bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological and immunohistochemical characterization of extranodal diffuse large‐cell lymphomas with prominent spindle cell features
Authors: Wang J , Sun N C J , Nozawa Y , Arber D A , Chu P , Chang K L , Weiss L M 
Published: March 2003

Histological and immunohistochemical characterization of extranodal diffuse large‐cell lymphomas with prominent spindle cell features Aims: To describe five cases of diffuse large‐cell lymphoma with prominent spindle cell components involving skin, nasal‐ocular mucosa, and soft tissue. Because of the spindle cell morphology, such cases must be differentiated from true sarcomas arising in or metastasizing to soft tissue, skin, bone, lymph node, or other organs and sites. Methods and results: Formalin‐fixed paraffin‐embedded archival tissue from five consultation cases of diffuse large‐cell lymphoma with prominent spindle cell features involving the skin, nasal‐ocular mucosa, and soft tissue in three male and two female patients was studied by histology and immunohistochemistry. Clinicopathological findings were also reviewed for all the patients. By morphology, initial evaluation of the cases suggested spindle cell sarcoma in two cases, inflammatory pseudotumour in one case, large‐cell lymphoma in another case, and one case was considered suspicious for malignant lymphoma. Immunohistochemistry demonstrated a B‐cell lineage in four of the spindle cell lesions, with a diagnosis of primary cutaneous CD30+ anaplastic large cell lymphoma made for the fifth case. Four of five cases also showed actin reactivity. Conclusions: Although extremely rare, lymphomas with prominent spindle cell morphology can be encountered in daily surgical pathology practice, and should be included in the differential diagnosis of spindle cell lesions in skin and soft tissue. The observed actin reactivity in four of the five spindle cell lymphomas may lead to a misdiagnosis of leiomyosarcoma if lymphoid markers are not included in the immunohistochemical panel.
Review. Histopathology and the ‘third great lie’. When is an image not a scientifically authentic image?
Authors: Suvarna S K , Ansary M A 
Published: March 2003

Histopathology and the ‘third great lie’. When is an image not a scientifically authentic image? This article considers the issues of image manipulation within the context of electronic/digital images. The possibility for such alterations has occurred with the increasing availability of simple and cheap computer software, permitting modification of digitized images as a whole, or in part. The concepts of acceptable, through to unacceptable, manipulations are discussed using macroscopic and histological illustration examples. The legal and editorial problems that this poses for medical and scientific publishing are also discussed, alongside examples of previous fraudulent image publications and the historical context of valid scientific images.
Mucinous metaplasia of the penis
Authors: Fang A W , Whittaker M A , Theaker J M 
Published: March 2003

Mucinous metaplasia of the penis Aims: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features. Methods and results: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin‐stained slides were examined by a single observer to detect the presence of mucin‐producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51–80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non‐specific balanitis. All four cases showed positive staining with both diastase periodic acid–Schiff and alcian blue. No mucin‐producing cells were identified in non‐inflamed or minimally inflamed specimens. Conclusions: Mucinous metaplasia of the penis is an uncommon but under‐recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.
Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer
Authors: Ueno H , Murphy J , Jass J R , Mochizuki H , Talbot I C 
Published: March 2003

Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer Aims: Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour ‘budding’ and attempted to establish its appropriate criteria. Methods and results: A total of 638 rectal cancer specimens was examined. We defined tumour `budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of `budding' foci within a microscopic field of × 250. Rectal cancer with high‐grade `budding' (≥ 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5‐year survival rates (40.7%) than patients with low‐grade `budding' (84.0%) (P < 0.0001). Based on multivariate analysis, tumour `budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two‐graded tumour `budding' in the intraobserver study was 0.84. Conclusions: Because of its value as a prognostic indicator and its reproducibility, tumour `budding' would be a good index to estimate the aggressiveness of rectal cancer.
Expression of metallothionein in lung carcinoma: correlation with histological type and grade
Authors: Theocharis S , Karkantaris C , Philipides T , Agapitos E , Gika A , Margeli A , Kittas C , Koutselinis A 
Published: March 2003

Expression of metallothionein in lung carcinoma: correlation with histological type and grade Aims: Over‐expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters. Methods and results: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin–biotin–peroxidase technique, using a monoclonal antibody against both metallothionein‐1 and ‐2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small‐cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein‐positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma. Conclusions: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small‐cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.
Immunohistochemical detection of CD30 remains negative in nodular lymphocyte‐predominant Hodgkin's disease using enhanced antigen retrieval
Authors: Roberts C , Jack F , Angus B , Reid A , Thompson W D 
Published: March 2003

Immunohistochemical detection of CD30 remains negative in nodular lymphocyte‐predominant Hodgkin's disease using enhanced antigen retrieval Aims: The aims of this study were to confirm that CD30 is reproducibly negative in cases of nodular lymphocyte‐predominant Hodgkin's disease (nLPHD), and its relationship to further antibody targets for the distinction of L&H cells from classical Hodgkin's and Reed–Sternberg cells. Methods and results: We examined 16 cases of nLPHD from two centres in the UK to characterize immunohistochemically L&H cells for CD30, EMA, J‐chain and Oct2, using different methods of antigen retrieval, antigen amplification and antigen detection systems. Two cases could not be stained with J‐chain and Oct2. All cases were negative for CD30 following manual and automated staining. Only one case became positive for EMA after manual staining using tyramide amplification. J‐chain and Oct2 were negative in all cases following manual staining. J‐chain showed a positive result of variable degree in all but one case using automated Dako ChemMateTM amplification system staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all cases following automated staining. Conclusions: CD30 remains negative in L&H cells of nLPHD using enhanced antigen retrieval and can therefore reliably be used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H cells, even after the use of enhanced antigen retrieval. J‐chain and Oct2 appear to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and should therefore be included in lymphoma panels. Automated enhanced staining, using standardized protocols, precoated slides and the full system of prepared reagents, further diminishes the occurrence of errors associated with manual staining, and thereby improves confidence and reliability in diagnosing nLPHD.
Nuclear to cytoplasmic compartment shift of the p33ING1b tumour suppressor protein is associated with malignancy in melanocytic lesions
Authors: Nouman G S , Anderson J J , Mathers M E , Leonard N , Crosier S , Lunec J , Angus B 
Published: March 2003

Nuclear to cytoplasmic compartment shift of the p33

ING1b

tumour suppressor protein is associated with malignancy in melanocytic lesions Aims: Cutaneous malignant melanoma is an unpredictable neoplasm. Studies of cell cycle and proliferation‐associated proteins may help in the understanding of the genesis of melanomas. The tumour suppressor gene TP53 has been shown to be involved in melanomas. However, the incidence of TP53 malfunction in cutaneous melanoma is unclear, and other regulators of cell cycle control are likely to be involved in both the development and progression of melanocytic neoplasia. A candidate is the ING1 gene, which co‐operates with TP53 in growth suppression and apoptosis. Thus loss of ING1 function may have similar consequences to loss of TP53 function and may contribute to tumorigenesis. Therefore we have studied the expression of p33ING1b protein in cutaneous melanocytic neoplasia. Methods and results: Sixty‐seven melanocytic lesions were studied by immunohistochemistry for the expression of p33ING1b. In our series there was loss of nuclear p33ING1b expression in invasive malignant melanoma compared with normal cutaneous melanocytes or the melanocytes of benign melanocytic naevi. This was associated with an enhancement of cytoplasmic p33ING1b expression which was particularly prominent in invasive malignant melanoma. Conclusions: Cytoplasmic immunostaining for p33ING1b using MAb GN2 is strongly associated with `activated' melanocytic lesions; therefore it is possible that this MAb could be of value in diagnostic practice. Furthermore, the reduction in p33ING1b expression and perhaps translocation from the nucleus to the cytoplasm may play a central role in the development and progression of melanomas.
Differential Ki67 and bcl‐2 immunoexpression in solid–glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin
Authors: Lopes J M , Nesland J M , Reis‐Filho J S , Holm R 
Published: March 2003

Differential Ki67 and bcl‐2 immunoexpression in solid–glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin Aims: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid‐glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl‐2 and bax in the spindle cell and in the solid‐glandular component of biphasic synovial sarcomas. We also performed a double‐immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti‐apoptotic protein bcl‐2 in neoplastic cells expressing either vimentin or cytokeratin. Methods and results: Immunohistochemistry for vimentin (10 cases), bcl‐2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double‐immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl‐2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl‐2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or χ2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P=0.0004, P=0.082, and P < 0.0001, respectively); on the other hand, the latter showed higher expression of bcl‐2 and vimentin than the former (P=0.0281 and P=0.059, respectively). Double immunohistochemistry analysis revealed higher co‐expression levels of cytokeratin/Ki67 and cytokeratin/bcl‐2 than the spindle cell component (P=0.015 and P < 0.0001, respectively); conversely, the latter presented higher co‐expression of vimentin/bcl‐2 than the former (P=0.0007). All cases showed no more than 10% of cells coexpressing cytokeratin/bcl‐2, cytokeratin/Ki67, and no case revealed cells coexpressing vimentin/Ki67. Conclusion: Our findings indicate that in biphasic synovial sarcoma the acquisition of epithelial phenotype (solid/glandular component) is associated with a high expression of pro‐apoptotic proteins and a high proliferative differentiation status, and conversely, mesenchymal phenotype (spindle cell component) is associated with a high expression of apoptosis‐inhibitor bcl‐2 and a low proliferative terminal‐type differentiation status.
p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma
Authors: Auepemkiate S , Boonyaphiphat P , Thongsuksai P 
Published: March 2003

p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma Aims: To determine whether the p53 protein expression which is involved in the genesis and progression of various malignant tumours may relate to age, sites or the aggressive histopathological feature of the basal cell carcinoma. Methods and results: One hundred and fifty‐eight basal cell carcinoma specimens from Songklanakarind Hospital, southern Thailand, collected from January 1992 to December 2000, were examined by immunohistochemistry using polyclonal anti‐p53‐CM1 (Novocastra Laboratories, Newcastle, UK; dilution 1:700). p53 protein expression was demonstrated in 48.7% of cases. The multivariate analysis showed that the aggressive infiltrative histopathological type was significantly associated with p53 expression (odds ratio 2.95, 95% confidence interval 1.10–7.90), whereas age, sun‐exposure site, cellular response and fibrosis were not. Conclusions: The p53 expression is found to be related to the aggressive histopathological feature, which may be of predictive value for the behaviour of basal cell carcinoma. However, this result does not support the relation between sun exposure inducing basal cell carcinoma and p53 protein expression.
Ulcerative terminal ileitis after BCG therapy for bladder carcinoma
Authors: Satgé D , Pommepuy I , Hassan T , Goburdhun J , Flejou J‐F 
Published: March 2003

Aim:  We evaluated the aetiology of ulcerative ileitis in a 77‐year‐old patient receiving BCG therapy for recurring bladder carcinoma.Methods and results:  Histological examination, laboratory data and the clinical history allowed us to exclude a classical cause such as Crohn's disease, tuberculosis or ischaemia. The important locoregional reaction suggests a BCG ileitis of the terminal ileum. Intestinal BCG ileitis has been exceptionally described after BCG vaccination.Conclusion:  Our observation of ulcerative ileitis indicates that a digestive tract location is possible as a reaction to BCG therapy.
Malignant mesothelioma: PAS–diastase positivity and inversion of polarity in intravascular tumour
Authors: Adams S A , Sherwood A J , Smith M E F 
Published: March 2003

Aims:  Periodic acid–Schiff (PAS)–diastase‐positive material was identified within pseudoglandular structures within the small intravascular component of two pleural malignant mesotheliomas. The aim of this study was to ascertain the nature of this material and to asses the polarity of the cells forming the pseudoglandular structure.Methods and results:  Immunohistochemistry was performed using antibodies to laminin and type IV collagen and the antibody HBME‐1. These demonstrated the material to be basement membrane rather than mucin. The apical polarity marker HBME‐1 was not related to the internal pseudoglandular structure but stained the periphery of intravascular tumour clumps.Conclusions:  Pseudoluminal PAS–diastase‐positive material in malignant mesothelioma may easily be mistaken for epithelial mucin, leading to an erroneous diagnosis of adenocarcinoma. The presence of basement membrane material in pseudolumina, as defined by the presence of laminin and type IV collagen, surrounded by tumour cells whose external surface expresses the apical polarity marker HBME‐1 implies inversion of polarity of tumour cells within vascular spaces.
Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem‐like cells: immunohistochemical, electron microscopic and immunoelectron microscopic findings
Authors: Xiao J‐C , Ruck P , Adam A , Wang T‐X , Kaiserling E 
Published: March 2003

Aims:  To investigate whether cells with features similar to those of the oval cells of rodents and the small epithelial cells (SEC) recently described in certain human liver diseases, i.e. hepatic progenitor cells, also occur in human liver cirrhosis.Methods and results:  Surgical specimens from 35 cases of hepatitis B virus‐positive cirrhosis (30 cases containing hepatocellular carcinoma) were investigated by immunohistochemical staining for cytokeratin 7 and albumin. Electron microscopic investigations, and immunoelectron microscopic investigations using the same antibodies and a double‐labelling technique were performed in 15 and seven cases, respectively. SEC were observed in proliferated bile ductules, at the margins of regenerating nodules and in the fibrous septa in all cases of cirrhosis. The SEC were morphologically similar to the SEC described previously, and to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, scanty electron‐dense or electron‐lucent cytoplasm, a high nucleo–cytoplasmic ratio, tonofilaments and intercellular junctions. Immunoelectron microscopy revealed that the SEC co‐expressed cytokeratin 7 and albumin. Both relatively undifferentiated SEC and SEC with morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found.Conclusions:  SEC that exhibit morphological and immunophenotypical features of the SEC seen in certain other liver diseases are found in cirrhosis. These findings further support the hypothesis that a bipotent hepatic stem cell that may give rise to biliary epithelial cells and hepatocytes exists in the human liver.
Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross‐react with virus and cardiac myosin
Authors: Fairweather D. , Lawson C. M. , Chapman A. J. , Brown C. M. S. , Booth T. W. M. , Papadimitriou J. M. , Shellam G. R. 
Published: March 2003

The laboratory‐adapted K181 strain of murine cytomegalovirus (MCMV) induces both acute and chronic myocarditis, associated with autoantibodies to cardiac myosin, in susceptible BALB/c mice. However, the K181 MCMV strain has been maintained in the laboratory for many years and may not resemble naturally occurring strains of MCMV in its ability to induce myocarditis. Accordingly, six different isolates of MCMV from wild Mus domesticus were compared with K181 MCMV for their ability to induce myocarditis and autoantibodies to cardiac myosin in BALB/c mice. These isolates were shown to induce acute myocarditis similar to K181 MCMV, with associated focal and diffuse myocardial inflammation. However, the levels of myocarditis induced by the wild isolates during the chronic phase of the disease (days 32–56 post‐infection) were low in contrast to the K181 strain. Interestingly, 30% of wild‐trapped mice showed histological evidence of myocarditis and all were sero‐positive to MCMV. Sera from BALB/c mice infected with wild MCMV isolates and from wild‐trapped mice contained antibodies that cross‐reacted with MCMV and cardiac myosin (S2 region). The cross‐reactive region of MCMV was found to be a 50 000–55 000 MW viral polypeptide. These findings suggest that molecular mimicry may be involved in the pathogenesis of autoimmune myocarditis following infection with both laboratory and wild MCMV strains.EDTA, ethylenediaminetetraacetic acid ELISA, enzyme‐linked immunosorbent assay H&E, haematoxylin and eosin HMM, heavy meromyosin i.p., intraperitoneal LMM, light meromyosin  mAb, monoclonal antibodies MCMV, murine cytomegalovirus MEF, mouse embryo fibroblasts MOBS, mouse osmolarity buffered saline MW, molecular weight OD, optical density PBS, phosphate buffered saline PFU, plaque‐forming units p.i., post‐infection PMSF, phenylmethylsulphonyl fluoride PVDF, polyvinylidene difluoride SDS–PAGE, sodium dodecyl sulphate–polyacrylamide gel electrophoresis.
Some Bence–Jones proteins enter cultured renal tubular cells, reach nuclei and induce cell death
Authors: Matsuura K. , Ikoma S. , Watanabe M. , Togawa A. , Sinohara H. 
Published: March 2003

SummaryEighteen monoclonal Bence–Jones proteins (BJPs) were examined for their effects on cultured LLC‐PK1 (porcine kidney proximal tubule) cells as well as for their amidase and DNase activities. Five proteins were found to enter the cell and to gain access to the nucleus without degradation of epitopes. Intranuclear BJPs ultimately induced DNA fragmentation and cell death. BJPs with relatively high amidase activity were cytotoxic. On the other hand, three of four BJPs with DNase activity had a cytocidal effect on cultured cells; the remaining BJP, which had a relatively high DNase activity but a very low amidase activity, failed to enter the cell and was not cytotoxic in vitro. These results suggest that catalytic and cytotoxic activities of some BJPs may make a significant contribution, in a substantial proportion of myeloma patients, to the development and/or deterioration of the disease.