bluuebunny/crossref_metadata_2025 huggingface dataset:
What does the British Library do for medical librarians?
Authors: DALE PETER
Published: March 2003

The author contends that most librarians are not fully aware of all the many and varied services offered by the British Library. In this article he outlines all of the services which are designed to help medical librarians. The various component parts of the British Library are considered in turn and it is found that all the Divisions have something worthwhile to offer.

Having described each service in some detail the author concludes by exhorting readers to tell British Library staff what they want from their national library. At the end of the article a list of contact addresses and telephone numbers is given.
Public libraries and blind people: what kind of relationship?
Authors: CRADDOCK PETER
Published: March 2003

In 1983/84 the British Library funded an investigation into public library provision for blind people1. The purpose of the survey was to contribute to a reassessment of services for blind and severely handicapped people. Findings suggest that few public libraries are active in this field, the majority considering their role to be mainly as a rtferral agency. Ways in which libraries could become more relevant and which would overcome the lack of availability of locally‐based services are outlined. A number of areas which merit further consideration are listed.
*New opportunities for NHS librarians and information scientists
Authors: BRITTAIN J. MICHAEL , MacDOUGALLt JENNIFER
Published: March 2003

The recent fundamental transformation in government policy on the National Health Service has far‐reaching implications for all types of health‐care information provision and use. This paper highlights the new opportunities, as well as the major issues, these developments have generated.
Malignant melanoma re‐excision specimens — how many blocks?
Authors: Martin  , Birkin  , Theaker
Published: March 2003

Aims:

Wide local excision is commonly undertaken as part of the further management of cutaneous melanoma. Although the original excision is usually complete, pathologists vary considerably in their macroscopic handling and sampling of the wide excision specimens. This study evaluates the sampling of re‐excision specimens and the information gained from histological examination of tissue blocks in order to develop guidelines for the handling of these specimens.

Methods and results:

The study group comprises 219 cases of melanoma which underwent initial biopsy followed by wider excision. The macroscopic appearance, number of blocks taken and presence of residual melanoma in the wide excision specimen was assessed. Residual melanoma was detected in the wide excision specimen in only four cases out of the 167 in which the original melanoma had been described as completely excised and in these cases the detection of a residual lesion reflected either advanced local disease at the time of the original excision, or an incompletely excised extensive radial growth phase. The sampling of wide excision specimens varied (range of blocks 1–12, average 3.1) but statistical analysis showed no undersampling of the wide excision specimens in which no residual lesion was found.

Conclusions:

These results show that detection of a residual lesion in wide excision specimens of melanomas previously completely excised is unusual and offers no additional clinically useful information. Random block taking in the abscence of a macroscopic abnormality is therefore unlikely to be clinically useful. Guidelines for the gross handling of these wide excision specimens are proposed which are likely to save resources in most histopathology departments by reducing block numbers.
Relationship between interleukin‐6 and proliferation and differentiation in cholangiocarcinoma
Authors: Sugawara H , Yasoshima M , Katayanagi K , Kono N , Watanabe Y , Harada K , Nakanuma Y
Published: March 2003

Aims

Interleukin‐6 (IL‐6) has been implicated as a mediator of growth control in several human neoplasms. The significance of IL‐6 expression in human cholangiocarcinoma was examined in this study.

Methods and results

IL‐6 expression was examined in 43 surgically resected cholangiocarcinomas and a cholangiocarcinoma cell line CCKS1, derived from abdominal metastasis of moderately differentiated adenocarcinoma, by immunohistochemical and in‐situ hybridization techniques. In non‐neoplastic bile ducts, IL‐6 was constitutively but weakly expressed. In surgical cases of cholangiocarcinoma, IL‐6 was frequently and strongly expressed in the cytoplasm of well‐differentiated cholangiocarcinoma, while its expression was decreased, and less intense or absent in moderately and poorly differentiated areas, respectively. IL‐6 mRNA was detected in the cytoplasm of carcinoma cells of two cases of cholangiocarcinomas positive for IL‐6. IL‐6 was detected in hepatic bile from two cholangiocarcinoma cases studied. The proliferation antigen Ki67 was found to be more frequently expressed in IL‐6 negative carcinoma cells than in IL‐6 positive carcinoma cells (P < 0.01). In cultured carcinoma cells line CCKS1, IL‐6, IL‐6 mRNA and IL‐6 receptor alpha chain were detected in the cytoplasm of carcinoma cells, suggesting an autocrine effect of IL‐6 on carcinoma cells.

Conclusion

IL‐6 expression is inversely related to cell proliferation and positively related to differentiation in cholangiocarcinoma.
Skeletal muscle regeneration mimicking rhabdomyosarcoma: a potential diagnostic pitfall
Authors: Guillou L , Coquet M , Chaubert P , Coindre J M
Published: March 2003

Aims

We report three cases of skeletal muscle regeneration, of which two mimicked a small round cell tumour, especially a rhabdomyosarcoma.

Methods and results

One case presented as an intramuscular mass, located in the right quadriceps of a 12‐year‐old male; the second patient was a 25‐year‐old football player who complained of painful left peroneus muscles; the third patient was a 22‐year‐old male who underwent an amputation of the right thigh 5 days after right leg amputation due to limb crush. Histologically, muscle biopsy specimens showed a proliferation of small round cells, either infiltrating the striated muscle in a diffuse manner or growing within and around necrotic myofibres. Immunohistochemically and ultrastructurally, the cellular population was composed of two types of cells: phagocytic cells the nuclei of which occasionally showed a wreathlike arrangement around necrotic myofibres resulting in structures resembling Langhans‐type multinucleated giant cells, and proliferating satellite cells showing enlarged nuclei, prominent nucleoli, mitotic figures, myogenic differentiation and fusion features in order to form regenerating myotubes.

Conclusions

Muscle regeneration is a benign process that may occasionally mimic a small round cell proliferation resembling a lymphoma or an alveolar rhabdomyosarcoma with which it should not be confused.
HIV‐associated lymphoepithelial cysts and lesions: morphological and immunohistochemical study of the lymphoid cells
Authors: Chetty R
Published: March 2003

Aims: To determine the morphology, immunophenotype and bcl‐2 protein status of intraepithelial lymphocytes in HIV‐positive lymphoepithelial lesions.

Methods and results

Seventeen cases (from adults and children) of HIV‐associated parotid and lung lymphoid lesions were examined. In addition, three lymphoepithelial cysts from HIV‐negative patients were studied in parallel. Immunohistochemistry was performed on paraffin embedded tissue with the following antibodies: CD20, CD79a, CD3, CD4, CD8, bcl‐2, CAM5.2, AE1/3, MIB1, kappa/lambda light chains and EBV‐LMP‐1. Heavy chain rearrangement was sought by polymerase chain reaction (PCR) in four of the cases. The lymphocytes participating in lymphoepithelial lesions of HIV‐positive patients had the morphology of centrocyte‐like cells with occasional cells resembling centroblasts. The majority of these cells were of B‐cell lineage, but occasional intraepithelial T‐cells (CD8 positive, CD4 negative) were also present. T‐cells also formed a significant component of the infiltrative lymphoid cells outside the lymphoepithelial lesions. These were mainly CD8 positive, but very occasional CD4‐positive T‐cells were also noted. None of the cases showed light chain restriction and the four cases did not demonstrate heavy chain rearrangement by molecular biology. The interesting finding was the absence of bcl‐2 expression by the intraepithelial lymphocytes. In contrast, the intraepithelial lymphocytes seen in the non‐HIV setting were strongly bcl‐2 positive. The majority of these were B‐cells, and very occasional CD8 and CD4 positive T‐cells formed the intraepithelial population.

Conclusion

It is postulated that this finding is due to the HIV causing down‐regulation of bcl‐2 protein.
Intra‐abdominal follicular dendritic cell tumour: a rare tumour in need of recognition
Authors: Shek T W H , Liu C L , Peh W C G , Fan S T , Ng I O L
Published: March 2003

Aims

Neoplasms of follicular dendritic cells are uncommon and the majority of them occur in lymph nodes. Rarely, they may occur inside the abdominal cavity. We describe two examples of intra‐abdominal follicular dendritic cell (FDC) tumour. One involved the liver and the other involved the ampulla of Vater. Our aims are to complement the current understanding on this disease and to alert histopathologists and clinicians to this rare entity.

Materials and results

The clinical and radiological findings of the two cases of intra‐abdominal follicular dendritic cell tumours were reviewed. The resected specimens were examined macroscopically and microscopically. Immunohistochemical studies, ultrastructural examination and in situ hybridization for Epstein–Barr virus were also performed. Both tumours could not be accurately diagnosed before pathological examination of the resected specimens. The soft to slightly firm consistency of the tumours resembled that of fixed brain tissue, and was distinctly different from hepatocellular carcinoma or pancreatic carcinoma. The fascicular arrangement of syncytial plump to spindle cells in a background of mixed inflammatory cells was the initial clue to the diagnosis, which was confirmed by the immunoreactivity of the tumour cells to follicular dendritic cell markers (CD21 and CD35), and by the demonstration of focal intercellular desmosome‐like junctions between the complex cytoplasmic processes of the tumour cells. The tumour cells in the liver tumour also showed presence of Epstein–Barr virus on in situ hybridization study.

Conclusions

Awareness of the entity and the ability to recognize this tumour by histopathologists are emphasized because the tumour closely mimics a wide variety of other tumours and tumour‐like lesions. Similar to the other reported FDC tumours of the liver, our case of hepatic follicular dendritic cell tumour is also positive for Epstein–Barr virus, suggesting that the virus may play a role in its pathogenensis.
Different numerical chromosomal aberrations detected by FISH in oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma
Authors: Poetsch  , Kleist  , Lorenz  , Herrmann
Published: March 2003

Aims

Little information is available about stage‐ or site‐specific chromosomal aberrations in head and neck squamous cell carcinoma (HNSCC). We tried to identify whether different patterns of chromosomal gain or loss in squamous cell carcinomas were associated with different stages or head and neck sites.

Methods and results

We investigated isolated interphase cells from paraffin sections of 53 squamous cell carcinomas of the head and neck region by fluorescence in situ hybridization techniques. We used centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumour samples showed aneuploidy for most chromosomes analysed. We were able to find differences in the chromosomal aberrations between the tumour sites and stages of the HNSCC investigated. The main numerical chromosomal abnormalities were an under‐representation of chromosomes 3 (26%), 6 (17%), 9 (26%), 10 (23%) and 18 (32%). The Y chromosome was lost in 53% of male tumours. A loss of chromosomes 3 and 10 was detected mostly in laryngeal SCC (39% and 30%, respectively); the under‐representation of chromosome 9 was predominantly seen in oropharyngeal SCC (54%) and a copy number decrease of chromosomes 18 was found in 57% of hypopharyngeal tumours.

Conclusion

Although the number of tumour samples investigated is rather low, our results suggest that the different tumour sites of HNSCC may also show different patterns of chromosomal changes.
Myxoid dermatofibroma
Authors: Zelger  , Calonje  , Zelger
Published: March 2003

Aims

This report presents seven cases of a rare variant of dermatofibroma, characterized by marked mucinous stromal changes.

Methods and results

In this retrospective clinicopathological study, lesions preferentially occurred on the lower extremities of young to middle‐aged females. Clinical (differential) diagnoses included: dermatofibroma (two cases), cyst, tophus, ganglion and neurofibroma. Histology revealed well circumscribed, faintly stained dermal to subcutaneous lesions which contained abundant stromal mucin. A variable amount of spindle‐shaped cells, occasional lymphocytes and fine collagen fibres were also seen. Epidermal hyperplasia above as well as storiform arrangement of spindle cells and some sclerotic collagen at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological features included: bizarre giant cells, perifollicular arrangement and seas of mucin with pseudovascular clefts in one case each. Immunohistochemically, all lesions were positive for KiM1p (> 50% of the cells). Moreover, two lesions showed moderate reactivity for factor XIIIa (10–25%), one each with NK1C3 (> 90%) and smooth muscle actin (50%), but were otherwise negative with a broad panel of markers. Electron microscopy in one case revealed large pools of mucin interspersed by a moderate number of fibrocytes with fine fibrillary collagen.

Conclusion

This series confirms myxoid dermatofibroma as a rare variant of fibrohistiocytic tissue response; our series also indicates that many of these lesions might be misinterpreted as cutaneous myxoma.
p53 immunoreactivity in endometrial metaplasia with dysfunctional uterine bleeding
Authors: Quddus M R , Sung C J , Zheng W , Lauchlan S C
Published: March 2003

Aim

Overexpression of p53 has been reported in endometrial carcinomas, especially in uterine papillary serous carcinoma (UPSC), to correlate with worse prognosis. Endometrial metaplasia is commonly encountered in patients with dysfunctional uterine bleeding (DUB) and may on occasion be difficult to distinguish from atypical endometrial hyperplasia or carcinoma on biopsies. The present study was initiated in the belief that metaplastic tissue might not show overexpression of p53 and would thus help to distinguish it from carcinomas of non‐endometrioid histology.

Methods    and results

Paraffin‐embedded tissue of endometrial biopsies with papillary metaplasia (22 cases), tubal metaplasia (five cases) and eosinophilic meta‐plasia (seven cases) from patients with DUB were immunostained for p53 immunoreactivity. No evidence of hyperplasia was noted in any of the cases selected for the study. Twenty‐eight cases of UPSC were included for comparison. Our study showed p53 overexpression in 25 of 28 (89%) UPSC. Weak and heterogeneous p53 immunoreactivity was present in 10 of 22 (45%) papillary metaplasias, four of five (80%) tubal metaplasias and four of seven (57%) eosinophilic metaplasias. Follow‐up of 16–45 (median 32) months was unremarkable except for one patient with eosinophilic metaplasia who had simple endometrial hyperplasia in subsequent biopsy.

Conclusions

The presence of weak and heterogeneous p53 immunoreactivity in metaplastic endometrium is unexpected and might be a consequence of DNA damage. Intense, diffuse and homogeneous p53 staining favours carcinoma.
Diabetic microangiopathy in the small bowel
Authors: De Las Casas  , Finley
Published: March 2003

Aims

Microangiopathic changes in the gastrointestinal tract of patients with diabetes mellitus are frequently mentioned in the clinical literature. To our knowledge, pathological studies documenting these changes in bowel biopsies have not been previously reported. In this report, we describe striking duodenal biopsy findings of diabetic microangiopathy in a patient with long‐standing insulin‐dependent diabetes mellitus and chronic diarrhoea.

Methods and results

The diagnosis was based on the histopathological and immunohistochemical findings in the appropriate clinical setting. Blood vessels within the duodenum displayed prominent mural thickening and luminal narrowing secondary to accumulation of hyaline material, which was periodic acid–Schiff positive and intensely stained with monoclonal antibodies against type IV collagen.

Conclusions

This is the first report of diabetic microangiopathy in a bowel biopsy. The pathogenesis, specificity and significance of these angiopathic changes, controversies about diabetic microangiopathy in the gastrointestial tract, and the association with hypertension are discussed.
Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma
Authors: Furubo  , Harada  , Shimonishi  , Katayanagi  , Tsui  , Nakanuma
Published: March 2003

Aims

The significance of molecular and genetic alterations of p53 and ras in the development and progression as well as the histological differentiation of intrahepatic cholangiocarcinoma (ICC) was evaluated.

Methods and results

We examined immunohistochemically ras p21 protein and p53‐related products (p53 protein, WAF‐1 and mdm‐2) in 43 cases of ICC. In addition, point mutations of ras and p53 were examined genetically in selected ICC cases by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and direct sequence analysis. Point mutation of K‐ras gene codon 12 was detected in three of 14 cases and one of 15 cases by PCR‐RFLP and direct sequence analysis, respectively. Immunoreactivity of ras p21 protein was not detected. Point mutation of p53 was detected in three of 15 cases. p53 protein was immunohistochemically detectable in 33 of 43 cases. Immunoreactivity of p53 was more frequent in well‐differentiated and less frequent in poorly differentiated cases. Immunoreactivity of WAF‐1 and mdm‐2 was seen in 16 and eight of 43 cases, respectively. Both proteins were frequently detected in the cases positive for p53 protein.

Conclusion

These results suggest that dysregulation of ras is involved in at least 20% of ICC and expression of p53 protein is more significantly involved in ICC, particularly in the well and moderately differentiated cases. While some cases of p53 expression may be explainable by point mutation of p53, there may be some epigenetic phenomena that stabilize p53 protein in ICC. That is, wild type p53 may be stabilized and then detectable by forming complexes with other molecules of p53 downstream effector genes, such as WAF‐1 and mdm‐2.
Myxoid tumours of soft tissue
Authors: Graadt van Roggen  , Hogendoorn  , M Fletcher
Published: March 2003

Myxoid tumours of soft tissue encompass a heterogeneous group of lesions characterized by a marked abundance of extracellular mucoid (myxoid) matrix. This group of tumours demonstrate significant variability in their biological behaviour thus including tumours which are entirely harmless, tumours with a tendency to recur locally but not metastasize, and malignant tumours. There appears to be a considerable degree of overlap clinically and morphologically between the various tumour types in this group, generating potential diagnostic problems for the clinician and pathologist alike. While diligent microscopy remains the basis of diagnostic pathology, the continuous developments and refinements within the fields of immunohistochemistry and molecular cytogenetics are providing substantial new information, allowing the development of new diagnostic criteria and hence facilitating an accurate diagnosis. It is the aim of this short review to highlight the most prevalent soft tissue tumours with predominantly myxoid morphology, to describe the features by which the majority of these myxoid lesions may be identified, and to discuss the differential diagnosis where appropriate.
Ultrastructural localization of E‐cadherin and α‐/β‐catenin in adenoid cystic carcinoma
Authors: Shibuya  , Ri  , Umeda  , Yoshikawa  , Masago  , Komori
Published: March 2003

Aims

To investigate the disturbance of intercellular adhesion in adenoid cystic carcinoma (ACC), we examined the ultrastructural localization of E‐cadherin (E‐cad), α‐catenin (α‐cat) and β‐catenin (β‐cat) in ACC, and compared it with that in the normal labial gland.

Methods and results

Using immuno‐electron microscopy, in the normal labial gland, E‐cad was found to be uniformly distributed along the plasmalemma, where cells were in close contact with each other, with junctional complexes, desmosomes and interdigitations; expression of α‐cat and β‐cat was also detected. In ACC, which was classified into tubular, cribriform and trabecular types, E‐cad expression seemed not to be uniform, but was observed to be along the plasmalemma where cell‐to‐cell contact was made. On the other hand, expression of α‐cat or β‐cat was uneven in the trabecular‐type cells which were very slender and grew in an infiltrative scattered pattern into the extracellular matrix; that was absent in the cribriform‐type cells which made contact with each other mostly at the tip of the cytoplasmic processes.

Conclusion

These findings suggest that the neoplastic cells of ACC express E‐cad for use in intercellular adhesion, but the cadherin–catenin complex might not operate properly, which is the cause of neoplastic cell dissociation, followed by invasion and metastasis.
Primary choriocarcinoma and human chorionic gonadotrophin‐producing giant cell carcinoma of the lung: are they independent entities?
Authors: Ikura  , Inoue  , Tsukuda  , Yamamoto  , Ueda  , Kobayashi
Published: March 2003

Aims

Human chorionic gonadotrophin (hCG) is a useful marker for chorionic proliferative disorders, such as choriocarcinoma. Although hCG synthesis in lung cancers is frequent, primary pulmonary choriocarcinoma (PCC) is rare. To clarify the differences between primary choriocarcinoma and hCG‐producing giant cell carcinoma (GCC) of the lung, we compared the clinicopathological and immunohistochemical findings of these tumours.

Methods and results

Three patients, one with PCC and two with hCG‐producing GCC, were included in this study. They were all middle‐aged men and habitual smokers. The growth of these tumours and the progression of the clinical courses were extremely rapid, and the patients all died within 8 months after the pulmonary tumours were found. Haemorrhagic appearance was a common macroscopic feature of the specimens obtained. Microscopically, both types of tumours mainly consisted of atypical polygonal cells. While PCC contained many syncytial trophoblast‐like multinucleated cells that had strong immunoreactivity for anti‐hCG, such cells were relatively few in hCG‐producing GCC. These histological and immunohistochemical findings reflected the serum test result for hCG, which was higher in the case of PCC.

Conclusions

There are a few differences between PCC and hCG‐producing GCC, as described above. Reliable distinction between them seems to be difficult for pathologists and worthless for clinicians.
Relationship between fascicle size and perineurial collagen IV content in diabetic and control human peripheral nerve
Authors: Williams P E , Lowry A , Hill R , Masson E
Published: March 2003

Aim: The relationship between perineurial collagen IV content and fascicle size was determined in diabetic and control human peripheral nerve.

Methods and results

Age‐matched diabetic and control sural nerve samples were immunostained using antibodies to collagen IV. The number of cell layers and the perimeter of the fascicle were measured and the collagen IV content of the perineurium determined. Using this method, a comparison could be made of collagen IV content in the perineuria of fascicles of different size. A positive linear relationship was found between fascicle size and the amount of collagen IV per unit of perineurium. The number of perineurial cell layers and the collagen IV content of the diabetic nerve did not differ from control values.

Conclusions

The linear relationship between fascicle size and perineurial collagen IV content per unit of perineurium underlines the importance of taking fascicle size into account when determining changes in basement membrane components associated with neuropathy. The results indicate that increased deposition of collagen IV is not involved in the early changes in the perineurial cell basement membrane and is thus not the primary factor involved in altered nerve function associated with diabetic neuropathy.
‘Mucin‐positive’ epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall
Authors: Cook D S , Attanoos R L , Jalloh S S , Gibbs A R
Published: March 2003

Aims

The histopathological, immunohistochemical and ultrastructural features of a primary ‘mucin‐positive’ epithelial mesothelioma of the peritoneum are reported to draw attention to a potential cause of diagnostic error.

Methods and results

Light microscopy showed an infiltrative neoplasm within the gastric wall and omentum which was composed of sheets of ‘signet‐ ring’ tumour cells and contained abundant diastase‐resistant periodic acid–Schiff‐positive material. Immunohistochemistry supported a mesothelial phenotype (cytokeratin AE1/3, thick membranous HBME‐1, focal thrombomodulin and calretinin expression and no reactivity for carcinoembryonic antigen, Leu‐M1 and Ber‐EP4). Ultrastructural features showed large cells with prominent intercellular desmosomes and numerous delicate, elongated microvilli. Within intracytoplasmic neolumina, crystalloidal ‘fern‐like’ bodies were identified with features similar to the ultrastructural appearances of hyaluronic acid crystals. Repeat histochemical analysis following hyaluronidase pretreatment revealed a significantly diminished diastase‐resistant periodic acid–Schiff reaction.

Conclusions

This case of primary peritoneal ‘mucin‐positive’ epithelial mesothelioma demonstrates morphological and histochemical mimicry with diffuse gastric adenocarcinoma. A similar case has not been previously reported in the peritoneum and an awareness of the tumour (with application of suitable ancillary studies) prevents misdiagnosis and assists in potentially difficult medicolegal cases.
Intravascular large B‐cell lymphoma with bone marrow involvement at presentation and haemophagocytic syndrome: two Western cases in favour of a specific variant
Authors: Dufau J P , Le Tourneau A , Molina T , Le Houcq M , Claessens Y E , Rio B , Delmer A , Diebold J
Published: March 2003

To report two cases of an unusual form of intravascular lymphoma, characterized by bone marrow involvement at presentation with haemophagocytic syndrome.

We describe the clinicopathological features of two patients with intravascular lymphoma primarily involving bone marrow. Both patients complained only of fever with pancytopenia and reactive haemophagocytic syndrome. Diagnosis was made on bone marrow examination, which showed large tumour cells of B‐cell lineage confined within the lumen of sinuses.

These two cases and five previous reports could represent a variant of intravascular lymphoma, characterized by early involvement of bone marrow without dissemination to other organs. This form of intravascular lymphoma, called IVL‐HS, seems to be an ‘Asian’ variant with a high prevalence in Asian people and a very low prevalence in Western countries. At a practical level, bone marrow biopsy may be useful in the diagnosis of intravascular lymphoma when the clinical presentation is restricted to fever of unknown origin with a reactive haemophagocytic syndrome.
Ultrastructural examination is essential for diagnosis of papillary meningioma
Authors: Al‐Sarraj S , King A , Martin A J , Jarosz J , Lantos P L
Published: March 2003

Aims: Papillary meningioma is a rare meningeal tumour. To date only a few cases have been reported and their immunohistochemical features have not been fully documented.

Methods and results: A 49‐year‐old woman presented with a 2‐month history of headaches and memory disturbance. CT and MRI imaging showed an enhancing pineal mass with extension into the occipital lobes and invasion of the splenium. At surgery, the tumour was found to be tough and vascular with a well‐defined capsule. No recurrence was noted 19 months after the operation. In another case a 44‐year‐old woman was admitted with 1‐month history of headaches, poor memory, imbalance and diplopia. CT scan showed a large hyperdense, uniformly, enhancing mass within the middle cranial fossa at the petrous ridge. The tumour recurred 19 and 25 months after first resection. The histology of both tumours was similar. The neoplasms contained polygonal cells with a moderate amount of cytoplasm, rounded regular nuclei and distinct cell borders. The cells were arranged radially around the blood vessels (perivascular pattern) and a papillary pattern was seen only focally. Mitotic figures were moderately frequent. Immunohistochemistry showed that both tumours were immunoreactive to vimentin and NSE, whereas GFAP, CAM5.2, EMA, S100 protein and synaptophysin were negative. Electron microscopy revealed interdigitating cell processes, desmosomes and intermediate filaments.

Conclusions: The histological and immunohistochemical features of these two tumours are complex and difficult to interpret. Although papillary meningiomas were considered in our initial differential diagnosis, the final conclusion was possible only when the ultrastructural features were revealed.
Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty
Authors: Thunnissen F B J M , Ambergen A W , Koss M , Travis W D , O'Leary T J , Ellis I O
Published: March 2003

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty

Although several articles on the methodological aspects of mitotic counting have been published, the effects of macroscopic sampling and tumour heterogeneity have not been discussed in any detail. In this review the essential elements for a standardized mitotic counting protocol are described, including microscopic calibration, specific morphological criteria, macroscopic selection, counting procedure, effect of biological variation, threshold, and the setting of an area of uncertainty (‘grey area’). We propose that the use of a standard area for mitotic quantification and of a grey area in mitotic counting protocols will facilitate the application of mitotic counting in diagnostic and prognostic pathology.
Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases
Authors: Fornelli A , Eusebi V , Pasquinelli G , Quattrone P , Rosai J
Published: March 2003

Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases

Aims: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported

Methods and results: The patients were a 65‐year‐old man and a 70‐year‐old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine‐type granules at the ultrastructural level.

Conclusions: The histogenesis of this heretofore undescribed combination is discussed.
`Microscopic colitis': classification and terminology
Authors: Warren B F , Edwards C M , Travis S P L
Published: March 2003

Microscopic colitis1–4 represents an area of communication difficulty, especially between gastroenterologists and histopathologists. The authors of this commentary welcome the paper of Libbrecht et al.5 in this issue of Histopathology which describes a form of microscopic colitis. This exemplifies the fact that the original classification of lymphocytic or collagenous colitis is a little limited for routine diagnosis and understanding of the aetiology of microscopic colitis. The unhelpful term `non‐specific colitis' is best avoided, so the classification of microscopic colitis needs to evolve.
Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival
Authors: Serio G , Scattone A , Pennella A , Giardina C , Musti M , Valente T , Pollice L
Published: March 2003

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival

Aims: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival.

Methods and results: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73‐year‐old male and one 23‐year‐old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular‐papillary features were noted. The tumour cells were positive for cytokeratins, HMBE‐1, calretinin, EMA and mitochondrion antibodies. The follow‐up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively).

Conclusions: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.
Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findings
Authors: Mooney E E , Nogales F F , Bergeron C , Tavassoli F A
Published: March 2003

Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findings

Aims:  To determine the morphological and immunohistochemical profile of retiform Sertoli–Leydig cell tumours and to compare the observed profile with that of adult rete ovarii.

Methods and results:  Nineteen retiform Sertoli–Leydig cell tumours were studied, eight by immunohistochemistry, and five examples of rete ovarii from adult females were also evaluated immunohistochemically. The patients ranged in age from 3 to 74 years with a mean age of 31 years. Four patients were virilized and had an abdominal mass; two were virilized with amenorrhoea and two had amenorrhoea alone. Eight presented with an abdominal mass and one patient was pregnant. Two tumours were incidental findings. Information on stage was available in 16 patients: 14 tumours were stage 1, one was stage 2, and one was stage 3. Fifteen tumours were of intermediate differentiation and four were poorly differentiated. Papillary structures were evident grossly in four cases. Microscopically, all cases had a retiform pattern in addition to varying quantities of sex cord, gonadal stromal and heterologous elements. Heterologous elements were present in 13 cases andconsisted of hepatocytes (n = 7), mucinous epithelium (n = 7) and skeletal muscle (n = 2). Immunohistochemical evaluation of eight tumours showed a more intense positivity for keratin in the retiform areas, whereas the gonadal stromal component had a more intense expression of inhibin. Inhibin stains Leydig cells strongly and hepatocytes moderately. Rete ovarii epithelium was positive for keratin and vimentin in the five cases studied, and for inhibin in one case. Follow‐up was available on 13 patients. Three tumours behaved in a malignant fashion: one each was stage 1, 2, and 3 at diagnosis.

Conclusions:  Immunohistochemistry is useful in distinguishing retiform Sertoli–Leydig cell tumours from other tumours that they may resemble. Inclusion of inhibin is essential in a panel of antibodies to evaluate these tumours. The clinical behaviour of these neoplasms cannot always be predicted from their morphology or clinical stage.
High molecular weight cytokeratin antibody (clone 34βE12): a sensitive marker for differentiation of high‐grade invasive urothelial carcinoma from prostate cancer
Authors: Varma M , Morgan M , Amin M B , Wozniak S , Jasani B
Published: March 2003

Aims:  There is no well‐established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34βE12 in differentiating high‐grade invasive urothelial carcinoma from prostate cancer.

Methods and results:  Formalin‐fixed paraffin‐embedded sections from 28 cases of high‐grade invasive urothelial carcinoma (20 not otherwise specified (UC‐NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34βE12 after microwave pretreatment or protease 24 predigestion. All cases of UC‐NOS expressed HMWCK on 34βE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34βE12, 85A12 was insensitive with 15% of UC‐NOS cases totally CEA‐negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti‐CEA and 34βE12 on microwaved sections, but all the cases were HMWCK‐negative using 34βE12 on sections pretreated by enzyme digestion.

Conclusions:  HMWCK antibody clone 34βE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high‐grade invasive urothelial carcinoma.
Inflammatory reactions in placental blood of Plasmodium falciparum‐infected women and high concentrations of soluble E‐selectin and a circulating P. falciparum protein in the cord sera
Authors: JAKOBSEN  , RASHEED  , BULMER  , THEISEN  , RIDLEY  , GREENWOOD
Published: March 2003

To better understand reasons for increased susceptibility to malaria in pregnancy; and the interrelationships between maternal malaria, local immune reactions and the development of the fetus, concentrations of soluble interleukin‐10 (IL‐10), cytokine receptors, adhesion molecules, a Plasmodium falciparum protein, glutamate‐rich protein (GLURP) and antibodies to P. falciparum rhoptry‐associated protein‐1 were measured among 105 Gambian women and their neonates. Peripheral blood concentrations of IL‐10, soluble cytokine receptors and soluble adhesion molecules were found to be different from those concentrations measured in the placenta. Markers of inflammatory reactions: IL‐10, sIL‐2R, sIL‐4R, and soluble tumour necrosis factor receptor I (sTNF‐RI) were found in high concentrations in the placenta, indicating that inflammatory reactions take place in the placenta which has been regarded as an immunoprivileged site. Concentrations of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and soluble intracellular adhesion molecule‐1 (sICAM‐1), potential adhesion receptors for malaria parasites, were associated with an active P. falciparum infection in the placenta although the associations did not reach significance. P. falciparum exoantigen, GLURP, was detected in cord blood indicating transplacental passage of malarial antigens. Concentrations of E‐selectin were higher in cord blood samples compared with peripheral blood samples. This appeared to be associated with development of cord endothelial cells and not with P. falciparum infection.
Emigration of mature T cells from the thymus is inhibited by the imidazole‐based compound 2‐acetyl‐4‐tetrahydroxybutylimidazole
Authors: Gugasyan‡  , Coward§  , O’Connor  , Shortman  , Scollay§
Published: March 2003

The primary role of the thymus is to provide mature T cells for the peripheral immune system. The mechanisms involved in the cellular export processes are as yet unknown. In this study, we examined the ability of 2‐acetyl‐4‐tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia caramel food colouring, to inhibit T‐cell export from the thymus. BALB/c mice were maintained on drinking water containing THI for 5 days. The mice showed a twofold increase in the total number of mature medullary thymocytes (CD4+CD8− and CD4−CD8+) as well as a slight decrease in the total number of immature double‐positive cells (CD4+CD8+). The mature single‐positive thymocytes were found to express high levels of the homing molecule L‐selectin, suggesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI‐treated mice were injected intrathymically with fluorescein isothiocyanate and the number of labelled T cells appearing in the lymph nodes and spleen was determined 16 hr later. A 10‐fold decrease in the number of CD4+ and CD8+ recent thymic emigrants in the lymph nodes and spleen of THI‐treated mice was observed. Previous studies have shown that THI does not affect other aspects of thymocyte development, such as proliferation and differentiation. Taken together, these results suggest that the immunosuppressive effects of THI may be due, in part, to preventing of the final step of T‐cell export out of the thymus.
Preservation of mucosal and systemic adjuvant properties of ISCOMS in the absence of functional interleukin‐4 or interferon‐γ
Authors: SMITH  , DONACHIE  , MCLAREN  , MOWAT A. McI.
Published: March 2003

Adjuvants are a critical component of non‐viable vaccine vectors, particularly for those to be used via mucosal routes. Although most adjuvants act by inducing local inflammatory responses, the molecular basis of many of these effects is unclear. Here we have investigated whether interleukin‐4 (IL‐4) and interferon‐γ (IFN‐γ) are required for the induction of local and systemic immune responses by oral and parenteral administration of ovalbumin (OVA) in immune stimulating complexes (ISCOMS), a potent mucosal adjuvant vector. Our results show that after oral or systemic immunization with OVA ISCOMS, IL‐4 knockout (IL4KO) and IFN‐γ receptor knockout (IFN‐γRKO) mice develop an entirely normal range of immune responses including delayed‐type hypersensitivity (DTH), serum immunoglobulin G (IgG) antibodies, T‐cell proliferation and cytokine production, class I major histocompatibility complex (MHC)‐restricted cytotoxic T lymphocyte (CTL) activity and intestinal IgA antibodies. These responses were of a similar magnitude to those found in the wild‐type mice, indicating that the immunogenicity of ISCOMS is not influenced by the presence of IL‐4 or IFN‐γ and emphasizing the potential of ISCOMS as widely applicable mucosal adjuvants.
Functional immaturity of rat alveolar macrophages during postnatal development
Authors: BAKKER J. M. , BROUG‐HOLUB E. , KROES H. , VAN REES E. P. , KRAAL G. , VAN IWAARDEN J. F.
Published: March 2003

Alveolar macrophages (AM) are important in the regulation of immune responses in the lung, through their role as scavenger cells and through the production of many bioactive factors. Because in early infancy pulmonary infections are a recurrent problem, we studied the postnatal functional maturation of AM in a rat model. AM were isolated from rat lungs by bronchoalveolar lavage at several time intervals after birth and tested for their ability to ingest Escherichia coli in the presence of surfactant protein A (SP‐A). Furthermore, their capacity to produce nitric oxide (NO) and interleukin‐1β (IL‐1β) after in vitro lipopolysaccharide (LPS) stimulation was analysed, as well as their capacity to downregulate proliferation of T cells from both mature and neonatal rats. SP‐A‐mediated phagocytosis of E. coli by AM was reduced in 14‐day‐old neonatal rats, as compared with mature rats (P≤0·05). Also the IL‐1β production by rat AM after LPS stimulation was impaired at 14 days of age, as compared with IL‐1β production by AM from mature rats (P≤0·05). In contrast, the LPS‐induced NO production by rat AM as well as the capacity to inhibit T‐cell proliferation were well developed at all ages tested. In conclusion, during postnatal development the rat AM is functionally immature, with respect to phagocytosis and secretion of inflammatory mediators. These differences may underly the enhanced susceptibility to pulmonary infections as found in human neonates.
Cross‐linking of Fcγ‐receptor on monocytes inhibits hepatitis C virus‐specific cytotoxic T‐lymphocyte induction in vitro
Authors: KANTO  , HAYASHI  , TAKEHARA  , KATAYAMA  , ITO  , MOCHIZUKI  , KUZUSHITA  , TATSUMI  , SASAKI  , KASAHARA  , HORI
Published: March 2003

In hepatitis C virus (HCV) infection, immune complex (IC)‐type virus particles are frequently observed in circulation. The IC leads to cross‐linking of Fcγ receptors (FcγR) on monocytes and exerts immunoinhibitory function. To test the roles of IC in HCV‐specific cytotoxic T lymphocyte (CTL) induction, we generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C patients with or without HCV‐IC‐ or immunoglobulin G (IgG)‐coated culture plates and compared their lytic activities. HCV‐IC or adherent IgG, which induces FcγR cross‐linking, significantly reduced CTL activity. Expression of B7‐1 on monocytes decreased on adherent IgG. In addition, tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti‐TNF‐α antibody during induction on adherent IgG inhibited lysis; however, anti‐TGF‐β completely reversed its inhibitory effect. These results demonstrated that HCV‐IC or adherent IgG impaired HCV‐CTL induction in vitro. The FcγR‐mediated CTL suppression occurred via decreased expression of monocyte B7‐1 and/or enhanced production of TGF‐β1.
Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen, II. Cellular, but not humoral, systemic immune responses against rabies virus immune‐stimulating complexes are macrophage dependent
Authors: CLAASSEN  , OSTERHAUS  , POELEN M. , VAN ROOIJEN N. , CLAASSEN
Published: March 2003

In this paper we describe the effect of depletion of splenic macrophages on the uptake, and immune response against, different formulations of rabies virus antigen. Splenic macrophages were removed by intravenous injection with clodronate liposomes. β‐propiolacton inactivated rabies virus (RV‐BPL) and immune‐stimulating complexes (iscom) containing these antigens were given to macrophage‐depleted and control mice. In the absence of phagocytic cells in the spleen, antigen is still trapped in the red pulp and to a lesser extent in the peri‐arteriolar lymphocyte sheaths (PALS) for both antigen formulations. The localization pattern in the main area of immune response induction, namely the follicles, was unaltered after macrophage depletion. Functionally, the depletion of splenic and liver macrophages had no influence on the induction of specific antibody responses in both RV‐BPL or RV‐iscom immunized mice, even though the latter presentation form was clearly associated with specific localization in the marginal metallophillic macrophages. In RV‐BPL immunized mice, macrophage depletion had no influence on proliferative T‐cell responses. However, macrophage‐depleted mice that were immunized with RV‐iscom showed a significant decrease in proliferative T‐cell responses. These results confirm existing ideas on the spleen as a physical filter rather than an induction site for humoral responses and shed new light on the efficient role of iscoms as antigen‐presenting moieties in relation to their specific in vivo localization patterns and partial macrophage dependency.