bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases
Authors: Bates  , Baithun  
Published: March 2003

AimsThe incidence, anatomical localization and histological appearances of secondary neoplasms of the urinary bladder are described, with emphasis on the points of distinction from primary tumours.Methods and resultsA retrospective study of cases at the Royal Hospitals Trust yielded a total of 282 secondary bladder neoplasms, representing 2.3% of all malignant bladder tumours in surgical specimens. The commonest primary sites were the colon (21% of secondary neoplasms), prostate (19%), rectum (12%) and cervix (11%). Most tumours from these sites reached the bladder by direct spread. The most common sites of origin of tumours metastatic to the bladder were stomach (4.3% of all secondary bladder neoplasms), skin (3.9%), lung (2.8%), and breast (2.5%). Secondary tumour deposits were almost always solitary (96.7%), and 54% were located in the bladder neck or trigone. Histologically, 54% of secondary tumours were adenocarcinomas. Immunohistochemical staining patterns with prostate‐specific acid phosphatase, prostate‐specific antigen, carcinoembryonic antigen, chromogranin and neurone‐specific enolase were similar in primary vesical and urachal adenocarcinomas and secondary adenocarcinomas from the gastrointestinal tract.ConclusionsThe incidence of secondary bladder tumours is comparable to that of nontransitional cell primary tumours. Few secondary tumours have distinctive histological features, hence knowledge of the history and clinical investigations are particularly important in their diagnosis.
Transitional cell carcinomas of the ovary and bladder are immunophenotypically different
Authors: Ordóñez  
Published: March 2003

AimsTransitional cell carcinoma (TCC) of the ovary is a subtype of ovarian cancer whose main characteristic is its histological resemblance to TCC of the bladder. Thrombomodulin (TM), a surface glycoprotein commonly expressed in normal and neoplastic urothelium, has been proven to be a good marker for TCC of the bladder. To better define the phenotype of TCC of the ovary, we investigated TM, cytokeratin 20 and carcinoembryonic antigen (CEA) expression in 15 TCCs of the ovary and compared their phenotype with that of 20 TCCs of the bladder, and 20 serous and 10 endometrioid carcinomas of the ovary.Methods and resultsImmunostaining was performed on formalin‐fixed, paraffin‐embedded tissue sections using the avidin–biotin–peroxidase complex method. All 20 TCCs of the bladder stained for TM and cytokeratin 20, and 13 stained for CEA. None of the TCCs of the ovary reacted for TM or cytokeratin 20, and only two expressed CEA. All of the serous and endometrioid carcinomas were negative for TM and cytokeratin 20. CEA positivity was observed in two of the serous carcinomas, but in none of the endometrioid carcinomas.ConclusionThe immunophenotype of TCC of the ovary is similar to that of other surface carcinomas of the ovary, but differs from that of TCC of the bladder. Since immunohistochemical procedures are often used in the diagnosis and classification of both primary and metastatic tumours, it is important to be aware of these differences in immunophenotype.
Reproducibility of the WHO/IASLC grading system for pre‐invasive squamous lesions of the bronchus: a study of inter‐observer and intra‐observer variation
Authors: Nicholson A G , Perry L J , Cury P M , Jackson P , McCormick C M , Corrin B , Wells A U 
Published: March 2003

Although many workers have graded pre‐invasive squamous lesions arising in the bronchus, there has been no consensus classification system until the latest edition of the WHO/IASLC histological classification of pulmonary and pleural tumours. Because the value of any such system is dependent on its reproducibility, we have circulated a series of such lesions to a panel of histopathologists to assess interobserver and intra‐observer variation when the WHO/IASLC classification was applied.Colour transparencies of 28 pre‐invasive squamous lesions were assessed by six histopathologists (two with a special interest in pulmonary pathology, two generalists and two trainees) on three separate occasions over a period of 3 months, using the criteria of the WHO/IASLC (mild, moderate and severe dysplasia, and in‐situ carcinoma). An additional category of metaplasia was added for those cases that showed no dysplasia. Weighted kappa coefficents of agreement (Kw) were used to evaluate paired observations with a standard quadratic weighting being employed, such that kappa coefficients corresponded to intra‐class correlation coefficients. Wilcoxon's sign‐ranked test was used to measure the statistical significance of group trends, when comparing kappa values for the three grading systems. Various 3‐point systems were also assessed, through combination of the above groups. Intra‐observer agreement was substantially better than interobserver variation (mean: 0.71 vs. 0.55). Between the various pathologist groups, inter‐observer variation was relatively minor, although intra‐observer variation was higher within the trainee pathologist group. Using weighted kappa values, there was no significant difference in either inter‐observer or intra‐observer agreement between the five point grading system and a 3‐point system of metaplasia/mild, moderate and severe/in‐situ grades. However, there was a significant increase in variation when a 3‐point system of metaplasia/mild, moderate/severe and in‐situ carcinoma was used.This study shows levels of interobserver and intra‐observer variation similar to those found in other grading systems in histopathology, with no significant decrease in variability found by abridging the system. The WHO/IASLC system is therefore recommended for future use in both clinical and research fields.
Histological, genomic and clinical heterogeneity of clear cell hepatocellular carcinoma
Authors: Emile J‐F , Lemoine A , Azoulay D , Debuire B , Bismuth H , Reynès M 
Published: March 2003

The aim of the study was to determine whether clear cell type hepatocellular carcinoma should still be regarded as a separate uniform diagnostic entity.We retrospectively studied 118 cirrhotic patients with hepatocellular carcinoma treated by orthotopic liver transplantation, and 31 noncirrhotic patients with hepatocellular carcinoma treated by either liver surgical resection or transplantation. The pathology of all liver resections was reviewed. Microsatellite instability was performed on paraffin‐embedded samples at loci located on chromosomes 2p, 3p, 5q, 8q, 9p, 13q, 16q and 17p. Among the 118 cirrhotic patients, 10 (8.5%) had a clear cell hepatocellular carcinoma; these had clinical characteristics and prognosis similar to the other cirrhotic patients. No genetic alterations were detected in these tumours. Among the 31 noncirrhotic patients, one (3.2%) had a clear cell hepatocellular tumour. This 170‐mm tumour had a lipid density on computed tomography, and its histology resembled chromophobe cell renal carcinoma. Furthermore, this tumour had unusual genomic alterations, with microsatellite instability in 6/8 chromosome loci.Clear cell hepatocellular carcinoma is a heterogeneous entity in which a chromophobe cell subtype should be identified.
Host ethnicity influences non‐Hodgkin’s lymphoma subtype frequency and Epstein–Barr virus association rate: the experience of a multi‐ethnic patient population in Malaysia
Authors: Peh S‐C 
Published: March 2003

Host ethnicity influences non‐Hodgkin’s lymphoma subtype frequency and Epstein–Barr virus association rate: the experience of a multi‐ethnic patient population in Malaysia Aims: The pattern of malignant lymphoma is known to vary in different populations. This study aims to elucidate the effect of ethnicity on subtype frequency of non‐Hodgkin’s lymphoma and EBV association rate. Methods and results: A total of 232 reconfirmed lymphoma cases in Malaysian patients were retrieved from the archives in the Department of Pathology, University Hospital, Kuala Lumpur. There were 24 (10%) Hodgkin’s and 208 (90%) non‐Hodgkin’s lymphomas, 173 of the latter were in adult group (aged ≥ 15 years). The ethnic composition were 41 Malays, 107 Chinese, 21 Indians and four none of the above. A male : female ratio of 2.4 : 1 was observed. Complete immunohistochemical studies in 158 cases revealed 36 (23%) T‐cell, 121 (76%) B‐cell and one (1%) null‐cell phenotype. Seventy‐five percent of the T‐cell lymphomas were peripheral T/NK‐cell types. Among the classifiable lesions, low‐grade/indolent lymphomas constituted 17%: 2% were the lymphocytic subtype and 10% were follicular lymphomas. Approximately one‐third of the follicular lymphomas occurred in Indian patients. The largest group of high‐grade lymphoma was diffuse large B‐cell type (46%), followed by peripheral T/NK‐cell (18%). A predominance of NK/T‐cell lymphomas occurred in Chinese (5/7), and all were EBV associated. Burkitt’s lymphoma accounted for 5% (eight cases), all were Chinese males, with a 38% EBV‐association rate. The frequency of EBV‐associated B‐cell lymphoma is three times more common in Chinese than Malays. The EBV positivity rate among lymphomas in ethnic Malay, Chinese and Indian patients was 5%, 15% and 22%, respectively, and in T‐ and B‐cell lymphomas was 36% and 7%, respectively. Conclusions: This Malaysian series reveals differences in the subtype frequencies of non‐Hodgkin’s lymphomas and EBV association rate amongst patients of various ethnic groups residing in the same environment.
Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B‐cell non‐Hodgkin’s lymphomas and multiple myeloma
Authors: Mendes R V , Martins A R , De Nucci G , Murad F , Soares F A 
Published: March 2003

Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B‐cell non‐Hodgkin’s lymphomas and multiple myeloma Aims: Nitric oxide synthases (NOS) are isoenzymes that catalyse the synthesis of nitric oxide (NO). The three main NOS isoforms are: NOS1 or neuronal, NOS2 or inducible, and NOS3 or endothelial. NO plays both physiological and pathological roles, depending on its rate of synthesis and concentration, cellular source and microenvironment. Apoptosis is an important biological factor in low‐grade lymphomas, and NO is able to prevent apoptosis. In‐situ expression of NOS and synthesis of NO have been shown in several malignant tumours, but not in lymphoid neoplasms. This study evaluates whether human B‐cell neoplasms express NOS isoforms, and nitrotyrosine (NY), which is usually interpreted as a marker of NO. Methods and results: We studied the expression of NOS‐IR isoforms and NY‐IR in 16 cases of B‐cell non‐Hodgkin’s lymphoma (NHL) (five follicle centre cell lymphoma, four small lymphocytic/CLL, and seven diffuse large cell lymphoma), and 10 cases of multiple myeloma (MM). NOS1 was expressed in 5/10 cases of MM, and 15/16 cases of NHL. NOS2 was detected in all cases of MM, and in 14/16 cases of NHL, whereas NOS3 was positive in 3/10 of MM and in only in 1/16 cases of NHL. The expression of NY‐IR was observed in 70% of MM cases, and in all cases of B‐cell NHL, in a dot‐like pattern in few tumour cells. Conclusions: B‐cell neoplasms express neuronal and inducible NOS, and nitrotyrosine. Taken together, our results suggest that B‐cell neoplasms can produce NO. The role of NO in the biology, diagnosis and prognosis of B‐cell neoplasms remains to be established.
Vascular endothelial growth factor expression correlates with tumour grade and vascularity in gliomas
Authors: Chaudhry I H , O'Donovan D G , Brenchley P E C , Reid H , Roberts I S D 
Published: March 2003

Vascular endothelial growth factor expression correlates with tumour grade and vascularity in gliomas Aims: Tumour vascularity and vascular endothelial growth factor (VEGF) expression were studied in 41 primary brain tumours of astrocytic and oligodendroglial origin, in order to define the potential role of VEGF in the vascularization and growth of these tumours. Methods and results: Two commercial monoclonal antibodies to the VEGF protein (from R&D Systems and NeoMarkers), raised against different isoforms, were utilized. Each monoclonal antibody consistently detected the expression of VEGF in different cell types. The R&D Systems antibody only produced surface staining of endothelial cells in tumour capillaries, whereas staining with the Neomarkers antibody was largely confined to tumour cell cytoplasm. High levels of staining were seen with the R&D Systems and NeoMarkers antibodies in 13 and 14 of 15 glioblastomas, respectively, four and three of five oligodendrogliomas, four and seven of 10 anaplastic astrocytomas, one and three of six low‐grade astrocytomas and none and none of five pilocytic astrocytomas. There was a close correlation between VEGF expression, tumour vascularity and grade. Conclusions: These findings support a role for VEGF in the angiogenesis of glioblastoma, anaplastic astrocytoma and oligodendroglioma. The distinct immunoreactivities of the two commercial monoclonal antibodies indicate either there is expression of different splice variants of VEGF or that the epitopes are differentially revealed during synthesis, secretion and receptor‐binding of the growth factor. This highlights the importance of using more than one antibody in the evaluation of tissue VEGF expression.
Cutaneous sclerosing Pacinian‐like perineurioma
Authors: Burgues O , Monteagudo C , Noguera R , Revert A , Molina I , Llombart‐Bosch A 
Published: March 2003

Cutaneous sclerosing Pacinian‐like perineurioma Aims: The term perineurioma has been used to designate a variety of clinically and histologically different proliferations of perineurial cells based on immunohistochemical and/or ultrastructural characterization. There are two different groups of neoplasms derived from perineurial cells: extraneural or soft tissue perineuriomas, and intraneural perineuriomas. Recently, a sclerosing variant of cutaneous perineurioma has been described. Methods and results: We report a case of a cutaneous form of perineurioma, combining features of the intraneural and sclerosing varieties, as well as showing a Pacinian pattern of growth. In order to assess the neoplastic nature of the lesion, we performed fluorescence in‐situ hybridization (FISH) analysis using a probe which maps to the chromosome band 22q11 and 22q13, allowing us to show deletion or loss of one chromosome 22 in the tumour cells. Conclusions: This case may be considered a new variant of perineurioma with Pacinian‐like features, for which we propose the designation ‘sclerosing Pacinian‐like perineurioma’.
Galectin‐3, a marker of well‐differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia
Authors: Coli A , Bigotti G , Zucchetti F , Negro F , Massi G 
Published: March 2003

Galectin‐3, a marker of well‐differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypiaAims: The distribution of galectin‐3, a widely recognized marker of well‐differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia.Methods and results: Twenty‐eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin‐3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin‐3‐positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin‐3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin‐3‐positive cases.Conclusions: Galectin‐3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.
Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis
Authors: Eimoto T , Kitaoka M , Ogawa H , Niwa H , Murase T , Tateyama H , Inagaki H , Soji T , Wang H J 
Published: March 2003

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis Aims: Malignant thymic tumour histologically resembling a soft tissue sarcoma is extremely rare and defined as sarcomatoid carcinoma in the recent World Health Organization (WHO) classification. We report two such cases in which the tumour cells showed a prominent rhabdomyoblastic differentiation and analyse whether these tumours retain an epithelial nature at least in part. Methods and results: One tumour occurred in a 51‐year‐old man (Case 1) and the other in a 40‐year‐old woman (Case 2). Microscopically, both tumours consisted essentially of two types of tumour cells: spindle and large round cells, with no apparent epithelial components. Osteosarcomatous small foci were also found in Case 2. Immunohistochemically, desmin and muscle‐specific actin were positive in the majority of both types of tumour cells, whereas myogenin was predominant in the spindle cells and myoglobin in the large round cells. Some of both types of cells expressed cytokeratin with co‐expression of myoglobin in the large round cells, but with no myogenin in the spindle cells. Some cytokeratin‐positive spindle cells were also negative for desmin. Ultrastructural examination of a recurrent tumour in Case 2 revealed some epithelial features among the spindle cells. Cytogenetic study of the same tumour showed a complex abnormality including der(16)t(1;16)(q12;q12.1), an identical pattern previously reported in a case of thymic squamous cell carcinoma. Conclusions: The findings support the definition in the WHO classification of sarcomatoid carcinoma that includes purely sarcomatous tumour as in the present cases. Occurrence of this type of tumour may indicate a relationship between thymic epithelial cells and myoid cells and/or a potential for divergent differentiation in thymic epithelial tumours.
Leiomyosarcoma of the head and neck: a clinicopathological study
Authors: Montgomery E , Goldblum J R , Fisher C 
Published: March 2003

Leiomyosarcoma of the head and neck: a clinicopathological study Aims: The behaviour of leiomyosarcoma is site‐related and there are few data on such tumours located in the head and neck. We studied the clinicopathological features of these lesions. Methods and results: Cases diagnosed as leiomyosarcoma of the head and neck were retrieved from the archives of three institutions. Immunohistochemistry was performed and follow‐up information was obtained. There were seven men and six women, aged 21–73 years, and lesions involved the neck (n=3), maxilla (n=4), buccal area (n=3), and maxillary sinus, nose, and pharynx (n=1 each). Tumours ranged from 10 to 80 mm. All tumours showed at least focally typical histological features of leiomyosarcoma with perpendicularly arranged fascicles of smooth muscle cells with blunt‐ended nuclei, eosinophilic cytoplasm and paranuclear vacuoles. They expressed muscle‐specific actin (8/9), smooth muscle actin (7/9), and desmin (10/12). Follow‐up information was available on nine patients. All had surgery, with radiation and/or chemotherapy in seven. Three (27%) recurred at 6–24 months; in one case twice. Five (56%) had metastases, including the three with prior recurrences at 1–128 months. Five (including two who received adjuvant therapy) were disease‐free at a median of 47 months, one was alive with metastatic disease at 24 months), and three were dead of disease (median 13 months). Conclusions: Head and neck leiomyosarcomas are rare and aggressive neoplasms which metastasize. Adjuvant therapy has limited effect.
Novel mode of action of the calcium antagonist mibefradil (Ro 40‐5967): potent immunosuppression by inhibition of T‐cell infiltration through allogeneic endothelium
Authors: Blaheta R. A. , Hailer N. P. , Brude N. , Wittig B. , Oppermann E. , Leckel K. , Harder S. , Scholz M. , Weber S. , Encke A. , Markus B. H. 
Published: March 2003

Cyclosporin A reduces the mitotic activity of allosensitized lymphocytes, but fails to limit emigration of these cells into the donor organ. However, the modulation of both lymphocyte proliferation and infiltration are desirable characteristics of immunosuppressive therapy. The calcium‐channel blocker, verapamil, has recently been shown to effectively prevent the transmigration of CD4+ and CD8+ T cells through allogeneic endothelium. Mibefradil (Ro 40‐5967) represents a new generation of calcium antagonists with high potency and long‐term activity. To evaluate the immunosuppressive potential of this drug, the influence of mibefradil on lymphocyte adhesion to, horizontal locomotion along, and penetration through allogeneic endothelium (HUVEC) was performed. When lymphocytes were prestimulated for 24 hr with mibefradil, adhesion and penetration were dose‐dependently reduced. The adhesion ID50 values were 3·4 μm (CD4+ T cells) versus 9·2 μm (CD8+ T cells) and 2·1 μm (CD4+ T cells) versus 3·9 μm (CD8+ T cells) with regard to penetration. Mibefradil also effectively blocked horizontal locomotion. Specific down‐regulation of T‐cell binding to the P‐selectin receptor (ID50: CD4+ T cells, 0·8 μm; CD8+ T cells, 1·2 μm) and to the intracellular adhesion molecule‐1 (ICAM‐1) receptor (ID50: CD4+ T cells, 1·9 μm; CD8+ T cells, 1·5 μm) by mibefradil seems to be responsible for the decreased adhesion and penetration rates. Reduction of intracellular F‐actin in T lymphocytes could diminish cell locomotion. In conclusion, the potent suppressive properties of mibefradil support its use as a co‐medication in cyclosporin A‐based immunosuppressive therapy.CsA, cyclosporin A HUVEC, human umbilical vein endothelial cells ICAM‐1, intercellular adhesion molecule‐1 LFA‐1, leukocyte function‐associated antigen‐1 PBL, peripheral blood lymphocytes PSGL‐1, P‐selectin glycoprotein ligand‐1.
Schistosomal egg antigen‐responsive CD8 T‐cell population in Schistosoma mansoni‐infected BALB/c mice
Authors: Pancré V. , Delacre M. , Herno J. , Auriault C. 
Published: March 2003

SummaryWe demonstrated here that schistosomal egg antigen (SEA) is able to stimulate an antigen‐specific, cytotoxic CD8+ T‐cell response in mice. Indeed, a single i.p. immunization with SEA resulted in the in vivo induction of significant cytotoxic T lymphocyte (CTL) activity in the spleen within 20 days. Effector cells were classic class I major histocompatibility complex (MHC)‐restricted CD8+ lymphocytes producing interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2), suggesting a type 1 response to SEA. We therefore investigated the relevance of these observations in the context of the Schistosoma mansoni parasite infection. CTL activity against SEA‐pulsed target cells was evidenced throughout the infection after in vitro stimulation of recovered splenic cells with SEA demonstrating that SEA‐specific CD8+ T cells with cytotoxic potentialities are present during infection. This activity was strongly increased after immunization of mice with SEA like the production of IFN‐γ in the sera. A marked reduction in the number of granulomas and of fibrosis with the presence of cells producing IFN‐γ in the liver was also observed leading to the survival of SEA‐immunized mice.