bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endolymphatic sac tumours
Authors: Kempermann G , Neumann H P H , Volk B 
Published: March 2003

This review article surveys clinical and pathological literature on endolymphatic sac tumours (ELST) and summarizes characteristics that describe the entity.ELST are rare neuroectodermal neoplasms in the petrous bone, originating from inner ear structures. They can be encountered sporadically or in von Hippel–Lindau disease. The most prominent symptom is sensorineural deafness. Historically, nomenclature of invasive adenoid tumours in the petrous bone has been divergent, the term papillary adenocarcinoma used most frequently. Histologically, they have a follicular or papillary and adenoid pattern that can be easily confused with various other neoplastic conditions including metastatic carcinoma. It remains to be verified whether similar tumours (papillary adenocarcinomas) can originate from the middle ear. Middle ear adenomas have a similar appearance but probably originate from neural crest cells in the middle ear. ELST can express a variety of epitopes (including cytokeratin and neuro‐ectodermal markers) which can be detected immunohistochemically.In cases of von Hippel–Lindau disease the cerebello‐pontine angle should be included in routine radiological examinations to detect ELST before the tumours lead to deafness. In apparently sporadic cases of ELST, genetic testing for von Hippel–Lindau disease should be considered. Correct distinction of ELST from metastatic carcinoma prevents futile searches for unknown primary tumours.
Direct sequencing of the p53 gene shows absence of mutations in endometrioid endometrial adenocarcinomas expressing p53 protein
Authors: Stewart R L , Royds J A , Burton J L , Heatley M K , Wells M 
Published: March 2003

AimsTo investigate the mutational status of the p53 gene (Tp53) in endometrial carcinomas expressing p53 protein by direct gene sequencing.Methods and resultsEighteen cases of endometrial carcinoma, selected on the basis of p53 protein expression as detected immunohistochemically by the monoclonal antibody DO7, were microdissected in the p53 positive areas. DNA was extracted and subjected to polymerase chain reaction (PCR) for exons 5–8 which code for conserved areas containing mutational hot‐spots. The PCR amplified material was then sequenced using an ABI automated sequencer and analysed using BLAST software at the NCBI web site. All sequences analysed were wild‐type.ConclusionThe results confirm that expression of p53 protein may occur in endometrial adenocarcinoma without mutation and may be due to stabilization of the protein during its normal function, possibly by an mdm2 mediated process.
p34cdc2 in invasive breast cancer: relationship to DNA content, Ki67 index and c‐erbB‐2 expression
Authors: Wiesener  , Hauser‐Kronberger  , Zipperer  , Dietze  , Menzel Ch , Hacker  
Published: March 2003

Aims: One‐hundred and eighty‐eight cases of human mammary carcinoma were examined immunohistochemically for their expression of Ki67, p34cdc2 and c‐erbB‐2. DNA image cytometry was performed to evaluate DNA ploidy, Auer type, S‐phase fraction (SPF), 5c exceeding rate (5cER) and 2c deviation index (2cDI).Methods and resultsOne‐hundred and sixty‐eight cases were invasive ductal carcinomas, 20 were of invasive lobular type. Routinely assessed oestrogen and progesterone receptor scores were available. The results were analysed statistically in comparison to tumour type, histopathological grade, lymph node status, menopausal status, patient age and overall survival. Ki67 (P < 0.002) and c‐erbB‐2 (P < 0.0001) correlated well with overall survival (P < 0.0008) and grade (P < 0.038) but not with lymph node status and tumour type. p34cdc2 showed a trend towards a positive correlation with Ki67 (P < 0.058) and a significant negative correlation with receptor status (P < 0.008) but with none of the other parameters examined.ConclusionsNo association between the DNA measured parameters (Auer type, SPF, 5cER and 2cDI) and survival was found. Our results suggest that c‐erbB‐2 and Ki67 are parameters which might, in combination with receptor status, help to define subgroups with different outcomes.
Interobserver agreement in the assessment of gastritis reversibility after Helicobacter pylori eradication
Authors: Tepeš  , Ferlan‐Marolt  , Juteršek  , Kavčič  , Zaletel‐Kragelj  
Published: March 2003

AimOur aim was to determine interobserver agreement in the application of the Sydney system to assess reversibility of gastritis after Helicobacter pylori eradication.Methods and resultsForty‐three patients with a Helicobacter pylori‐positive duodenal ulcer disease were included in the study. All patients included had successful H. pylori eradication after different antimicrobial drug combinations. Biopsy samples were collected from antrum and body, according to the Sydney recommendations, before antimicrobial therapy, 2 months after and at yearly intervals during 2–4 years of follow up. Three pathologists, who were blind to clinical data, evaluated histological changes in 221 antral and 219 body specimens stained with haematoxylin and eosin and with Warthin Starry. The percentage of pairwise agreement, kappa and weighted kappa statistic were used. Agreement in recognizing the presence of H. pylori colonization of the gastric mucosa, activity of inflammation and intestinal metaplasia was over 90%. Agreement in recognizing chronic inflammation in the body and atrophy in the antrum was between 78 and 89% respectively. The kappa values were excellent (more than 0.75) for the grade of H. pylori in the body, good (between 0.50 and 0.75) for the grade of H. pylori in the antrum, grade of inflammatory activity and intestinal metaplasia in the antrum and moderate to good (0.38–0.53) for the grade of chronic inflammation. Kappa values were poor to good (from 0.17 to 0.57) only in evaluation of the grade of atrophy.ConclusionInterobserver agreement in the application of the Sydney system to reversibility of gastritis after H. pylori was good. More strict criteria should be used for atrophy and to differentiate normal and mild chronic inflammation.
Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation
Authors: Chinyama  , Marshall  , Owen  , Mason  , Kothari  , Wilkinson  , Sanderson  
Published: March 2003

AimsChanges in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential.Methods and resultsTissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high‐grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin‐secreting carcinomas (4/28; 14%) irrespective of the tumour stage.ConclusionDespite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.
Varied B‐cell immunophenotypes of Hodgkin/Reed–Sternberg cells in classic Hodgkin's disease
Authors: Watanabe  , Yamashita  , Nakayama  , Hasegawa  , Kojima  , Nagasawa  , Mori  
Published: March 2003

AimsRecent analyses have suggested that Hodgkin's or Reed–Sternberg (HRS) cells in most cases of classic Hodgkin's disease are derived from germinal centre B‐cells. However, there is controversy over which B‐cell antigens are expressed in HRS cells.Methods and resultsWe studied 51 cases of classic Hodgkin's disease to immunohistochemically characterize HRS cells for pan‐B‐cell markers and specific markers for plasma cells. HRS cells expressed CD20 (L26) in 18 cases (35%), CD19 (B4) in nine (18%) and CD79a (mb‐1) in 13 (25%). Furthermore, HRS cells were positive for CD138 (B‐B4) in 24 cases (45%) and for PCA‐1 in 24 (45%). In 41 (80%) cases, HRS cells expressed more than one B‐cell marker. We then subclassified cases into those positive for plasma cell markers (n = 27) (group 1) and those negative for them (n = 24) (group 2). The average age in group 1 (40 years) was younger than in group 2 (54 years) (P < 0.05). The percentage of nodular sclerosis (NS) subtype in group 1 (52%) was 1.5 times greater than in group 2 (33%) (P < 0.05). With regard to Epstein–Barr virus encoded small RNA (EBER) in‐situ hybridization, 14 cases (64%) were positive in group 2, but only seven cases (31%) were positive in group 1 (P < 0.025).ConclusionIn most cases of classic Hodgkin's disease, HRS cells expressed later stage of B‐cell development. We consider that two different clinicopathological groups may correlate with the two different expressions of B‐cell markers.
Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma
Authors: Miyagi J , Tsuhako K , Kinjo T , Iwamasa T , Hashimoto H , Ishikawa S 
Published: March 2003

AimsPrimary rhabdoid tumour of the lung is rare, and histological and biological characteristics have not been fully documented. We describe three cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and investigate the histological features and biological characteristics.Methods and resultsThree cases were obtained from a total 902 cases of surgically removed primary lung tumours between 1986 and 1998. The rhabdoid cells were found to occupy about 50–90% of each tumour. All of the tumours had nonrhabdoid adenocarcinoma foci in the centre of the tumours. Transition between the adenocarcinomatous and rhabdoid components was demonstrated. Detailed immunohistochemical studies were carried out. The epithelial markers, cytokeratins and epithelial membrane antigen (EMA), were strongly expressed in rhabdoid and adenocarcinomatous components. Furthermore, surfactant apoprotein A was positive in both components in one case, but myoglobin, MyoD and HHF35 were not expressed. Vimentin was strongly and diffusely stained in all cases. The neuroendocrine markers, chromogranin A (all cases), neuron‐specific antigen (NSE) (two cases) and CD56 (one case) were occasionally positive in only a small number of the rhabdoid tumour cells. GM‐CSF was positively stained in one case, and the dedifferentiated characteristics of the rhabdoid cells was suggested. Proliferative cell nuclear antigen (PCNA) was strongly demonstrated in the rhabdoid tumour cells (all cases). To gain better understanding the highly proliferative characteristics of the tumours, p53 gene (exons 5–8) mutation was examined by DNA sequencing analysis; mutation of the p53 DNA was not detected. Overexpression of p53 protein was also not demonstrated in all cases. HPV6 was demonstrated in one case by PCR method and also non‐isotopic in‐situ hybridization (NISH). Two cases died in a short period of time (3 years and 4 months, respectively).ConclusionThe rhabdoid cells in these three cases were considered to represent the dedifferentiated components of the accompanying adenocarcinoma. Dedifferentiated characteristics (neuroendocrine markers, GM‐CSF, vimentin, and the aggressive behaviour) were evident.
Expression of VCAM‐1, ICAM‐1, E‐ and P‐selectin and tumour‐associated macrophages in renal cell carcinoma
Authors: Hemmerlein B , Scherbening J , Kugler A , Radzun H‐J 
Published: March 2003

AimsNeoangiogenesis is accompanied by an increase in endothelial surface, which can support infiltration by immune cells depending on adhesion molecule expression. Therefore, the expression of cell adhesion molecules on microvessels and epithelial cells was analysed in renal cell carcinomas as compared to tumour‐free tissue.Methods and resultsPECAM‐1, CD34, ICAM‐1, VCAM‐1, VLA‐4, P‐ and E‐selectin, the macrophage antigens Ki‐M1P and Mac‐1, and lymphocyte function antigen LFA‐1 were identified immunohistochemically. VCAM‐1, ICAM‐1, and E‐selectin were equally or less expressed, whereas P‐selectin was increased on microvessels in tumour tissue. The density of VCAM‐1‐positive tumour microvessels correlated positively with an advanced tumour stage and E‐ and P‐selectin‐positive tumour microvessels with the amount of associated macrophages. The expression of ICAM‐1 and VCAM‐1 on neoplastic epithelia correlated with an increased density of macrophages and a minor degree of tumour differentiation.ConclusionsThe positive correlation of macrophage infiltration and expression of cell adhesion molecules on tumour microvessels and epithelia with minor tumour differentiation and an advanced stage indicates that adhesion molecule expression is not associated with an effective antitumour function of macrophages
Microcystic adenoma of the pancreas (glycogen‐rich cystadenoma) with stromal amyloid deposits
Authors: Tripodi S A , Civitelli S , Schürfeld K , Cintorino M 
Published: March 2003

AimsWe report a case of a pancreatic glycogen‐rich microcystic serous adenoma with stromal amyloid deposits, focusing on the significance of isolated amyloid deposits in tumours.Methods and resultsThe architectural pattern was characterized by thin‐walled cysts lined by a single layer of flat or cuboidal epithelial cells intensely stained by the PAS‐reaction only before diastase digestion, suggesting the presence of glycogen. Tumour stroma was composed of broad fibrocollagenous tissue with lamellar hyalinized areas which were positively stained by Congo red and showed green birefringence and dichroism with polarized light. For amyloid protein characterization, immunohistochemical studies were performed with anti‐β amyloid protein and anti‐amyloid precursor pre‐A4695. The former antibody diffusely stained tumour stroma, while the latter stained only scattered stroma cells.ConclusionsThis is the first documented case of amyloid deposition in pancreatic serous adenoma. We indicate that the source of amyloid is an APP‐like precursor secreted by stromal myofibroblasts.
Cotyledonoid hydropic intravenous leiomyomatosis: a new variant leiomyoma
Authors: Jordan L B , Al‐Nafussi A , Beattie G 
Published: March 2003

Cotyledonoid hydropic intravenous leiomyomatosis: a new variant leiomyoma Aims: We present the histopathological findings of a series of six cases of a benign uterine smooth muscle tumour with an unusual growth pattern. Methods and results: All cases have the appearances of the recently described dissecting (cotyledonoid) leiomyoma. In addition, three of these lesions demonstrate the features of intravenous leiomyomatosis with varying degrees of hydropic degeneration. Conclusions: This combination of phenotypes has not previously been described within the literature; therefore we propose that these are classified as examples of `cotyledonoid hydropic intravenous leiomyomatosis', a new variant of unconventional leiomyoma.
Ultrastructural and immunohistochemical characterization of the so‐called giant multinucleate cells in cutaneous collagenomas
Authors: Ramos D , Monteagudo C , Carda C , Ramón D , González‐Devesa M , Llombart‐Bosch A 
Published: March 2003

Ultrastructural and immunohistochemical characterization of the so‐called giant multinucleate cells in cutaneous collagenomasAims:  This study was undertaken to compare the histopathological, immunohistochemical and ultrastructural features of the so‐called giant multinucleatecells in cutaneous collagenomas: giant‐cell collagenoma and solitary sclerotic fibroma.Methods and results:  We studied four collagenomas: one giant‐cell collagenoma and three solitary sclerotic fibromas. All the cases showed an indolent clinical presentation and were histologically constituted by a well‐demarcated dome‐shaped proliferation of coarse collagen bundles with a varying number of interspersed giant multinucleate cells and stellate mononuclear cells. The immunohistochemical study on paraffin sections revealed that neoplastic cells in both collagenomas were vimentin and CD34‐positive, whereas FXIIIa was only expressed in solitary sclerotic fibromas. In regard to the so‐called giant multinucleate cells, we have ultrastructurally found that these cells were ‘real’ multinucleate cells in giant‐cell collagenoma, whereas in solitary sclerotic fibromas they consisted of closely packed aggregates of individual stellate mononuclear cells. Moreover, perinuclear cisternae focally containing finely textured material of moderate density were unexpectedly found in giant cells of giant‐cell collagenoma, a finding which was not observed in solitary sclerotic fibromas. Additionally, a characteristic cell–cell interaction between tumour cells and mast cells was encountered in all collagenomas.Conclusions:  This study supports a distinctive immunohistochemical and overall ultrastructural profile of giantmultinucleate cells in giant‐cell collagenoma and solitary sclerotic fibroma, which suggests a different pattern of differentiation for these two related cutaneouslesions.
Polymorphous low‐grade adenocarcinoma of the salivary glands with transformation to high‐grade carcinoma
Authors: Simpson R H W , Reis‐Filho J S , Pereira E M , Ribeiro A C , Abdulkadir A 
Published: March 2003

Aims:  Polymorphous low‐grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland‐looking tumour cells arranged in diverse architectural patterns. It is considered to be of low‐grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low‐grade adenocarcinoma to a histologi‐cally high‐grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples.Methods and results:  Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low‐grade adenocarcinoma. In one case there was a second component of high‐grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high‐grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low‐grade adenocarcinoma profile and absence of androgen receptor expression.Conclusions:  Polymorphous low‐grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low‐grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low‐grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.
An allogeneic microenvironment influences the phenotype of intermediate T‐cell receptor cells expanding in MRL‐ lpr/lpr mice
Authors: Tsukahara A. , Iiai T. , Moroda T. , Tada T. , Suzuki S. , Takeda K. , Hatakeyama K. , Abo T. 
Published: March 2003

MRL‐lpr/lpr (lpr) mice fall victim to autoimmune disease owing to a lymphoproliferative disorder mainly of double‐negative (DN) CD4− CD8−αβT cells expressing a low density of interleukin‐2 receptor β‐chain (IL‐2Rβ). It was previously revealed that the lpr gene is a defective Fas gene, into which an early transposon (ETn) of retrovirus is transfected. As a result of the failure of apoptosis, intermediate T‐cell receptor (TCR) cells (i.e. TCRint cells) with DN phenotype abnormally accumulate in the periphery of lpr mice. We investigated herein how these TCRint cells are selected in terms of CD4, CD8 and TCR in lpr mice. When a whole fraction of mononuclear cells (MNC) in various immune organs of lpr mice was injected into scid mice (allogeneic circumstance), CD8+ TCRint cells mainly expanded. They had a high density of IL‐2Rβ. This was true when bone marrow cells of lpr mice were injected into scid mice. On the other hand, when MNC of the spleen and bone marrow in lpr mice were injected into irradiated (9 Gy) lpr mice (syngeneic circumstance), the major expanding cells were DN TCRint cells expressing a low density of IL‐2Rβ. A cell‐sorting experiment for purified fractions demonstrated that only CD8+ cells reconstituted TCRint cells in scid mice. Namely, DN CD4− CD8− cells as well as CD4+ cells which once acquired the mature phenotype, no longer switched their phenotype. These results suggest that the phenotype of TCRint cells is influenced by the surrounding microenvironment.int, intermediatelpr, MRL‐lpr/lpr miceMNC, mononuclear cellsIL‐2Rβ, interleukin‐2 receptor β‐chain.
Biological activities of C3βc, a novel neutrophil chemoattractant derived from the β‐chain of rat complement C3
Authors: Nakagawa H. , Sunada Y. , Ando Y. 
Published: March 2003

Biological activities of C3βc, which is a C‐terminal fragment of the β‐chain of rat complement C3, have been studied by in vivo and in vitro experiments. C3βc was purified as a novel neutrophil chemoattractant from the exudate of the chronic phase of rat carrageenin‐induced inflammation. The purified C3βc induced neutrophil chemotaxis in vivo when C3βc was injected into the preformed air‐pouch on the back of rats. C3βc transiently increased the intracellular free Ca2+ concentration of neutrophils, and enhanced the adhesion of neutrophils to fibrinogen in vitro, suggesting that C3βc has the ability to express an adhesion molecule of rat neutrophils. In addition, C3βc at low concentrations (10−10–10−11 m) stimulated rat macrophages to produce cytokine‐induced neutrophil chemoattractant‐2, a member of the interleukin‐8 family. Furthermore, C3βc enhanced vascular permeability in vivo, which is suppressed by cyproheptadine, suggesting that C3βc may have the characteristics of an anaphylatoxin. Our results suggest that C3βc contributes to oedema formation and neutrophil accumulation at inflammatory sites in rats.BSA, bovine serum albumin CINC, cytokine‐induced neutrophil chemoattractant DMEM, Dulbecco’s modified Eagle’s minimal essential medium ELISA, enzyme‐linked immunosorbent assay fMLP, N‐formyl‐methionyl‐leucyl‐phenylalanine IL, interleukin LPS, lipopolysaccharide PBS, phosphate‐buffered saline.