bluuebunny/crossref_metadata_2025 huggingface dataset:
Is a Fellow a dinosaur? A description of routes to Fellowship
Authors: LEWIS M. JOY
Published: March 2003

There are various ways of gaining the Fellowship of the Library Association (FLA) and these are outlined and discussed. The Fellowship is set in its historical context and recent developments including the work of the Board of Fellowship are explained. The author's views on the value, both personal and professional, of this distinction to its holders are indicated.
Medical libraries in Iceland
Authors: OLAFSSON HELEN A.
Published: March 2003

This paper gives an account of the development and current activities of medical libraries in Iceland. The future goals of the medical librarians, which are to extend services to groups at present neglected and to establish a resource collection, are discussed.
The Net Book Agreement and Health Service libraries
Authors: STRANGE ANNE , HOCHLAND ERNEST
Published: March 2003

Can Health Services libraries obtain from the Publishers' Association a library licence and thereby receive, from the booksellers they choose to name on their licence, a discount of 10%? Furthermore, can an ‘umbrella licence’ be obtained which covers a group of libraries within one region? The answer to both these questions is now ‘yes’, following a series of negotiations between the North West Regional Health Authority and the Publishers Association.
Planning a new medical library: a personal perspective and review of the literature*
Authors: DORAN BEATRICE M.
Published: March 2003

Principles of library planning and a review of the literature in relation to the planning of a new library for the Royal College of Surgeons in Ireland are discussed. The role of the Librarian with regard to planning, the importance of the Library brief, the impact of technology on library buildings, and the provision of adequate accommodation for collections, readers and staff are considered.
The health system and medical information services in Sri Lanka
Authors: KORALE S. R.
Published: March 2003

Set against the background of the geographical, social and economic conditions of the country this paper outlines the structure of the health‐care system in Sri Lanka and describes the development of a health‐information system to support the information needs generated. Current developments including the role of the Health Literature, Library and Information Service (HELLIS; Sri Lanka) network and services are discussed, and problems enumerated. In conclusion the paper argues for the designation of one library, capable of being developed as a centre of excellence and with staff trained to exploit the new technologies, particularly CD‐ROM, to provide a central core facility for the country as a whole.
Downloading from medline: a comparison of personal database software.
Authors: HERMAN DIANA
Published: March 2003

The compatibility of downloaded medline references with software packages designed for maintenance of personal bibliographic databases is considered. The nine packages reviewed enable one to import batches of records downloaded from one or more presentations of the medline database, online or cd‐rom; and enable the user to re‐format records into the various styles required by journal editors. Some basic features of the packages are tabulated, and details of record‐importing facilities are described. Details of suppliers and prices are given.
ADONIS—latest developments and its role in the changing publisher/library relationship
Authors: COMPIER HENK C. J. , CAMPBELL ROBERT M. , ADONIS B. V.
Published: March 2003

This article describes recent developments in the ADONIS concept, including technical advances, expansion of services and implications for the future.
Who uses NHS libraries? Preliminary results from a survey of postgraduate medical libraries in North East Thames
Authors: HEWLETT JOHN
Published: March 2003

Recent changes have made Regional Deans fund‐holders for postgraduate medical education. Allocations from the Dean's budget often fund NHS library infrastructure and associated costs arising from the information and study needs of junior medical staff. To provide adequate levels of stock and services for all library users requires funding from all appropriate sources.

This paper describes a survey carried out in North East Thames to facilitate appropriate funding by and for user groups other than junior doctors.

The wide variation in results is discussed. The survey is not seen as definitive, but as part of the beginning of the evolutionary process of allocating funds for libraries serving postgraduate medical education and other users. Further research is suggested, particularly in other Regions, to provide comparative data.
A comparison of the currency of secondary information sources in the biochemical literature. II. MEDLINE online and on CD‐ROM
Authors: GRAINGER FELICITY , LYON ELIZABETH
Published: March 2003

The currency of selected versions of the MEDLINE database on CD‐ROM and in online format was studied. The arrival of issues from 72 monthly journals and nine weekly titles during a 3‐month period was monitored and their appearance in the various MEDLINE formats were recorded. Availability data for MEDLINE published by the National Library of Medicine were used as a baseline and subsequent distribution delays for the different MEDLINE formats were calculated. The study suggests a delay of approximately 2 weeks for indexing and mounting the MEDLINE file on to host computers for online access. A delay of 68 weeks was calculated for the MEDLINE data to be encoded on to compact disk, shipped and posted to the library customer. The currency of the MEDLINE database formats was compared with a weekly current‐awareness service, CURRENT CONTENTS ON DISKETTE LIFE SCIENCES (CCOD). The majority of papers were indexed and distributed in CCOD within 10 weeks of publication date. Most papers appeared within 15 weeks in the online MEDLINE format and within 20 weeks in CD‐ROM MEDLINE. The primary journal arrived at the library site within 5 weeks in most cases.
Editorial: ethical and legal issues—dilemmas and duties
Authors: MORGAN PETER
Published: March 2003

‘Man is an animal with primary instincts of survival. Consequently, his ingenuity has developed first and his soul afterwards. Thus the progress of science is far ahead of man's ethical behaviour.’ Charlie Chaplini
The move to community care and the impact of long‐term disability on health service provision: some implications for library services
Authors: PROCTER SUSAN
Published: March 2003

This paper describes the epidemiological and demographic trends underpinning the current shift to primary health care heralded by the Community Care Act. It suggests that the health service is increasingly treating people suffering from long‐term disability. Hospitals no longer provide an appropriate setting for the management of long‐term disability as hospital‐based practitioners cannot integrate treatment modalities into the everyday life experiences of the patient. Community care introduces a social dimension to the traditional medical model of health. The paper examines the information needs generated by both the social model and the medical model of health and considers the types of information required by each model. It concludes by discussing the potential for librarians to influence health care provision via the type of information they make available to practitioners.
Changes in the National Health Service and the effects on the hospital library service: case study based on the Cumberland Infirmary
Authors: GOUNDRY PAULINE
Published: March 2003

The perception of change so often differs from the reality. This article traces the effect on one hospital library of some of the major changes within the NHS during the past 10 years. It explores the importance of external factors such as location and proximity to other professional groups and questions the survival of the multi disciplinary hospital library.
Adoption of Internet technology by UK postgraduate centres: a questionnaire survey
Authors: Jordaan Marieke , Jones Richard
Published: March 2003

A survey of UK postgraduate centres during September 1997 found that almost 60% were connected to the Internet, but librarians were still the largest user group, few had more than one access point and support to users was limited. Significant progress was made during the following 18 months—by April 1999 all but one of the remaining sites had Internet access in either the postgraduate centre or in a separate library. Lack of funds and decisive policy were stated to be the most common reasons for delay in connecting. The Internet was rated highly as source of the latest research information and support for evidence‐based medicine and continuing education. Expansion of the role of librarians to include assistance with sophisticated searches seemed a logical move to the majority, yet the survey suggests that a significant investment in time and money will be required to support the use of the Internet in continuing medical education in the broadest sense. It is likely that the traditional boundaries between IT departments, libraries and user groups will need to be redrawn if the technology is to be exploited effectively.
Type 1 protein tyrosine kinases in benign and malignant breast lesions
Authors: Suo  , Emilsen  , Tveit  , Nesland
Published: March 2003

Aims: To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.

Methods and results

Fifty‐three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty‐three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c‐erbB‐2 protein and 17% (9/53) c‐erbB‐3 protein, while no expression of c‐erbB‐2 and c‐erbB‐3 proteins was found in the benign tumours. Contrary to previous reports, we observed c‐erbB‐4 receptor protein to be less expressed in the malignant breast tumours. The ‘normal’ breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c‐erbB‐4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c‐erbB‐4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c‐erbB‐2, c‐erbB‐3 and phosphotyrosine are largely in line with what has been reported, we found the c‐erbB‐4 protein expression to be decreased in the malignant tumours.
Ki67 labelling index correlates with stage and histology but not significantly with prognosis in thymoma
Authors: Pan C‐C , M‐T Ho D , Y‐K Chen W , Huang C‐W , Chiang H
Published: March 2003

Aims

There have been several cell kinetic studies of thymoma, but the effectiveness of using Ki67 antibody as a tool to measure proliferative activity in this tumour was rarely evaluated. We carried out an immunohistochemical study using this antibody to assess the clinicopathological correlation and the prognostic significance of this technique.

Methods and results

Ninety‐one cases of thymoma were collected. Double immunostaining with Ki67 and cytokeratin KL‐1 antibodies was performed on paraffin sections. Ki67 labelling index (LI) was expressed as a percentage of Ki67 immunopositive nuclei by counting at least 1000 epithelial cells. The LIs were correlated with stages, histological subtypes based on both Lattes–Bernatz and Müller–Hermelink–Kirchner classifications, and length of survival. There were statistically significant differences of LIs between stage I and stage III and between stage I and stage IV tumours. Histologically, statistically significant differences were identified between predominantly epithelial thymoma and every other subtype of the Lattes–Bernatz classification and between well‐differentiated thymic carcinoma and medullary or mixed thymomas of the Müller–Hermelink–Kirchner classification. Regarding the prognostic implication of Ki67 LI, although there appeared a trend that patients with tumours of higher LIs had slightly worse survival, the difference was not statistically significant in both univariate and multivariate survival analyses.

Conclusions

We have demonstrated the proliferative potential in thymoma is associated with stage and histology. However, its clinical usefulness is limited on account of the overlap of LIs and lack of prognostic significance.
Problems arising from Eastern and Western classification systems for gastrointestinal dysplasia and carcinoma: are they resolvable?
Authors: Riddell R H , Iwafuchi M
Published: March 2003

It has become increasingly apparent that the Japanese and Western systems of classifying dysplasia and carcinoma in the gastrointestinal tract are not the same. The implication of these differences is that in an article in a Western journal on gastrointestinal ‘cancer’ originating from Japan, it is often impossible to repeat the study to confirm or refute it, because of these differences in definitions. Although there is no reason why it should not be just as much of a problem if Western research is published in Japanese journals, this is currently not a major problem. The terminological differences do not mean that one is right and one wrong; they are simply different.  We had an opportunity to look at these differences in detail in a series of 100 gastric biopsies. In this review, we outline these differences and indicate the similarities, differences and problems between these two systems. ‘Carcinoma’ is diagnosed in Japan by virtue of its structural and cytological features, but by invasion in the Western system. Adenoma does not mean a dysplastic lesion in the Japanese system (although it can) but in most cases is similar to low‐grade dysplasia irrespective of the macroscopic/endoscopic appearances (hence flat and depressed adenomas in the Japanese system); however, most examples of high‐grade dysplasia in the Western system, as well as some low‐grade dysplasia, becomes ‘cancer’ in the Japanese system. Conversely, both have conceptual areas that are useful in the other's system. Because we were ultimately able to use each other’s systems, we were able to show where these systems come together and diverge. These provide hope that a common classification encompassing both systems that allows communication between both systems is feasible.
Primary malignant peripheral nerve sheath tumour of the heart
Authors: Pauwels  , Dal Cin  , Sciot  , Lammens  , Penn  , Van Nes  , Kwee  , Van Den Berghe
Published: March 2003

Aims

Malignant peripheral nerve sheath tumour (MPNST) is an unusual sarcoma of the heart and should be differentiated from other spindle cell sarcomas.

Methods and results

We combined morphological, immunohistochemical and cytogenetic techniques in the differential diagnosis, particularly from monophasic synovial sarcoma. The tumour consisted of dense fascicles, alternating with hypocellular, myxoid zones. There was a marked herniation of tumour cells into the vascular lumen. Immunohistochemically, the tumour cells expressed vimentin and focally S100 protein. There was no expression of cytokeratin or epithelial membrane antigen (EMA). Although we found a complex karyotype, the finding of involvement of 17q11, the loss of chromosome 22, and the absence of a t(X;18)(p11.2;q11.2), which characterizes synovial sarcoma, allowed us to the final diagnosis of malignant peripheral nerve sheath tumour.

Conclusion

MPNST of the heart can be diagnosed by combining morphological and immunohistochemical date. Cytogenetics can be useful in reaching a correct diagnosis, also by helping to rule out monophasic synovial sarcoma.
CA125 and thyroglobulin staining in papillary carcinomas of thyroid and ovarian origin is not completely specific for site of origin
Authors: Keen  , Szakacs  , Okon  , Rubin  , Bryant
Published: March 2003

Aims

A 70‐year‐old woman presented with metastatic psammoma body‐rich papillary carcinoma in a supraclavicular lymph node. No primary site was evident. The tumour showed strong staining for CA125 and weak staining for thyroglobulin. Prompted by this case we aimed to assess the reliability of immunostaining for CA125 and thyroglobulin in making the distinction between thyroid and ovarian papillary carcinoma.

Methods and results

Nine papillary carcinomas of the thyroid and 17 serous papillary carcinomas of the ovary were stained for CA125 and thyroglobulin, as well as CAM 5.2, LP 34, carcinoembryonic antigen (CEA), S100 and diastase/periodic acid–Schiff. Nine of nine thyroid carcinomas stained for thyroglobulin; in addition CA125 was positive in four of nine. Normal surrounding thyroid also showed some reaction. Seventeen of 17 ovarian serous carcinomas were positive for CA125; in addition one case showed moderately strong staining for thyroglobulin. Mucin stains were positive in 14/17 ovarian serous carcinomas, but negative in all thyroid carcinomas. The other antibodies assessed showed no useful differences in staining frequency.

Conclusion

Many cases of papillary carcinoma of the thyroid show CA125 staining, and this feature therefore has little positive predictive value for an ovarian origin. Occasional cases of ovarian papillary carcinoma may show staining for thyroglobulin, and this result should therefore be interpreted cautiously.
Extra‐medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases
Authors: Menasce  , Banerjee  , Beckett  , Harris
Published: March 2003

Aims

To describe the clinicopathological and immunophenotypic features of 26 cases of extra‐medullary myeloid tumour (EMMT)/granulocytic sarcoma, which remains poorly recognized and is frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist.

Methods and results

Haematoxylin and eosin (H & E) sections of 26 cases of EMMT were re‐examined. Immunostains for myeloperoxidase, lysozyme, neutrophil elastase, LCA, CD79a, CD20, CD43, CD45RO, CD3, CD30, CD15, CD68, MAC387, VS38C, MIC2, and the Leder stain for naphthol‐ASD‐chloroacetate esterase were performed on all cases. Clinical and follow‐up data were obtained through a questionnaire to the referring pathologist or from the notes of the patients where available. In the 10 cases with known myeloproliferative disease, the initial diagnosis was correct in 10 whereas all cases presenting with EMMT without a previous history of myeloproliferative disorder had an initial incorrect diagnosis. The most common suggested diagnosis was that of a non‐Hodgkin's lymphoma. The morphology of the tumours varied from well differentiated which included all stages of myeloid differentiation to poorly differentiated or blastic showing little or no evidence of myeloid differentiation. The proportion of positive cells for each stain varied. Chloroacetate esterase, myeloperoxidase and CD15 stained a large proportion of cells of the majority of the well differentiated tumours and a smaller proportion of the poorly differentiated/blastic tumours with very focal staining of some of the cases. Lysozyme and CD43 were the most sensitive of the markers staining a large proportion of cells of the majority of the tumours in both groups. Neutrophil elastase was the least sensitive of the markers of myeloid differentiation. CD79a, CD20, CD3 and CD30 were negative in all cases. CD43 was positive in all cases. CD68 stained a substantial number of cells in the majority of tumours. A smaller proportion of the tumours stained with MAC387. Four of the tumours showed positivity for MIC2. One tumour was positive for VS38C.

Conclusion

This series documents continuing difficulties in the diagnosis of EMMT. Even well differentiated tumours are frequently mistakenly diagnosed as malignant lymphomas when they present without any history of antecedent myeloproliferative disorder. Careful evaluation of morphology for evidence of myeloid differentiation and a high index of suspicion when confronted with a less differentiated neoplasm are required to avoid this important diagnostic error. We suggest that a panel which includes chloroacetate‐esterase, myeloperoxidase, lysozyme and CD43, together with other B‐ and T‐lineage markers, in particular CD79a and CD3 should be used to confirm the diagnosis.
Benign vascular neoplasms of the spleen with myoid and angioendotheliomatous features
Authors: Kraus  , Dehner
Published: March 2003

Aims

To present the clinical light microscopic and immunophenotypic features of a distinctive vascular neoplasm of the spleen.

Methods and results

Two of the splenic lesions arose in children, and one was found in an adult. They ranged from 19 to 40 mm diameter and histologically were quite similar. Sheets of large epithelioid cells with a spectrum of nuclear configurations ranging from oval and vesicular to twisted and hyperchromatic were noted in each case. Distinct or prominent nucleoli were present in many cells, and occasional cells had nuclear pseudoinclusions. In two cases, bands of basophilic, fibroblast‐rich stroma with scattered chronic inflammatory cells were present. The mitotic rate ranged from 0/10 high‐power fields (HPF) to 0.5/10 HPF in these epithelioid cells. The vascular nature of these tumours was manifested as a sieve‐like array of round, erythrocyte‐filled spaces, most with attenuated and cytologically bland lining cells. The polygonal, epithelioid cells exhibited the following phenotype: smooth muscle actin (SMA)+, muscle specific actin (MSA)+, vimentin+, CD31−, CD34−, CD21−, CD8−, CD68− (2/3 cases), S100−, while the lining cells were CD34+, vimentin+ and SMA−, with variable CD31 and factor VIII related antigen expression. Elongated SMA+, MSA+ cell processes were evident in one case, reminiscent of previously characterized myoid elements of the normal spleen. An uneventful follow‐up was noted for all three patients.

Conclusions

The histology and immunophenotype set these neoplasms apart from classic hamartomas, haemangiomas and previously characterized (haem)angioendotheliomas of the spleen, and may represent proliferations of myoid elements native to the spleen.
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

Aims

The 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 results

A 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.

Conclusions

The 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

Aims

Transitional 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 results

Immunostaining 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.

Conclusion

The 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.
The role of the histopathologist in the management of testicular germ cell tumour in adults
Authors: Parkinson M C , Harland S J , Harnden P , Sandison A
Published: March 2003

In the last 20–30 years the availability of effective chemotherapy and more accurate clinical staging has greatly improved the prognosis for patients with testicular germ cell tumours. Initially, such treatment appeared to diminish the role of histopathology to the distinction between seminoma and nonseminomatous germ cell tumour (NSGCT) in the primary specimen. However, histopathology has evolved as a prognostic tool indicating the risk of relapse in various defined clinical contexts thereby facilitating therapeutic decisions. The clinical emphasis has been on quality of life and reduction of therapy both in terms of the number of patients treated and the number of chemotherapy courses given to each patient. The treatment of adult testicular germ cell tumours may differ between countries but protocols are established. Therefore it is appropriate to discuss the role of histopathology during this era of relative therapeutic stability.
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 atypia

Aims: 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.
The requirement of localized, CR2‐mediated, alternative pathway activation of complement for covalent deposition of C3 fragments on normal B cells
Authors: OLESEN  , JOHNSON  , DAMGAARD  , LESLIE
Published: March 2003

We have shown previously that normal B cells share, with Epstein–Barr virus‐transformed and malignant B cells, the ability to activate the alternative pathway (AP) of complement in vitro, resulting in the deposition of C3 fragments on the cell surface. Complement receptor type 2 (CR2, CD21) has been implicated directly as the site for formation of an AP convertase, which provides nascent C3b for deposition at secondary sites on the B‐cell surface. In the present study, we have examined C3 fragment deposition in vitro in more detail by (1) assessing the importance of locally generated C3b for the deposition process, (2) investigating whether CR2 is the sole requirement for conferring AP activation capacity on a cell, and (3) determining whether CR2’s function, as an AP activator, has different structural requirements from ligand binding. Increasing the availability of native C3, by increasing the serum (NHS) concentration, resulted in enhanced C3 fragment deposition on the B cells, whereas use of factor I‐depleted NHS, which showed massive fluid phase C3 conversion during the incubation, diminished the deposition. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) and Western blotting of untreated and hydroxylamine‐treated lysates from B cells, after in vitro activation, revealed that the majority of C3 fragments (primarily iC3b and C3dg) had been covalently bound to the cell surface. Transfection of COS cells with wild‐type CR2 or a deletion mutant lacking 11 of the molecule’s 15 homologous domains, but retaining the ligand‐binding site, revealed that expression of intact CR2 conferred a 12‐fold increase in AP‐activating capacity on these cells, while no increase in AP activity was apparent on cells transfected with the mutant CR2.
Cloning and sequencing of a cDNA encoding chicken mannan‐binding lectin (MBL) and comparison with mammalian analogues
Authors: LAURSEN  , DALGAARD  , THIEL  , LIM  , JENSEN  , JUUL‐MADSEN  , TAKAHASHI  , HAMANA  , KAWAKAMI  , JENSENIUS
Published: March 2003

The serum lectin, mannan‐binding lectin (MBL) (also denoted mannan‐binding protein or mannose‐binding protein, MBP) has been identified in mammals (humans, monkey, cow, rabbit, mouse and rat). Upon binding to carbohydrates on the surface of microorganisms, MBL mediates activation of the complement system, leading to killing of the microorganism. MBL thus exerts a role in the innate immune defence. We have described the isolation and partial characterization of an analogous protein in chicken serum. Oligonucleotides based on the N‐terminal sequence of this protein were used in a reverse transcription–polymerase chain reaction (RT–PCR) with chicken liver RNA as template. The PCR product was sequenced and found to encode part of the NH2 terminus of chicken MBL. A perfect match probe was synthesized and used to screen a chicken liver cDNA library. The isolated clones carried a cDNA insert of 1692 bp with an open reading frame of 714 bp encoding a mature protein of 238 amino acids including a signal peptide of five amino acids. The deduced amino acid sequence agrees with those determined by conventional amino acid sequence analysis of the peptides except for four residues. We have compared the deduced primary structure of chicken MBL with the mammalian analogues. The phylogenetic analysis indicates that the gene duplication leading to two different MBL forms in mammals occurred after the split from birds and reptiles. This concurs with the finding of only one form of MBL in chickens.