bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal hyperplastic hepatocellular nodules in hepatic venous outflow obstruction: a clinicopathological study of four patients and 24 nodules
Authors: Ibarrola C , Castellano V M , Colina F 
Published: December 2004

Aims : In hepatic venous outflow obstruction (Budd–Chiari syndrome), focal hepatocellular nodules are occasionally discovered showing variable morphology. These could be interpreted either as neoplastic (adenoma), regenerative (large regenerative nodule) or reactive to abnormal vasculature (focal nodular hyperplasia). The aim of this study was to investigate their histogenesis and to determine their morphological characteristics in order to provide diagnostic criteria.Material and methods : Twenty‐four hepatocellular nodules were studied, which were found in three explanted livers and in one additional autopsied liver from four patients with Budd–Chiari syndrome. As controls, we employed three explanted livers without nodules from patients who also suffered from Budd–Chiari syndrome. We attempted to classify the nodules morphologically as either adenoma‐like, large regenerative nodule or focal nodular hyperplasia‐like, using criteria from the literature.Results : Out of the four cases, we observed two nodules in each of two livers, five in the third one and up to 15 in the remaining one. The size of the nodules ranged from 4 to 25 mm. Eleven nodules could be categorized as large regenerative nodules (two of them with a central scar), seven as focal nodular hyperplasia‐like and six as adenoma‐like. Some large regenerative nodules showed proliferated arteries with muscular hyperplasia similar to that seen in focal nodular hyperplasia. In the individual livers we could find nodules of various categories. Patchy or diffuse monoacinar regeneration was seen in most cases (six out of seven cases) in the macroscopically non‐nodular liver parenchyma. In addition, thrombotic obstruction of portal vein branches was present in all except one of the nodular cases, but in none of the controls. Thus, it appears that portal venous obstructions are frequently, but not invariably associated with the development of nodules.Conclusions : The hepatocellular nodules seen in livers from patients with Budd–Chiari syndrome share morphological characteristics with large regenerative nodules, focal nodular hyperplasia and hepatocellular adenomas. Their multiplicity, the existence of mixed lesions, the frequent hepatocellular regenerative background as well as the frequently associated portal venous obstructions suggest that these nodules are regenerative in nature and conditioned by an uneven blood perfusion throughout the liver. In their differential diagnosis, the clinicopathological context in which they occur is of paramount importance and should allow recognition that those resembling adenomas may not be true neoplasms.
Combined status of MUC1 mucin and surfactant apoprotein A expression can predict the outcome of patients with small‐size lung adenocarcinoma
Authors: Tsutsumida H , Goto M , Kitajima S , Kubota I , Hirotsu Y , Yonezawa S 
Published: December 2004

Aim : Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Here, we aim to report a unique method to predict the recurrence and outcome of patients with pulmonary adenocarcinomas.Methods and results : Immunohistochemical expression of MUC1 mucin and surfactant apoprotein A (SP‐A) was examined in 185 cases of surgically removed lung adenocarcinomas of non‐bronchioloalveolar type smaller than 30 mm. Staining results were evaluated semiquantitatively, and the expression of MUC1 and SP‐A was compared in each case. There were 140/185 (76%) cases showing MUC1 expression higher than SP‐A expression (MUC1>SP‐A), and 45/185 (24%) cases showing MUC1 expression lower than or equal to SP‐A expression (MUC1≤SP‐A). Recurrence was observed in 24% (34/140) of the patients with a MUC1>SP‐A pattern, but in 7% (3/45) of the patients with a MUC1≤SP‐A pattern after the median observation period of 41 months (1–99 months) (P < 0.01). The MUC1>SP‐A group showed higher recurrence and worse survival than the MUC1≤SP‐A group by Kaplan–Meier's method (P < 0.01 and P < 0.005). Even in the patients with apparently favourable prognostic factors (well‐differentiated adenocarcinoma or no lymph node metastasis), recurrence and survival were different between the two groups.Conclusions : A high MUC1/SP‐A ratio is strongly associated with a poor outcome in patients with small‐size lung adenocarcinoma.
Polymorphous low‐grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location
Authors: Nagao T , Gaffey T A , Kay P A , Minato H , Serizawa H , Lewis J E 
Published: December 2004

Aims : Polymorphous low‐grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands.Methods and results : Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20–30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an ‘Indian‐file’ array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for α‐smooth muscle actin, muscle‐specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour.Conclusions : PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.
Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis
Authors: Martín P , Santón A , Bellas C 
Published: December 2004

Aims:  Differential diagnosis between multiple myeloma (MM), monoclonal gammopathy of uncertain significance (MGUS), and polyclonal plasmacytosis may be difficult in cases with not much bone marrow infiltration. Normal plasma cells express the antigens CD138, CD38, CD19, CD10 and D‐related human leucocyte antigen (HLA‐DR). Myelomatous plasma cells lack B lymphoid‐associated markers and may express cell surface antigens associated with other haematopoietic lineages such as NCAM/CD56 (neural cell adhesion molecule). Recently, a monoclonal antibody, anti‐CD56, has become available that can be used in fixed tissues embedded in paraffin, and it has been reported that osteoblastic cells of trabecular bone strongly express NCAM/CD56.Methods and results:  We analysed NCAM molecule expression in 35 samples from patients with plasma cell disorders: 14 cases of MM, 16 cases of MGUS, and five cases of polyclonal plasmacytosis using immunohistochemistry in parallel in bone marrow core biopsies processed routinely and in bone marrow smears from the same patients. Of the MM samples 78% were CD56+ in smears and 92% positive in biopsies. We did not find strong CD56 expression in MGUS samples. One of five samples of polyclonal plasmacytosis was CD56+. A case was considered to be positive for CD56 expression if >50% of the CD138+ plasma cells expressed NCAM with an intensity on a par with that of the osteoblasts.Conclusion:  We conclude that CD56 antibody is a very useful marker in the study of plasma cell proliferation in bone marrow biopsies and in bone marrow aspirates and is a great help in discriminating between MM, MGUS, and polyclonal plasmacytosis, especially in those cases with low infiltration.
Preferential HER‐2/neu overexpression and/or amplification in aggressive histological subtypes of invasive breast cancer
Authors: Varga Z , Zhao J , Öhlschlegel C , Odermatt B , Heitz P U 
Published: December 2004

Aims:  To investigate whether alterations of the HER2 gene occur more frequently in histologically unfavourable subtypes of invasive breast cancer.Methods:  The study was composed of nine invasive apocrine, six lipid‐rich, 12 glycogen‐rich, 11 micropapillary and 33 pleomorphic lobular breast carcinomas. Lymph node involvement was represented in all subgroups. HER2 status was confirmed in all cases by using immunohistochemistry (CB11, Herceptest) and fluorescent in‐situ hybridization (FISH) analysis (Vysis).Results:  Micropapillary and apocrine carcinomas showed the highest rate of protein overexpression (72% and 66%) and gene amplification (45% and 44%). Protein overexpression was common in poorly differentiated pleomorphic lobular carcinomas (56%); however, this subgroup failed to show an increased number of gene copies by FISH (31%). The incidence of HER2 overexpression (33% and 50%, respectively) and gene amplification (25% and 33%, respectively) among glycogen‐rich and lipid‐rich carcinomas was not higher than that observed in breast cancer generally.Conclusion:  Our data suggest that preferential involvement of the HER2 gene in micropapillary and apocrine breast carcinomas may contribute to their aggressive behaviour.
Metastasis in pleural mesothelioma. Immunohistochemical markers for disseminated disease
Authors: Lumb P D , Suvarna S K 
Published: December 2004

Aims:  To examine 13 cases of mesothelioma with metastases and compare these with 29 biopsy samples of patients without metastases. Metastatic disease was defined as tumour in which tumour appeared in a different cavity/tissue of the body and which showed no direct spread. Consequently, mediastinal nodal and parenchymal lung spread was excluded.Methods and results:  Standard sections were prepared and stained according to the manufacturers' protocols. The antibodies used were MIB‐1, nm23, Bcl‐2, MMP‐9, EMMPRIN (CD147) and α‐catenin. Scoring employed a grading system (0/1/2/3), and was performed by two pathologists independently. The tissues revealed no significant staining differences for MIB‐1, Bcl‐2, MMP‐9 or EMMPRIN, and therefore no linkage to metastatic potential was determined. α‐Catenin showed a diminished level of expression in cases of metastatic mesothelioma (P = 0.024), possibly reflecting dimished catenin–cadherin binding and paralleling data from other tumours. nm23 showed greater staining in metastatic tumours when compared with the controls (P = 0.001). Intriguingly, the nm23 staining pattern was the reverse of that expected. This reversed pattern has been noted before in other tumours and therefore a biological prognostic event may exist for this antibody test and mesothelioma metastasis.Conclusion:  There may be a place for nm23 and possibly α‐catenin in immunohistochemical assessment of mesothelioma metastatic potential. However, MIB‐1, Bcl‐2, MMP‐9 and EMMPRIN (CD147) do not show significant staining results.
Expression of stromelysin‐1 (MMP‐3), gelatinase B (MMP‐9), and plasminogen activator system during fetal calvarial development
Authors: Zeitler P , Pahnke J , Marx A 
Published: December 2004

Aims:  To investigate whether degrading proteases can be found in patent calvarial sutures. Sutural growth and fusion means replacement of the sutural connective tissue, rich in fibronectin and collagen type V, by expanding calvarial bone. Proliferation of one tissue into the border area of another implies the presence of enzymes able to degrade extracellular matrix (ECM). An important family of proteases is the matrix metalloproteinases (MMPs), as is the plasminogen/plasmin system.Methods and results:  Expression of two MMPs with substrate specifity for fibronectin and collagen type V and of the plasminogen activator system was studied by immunohistochemistry in samples of human fetal calvariae (age range weeks 19–35 of gestation). In all cases, intense staining for MMPs, urokinase, and urokinase receptor was found in the sutural connective tissue and along the outer and inner borders of calvarial bone.Conclusions:  Our findings suggest that degradation of sutural connective tissue takes place during sutural growth. This might facilitate proliferation of calvarial bone. Recently, it was shown that an important regulatory mechanism of sutural growth is apoptosis of osteoblasts in the osteogenic front. Intact fibronectin is known to prevent apoptosis of proliferating osteoblasts while fibronectin degradation induces their apoptosis.
Expression of TTF‐1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade
Authors: Jerome Marson V , Mazieres J , Groussard O , Garcia O , Berjaud J , Dahan M , Carles P , Daste G 
Published: December 2004

Aims:  To assess cytokeratin (CK) and thyroid transcription factor (TTF)‐1 expression in primary epithelial lung tumours by comparison with non‐pulmonary carcinomas and to correlate it with their histological type and grade.Methods and results:  Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF‐1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large‐cell neuroendocrine carcinomas, 40% of large‐cell carcinomas, 23% of squamous carcinomas) but also in 27% of non‐pulmonary adenocarcinomas. Addition of an anti‐CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive ‘dot‐like’ pattern is very suggestive of high‐grade neuroendocrine carcinoma. TTF‐1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade.Conclusions:  Immunohistochemical expression of CKs and TTF‐1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non‐pulmonary carcinomas.
Increased cell size and Akt activation in HER‐2/neu‐overexpressing invasive ductal carcinoma of the breast
Authors: Sastre‐Garau X , Genin P , Rousseau A , Al Ghuzlan A , Nicolas A , Fréneaux P , Rosty C , Sigal‐Zafrani B , Couturier J , Thiery J‐P , Magdelénat H , Vincent‐Salomon A 
Published: December 2004

Aims:  To determine whether cell size is related to HER‐2/neu status and/or to Akt activation in breast carcinomas. HER‐2/neu overexpression is observed in 20–30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER‐2/neu activation. Akt has been found to be involved in the HER‐2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models.Methods and results:  A case–control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER‐2/neu overexpression and 20 HER‐2/neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin‐fixed histological sections using an anti‐phosphorylated‐Akt (Ser473) antibody.Results:  HER‐2/neu‐overexpressing carcinomas had a mean nuclear size of 75 ± 22.2 µm2 and a mean cytoplasmic size of 187 ± 52.3 µm2. Both values were higher than the nuclear and cytoplasmic size of HER‐2/neu‐negative cases (nucleus = 58 ± 24.5 µm2, cytoplasm = 133 ± 56.6 µm2; P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 µm2 were HER‐2/neu‐positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER‐2/neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER‐2/neu‐positive and in 10% (2/19) of HER‐2/neu‐negative cases (P = 0.02).Conclusions:  HER‐2/neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER‐2/neu‐overexpressing breast carcinomas may provide useful information for optimized individual HER‐2/neu‐targeted therapy.
Expression of cholesteryl ester transfer protein (CETP) in germinal centre B cells and their neoplastic counterparts
Authors: Ito K , Ishikawa F , Kanno T , Ishikawa Y , Akasaka Y , Akishima Y , Ishii T , Terayama Y , Sugimoto M , Watanabe T , Mori S 
Published: December 2004

Aims:  Cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. Previous studies on human tissues have determined that the spleen contains large amounts of CETP mRNA, while the exact location of CETP in such organs remains unknown. In the present study, our aim was to locate CETP protein expression at the cellular level in human normal and neoplastic lymphoid organs.Methods and results:  In‐situ hybridization (ISH) and immunohistochemistry were applied to pathology specimens. A specific rabbit anti‐CETP antibody was used for immunohistochemical analysis, together with another CETP‐specific monoclonal antibody. A riboprobe for ISH was derived from CETP cDNA. Immunohistochemically, CETP was localized in germinal centre B cells and a proportion of marginal zone B cells. ISH showed that CETP mRNA was located mostly in the same areas. When 141 malignant lymphomas of various subtypes were studied, high expression of CETP, equivalent to that found in normal germinal centre B cells, was demonstrated in lymphoma subtypes that are currently regarded as the neoplastic counterparts of primarily germinal centre B cells.Conclusion:  CETP localizes B cells in germinal centres, a proportion of post‐germinal centre B cells and their neoplastic counterparts.
Cellular composition of pancreas‐associated lymphoid tissue during human fetal pancreatic development
Authors: Korpershoek E , Leenen P J M , Drexhage H A , De Krijger R R 
Published: December 2004

Aim : To study human fetal pancreatic tissue between 15 weeks of gestation and term, analysing the development of pancreatic lymphoid tissue and focusing on the presence and maturational status of dendritic cells (DCs). During normal human fetal pancreatic development lymphoid tissue arises in and around the pancreas. DCs are antigen‐presenting cells which are capable of initiating immunity, but are also essential in inducing and maintaining T‐cell tolerance.Methods and results : First, the presence and general composition of intra‐ and peripancreatic lymphoid tissue was investigated by histology and immunohistochemistry with antibodies to CD3, CD4, CD8, CD14, CD20, CD68, and CD79. Intrapancreatic lymphoid tissue (IPLT) appeared to be present only from 29 weeks of gestation onwards, and had a similar composition to peripancreatic lymphoid tissue (PPLT), which was found in all 23 specimens examined. Both forms of lymphoid tissue had an architecture similar to lymph nodes, with separate B‐ and T‐lymphocyte areas and scattered macrophages. DCs were investigated in detail by immunohistochemistry for CD1a, CD83, CD86, CD123, Langerin, and DC‐LAMP. Both Langerin, a marker for immature DCs, as well as DC‐LAMP, a marker for mature DCs, were expressed by cells in both the IPLT and PPLT at all ages examined.Conclusion : The presence of DCs at all developmental stages, expressing various maturation‐related markers, in addition to the general composition of the human fetal PPLT and IPLT suggests that this is fully functional and has a function comparable to peripheral lymph nodes.
Surgical excision is warranted following a core biopsy diagnosis of mucocoele‐like lesion of the breast
Authors: Carder P J , Murphy C E , Liston J C 
Published: December 2004

Aims:  Mucocoele‐like lesions (MLLs) of the breast are unusual lesions in which mucin‐filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin‐filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option.Methods and results:  Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy.Conclusion:  Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin‐filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.
The spectrum of pathological changes in severe acute respiratory syndrome (SARS)
Authors: Cheung O Y , Chan J W M , Ng C K , Koo C K 
Published: December 2004

Aims:  To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease.Methods and results:  Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy.Conclusions:  The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.