regression of malignant tumors is extremely rare, occurring in only one of 60,000 to 100,000 patients. Although in rare cases spontaneous regression is known to occur in patients with testicular seminomas, only one case of spontaneous regression of a primary pineal germinoma has so far been reported. In the present case a 17-year-old man presented with headache. A tumor in the pineal body and acute hydrocephalus were revealed by head computerized tomography (CT) and magnetic resonance (MR) imaging, and VP shunt placement was performed. Computerized tomography scanning of the head was performed four times during a 2-week period following the operation, and the patient was temporarily discharged to return to school. At the time of discharge, CT scanning demonstrated no change in the size of the tumor. Two months later, the patient was readmitted to the hospital to undergo surgery. At that time, head MR imaging revealed regression of the tumor. The pathological diagnosis of the lesion was germinoma. The patient underwent three courses of chemotherapy, during which carboplatin and etoposide were administered, in addition to a 24-Gy dose of radiotherapy. No manifestations of nerve impairment were noticed, and the patient was observed on an outpatient basis. The authors think that the factors involved in tumor regression included the effects of the VP shunt, the effects of radiation absorbed during head CT scanning, and the role of the patient's own immune response. However, no conclusion has been reached concerning the actual cause.

Mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes (MELAS) with prominent degeneration of the intestinal wall and cactus-like cerebellar pathology.

A 67-year-old woman had frequent subacute ileus, hearing difficulty, muscle atrophy and stroke-like episodes. Computed tomography revealed multiple low-density areas, which did not correlate with the vascular supply, in the cerebral cortex. She had metabolic disturbance comprising lactic acidosis and elevated pyruvate level. Her skeletal muscle biopsy specimen showed ragged-red fibers, and mitochondrial DNA analysis revealed a point mutation at position 3243, findings consistent with MELAS. Examination of her small intestine revealed a necrotic zone and numerous abnormal large mitochondria in the smooth muscle cells, vascular media and endothelium, and intestinal ganglion cells. The cerebral cortex showed multiple microcystic necrotic foci in cerebral cortex. Cactus-like pathology resembling the changes associated with Menkes' kinky hair disease and torpedoes were observed in the cerebellar Purkinje cells. The intestinal dysmotility due to MELAS and cerebellar changes were presumed to be associated with a disturbance of copper metabolism.

Adhesion molecule detection in a case of early cerebral malaria: immunohistochemical and electron microscopic findings.

A case of early cerebral malaria caused by Plasmodium falciparum was studied. P-selectin glycoprotein ligand 1 (PL1) was detected along the inner surface of the infected red blood cells (IRBCs), which ordinarily are not positive for PL1 immunohistochemically, suggesting PL1 being the product of parasite. The electron microscopic finding showed granular deposits in the corresponding lesion, consistent with PL1 deposition, in the IRBCs firmly attached to the endothelium of small cerebral vessels. Most of the IRBCs were round shaped as though they lost their capacity to change shape. The therapeutic strategy was expected against adhesion molecules such as PL1 and for maintaining or restoring the metamorphic capacity of IRBCs.

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Cystic struma ovarii: imaging findings.

We report three cases of cystic struma ovarii not associated with any solid component. One case was a thin-walled unilocular mass, and the other two cases were multilocular cystic masses. An area of signal void on T2-weighted images and intermediate intensity on T1-weighted images was noted in the two multilocular cases. Preoperative diagnosis was difficult in each case, but struma ovarii should be included in differential diagnoses even in the case of a completely cystic ovarian mass.

Mosaic-like distribution of endothelial cell antigens in capillaries and juxta-alveolar microvessels in the normal human lung.

The distribution patterns of endothelial cell antigens, including thrombomodulin and von Willebrand factor (vWf), were studied in normal lung tissues obtained from distant areas of solitary nodules (seven adenocarcinomas and four hamartomas). By single immunoalkaline phosphatase and dual immunofluorescence stainings, the plasma membranes of alveolar capillary endothelium showed linear distribution of thrombomodulin, but their cytoplasm was rarely reactive for vWf (thrombomodulin-dominant pattern). Microvessels with a diameter larger than 10 microm located in the connective tissue zones demonstrated band-like reaction for vWf in their cytoplasm, and their plasma membranes often lacked reactivity for thrombomodulin (vWf-dominant pattern). The juxta-alveolar microvessels located along the borders between the alveolar- and connective-tissue zones showed mosaic-like pattern of distribution for these antigens. The pulmonary venules and peribronchial microvessels measuring up to 40 microm in diameter, demonstrated the expression of thrombomodulin along the plasma membrane, and that of vWf in the cytoplasm. Capillaries of the bronchial circulation were also characterized by mosaic-like pattern of distribution. Both antigens were often expressed in a single cytoplasmic segment. The heterogeneous distribution pattern of these antigens suggests topographic difference in endothelial cell function to maintain coagulatory and anticoagulatory balance in the normal human lung.

Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.

OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.

[The relationship between p53 protein and c-erb B-2 expression and apoptosis in colorectal cancer].

In order to elucidate the relationship between tumor growth and various kinds of gene expression and the occurrence of apoptosis in the front portion of neoplastic invasion, 57 advanced colorectal cancers were studied by immunohistochemical staining of p53, c-erb B-2, the TUNEL method and electron microscopy. Light microscopically, the columnar epithelial cells of adenocarcinoma frequently showed a decrease in high and a fall off into the lumen in tumor invasive forefront. Immunohistochemically the positive rate of p53 and c-erb B-2 in tumors with high vascular invasion were higher (p < 0.05) than in those with low vascular invasion. There was a close correlation between the vascular or lymphatic invasion and positive immunoreactivity of p53 and c-erb B-2. The apoptosis index was demonstrated to be related to vessel invasion, over expression of p53 and inflammatory cell infiltration around the front portion of the tumor invasion. These results suggested that p53. c-erb B-2 and the apoptosis index should be evaluated in conjunction with the prognostic factors in colorectal cancer. The infiltrative inflammatory cells may induce apoptosis of the tumor cells.

New method of bladder biopsy using combined aspiration and snare.

A method of multiple random biopsy combined with bladder wall aspiration and snare in bladder cancer is presented. Our method was used on 23 patients with clinically superficial bladder cancer and was found to have advantages in obtaining an adequate amount of tissue with minimal thermal degeneration.

A case report of renal cell tumor in a 45-year-old female mimicking lower portion nephrogenesis.

This report describes a renal tumor with an unusual histology in a 45-year-old woman. The tumor was white in color, different from usual renal cell carcinoma, and mainly consisted of variously shaped tubules formed by flat or cuboid cells within marked edematous stroma. Elaborated branching or tubules arranged in a papillary pattern with focal spindle-shaped cell proliferation were characteristic features. Immunohistochemical staining expressed diffusely positive for vimentin and S-100 protein, partially positive for cytokeratin and epithelial membrane antigen and negative for Leu-M1, Leu-7, CD34 and markers for muscle cells. Ultrastructural studies of the tumor cells showed adenocarcinoma-like characteristics. According to these histological, immunohistochemical and electron microscopy findings, it is suggested that this tumor be designated as unclassified renal cell carcinoma with histology mimicking lower-nephron nephrogenesis.

[Three cases of adenomatoid tumor of the uterus].

Adenomatoid tumors arising in the uterus are not well-recognized and sometimes mistaken for other benign or malignant neoplasms. This study describes three cases of uterine adenomatoid tumors with clinical, light microscopic, histochemical and electron microscopical studies. Four distinctive histologic patterns (solid, adenoid, angiomatoid, cystic) were identified. Acid mucopolysaccharide was present in three cases and was digested by hyaluronidase. Immunohistochemically, tumor cells were positive for cytokeratin and vimentin. Electron microscopy revealed microvilli, intermediate filaments and dilated intercellular spaces. This gives further support to a mesothelial origin of the adenomatoid tumor. Interestingly, one case showed that the adenomatoid tumor was multiple and one nodule was connected with leiomyomatous nodule. In the other case, the tumor was large 5 x 4 x 4.5 cm). These features were unusual.