bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histogenesis of gastric foveolar metaplasia following duodenal ulcer: a definite reparative lineage of Brunner's gland
Authors: Kushima R , Manabe R , Hattori T , Borchard F 
Published: March 2003

AimsWe aimed to clarify the histogenesis of gastric metaplasia in the duodenal mucosa, particularly in association with a reparative lineage of Brunner's glands.Methods and resultsUsing immunohistochemical methods with recently developed antimucin monoclonal antibodies (mAbs) that distinguish foveolar and deep mucins of the gastric type, as well as mAb MIB‐1, the histogenesis of gastric metaplasia was investigated in the duodenal wall of 20 surgically resected specimens. In duodenal ulcers extending into Brunner's glands with destruction of the muscularis mucosae, proliferating cells positive for MIB‐1 were scattered in Brunner's glands. Interestingly, a group of proliferating cells was often seen next to the ulcerated surface. These cells were also positive for M1 (gastric‐foveolar type mucin) but negative for M2 (deep gastric and Brunner glands' mucin). In regenerating ducts through granulation tissue, the proliferating cell zone was elongated, above which foveolar‐type cells positive for M1 but negative for M2 were detected, indicating that the G‐zone is newly established in Brunner's glands at the floor of an ulcer to produce gastric‐foveolar cells. Subsequently, an organoid growth of the normal stomach mucosa is completed in the duodenum.ConclusionsThis study indicates a possible histogenetic pathway of gastric metaplasia in close association with a reparative lineage of Brunner's glands, suggesting that the occurrence of the gastric‐foveolar type epi‐thelium is not a simple expansion of Brunner's duct but a true metaplasia.
Down‐regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions
Authors: Saegusa M , Nitta H , Hashimura M , Okayasu I 
Published: March 2003

AimsAlthough p27Kip1(p27) is a cyclin‐dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown.Methods and resultsSeventy‐six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = − 0.639, P < 0.0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P < 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident.ConclusionLoss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.
Development of dysplastic mucinous epithelium from endometriosis of the appendix
Authors: Mai  , Burns  
Published: March 2003

AimWe report an unusual case of mucinous metaplasia and epithelial dysplasia occurring in endometriotic epithelium in the appendix.Methods and resultsA 39‐year‐old woman developed an appendiceal endometriosis in which the endometrial glands displayed extensive areas consisting of mucinous epithelium and Paneth cells. Focally the mucinous epithelium showed low‐grade epithelial dysplasia. These changes occurred in portions of the endometriotic tissue closest to the appendiceal lumen. Both the intestinal and endometrial epithelial components were surrounded by typical endometrial‐type stroma showing positive reactivity for oestrogen receptor.ConclusionsFormation of the mucinous epithelium most likely represents a metaplastic process of the endometrial epithelium rather than a result of a simple ‘collision’ of the appendiceal and endometrial epithelium. Further support for this being a metaplastic process was the presence of glandular structures containing a mixture of mucinous cells, goblet cells, Paneth cells, ciliated and nonciliated endometrial cells, and ciliated and nonciliated mucinous cells, all showing the same positive reactivity for oestrogen receptor. The disposition of mucinous epithelium in the foci of endometriosis in this case suggests that the appendiceal mucosa or extracellular mucin may play a role as an inducer of mucinous cell metaplasia in endometriotic epithelium.
Small epithelial cells in extrahepatic biliary atresia: electron microscopic and immunoelectron microscopic findings suggest a close relationship to liver progenitor cells
Authors: Xiao  , Ruck  , Kaiserling  
Published: March 2003

Aims: It is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver. The aim of this study was to investigate whether cells with ultrastructural and immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia.Methods and resultsLiver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes.ConclusionsThe findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.
Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in‐situ and invasive carcinomas
Authors: Gobbi  , Arteaga  , Jensen  , Simpson  , Dupont  , Olson  , Schuyler  , Plummer  , Page  
Published: March 2003

AimsLoss of transforming growth factor beta type II receptor (TGFβ‐RII) expression has been associated with resistance to TGFβ‐mediated inhibition of cell proliferation and tumour progression. We investigated whether the expression of TGFβ‐RII is related to the progression of human breast cancer and whether there is a correlation between TGFβ‐RII expression and phenotypic markers of biological aggressiveness.Methods and resultsImmunohistochemical methods were used to detect TGFβ‐RII in archival breast samples including benign proliferative lesions, ductal carcinoma in situ (DCIS) and invasive mammary carcinomas (IMC). Neoplastic cells showed reduced expression of TGFβ‐RII in comparison to the normal breast tissue and benign lesions. There was a significant inverse correlation between loss of TGFβ‐RII expression and tumour grade within both DCIS (P = 0.004) and IMC (P = 0.001) groups. There was an inverse correlation between TGFβ‐RII expression and both mitotic count (P = 0.001) and clinical stage (P = 0.004). Oestrogen receptor (P = 0.07) and lymph node status (P = 0.10) were not significantly associated with TGFβ‐RII expression.ConclusionsThese data indicate that decreased expression of TGFβ‐RII may contribute to breast cancer progression and is related to a more aggressive phenotype in both in‐situ and invasive carcinomas.
The cytokeratin profile of medullary carcinoma of the breast
Authors: Tot T 
Published: March 2003

Aims : The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined. Methods and results : Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8–18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty‐five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5–6 positivity. No association between the cytokeratin–vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases. Conclusions : Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.
Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis‐related dysplasia
Authors: Wong N A C S , Mayer N J , MacKell S , Gilmour H M , Harrison D J 
Published: March 2003

Aims : To assess whether Ki67 and p53 immunostaining may assist the diagnosis and grading of ulcerative colitis‐related dysplasia. Methods and results : Location of Ki67 staining and location and intensity of p53 staining were assessed in ulcerative colitis (UC) cases showing the features of high‐grade dysplasia (HGD, n = 14), low‐grade dysplasia (LGD, n = 22), ‘indefinite for dysplasia’ (n = 12), or regenerative atypia (RA, n = 22). Good intra‐ and inter‐observer reproducibilities were demonstrated in the performance of these assessments. All the dysplasia cases showed extension of Ki67 staining above the basal third of the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. Conclusions : Restriction of Ki67 staining to the basal third of the crypt appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the basal two‐thirds of the crypt appears to exclude a diagnosis of HGD.
Calretinin expression in ameloblastomas
Authors: Altini M , Coleman H , Doglioni C , Favia G , Maiorano E 
Published: March 2003

AimsCalretinin is a 29‐kDa calcium‐binding protein which is expressed in the central and peripheral nervous systems as well as in many other normal and pathological human tissues. The objective of this study was to determine whether calretinin was expressed in the epithelium of ameloblastomas.Methods and resultsTwenty‐seven cases of unicystic ameloblastoma and 31 cases of solid and multicystic ameloblastoma were studied. Five‐micron sections were immunohistochemically stained using either antiserum 7696 from Swant, or antiserum 18–0211 from Zymed with a standard ABC method. The results were identical with the two antisera. Positive staining was seen in 22 cases (81.5%) of unicystic ameloblastomas. This generally consisted of diffuse, intense nuclear and cytoplasmic staining of several cell layers of the more superficial cells both in the characteristic and nondescript areas of the cyst linings. In the solid and multicystic ameloblastomas, staining occurred in 29 (93.5%) of the cases. The staining was almost always restricted to the stellate reticulum‐like epithelium, was generally intense and diffuse in distribution. Areas of squamous metaplasia stained particularly intensely as did the cells surrounding micro‐ and macro‐cysts. In both groups of lesions, most of the cases that did not stain were intensely inflamed.ConclusionsThe biological significance of calretinin expression in ameloblastomas is not known and its use as a distinctive, specific immunohistochemical marker for ameloblastic tissues remains to be confirmed. However, the results of this study raise the possibility that calretinin may be an important diagnostic aid in the differential diagnosis of cystic and solid ameloblastic tumours.
Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP Study Group
Authors: Vanni R , Fletcher C D M , Sciot R , Dal Cin P , De Wever I , Mandahl N , Mertens F , Mitelman F , Rosai J , Rydholm A , Tallini G , Van Den Berghe H , Willén H 
Published: March 2003

Aims : Cutaneous benign fibrohistiocytic tumours are among the most common soft tissue lesions. Their biological nature, in particular whether they are neoplastic or reactive, has long been disputed. Some morphological subtypes can be confused with sarcoma. Since available karyotypic data in these lesions are scarce, this study was undertaken to determine whether their cytogenetic analysis might demonstrate clonality and might help in differential diagnosis. Methods and results : Thirteen karyotyped benign cutaneous fibrous histiocytomas (BFH) were morphologically reassessed and classified as ordinary BFH (eight cases), cellular BFH (four cases), and one ankle‐type lesion. Five cases (38%) showed clonal cytogenetic changes, although the aberrations varied and did not correlate with histological subtypes. Karyotypic aberrations were more common in cellular BFH (3/4) than in the ordinary BFH (2/8). Conclusions : The demonstration of clonal chromosome abnormalities, in at least some cases, supports the neoplastic nature of cutaneous BFH. The karyotypic changes identified are different from those in dermatofibrosarcoma, with which cellular BFH is often confused histologically.
Inducible nitric oxide synthase expression is increased in the brain in fatal cerebral malaria
Authors: Maneerat Y , Viriyavejakul P , Punpoowong B , Jones M , Wilairatana P , Pongponratn E , Turner G D H , Udomsangpetch R 
Published: March 2003

Aims : Nitric oxide (NO) has been hypothesized to play a major role in the pathogenesis of cerebral malaria caused by P. falciparum infection. NO may act as a local neuroactive mediator contributing to the coma of cerebral malaria (CM). We hypothesized that increased expression of inducible nitric oxide synthase (iNOS) may cause increased release of NO, and examined the expression and distribution of iNOS in the brain during CM. Material and results : Brain tissues from fatal cases of cerebral malaria in Thai adults were examined using immunohistochemical staining to detect iNOS. The distribution and strength of staining was compared between 14 patients with CM, three of whom were recovering from coma, and controls. iNOS expression was found in endothelial cells, neurones, astrocytes and microglial cells in CM cases. There was also strong staining in macrophages surrounding ring haemorrhages. iNOS staining was decreased in recovering malaria cases compared to acute CM, and was low in controls. Quantification showed a significant association between the intensity and number of iNOS positive vessels with the severity of malaria related histopathological changes, although the total number of cells staining was not increased compared to recovering CM cases. Conclusions : This study indicates that an acute induction of iNOS expression occurs in the brain during CM. This occurs in a number of different cells types, and is increased in the acute phase of CM compared to cases recovering from coma. As NO may activate a number of secondary neuropathological mechanisms in the brain, including modulators of synaptic function, induction of iNOS expression in cerebral malaria may contribute to coma, seizures and death.
Interleukin‐13 and interleukin‐13 receptor in Hodgkin's disease: possible autocrine mechanism and involvement in fibrosis
Authors: Ohshima K , Akaiwa M , Umeshita R , Suzumiya J , Izuhara K , Kikuchi M 
Published: March 2003

Aims: Hodgkin's disease (HD) is characterized by the presence of Hodgkin and Reed–Sternberg (H–RS) cells against a hyperplastic background of reactive cells such as lymphocytes, histiocytes, plasma cells, eosinophils, neutrophils, and stromal cells. There is ample evidence to suggest that proliferation and survival of HD‐derived cells is due to cytokine signalling. Recently, high expression of interleukin (IL)‐13 was described in HD‐derived cell lines. Here we investigated the possible involvement of IL‐13 in the pathophysiology, especially autocrine pathways of H–RS cells.Methods and results: The expression of IL‐13 and IL‐13 receptor (IL‐13R) was determined by immunostaining and reverse transcriptase‐polymerase chain reaction in 39 cases of HD, including 17 cases with nodular sclerosis (NS) type, 19 cases with mixed cellularity (MC), and three cases with lymphocyte predominance (LP) type. Expression of IL‐13 was confined to H–RS cells and a few lymphocytes. IL‐13R was expressed in H–RS cells, lymphocytes, histiocytes, fibroblasts, and endothelial cells. H–RS cells of MC and NS types frequently expressed both IL‐13 and IL‐13R. However, the number of IL‐13‐positive H–RS cells was statistically higher in NS‐type than in MC‐type, but the number of IL‐13R was similar. IL‐13R‐positive fibroblasts were frequently encountered in NS‐type. H–RS cells of LP type rarely expressed IL‐13.Conclusions: Our results suggest that IL‐13 might be involved in autocrine pathways of H–RS cells and fibrosis at least in NS‐type. Our results also indicated that in addition to the morphological and phenotypic differences, the neoplastic cells of LP type might be functionally different from H–RS cells of MC‐ and NS‐types.
Myocardial fibrosis assessment by semiquantitative, point‐counting and computer‐based methods in patients with heart muscle disease: a comparative study
Authors: Vasiljević J D , Popović Z B , Otašević P , Popović Z V , Vidaković R , Mirić M , Nešković A N 
Published: March 2003

Aims: No study has directly compared different histomorphometric methods of quantification of myocardial fibrosis. Therefore we compared the results of semiquantitative, point‐counting and computer‐based methods in the assessement of myocardial fibrosis in a consecutive series of endomyocardial biopsy samples from patients with heart muscle disease.Methods and results: Histological samples (at least three per patient) were obtained by endomyocardial biopsy from 11 patients with focal myocarditis and from 24 ambulatory patients with idiopathic dilated cardiomyopathy, or during surgery in 10 patients who underwent partial left ventriculectomy. Samples were cut and stained with Masson‐trichrome for better contrast. From each sample, a representative field was digitized, and the amount of fibrosis was assessed by semiquantitative scoring, by point‐counting, and by computer‐based software. Semiquantitative scoring correlated with both point‐counting (Spearman's r = 0.69, P < 0.0001) and computer‐based (Spearman's r = 0.83, P < 0.0001) methods. There was also a good correlation between point‐counting and computer‐based methods (r = 0.71, P < 0.0001). However, when compared with the point‐counting method, the computer‐based method overestimated percent fibrosis by 3.0 ± 6.7% (P = 0.004). This overestimation correlated with the mean percent fibrosis (r = 0.38, P = 0.014).Conclusions: Our data show good correlations between the three methods of myocardial fibrosis assessment. However, systematic differences between them emphasize that this should be taken into consideration when comparing results of the studies using different methods of fibrosis assessment.
Intra‐abdominal spindle cell lesions: a review and practical aids to diagnosis
Authors: Al‐Nafussi A , Wong N A C S 
Published: March 2003

Intra‐abdominal spindle cell lesions: a review and practical aids to diagnosis Intra‐abdominal spindle cell lesions are uncommon and often present a diagnostic challenge. An important group of such lesions are the gastrointestinal stromal tumours. Other intra‐abdominal spindle cell lesions include fibromatosis, various sarcomas—in particular, leiomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumour—and, in women, endometrial stromal sarcoma. Less common lesions are inflammatory myofibroblastic tumours, the mesenteric spindle cell reactive lesions, retroperitoneal fibrosis, and solitary fibrous tumour. A variety of intra‐abdominal tumours of nonmesenchymal origin may have a spindle cell/sarcomatoid morphology; these include sarcomatoid carcinoma, malignant melanoma and, in women, sarcomatoid granulosa cell tumour. Finally, metastatic sarcomas from pelvic or extra‐abdominal organs need also be considered. A set of practical aids to the diagnosis of intra‐abdominal spindle cell lesions is presented to assist pathologists dealing with such lesions, particularly with regards to the consideration of differential diagnoses.
Development of follicular dendritic cell sarcoma in hyaline‐vascular Castleman’s disease of the nasopharynx: tracing its evolution by sequential biopsies
Authors: Chan A C L , Chan K W , Chan J K C , Au W Y , Ho W K , Ng W M 
Published: March 2003

Development of follicular dendritic cell sarcoma in hyaline‐vascular Castleman’s disease of the nasopharynx: tracing its evolution by sequential biopsies Aims: Hyaline‐vascular Castleman’s disease (HVCD) and follicular dendritic cell (FDC) sarcoma occurring in the nasopharynx are both extremely rare. We report the first case of transformation of the former into the latter as documented by sequential biopsies. The steps involved in the transformation were described in detail and the possible role of p53 studied. Methods and results: The patient presented at the age of 23 years with nasopharyngeal HVCD. Hyaline‐ vascular Castleman’s disease with FDC overgrowth was diagnosed in a recurrence 8 years later, and a frank FDC sarcoma developed at the same site 11 years after initial presentation. The patient remained disease‐free 3 years after excision and adjuvant chemotherapy. The FDC sarcoma comprised swirling fascicles of spindly cells with indistinct cell borders. The tumour cells expressed the FDC markers CD21, CD35 and CNA.42 and in‐situ hybridization for Epstein–Barr virus‐encoded RNAs was negative. Over‐expression of p53 protein was observed in the FDC sarcoma and an increased number of weakly p53‐positive spindly cells could also be demonstrated in the HVCD specimen. This finding suggested a possible role of p53 in the evolution from HVCD to FDC sarcoma. Critical analysis of the literature shows that, among the 13 reported cases of FDC sarcoma associated with Castleman’s disease, possible progression from the latter to the former is documented in only two cases. Conclusions: The sequential changes observed in the current case provide further evidence to strengthen the role of HVCD as a possible precursor of FDC sarcoma. There is a possible role of p53 in the transformation process but confirmation by future studies is needed.