Intravascular papillary endothelial hyperplasia in the kidney of a child.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion which is thought to represent an unusual form of organizing thrombus. A case of IPEH in the kidney of a 7-year-old girl is described. She suffered from intermittent flank pain and gross hematuria for 6 months. On radiological examinations, well-defined hypoechoic lesions were identified in the medullary portion of the left kidney. A well-demarcated, sponge-like mass was noted on gross examination. It was an intravascular mass lined by a fibrous capsule of various thicknesses. It was characterized by papillary fronds lined with benign endothelial cells. This is the first description of a renal IPEH in a child.

Pelvic aspergillosis with tubo-ovarian abscess in a renal transplant recipient.

Common clinical manifestations of aspergillosis in renal transplant recipients are fever and pulmonary infiltrates, but involvement of the reproductive system is rare. We report a case of pelvic aspergillosis with tubo-ovarian abscess in a renal transplant patient. The patient received a cadaveric renal transplantation, and two episodes of acute rejection were treated with methylprednisolone pulse therapy. Surgical biopsy specimens of pelvic abscess detected by ultrasonogram and CT revealed Aspergillus. With amphotericin B treatment, the patient is well with normalization of erythrocyte sedimentation rate and C-reactive protein.

Quantitative histopathological evaluation of vocal cord dysplasia with particular emphasis on nuclear orientation.

We have applied morphometry on formaldehyde-fixed, H & E-stained diagnostic laryngeal biopsies from 7 patients with mild dysplasia and 7 with severe dysplasia/carcinoma in situ, in search of objective parameters required for reproducible histopathological grading of epithelial dysplasias. Special emphasis has been put upon the individual nuclear polarity as a spatial variable. Also included were 4 specimens with normal epithelium. By means of a semiautomatic digitizing tablet, the nuclear and epithelial area, formfactor and the polarity variation between the longitudinal axes of adjacent nuclei were measured in the basal, parabasal, middle and luminal layers of the epithelium. N:C-ratio, mean values of nuclear area, formfactor or their coefficient of variation could not distinguish between mild and severe dysplasia. The variations in neighboring nuclear polarity, however, revealed a highly significant distinction between mild and severe dysplasia (p less than 0.001). This parameter may therefore have diagnostic potential.

Diagnostic value of p53 protein and flow cytometric DNA analysis in the study of serous effusions.

OBJECTIVE: To investigate the diagnostic value of p53 protein and DNA analysis in the study of serous effusions. STUDY DESIGN: A total of 76 samples of serous effusions were studied by immunohistochemistry for p53 protein and flow cytometric (FCM) DNA analysis. The results were correlated with final cytologic diagnoses, which were confirmed by immunohistochemistry using antibodies against cytokeratin, carcinoembryonic antigen, epithelial membrane antigen and fibronectin. RESULTS: Final cytologic diagnoses included 28 malignant effusions and 48 benign effusions. No expression of p53 protein was seen in benign effusions. In contrast, p53 protein expression was seen in 19/28 (sensitivity 68%) malignant effusions. FCM detected aneuploid cells in 12/28 (43% sensitivity) of malignant and 0/46 of benign effusions. Immunohistochemical determination of p53 protein combined with FCM DNA analysis increased sensitivity to 79%. CONCLUSION: Immunohistochemical determination of p53 protein and FCM DNA analysis can aid in making an accurate and specific diagnosis of serous effusions, but the principal limitation of these tests is their relatively low sensitivity.

Fine needle aspiration cytology of Langerhans cell histiocytosis confined to lymph nodes. A case report.

BACKGROUND: Lymph node involvement in Langerhans cell (LC) histiocytosis (LCH) can be seen as a component of the systemic form, or it may be the initial and sometimes exclusive manifestation of the disease. Descriptions of patients with LCH whose disease is confined to lymph nodes are rare. CASE: We present a case of LCH confined to lymph nodes initially diagnosed by fine needle aspiration (FNA) cytology in a 43-year-old male. The cytologic findings in LCH included high cellularity, isolated LCs with prominent nuclear indentations and grooves, multinucleate giant cells, eosinophils and lymphocytes. Confirmation of LCH was obtained by positive S-100 protein immunohistochemical staining and the demonstration of Birbeck granules on electron microscopy. CONCLUSION: The presence of LCs with prominent nuclear indentations and grooves is characteristic of LCH confined to lymph nodes and serves as a key point in suggesting the diagnosis of LCH.

Fine needle aspiration cytology of anaplastic carcinoma with osteoclastlike giant cells of the thyroid. A case report.

BACKGROUND: Multinucleated giant cells of osteoclastlike appearance are seen in some anaplastic carcinomas, but only three cases in which the diagnosis was made by aspiration cytology are reported in the international medical literature. CASE: A 66-year-old female presented with a history of a palpable neck mass. The diagnosis of fine needle aspiration cytology was anaplastic thyroid carcinoma with osteoclastlike giant cells. Immunohistochemical staining and DNA ploidy analysis were done. CONCLUSION: Osteoclastlike giant cells have an origin different from that of the anaplastic component. DNA aneuploidy was noted in our case.

Immunohistochemical panel for distinguishing between carcinoma and reactive mesothelial cells in serious effusions.

OBJECTIVE: This study was designed to assess whether a new panel of antibodies is a useful adjunct in the differential diagnosis of carcinoma and reactive mesothelial cells. STUDY DESIGN: Complete, one-hour immunohistochemistry using antibodies against cytokeratin (CK), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and fibronectin was applied to cell blocks from 76 pleural and peritoneal fluid specimens. Fifty patients with histologically diagnosed primary carcinomas and 26 without evidence of malignancy were included. The results were correlated with routine cytologic results. RESULTS: The final cytologic diagnoses were 28 malignant effusions and 48 benign effusions. CEA and EMA were present in 25 (89%) and 24 (86%) of 28 carcinoma cases, respectively. These determinants were absent from reactive mesothelial cells. Fibronectin strongly labeled reactive mesothelial cells, with no staining of carcinoma cells. Carcinoma cells expressed at least two antibodies to CK, CEA and EMA and were negative to fibronectin. Reactive mesothelial cells expressed both CK and fibronectin. In 6 of 28 carcinoma cases (21%) the immunohistochemical panel identified carcinoma cells that were not recognized initially on routine cytologic examination. CONCLUSION: A panel of CEA, EMA and fibronectin monoclonal antibodies appears to be suitable for distinguishing between carcinoma cells and reactive mesothelial cells in serous effusions.

Lymphonodular cryptococcosis diagnosed by fine needle aspiration cytology in hyper-IgM syndrome. A case report.

BACKGROUND: Most cases of cryptococcosis are diagnosed when signs of meningitis have appeared. We report a case of lymphonodular cryptococcosis that was diagnosed by fine needle aspiration cytology (FNAC), excisional biopsy of a cervical lymph node and culture of aspirated material. CASE: An 11-year-old boy presented with a history of fever and enlarged bilateral cervical lymph nodes of two weeks' duration. Past medical history included immunoglobulin replacement for hyper-IgM syndrome for the previous eight years. FNAC smears from a cervical lymph node showed numerous yeasts of various sizes, ranging from 5 to 15 microns in diameter, located in the cytoplasm of multinucleated giant cells and in the background. In air-dried, Diff-Quik-stained slides, the yeasts stained blue and were surrounded by clear halos. Aspirated material collected in the syringe was cultured, and Cryptococcus neoformans was isolated. CONCLUSION: This case report suggests that a combination of FNAC and culture is a simple and useful method of diagnosing fungal infections. Early diagnosis by FNAC makes possible the early initiation of treatment.

Expression of cyclooxygenase-2 in epithelial ovarian tumors and its relation to vascular endothelial growth factor and p53 expression.

The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in epithelial ovarian tumors and its correlation with vascular endothelial growth factor (VEGF) and p53 expression. Immunohistochemical studies with anti-COX-2, anti-VEGF, and anti-p53 antibodies were carried out in 54 malignant and 23 borderline epithelial ovarian tumors. Elevated COX-2 expression was detected in 77.8% of ovarian carcinomas, which was significantly higher than that of borderline tumors (26.1%) (P < 0.001). In ovarian carcinomas, there was no significant correlation between COX-2 expression and other clinicopathologic features. Elevated VEGF expression was detected in 74.1% of ovarian carcinomas, and p53 expression was found in 64.8% of ovarian carcinomas. COX-2 expression was statistically correlated with elevated VEGF expression (P < 0.001) and p53 positivity (P < 0.05). On a univariate analysis, FIGO stage (P < 0.0001), histologic type (P= 0.0104), and COX-2 expression (P= 0.0135) were significant prognostic factors for overall survival. In a multivariate analysis, FIGO stage (P < 0.0001) was the only independent prognostic factor for poor survival. These findings suggest that COX-2 may play a role in the progression of epithelial ovarian tumors and that COX-2 expression may contribute to ovarian tumor angiogenesis by stimulating VEGF expression. p53 may be responsible for the regulation of COX-2 expression.

The association between CD99 and LMP-1 expression in nasopharyngeal carcinoma.

AIM: To characterize the roles of LMP-1 and CD99 in nasopharyngeal carcinogenesis, we undertook this pilot study of LMP-1 and CD99 expressions in nasopharyngeal cancer (NPC). MATERIALS AND METHOD: 40 NPC tissue samples were grouped according to the WHO classification. Immunohistochemical studies were performed using monoclonal antibodies against EBV latent membrane protein 1 (LMP-1) and CD99 protein. In addition, CD99 expression was evaluated in 10 samples of non-neoplastic nasopharyngeal epithelium. RESULTS: LMP-1 was detected in 12 of the 40 (30.0%) cases and its expression was found to be confined to epithelial tumor cells. WHO type I NPC samples were completely negative for LMP-1, whereas WHO type III NPC samples showed highest expression. Interestingly, CD99 was expressed in all of the non-neoplastic nasopharyngeal epithelium samples along the cytoplasmic border. CD99 expression was noted in NPC tumor cells (5 of the 40 cases, 12.5%) and in surrounding lymphoid stroma (23 of the 40 cases, 57.5%), but was not expressed in WHO type I NPC. In the 12 LMP-1 positive cases, 9 cases (75.0%) were CD99 negative, and 3 cases (25.5%) were CD99 positive. There was a statistical significance between LMP-1 and CD99 expression in lymphoid stroma. CONCLUSION: Our results suggest that the LMP-1 induced down-regulation of the CD99 pathway is important in nasopharyngeal carcinogenesis, and that the expression of CD99 in lymphoid stroma may regulate immune response to NPC.

Loss of heterozygosity on chromosome XP22.2-p22.13 and Xq26.1-q27.1 in human breast carcinomas.

In an attempt to investigate the X chromosome harboring putative tumor suppressor genes (TSGs) in sporadic breast carcinoma, we performed loss of heterozygosity (LOH) studies on 23 breast carcinomas using 15 polymorphic markers covering the whole X chromosomes. Matched DNA extracted from tumor samples and corresponding normal tissues were analyzed by polymerase chain reactions (PCR) using microsatellite markers. In 10 cases (43.5%), LOH was detected for at least 1 of the 15 polymorphic markers of the X chromosome tested. Four cases carried a LOH at Xp, and three cases LOH on Xp and Xq. Three cases carried a LOH Xq. Percentage of LOH was relatively high in DXS987 (26.7%), DXS999(30.0%), HPRT(21.4%), DXS1062(23.1%) loci. Common regions of deletions were found on Xp22.2-p22.13 (30% of LOH) measuring about 4.5Mb and Xq26.1-q27.1 (23.1% of LOH) measuring 10 Mb. The deleted allele was an active copy of the X chromosome. The results indicate the TSGs on the X chromosome are involved in breast cancer.

Analysis of clonality by X chromosome inactivation in uterine cervix cancer.

The determination of a unicellular or a multicellular origin of a tumor is an important due for understanding its etiology. To investigate this issue, we performed clonality assay of cervix cancer using polymerase chain reaction based on highly polymorphic locus of the androgen receptor gene, in which methylation of DNA correlates with inactivation of X chromosome. DNA samples were obtained from formalin-fixed, paraffin-embedded tissue of 20 invasive epidermoid carcinomas and 10 carcinoma in situ. Seven of ten carcinoma in situ, heterozygous for the androgen receptor locus, were monoclonal pattern. Among twenty invasive epidermoid carcinomas, eighteen of which showed heterozygous, twelve were monoclonal pattern and six were polyclonal pattern. We conclude that carcinoma in situ arises from a single cell. In invasive epidermoid carcinoma, most cases were monoclonal, although some cases were polyclonal. These suggest that invasive carcinoma of the cervix does not always arise from a single cell, but may arise from several cells with different mechanisms.

Loss of heterozygosity at chromosome segments 8p22 and 8p11.2-21.1 in transitional-cell carcinoma of the urinary bladder.

To identify the putative tumor-suppressor gene (TSG) involved in transitional-cell carcinoma (TCC) of the urinary bladder, we undertook an allelotyping analysis in 48 cases of TCC. Relatively high percentages of allelic loss were found in 2p (5 of 23, 21.7%), 8p (9 of 21, 42.9%), 9p (4 of 20, 20.0%), 12q (6 of 28, 21.4%), 15q (1 of 5, 20%; 4 of 20, 20%), 17p (7 of 26, 26.9%) and 22q (6 of 23, 26.1%). On the basis of these results, fine-deletion mapping was performed on chromosome 8 in 52 cases by PCR of 15 microsatellite markers. Two distinct regions of common deletion were found. A 10 cM telomeric region was located to 8p22, defined by D8S511 and D8S258. A 17 cM centromeric region was located to 8p11.2-21.1, flanked by D8S298 and D8S535. The distance between the telomeric and the centromeric regions of common deletion was 3 cM. Loss of heterozygosity of 8p22 was frequently observed in tumors of high grade or advanced stage.

The biologic role of ganglioside in neuronal differentiation--effects of GM1 ganglioside on human neuroblastoma SH-SY5Y cells.

Human neuroblastoma SH-SY5Y cell is a cloned cell line which has many attractive features for the study of neuronal proliferation and neurite outgrowth, because it has receptors for insulin, IGF-I and PDGF. Gangliosides are sialic acid containing glycosphingolipids which form an integral part of the plasma membrane of many mammalian cells. They inhibit cell growth mediated by tyrosine kinase receptors and ligand-stimulated tyrosine kinase activity, and autophosphorylation of EGF(epidermal growth factor) and PDGF receptors. The experiment was designed to study the effects of GM1 ganglioside on growth of human neuroblastoma SH-SY5Y cells stimulated with trophic factor in vitro. The cells were plated in Eagle's minimum essential medium without serum. The number and morphologic change of SH-SY5Y cells were evaluated in the serum free medium added GM1 ganglioside with insulin or PDGF. SH-SY5Y cells were maintained for six days in serum-free medium, and then cultured for over two weeks in serum-free medium containing either insulin or PDGF. The effect of insulin on cell proliferation developed earlier and was more potent than that of PDGF. These proliferative effects were inhibited by GM1 ganglioside, and the cells showed prominent neurites outgrowth. These findings suggest that GM1 ganglioside inhibits the cell proliferation mediated by tyrosine kinase receptors and directly induces neuritogenesis as one of the neurotrophic factors.

Analysis of Epstein-Barr virus in Hodgkin's disease: experience of a single university hospital in Korea.

Hodgkin's disease is known to be associated with Epstein-Barr virus (EBV) infection in Western countries, and viral nucleic acids and proteins have been identified within Reed-Sternberg (RS) cells, which are the histopathologic hallmark of the disease process. Twenty-five cases of Hodgkin's disease from a single university hospital in Korea were studied for evidence of EBV by in situ hybridization for EBV DNA and RNA and immunohistochemistry for an EBV latent protein. EBV nucleic acids were studied by a rapid (60 minutes) in situ hybridization procedure, which utilized biotinylated DNA probes specific for the following nucleic acid sequences: (1) EBV EBER1 RNA (an abundant RNA sequence expressed during latent EBV infection), (2) EBV NotI repeats (a tandemly repeated DNA sequence, which has been established to identify amplified EBV genome in lytic EBV infection), and (3) BAM HI W (a DNA sequence reiterated 11 times within the viral genome). In addition, immunohistochemistry for EBV latent membrane protein, a protein that is capable of inducing cellular transformation in cell culture, was also performed. EBV was identified within the neoplastic RS cells by at least one method in 19/25 cases (76%). The mixed cellularity subtype was the most common subtype associated with EBV infection (11/13-85%). In situ hybridization for EBV EBER1 RNA was the most sensitive method for EBV detection and was present in 17/25 cases. A significant proportion of Korean Hodgkin's disease cases is associated with EBV infection.

Autoradiographic and immunohistochemical study on the proliferative kinetics of intestinal metaplasia.

In order to elucidate the proliferative behavior of the intestinal metaplasia around gastric cancer, the authors used both in vitro tritiated thymidine (3H-thymidine) autoradiography and in vivo bromodeoxyuridine (BrdUrd) immunohistochemistry for labeling the proliferative cells of the normal pyloric glands and metaplastic gastric glands. The results of the methods were comparable: The labeling pattern and the rate of labeling were very similar. In the normal pyloric mucosa, the labeled cells were confined to the isthmus region, indicating that pyloric glandular cells are normally renewed from the isthmus region. On the other hand, a zone of the labeled cells was found in the lower half of the intestinalized mucosa, indicating that cell proliferation took place deep in the mucosa, just like the case of normal intestinal glands. The labeling indices of the pyloric mucosa were 19.4% by autoradiography and 18.0% by immunohistochemistry, and that of the intestinalized gastric glands were 25.2% by autoradiography and 24.2% by immunohistochemistry. In conclusion, both 3H-thymidine autoradiography and BrdUrd immunohistochemistry showed that the proliferative kinetics of the intestinalized gastric glands was similar to that of the normal intestinal glands rather than the pyloric glands, i.e. a lower level of proliferative zone and higher labeling index were present.

DNA ploidy and proliferative activity in bcl-2 expressed non-small cell lung cancer.

OBJECTIVES: The expressions of bcl-2 have been reported recently in non-small cell lung carcinoma (NSCLC*). As oncogensis is believed to involve a number of genetic alterations, there can be differences in DNA ploidy or proliferative activity even in bcl-2 positive cases according to the superimposed genetic events. SUBJECTS AND METHODS: On the assumption that we might further discern the biologic behavior of bcl-2 positive NSCLC according to the status of DNA ploidy and proliferative activity, we conducted a study for bcl-2 expression with immunohistochemical staining and DNA analysis on 52 surgical specimens of NSCLC. RESULTS: The bcl-2 was positive in 52% (27/52) of specimens, According to the status of bcl-2 expression, there were no significant differences in tumor stages, performance status score and survival time. Among bcl-2 positive NSCLC, aneuploidy and high proliferative activity were noted in 40% and 44%, respectively. In cases with squamous cell carcinoma (SQC**), the proportion of aneuploidy was significantly higher in bcl-2 positive group compared to bcl-2 negative group (p < 0.01), which could not be explained with the sole effect of bcl-2. In bcl-2 positive NSCLC, there was no significant survival difference by the status of DNA analysis results. With a Coxproportional hazard model, only T stage was an independent prognostic factor. CONCLUSION: In bcl-2 expressed NSCLC, proliferative activity and DNA ploidy were not homogeneous, suggesting other genetic alterations. This may explain our results which showed no differences in survival according to the status of the bcl-2 expression.

Comparison between flow cytometry and image cytometry in ploidy distribution assessments in gynecologic cancer.

The DNA content in 37 tumors from 34 women with gynecological cancer was measured by flow cytometry (FCM) and interactive image cytometry (ICM). Agreement was obtained in 81% of cases as regards ploidy levels, but seven tumors (19%) showed different ploidies. Of these, five were classified as diploid by FCM but either aneuploid (three cases) or polyploid (two cases) by ICM. Two other tumors were aneuploid by ICM but polyploid (one case) and unclassifiable (one case) by FCM. All tumors classified as aneuploid by FCM were also aneuploid by ICM, and all tumors classified diploid by ICM were also diploid by FCM. Of six patients whose tumors were classified as euploid (five diploid and one polyploid) by FCM but classified as aneuploid by ICM, five relapsed, and three of these have died of disease. On the basis of these findings, it is concluded that ICM must be performed in cases classified as diploid by FCM to ensure that small subpopulations of aneuploid tumor cells are not overlooked.

A case of xanthogranulomatous cholecystitis.

Xanthogranulomatous cholecystitis (XGC) is an uncommon, focal or diffuse destructive inflammatory disease of the gallbladder that is assumed to be a variant of conventional chronic cholecystitis. A 36-year-old male was admitted to Chonnam National University Hospital with a 10-day history of right upper quadrant pain with fever. 15 years ago, he was first diagnosed as having hemophilia A, and has been followed up in the department of Hematology. Computed tomogram (CT) revealed a well-marginated, uniform, marked wall thickening of the gallbladder with multiseptate enhancement. Magnetic resonance imaging (MRI) demonstrated diffuse wall thickening of the gallbladder by viewing high signal foci with signal void lesions. After factor VIII replacement, exploration was done. On operation, the gallbladder wall was thickened and the serosa were surrounded by dense fibrous adhesions which were often extensive and attached to the adjacent hepatic parenchyma. There was a small-sized abscess in the gallbladder wall near the cystic duct. Dissection between the gallbladder serosa and hepatic parenchyma was difficult. Cross sections through the wall revealed multiple yellow-colored, nodule-like lesions ranging from 0.5-2 cm. There were also multiple black pigmented gallstones ranging from 0.5-1 cm. The pathologic findings showed the collection of foamy histiocytes containing abundant lipid in the cytoplasm and admixed lymphoid cells. Histologically, it was confirmed as XGC. We report a case with XGC mimicking gallbladder cancer in a hemophilia patient.

Value of morphometric nuclear image analysis using the Feulgen reaction in renal cell carcinoma.

OBJECTIVE: To evaluate retrospectively the ability of morphometric nuclear image analysis to predict survival in patients with renal cell carcinoma. STUDY DESIGN: The subjects were 40 patients with previously untreated renal cell carcinoma. Pathologic stage was determined using Robson's stage system. Nuclear grade was assigned according to the criteria of Fuhrman et al. We used the Feulgen staining technique, which has been widely used for the histochemical assessment of nuclear DNA content. A minimum of 300 nuclei were analyzed from each subject. Five variables in morphometric nuclear image analysis were measured: nuclear area, nuclear perimeter, nuclear ellipticity, nuclear regularity and DNA content. Cox's proportional hazard model was applied to identify prognostic usefulness with respect to survival time. RESULTS: All nuclear morphometric variables but nuclear regularity correlated with tumor grade. According to univariate survival analyses, Robson stage and nuclear ellipticity revealed a prognosis on survival with statistical significance. After adjustments for age and sex, nuclear ellipticity remained the only significant prognostic factor related to survival (P < .01). The survival rates were relatively high for patients with nuclear ellipticity > 773 as compared to those with nuclear ellipticity < 773 (P < .05). CONCLUSION: These findings indicate that morphometric nuclear image analysis using the Feulgen reaction is a reliable and efficient technique and that nuclear ellipticity is the most discriminating morphometric variable for predicting the prognosis of renal cell carcinoma patients.