bluuebunny/crossref_metadata_2025 huggingface dataset:
A Consistent Approach to Cost Efficiency Measurement*
Authors: Bitros George C. , Tsionas Efthymios G.
Published: December 2004

Consistent specifications of the allocative inefficiency function in ‘cost plus input share equations’ systems may be difficult, if not impossible, to find because most plausible ones violate certain reasonable a priori conditions. Moreover, the models to which they lead give rise to highly non‐linear likelihood functions that are very hard to estimate. In an effort to confront these difficulties, this paper adapts an idea first suggested by Greene (1993) that allocative inefficiency ought to be related to input prices and allocative distortions in the input share equations. The system of ‘cost plus input demand equations’ that emerges is estimated by standard seemingly unrelated regression (SUR) techniques using data from private and state firms that operated in Greek manufacturing during the 1979–88 period. Among other findings, the estimates show that overall inefficiency for private and state firms was 63.5% and 102.2%, respectively in comparison with the least inefficient firms in their class. In relative terms these figures imply that state firms were almost 61% less efficient than private firms were. Technical and allocative reasons amounting to 64% and 36%, respectively, accounted for this excess inefficiency of state firms, in addition to differences in the utilization of labour, capital and debt. Lastly, it is found that the magnitudes of technical and allocative inefficiencies depend critically upon a self‐consistent specification of the allocative inefficiency function.
Spawning migrations of the chub in the River Spree, Germany
Authors: Fredrich F. , Ohmann S. , Curio B. , Kirschbaum F.
Published: December 2004

Out of 52 chub Leuciscus cephalus tagged with internal radio‐transmitters, 46 migrated to spawning grounds in the River Spree, Germany. All chub started their first spawning migration on 21–22 May in both years of study, 1995 and 1996. They arrived at three different spawning grounds within a day and left after 1 to 6 days to return to their original sites. On 17 and 18 June 1995 and 1996 chub started their second spawning migration with the same pattern as the first. About 60% of all migrating chub moved between 1 and 13 km upstream to the nearest spawning ground. Some exceptions were observed: a few chub did not use the nearest spawning ground, some chub used different spawning grounds at first and second spawning or moved downstream to a spawning ground. Spawning grounds were characterized by 0·4 m s−1 current velocity, shallow depth (0·1–0·8 m) and a stony bottom, where most eggs adhered.
Disease resistance, stress response and effects of triploidy in growth hormone transgenic coho salmon
Authors: Jhingan E. , Devlin R. H. , Iwama G. K.
Published: December 2004

Diploid and triploid coho salmon Oncorhynchus kisutch transgenic for growth hormone (GH) and control coho salmon were compared for differences in disease resistance and stress response. Resistance to the bacterial pathogen Vibrio anguillarum was not affected in transgenic fish relative to their non‐transgenic counterparts when they were infected at the fry stage, but was lower in transgenic fish when infected near smolting. Vaccination against vibriosis provided equal protection to both transgenic and non‐transgenic fish. Triploid fish showed a lower resistance to vibriosis than their diploid counterparts. Diploid transgenic fish and non‐transgenic fish appeared to show similar physiological and cellular stress responses to a heat shock. These studies provide information useful for both performance and ecological risk assessments of growth‐accelerated coho salmon.
Pleomorphic adenoma with extensive necrosis: report of two cases
Authors: Chen YK , Lin CC , Lai S , Chen CH , Wang WC , Lin YR , Hsue SS , Lin LM
Published: December 2004

Pleomorphic adenoma (PA) is the most common neoplasm for both the major and minor salivary glands. While PA is occasionally associated with cystic change or hemorrhage necrosis, spontaneous infarction appears to be very uncommon. We report two unusual cases of extensive necrosis of PA; one occurred in the palate with the necrotic tumor mass slipping into the oral cavity. This phenomenon, possibly associated with incision biopsy, has never been described previously. A second case, arising in the parotid with spontaneous tumor necrosis, poses some dilemma in differential diagnosis.
Inhibition of adherence of Candida albicans and Candida dubliniensis to a resin composite restorative dental material by salivary secretory IgA and monoclonal antibodies
Authors: Elguezabal N , Maza JL , Pontón J
Published: December 2004

Objective:  The attachment of Candida to oral surfaces is a crucial step in the colonization of the oral cavity and the eventual development of oral diseases caused by this microorganism. Inhibition of adhesion is one of the strategies currently studied to prevent Candida infections. The main objective of this study was to investigate the inhibitory effect of the human salivary components on the adherence of Candida albicans and C. dubliniensis to Herculite, a widely used resin composite restorative dental material. We have also investigated the influence on the adherence of three monoclonal antibodies (mAbs) directed against C. albicans cell wall antigens.

Design:  The adhesion of three strains of C. albicans and one strain of C. dubliniensis was studied by a visual method after incubating the fungus and the resin in presence and in absence of human whole saliva, secretory immunoglobulin A (sIgA) and three mAbs directed against C. albicans cell wall surface antigens.

Results:  Adherence of C. albicans was inhibited by whole saliva (41.7%), salivary sIgA (55.7%) and the salivary components that bind to the cell wall (36.7%). Whole saliva significantly reduced the adhesion of C. dubliniensis to Herculite to 45.3% of the control level. Saliva previously adsorbed with fungal cells or sIgA depleted saliva had no effect on adherence. An inhibition in the adhesion of C. albicans and C. dubliniensis to Herculite similar to that shown by whole saliva was also observed when mAbs C7 and 26G7 were used. However, mAb 21E6 increased adhesion of all the strains to Herculite.

Conclusions:  The results suggest that sIgA, as well as whole saliva, are important in blocking adherence of C. albicans and C. dubliniensis to Herculite and that this effect can be reproduced with mAbs directed against the cell wall surface of C. albicans.
A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma
Authors: Thosaporn W , Iamaroon A , Pongsiriwet S , Ng KH
Published: December 2004

Objectives:  The aim of the present study was to compare the proliferation index of the epithelial cells between odontogenic keratocysts (OKC), orthokeratinized odontogenic cysts (OOC), dentigerous cysts (DC), and ameloblastomas.

Materials and methods:  The proliferation index, employing a novel cell proliferation marker IPO‐38, was studied by the immunohistochemical technique in 10 OKC, seven OOC, eight DC and 10 ameloblastomas.

Results:  The ameloblastoma had no higher labeling index (LI) of IPO‐38 than the OKC (P = 0.910) but had higher LI than the OOC (P = 0.001) and DC (P = 0.000); the OKC had higher LI than the OOC (P = 0.002) and DC (P = 0.000); and the OOC had higher LI than the DC (P = 0.011). IPO‐38‐positive cells in the OKC and OOC were located principally in the suprabasal cell layers while the ameloblastoma were found in the peripheral portion in particularly, the follicular and plexiform types.

Conclusion:  These findings support previous studies that the proliferation indices are useful in predicting the different biological behavior of the odontogenic lesions and the OKC should be regarded as a benign tumor rather than simply an odontogenic cyst.
Partnering Managed Care and Community‐Based Services for Frail Elders: The Care Advocate Program
Authors: Wilber Kathleen H. , Allen Douglas , Shannon George R. , Alongi Sam
Published: December 2004

OBJECTIVES:To describe a demonstration program that uses master's‐level care managers (care advocates) to link Medicare managed care enrollees to home‐ and community‐based services, testing whether referrals to noninsured services can reduce service usage and increase member satisfaction and retention.

DESIGN:Using an algorithm designed to target frail, high‐cost users of Medicare insured healthcare services, the program partners PacifiCare's Secure Horizons and four of its medical groups with two social service organizations.

SETTING:Three care advocates located in two community‐based social services agencies using telephone interviews to interact with targeted elders living in the community.

PARTICIPANTS:Three hundred ninety PacifiCare members aged 69 to 96 receiving care from four PacifiCare‐contracted medical groups.

INTERVENTION:The 12‐month intervention provides telephone assessment, links to eight types of home‐ and community‐based services, and monthly follow‐up contacts.

MEASUREMENTS:Sociodemographic characteristics of intervention participants, types of service referrals, and acceptance rates.

RESULTS:Lessons learned included the importance of building a shared vision among partners, building on existing relationships between members and providers, and building trust without face‐to‐face interactions.

CONCLUSION:The program builds on current insured case management services and offers a practical bridge to community‐based services.
Deep dermatofibrosarcoma protuberans: a subcutaneous variant
Authors: Diaz‐Cascajo C. , Weyers W. , Rey‐Lopez A. , Borghi S.
Published: December 2004

Aims

Dermatofibrosarcoma protuberans (DFSP) is a distinctive cutaneous spindle cell neoplasm that invariably infiltrates the subcutaneous tissue. Other reports have suggested that exceptional cases of DFSP may be confined to the subcutaneous tissue and lack dermal involvement. We wish to confirm this observation by describing cases of a rare variant of DFSP confined to the subcutaneous tissue, and analyse possible histogenetic implications.

Methods and results

Three cases of DFSP located in the subcutaneous tissue are reported. Multiple step sections demonstrated the lack of dermal involvement in two of them, whereas the third case infiltrated the dermis at the junction with the subcutis minimally in one of five blocks. Immunohistochemical studies using a battery of monoclonal antibodies were performed. All the tumours stained strongly for vimentin and CD34.

Conclusions

Because of the lack of dermal involvement in two cases and only minimal dermal involvement in one case, we called this variant deep DFSP. Except for deep setting of the tumour, deep DFSP is indistinguishable from typical DFSP clinically, histologically and immunohistochemically. The existence of deep DFSP provides evidence that specific structures of the skin may be not involved in this tumour's histogenesis.
Lymphoblastic lymphoma of natural killer cell origin, presenting as pancreatic tumour
Authors: Tamura H. , Ogata K. , Mori S. , An E. , Tajika K. , Sugisaki Y. , Dan K.
Published: December 2004

Aims

We describe the first case of lymphoblastic lymphoma (LBL) of natural killer (NK) cell origin initially presenting as a pancreatic tumour, and review this type of lymphoma.

Methods and results

A 38‐year‐old woman with abdominal pain was found to have a pancreatic mass. Twenty days later, she developed diffuse lung infiltrates and leucoerythroblastosis of the peripheral blood, and her bone marrow was diffusely infiltrated with blasts. The blasts were positive for CD56, CD16 and P‐glycoprotein, but lacked cytoplasmic azurophilic granules, T, B and myeloid cell markers on the cell surface, rearrangement of the genes for T‐cell receptor and immunoglobulin, and the Epstein–Barr virus (EBV) genome. The diagnosis was LBL of NK cell origin. She received aggressive therapy, but died of the lymphoma. In contrast to ordinary NK‐cell lymphoma, this case and reported cases of LBL of NK‐cell origin showed the following common characteristics. The tumour cells often lack cell surface CD2, cytoplasmic CD3, cytoplasmic azurophilic granules, and EBV genome. The prognosis was extremely poor.

Conclusions

LBL of NK‐cell origin should be included in the differential diagnosis of pancreatic tumours. To fully characterize this type of lymphoma, further cases must be evaluated.
Verrucous angiosarcoma of the skin: a distinct variant of cutaneous angiosarcoma
Authors: Diaz‐Cascajo C. , Weyers W. , Borghi S. , Reichel M.
Published: December 2004

Aims

Cutaneous angiosarcoma is a malignant vascular neoplasm with well established clinical and histopathological features. Epidermal changes in cutaneous angiosarcoma other than atrophy and necrosis have not been described. In this study, we report three cases of a peculiar variant of angiosarcoma with striking verrucous changes of the overlying epidermis.

Methods and results

On light microscopy, verrucous changes characterized by marked pseudocarcinomatous epithelial hyperplasia with hypergranulosis, compact orthokeratosis, and papillomatosis were present overlying an angiosarcoma in the dermis. Clinically the lesions presented as violaceous to brown scaly verrucous nodules or plaques. All lesions developed on an extremity.

Conclusions

Verrucous epidermal changes seem to be a manifestation of pseudocarcinomatous hyperplasia, presumably caused by lymphoedema and the superficial setting of the tumour in the papillary dermis. It is important to be aware of this presentation of angiosarcoma because verrucous epidermal changes may be seen in a wide variety of skin diseases. Furthermore, a biopsy that includes the dermis is necessary to ensure that the angiosarcoma underlying the hyperplastic epidermis is correctly identified. The descriptive appellation verrucous angiosarcoma of the skin is proposed to designate a newly recognized variant of angiosarcoma.
Microlithiasis in parotid sialadenosis and chronic submandibular sialadenitis is related to the microenvironment: an ultrastructural and microanalytical investigation
Authors: Triantafyllou A. , Harrison J.D. , Donath K.
Published: December 2004

Aims

Microlithiasis was investigated in parotid sialadenosis and chronic submandibular sialadenitis to determine if it relates to the glandular microenvironment as has been found experimentally.

Methods and results

Semithin sections were stained by a mixture of methylene blue and Azure II followed by basic fuchsin, which stains calcified parts of microliths red and organic parts green, and ultrathin sections were examined electron microscopically and microanalytically. Microliths in sialadenosis were found in periacinar stroma, in which necrotic acinar cells were found, and in parenchyma, and consisted of consolidated organic material with little or no crystalline calcium. Microliths in sialadenitis were found in stroma, particularly around intercalary ducts, in lumina and in parenchyma, and contained much crystalline calcium. Macrophages enclosed some microliths.

Conclusions

The paucity of calcium in microliths in sialadenosis and the abundance in sialadenitis relates to the glandular calcium. The periacinar distribution of microliths in sialadenosis possibly relates to formation in periacinar necrotic debris. The distribution of microliths in sialadenitis around intercalary ducts possibly relates to formation in matrix vesicles formed from atrophic parenchyma, and in lumina to formation in stagnant secretory material. Microliths appear to be scavenged by macrophages. Thus the experimental finding that salivary microlithiasis relates to the microenvironment pertaining in humans.
Spindle and cuboidal renal cell carcinoma, a tumour having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/ spindle and cuboidal renal cell carcinoma components
Authors: Hes O , Hora M , Perez‐Montiel D M , Suster S , Curík R , Sokol L , Ondic O , Mikuláštík J , Betlach J , Peychl L , Hrabal P , Kodet R , Straka L , Ferák I , Vrabec V , Michal M
Published: December 2004

Aims:  We present the largest series of an unclassified subtype of renal cell carcinoma, which seems to be a distinct morphological entity and which is sometimes designated as spindle and cuboidal renal cell carcinoma.

Methods and results:  Eleven cases of spindle and cuboidal renal cell carcinoma were found among 7000 primary renal cell tumours in Pilsen's routine and consultation files. The patients were five men and six women. They ranged in age from 22 to 65 years (mean 56.8). Microscopically, the tumours were composed of two main populations of cells. First, the preponderant type of cells was formed by flattened, spindle cells with sparse cytoplasm. The second cell type was a small cuboidal cell with clear to light eosinophilic cytoplasm. Spindle‐shaped cells were arranged in a fascicular pattern often reminiscent of low‐grade smooth muscle tumours. Solid areas of spindle cells were also present. Small cuboidal cells formed sparse tubular structures lined by a row of single cells. In addition to all previous published cases of spindle and cuboidal renal cell carcinoma we observed an association of nephrolithiasis in our cases. It was seen in 3/11 of our patients. A previously unreported feature is the occurrence of a conventional renal cell carcinoma component in one of our cases. Seven of our patients are currently well without signs of recurrence or metastasis, one had metastasis in a regional lymph node at the time of nephrectomy, one died of an unrelated condition, and two were lost to follow‐up.

Conclusions:  We present 11 cases of spindle and cuboidal renal cell carcinoma, which is believed to be a distinctive morphological entity. Our cases were histologically, immunohistochemically and ultrastructurally similar to the previously reported cases of spindle and cuboidal renal cell carcinoma. In contrast to all previously reported cases of spindle and cuboidal renal cell carcinoma, we observed an association with nephrolithiasis in three of our cases; moreover, one of our tumours had a conventional renal cell carcinoma component and another revealed a metastatic focus in a regional lymph node. None of our patients died of the disease. This study confirms that spindle and cuboidal renal cell carcinoma has a low malignant potential.
Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma
Authors: Matsukita S , Nomoto M , Kitajima S , Tanaka S , Goto M , Irimura T , Kim Y S , Sato E , Yonezawa S
Published: December 2004

Aims:  Mucinous carcinoma of the breast usually shows less frequent lymph node metastasis and more favourable outcome compared with invasive ductal carcinoma. The aim of this study is to compare the expression profiles of several mucins in mucinous carcinomas and invasive ductal carcinomas to gain insight into the relationship between the less aggressive biological nature of mucinous carcinoma and the role of mucins.

Methods and results:  We examined the expression profiles of MUC1 (membrane‐bound mucin) of different glycoforms (from non‐glycosylated form to fully glycosylated form), MUC2 (intestinal type secretory mucin), MUC5AC (gastric surface type secretory mucin) and MUC6 (gastric pyloric gland type secretory mucin) in 17 mucinous carcinomas and 46 invasive ductal carcinomas using immunohistochemistry. Various glycoforms of MUC1 were expressed frequently in both mucinous carcinomas (65–100%) and invasive ductal carcinomas (92–100%), although non‐glycosylated MUC1 (MUC1/CORE) and fully glycosylated MUC1 (MUC1/HMFG‐1) showed significantly lower expression rates in mucinous carcinomas compared with those in invasive ductal carcinomas. The expression rates of MUC2 (94%) and MUC6 (71%) in mucinous carcinomas were significantly higher than those of MUC2 (15%) and MUC6 (15%) in invasive ductal carcinomas. There was no significant difference in the expression rate of MUC5AC in mucinous carcinomas (12%) and that in invasive ductal carcinomas (4%).

Conclusions:  The expression rate of MUC1/CORE and MUC1/HMFG‐1, which is related to poor prognosis in the gastric and colorectal cancers, is low in mucinous carcinomas. The high expression rate of gel‐forming secretory mucins (MUC2 and MUC6) in mucinous carcinoma suggests that high production of these types of mucins may act as a barrier to cancerous extension resulting in their less aggressive biological behaviour.
Focal nodular hyperplasia‐like areas in cirrhosis
Authors: Quaglia A , Tibballs J , Grasso A , Prasad N , Nozza P , Davies S E , Burroughs A K , Watkinson A , Dhillon A P
Published: December 2004

Aims:  Focal nodular hyperplasia‐like lesions have rarely been described in cirrhotic livers. We describe five cases of such lesions.

Methods and results:  Between 1998 and 2001, 146 liver transplants were performed at the Royal Free Hospital for cirrhosis of the liver. Nodular lesions identified in the livers removed at transplantation were defined histologically according to the International Working Party classification (Hepatology 1995; 22; 983). They were present in 63 of these livers, as follows: 36 dysplastic nodules, 121 macroregenerative nodules, and 71 hepatocellular carcinomas. In five patients, an additional 12 nodules (size range 4–23 mm, median 10.5 mm) showed histological features suggestive of focal nodular hyperplasia including mildly inflamed vascular fibrous septa, and ductular proliferation. Pre‐transplantation imaging showed features suspicious for hepatocellular carcinoma, in three of these lesions (12, 23 and 23 mm diameter) from two different patients. These lesions were histologically indistinguishable from focal nodular hyperplasia occurring in non‐cirrhotic livers, with fibrous scars and septa which contained vascular and ductular structures.

Conclusions:  It is important to recognize that these lesions may occur in the context of cirrhosis and that they should be considered in the differential diagnosis with hepatocellular carcinoma, dysplastic nodules and macroregenerative nodules.
Follicular lymphoma with marginal zone differentiation: cytogenetic findings in support of a high‐risk variant of follicular lymphoma
Authors: Goodlad J R , Batstone P J , Hamilton D , Hollowood K
Published: December 2004

Aims:  The pathogenesis and clinical significance of marginal zone differentiation in follicular lymphoma remains to be determined, although genetic alterations are likely to be important determinants of both. We therefore report the cytogenetic findings in three cases of follicular lymphoma with marginal zone differentiation studied by routine karyotyping and in‐situ hybridization.

Methods and results:  The morphology and immunophenotype of each case was typical of follicular lymphoma displaying marginal zone differentiation. Karyotyping, performed on GTL‐banded preparations of cell cultures derived from fresh lymph node tissue, revealed a complex karyotype in all three cases, including t(14;18)(q32;q21) and abnormalities associated with progression and/or transformation of follicular lymphoma. In addition, trisomy 3 was found in one case and translocations between the q27‐29 region of chromosome 3 and chromosome 2 in the other two cases; the latter was identified only in subclones derived from less complex stem lines possessing t(14;18). In‐situ hybridization, performed on sections cut from routinely processed paraffin‐embedded tissue blocks, localized cells possessing these abnormalities of chromosome 3 to both the follicular and marginal zone components of two lymphomas studied in this way.

Conclusions:  Trisomy 3 and alterations involving the q27‐29 region of chromosome 3 are implicated in the pathogenesis of de novo marginal zone lymphoma. Their presence in the current cases indicates that they may also be responsible for marginal zone differentiation in follicular lymphoma when cells harbouring these genetic alterations are exposed to the appropriate microenvironment. Our findings are consistent with follicular lymphoma with marginal zone differentiation as a high‐risk variant of follicular lymphoma.
Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3)
Authors: Lee A H S , Denley H E , Pinder S E , Ellis I O , Elston C W , Vujovic P , Macmillan R D , Evans A J ,   for the Nottingham Breast Team
Published: December 2004

Aims:  The UK National Health Service Breast Screening Programme has proposed five categories for reporting breast needle core biopsies. The majority of cores are reported as benign (B1), normal (B2) or malignant (B5). The predictive value of the two borderline categories suspicious of malignancy (B4) and lesion of uncertain malignant potential (B3) was studied.

Methods and results:  Over a 2‐year period a total of 3822 breast needle core biopsies were performed, with 2997 from symptomatic patients and 825 from women undergoing mammographic screening, including 43 B4 reports (40 patients) and 120 B3 reports (116 lesions in 115 patients). The frequencies of B4 (2.5% versus 0.7%) and B3 cores (7.3% versus 2.0%) were both higher in screening than in symptomatic patients. B4 was most commonly used for small fragments of atypical cells separate from the main core or focal atypical intraductal proliferations. The criteria for calling a core B3 were: atypical intraductal epithelial proliferations (including foci that in excision specimens would be classified as atypical ductal hyperplasia), lobular neoplasia, radial scar, papillary lesion, fibroepithelial lesion with cellular stroma and spindle cell proliferations. Excision biopsies were performed in 39 patients with B4 core and 96 with B3 core. Invasive carcinoma or ductal carcinoma in situ was seen in 33 of the patients with B4 (85%) and in 29 of those with B3 cores (25%). Some categories of B3 core were associated with a higher rate of malignancy (40% for atypical intraductal epithelial proliferations and 46% for lobular neoplasia).

Conclusions:  The positive predictive value for carcinoma is high following a B4 core (86%). The lesion should be excised, but definitive cancer treatment is not appropriate. In some cases a definite diagnosis of malignancy can be made on repeat core. The B3 group is more heterogeneous and has a lower rate of malignancy on further biopsy (25%). The majority of B3 lesions require excision. All these patients should be discussed at multidisciplinary meetings.
The autopsy: complete or not complete?
Authors: Benbow E W , Roberts I S D
Published: December 2004

Less invasive or non‐invasive alternatives to the complete autopsy have been sought for some time, and a range of methods, ranging from needle sampling to endoscopy to magnetic resonance imaging, have been considered. Evaluations of these methods are few and far between, but generally confirm the predictable conclusion that incomplete autopsies provide incomplete information. It is not difficult to envisage a situation whereby pressure for non‐invasive autopsies will allow them to become prevalent, whether properly evaluated or not. However, used appropriately, non‐invasive or less invasive autopsies may be valuable tools capable of answering specific questions in situations where it is not possible to perform a complete autopsy.
Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French Multicentre GEFPICS* Study
Authors: Vincent‐Salomon A , MacGrogan G , Couturier J , Arnould L , Denoux Y , Fiche M , Jacquemier J , Mathieu M‐C , Penault‐Llorca F , Rigaud C , Roger P , Treilleux I , Vilain M‐O , Mathoulin‐Pélissier S , Le Doussal V
Published: December 2004

Aims:  HER2 protein is over‐expressed in 15–30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in‐situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2‐IHC compared with HER2‐FISH taken as the reference method.

Methods and results:  Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in‐house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti‐HER2 antibodies. Two cut‐off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty‐four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat‐induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over‐expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut‐offs, respectively. The corresponding accuracy rates were 93% and 95%.

Conclusions:  This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in‐house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti‐HER2 antibody and the use of specific controls were crucial for HER2‐IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2‐IHC results as a continuous variable, and taking 60% invasive stained cells as the cut‐off for HER2 over‐expression.
Concordance of FIGO grade of endometrial adenocarcinomas in biopsy and hysterectomy specimens
Authors: Mitchard J , Hirschowitz L
Published: December 2004

Aims:  We compared the FIGO grade of endometrial adenocarcinomas in endometrial samples and subsequent hysterectomy specimens, between 1997 and 2000 in a general pathology department. Our aims were to assess concordance, and the influence of the sampling technique, patient age, reporting pathologist and interval between the biopsy and definitive surgery. In order that the study reflected working practice, the tumour grade given by the reporting pathologist was used whenever possible.

Methods and results:  Endometrial samples and the subsequent hysterectomy specimens from 125 patients were studied. The comparative FIGO grades were analysed with reference to biopsy type, patient age, reporting pathologist and interval between biopsy and hysterectomy. Concordance was 45% for grade 1, 63.3% for grade 2 and 75.6% for grade 3 carcinomas, the overall concordance being 64.5%. The concordance for grade 3 tumours was significantly higher than for grade 1. The predictive accuracy was independent of biopsy type, patient age, the interval between biopsy and hysterectomy, and whether the same pathologist reported both specimens.

Conclusions:  Irrespective of the sampling device used, patient age, time‐lapse between biopsy and hysterectomy, or whether the same pathologist reported both specimens, the grade of endometrial adenocarcinoma often differs in the initial biopsy sample from that in the final hysterectomy specimen. This may have important implications for patient management, especially for tumours that yield low‐grade biopsies.
Colorectal mass lesions masquerading as chronic inflammatory bowel disease on mucosal biopsy
Authors: Gupta J , Shepherd N A
Published: December 2004

Aims:  We bring to the attention of diagnostic pathologists a further cause of mimicry of chronic inflammatory bowel disease on mucosal biopsy, namely intramural and subserosal colorectal mass lesions.

Methods and results:  In a 10‐year prospective study in one centre, we describe 26 cases in which the initial colonoscopic biopsies suggested a diagnosis of chronic inflammatory bowel disease, whereas subsequent information indicated that the mucosal changes were due to underlying mass lesions, without evidence of chronic inflammatory bowel disease. These mass lesions included underlying primary adenocarcinoma, metastatic carcinoma, pneumatosis, endometriosis and complicated diverticular disease.

Conclusions:  In the colon and rectum, intramural and subserosal mass lesions are a significant cause of chronic inflammatory bowel disease mimicry. Possible pathogenic mechanisms include mechanical effects, lymphatic obstruction by underlying tumour, relative mucosal ischaemia and mucosal prolapse. Since the changes seen on mucosal biopsies are a secondary phenomenon, we tentatively suggest that ‘secondary colitis’ may be an appropriate appellation.
Accuracy of magnetic resonance imaging in determining cause of sudden death in adults: comparison with conventional autopsy
Authors: Roberts I S D , Benbow E W , Bisset R , Jenkins J P R , Lee S H , Reid H , Jackson A
Published: December 2004

Aim:  To determine the accuracy and define the limitations of post mortem magnetic resonance imaging (MRI) in determining the cause of sudden death in adults.

Methods and results:  Sudden unexpected adult deaths in the community, reported to the Coroner (n = 10), excluding suspicious, violent or potentially drug‐related deaths, were submitted to whole body MRI, followed by full invasive autopsy. The MRI scans were reported independently by four radiologists, blinded to the autopsy findings; two had previous experience of post mortem MRI. An abnormality that related to the cause of death as identified at autopsy, was identified by at least one radiologist in eight cases. These were pulmonary consolidation (autopsy finding pneumonia) (n = 1), pneumoperitoneum (autopsy finding perforated peptic ulcer) (n = 2), left ventricular failure (autopsy finding ischaemic heart disease) (n = 4), and disseminated bronchial carcinoma (n = 1). However, in only one case were all radiologists able to provide a confident cause of death (disseminated bronchial carcinoma). In two cases, in which death occurred 2–6 days and 3–6 days before MRI, early decomposition prevented interpretation of the images. Severe coronary artery atheroma was detected at autopsy in 7/10, but these lesions were not detected by MRI. Previous experience in reporting post mortem MRI, without autopsy comparison, did not result in more accurate interpretation of the images.

Conclusions:  This pilot study suggests that post mortem MRI can identify some abnormalities relating to the common causes of sudden death in adults, but there is a need for greater experience in correlating MRI with autopsy findings before a reliable cause of death can be made by MRI alone. Inability to image coronary artery lesions, differentiating thrombus from clot and pulmonary oedema from pneumonic exudates, are specific problems that may be corrected with greater experience and higher resolution scans.
Expression of maspin is up‐regulated during the progression of mammary ductal carcinoma
Authors: Umekita Y , Yoshida H
Published: December 2004

Aims:  The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down‐regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS).

Methods and results:  To clarify whether there is down‐regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo‐necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative.

Conclusions:  These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up‐regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.
Cyclooxygenase‐2 expression in thyroid neoplasms
Authors: Ito Y , Yoshida H , Nakano K , Takamura Y , Miya A , Kobayashi K , Yokozawa T , Matsuzuka F , Matsuura N , Kuma K , Miyauchi A
Published: December 2004

Aims:  Previous studies have demonstrated that cyclooxygenase‐2 (COX‐2) plays a role in carcinogenesis and carcinoma development. In this study, we investigated its expression in thyroid neoplasms in order to elucidate its role.

Methods and results:  COX‐2 expression was studied immunohistochemically in 20 anaplastic (undifferentiated) carcinomas, 49 papillary carcinomas, 22 follicular carcinomas and 15 follicular adenomas. Positive staining was only occasionally seen in normal follicles or stromal cells. COX‐2 over‐expression was found in only 20.0% of follicular adenomas and 40.9% of follicular carcinomas. In papillary carcinomas, the incidence (81.3%) was significantly higher (P < 0.0001) than in follicular carcinomas, although COX‐2 expression was reduced in cases with old age (P = 0.0190), large size (P = 0.0028), advanced stage (P = 0.0225), satellite tumours (P = 0.0363), and the presence of solid, scirrhous or trabecular growth patterns (P = 0.0018). Undifferentiated carcinomas less frequently over‐expressed COX‐2 (P = 0.0004), with an incidence of 40.0%.

Conclusions:  These results indicate that the up‐regulation of COX‐2 may contribute predominantly in the early phase of papillary carcinoma progression, whereas it plays a more adjuvant role in follicular carcinoma progression.
Cyclooxygenase‐2 is expressed frequently and early in Barrett's oesophagus and associated adenocarcinoma
Authors: Lagorce C , Paraf F , Vidaud D , Couvelard A , Wendum D , Martin A , Fléjou J‐F
Published: December 2004

Aims:  To establish the prevalence of cyclooxygenase‐2 (COX‐2) expression in a large series of resected Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis.

Methods:  COX‐2 expression was assessed by immunohistochemistry in resected surgical specimens of 66 Barrett's adenocarcinomas and 32 cases of Barrett's mucosa (with dysplasia in 17 cases).

Results:  Epithelial expression of COX‐2 protein was increased in Barrett's mucosa compared with normal oesophagus. Epithelial expression of COX‐2 was found in 91% of Barrett's specialized mucosa negative for dysplasia, 94% of Barrett's mucosa with dysplasia, and 97% of Barrett's adenocarcinoma. COX‐2 expression was significantly higher in the well‐differentiated adenocarcinomas when compared with the poorly differentiated tumours. There was no significant correlation between COX‐2 expression and the other pathological features of the tumours. Survival analysis showed no significant prognostic value for COX‐2.

Conclusion:  Our results confirm up‐regulation of COX‐2 in Barrett's oesophagus—metaplastic and dysplastic—and in Barrett's adenocarcinoma. Increased COX‐2 expression did not differ during the progression from Barrett's oesophagus negative for dysplasia to Barrett's adenocarcinoma and is related to adenocarcinoma whose histology is well differentiated. This suggests that enhanced expression of COX‐2 may occur early during Barrett's‐associated neoplastic transformation.
Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma
Authors: Sington J D , Morris L S , Nicholson A G , Coleman N
Published: December 2004

Aims:  The differentiation of benign pleural conditions from malignant mesothelioma may be difficult, especially with a small biopsy. We have tested the hypothesis that assessment of the cell cycle status is of value in the histopathological diagnosis of such biopsies, by comparing 33 malignant mesotheliomas with 36 cases of reactive mesothelial hyperplasia and reactive pleural fibrosis.

Methods and results:  Biopsies were investigated for proliferative status by immunostaining for a novel antibody, MCM2, all of which showed nuclear expression of MCM2 at higher frequency than Ki67 (P < 0.0001). Counts in areas of maximum tumour staining showed significantly higher labelling indices (LIMax) in epithelioid and sarcomatoid mesotheliomas compared with reactive mesothelial hyperplasia and reactive pleural fibrosis (P < 0.0001 for both). Average counts (LIAve) revealed a significant increase in epithelioid mesothelioma compared with reactive mesothelial hyperplasia (P < 0.0001).

Conclusion:  We consider MCM2 to be a useful adjunct in the differential diagnosis of malignant mesothelioma.
Synovial sarcoma in older patients: clinicopathological analysis of 32 cases with emphasis on unusual histological features
Authors: Chan J A , McMenamin M E , Fletcher C D M
Published: December 2004

Aims:  To analyse the clinicopathological features of synovial sarcoma presenting in patients over 60 years of age, an uncommon subset which have not been specifically studied.

Methods and results:  Thirty‐two cases of primary synovial sarcoma in patients aged ≥60 years were retrieved from the authors' consultation files. These were analysed histologically and immunohistochemically and clinical follow‐up was obtained in 26 cases (median duration 41 months). Mean age at diagnosis was 71.6 years (range 60–84) with 19 females and 13 males. Anatomical sites were lower limb (n = 13), upper limb (n = 5), lung/pleura (n = 5), trunk (n = 4), head/neck (n = 3), mediastinum (n = 1) and scrotum (n = 1). Histologically, 23 were monophasic and nine were biphasic; 14 were poorly differentiated, of which five showed focally marked pleomorphism. Unusual features in two cases each included organoid nodules, granular cell change, squamous metaplasia and papillary architecture. Ten patients developed local recurrence and 11 developed metastases, of whom seven died. Large tumour size, poorly differentiated morphology and high mitotic rate correlated with poor outcome.

Conclusions:  Less than 10% of synovial sarcomas occur in patients over 60, in which age group this diagnosis is often not considered. Despite inevitable bias in consultation material, it seems that these cases, when compared with younger age groups, more often show poorly differentiated histology and more often develop at unusual locations.
Basal cell adenocarcinoma in minor salivary glands
Authors: Jayakrishnan A , Elmalah I , Hussain K , Odell E W
Published: December 2004

Basal cell adenocarcinoma is a rare and relatively recently characterized malignant salivary gland tumour, the malignant counterpart of basal cell adenoma. Diagnosis depends on finding features similar to adenoma but with an infiltrative growth pattern and exclusion of adenoid cystic carcinoma, sialoblastoma and basaloid squamous carcinoma. Basal cell adenocarcinoma is very rarely reported in minor salivary glands. We report three cases of basal cell adenocarcinoma affecting the labial, buccal and palatal minor salivary glands. One recurred following complete removal but with lesional disruption and further local wide excision appeared curative. A further lesion failed to recur in 5 years' follow‐up despite marginal excision and a third after 3 years' follow‐up. Basal cell adenocarcinoma is considered a low‐grade malignancy, and in the minor glands wide excision and radiotherapy are recommended. However, the reported lesions appear to have a more indolent behaviour than previously reported lesions in minor glands.
Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach
Authors: Wong N A C S , Young R , Malcomson R D G , Nayar A G , Jamieson L A , Save V E , Carey F A , Brewster D H , Han C , Al‐Nafussi A
Published: December 2004

Aims:  Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs.

Methods and results:  Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl‐2 and cyclin D1. Complete follow‐up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c‐kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease‐specific survival: size ≥50 mm; necrosis, no intratumoral lymphocytes; mitotic count ≥5/50 high power fields; Ki67 labelling index ≥5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators.

Conclusions:  Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl‐2 and cyclin D1 immunohistochemistry provide no additional prognostication.
Myxoglobulosis in oral extravasation mucocele: an entity?
Authors: Shah K A
Published: December 2004

Aims:  Myxoglobulosis is a recognized variant of mucocele of the vermiform appendix. Myxoglobulosis has recently been reported in extravasation mucocele of the oral cavity. This morphological study was carried out to identify the prevalence and possible pathogenesis of this unusual feature.

Materials and methods:  A retrospective review of archival material diagnosed as oral cavity mucocele was undertaken. This covered a period of 32 months and consisted of 76 cases. In accordance with the proposed traumatic origin of extravasation mucocele, histological changes were classified on the basis of mucin extravasation and cyst formation. Globular structures, as described in the reports of myxoglobulosis, were looked for, as were changes that could be ascribed to their formation.

Conclusions:  Globular structures were noted in 22 (31%) of 71 cases of extravasation mucocele. They were present within cysts (11 samples) and in extraluminal connective tissue in the rest. They appeared to originate from alterations in connective tissue collagen following mucin extravasation. Their structure is different from that described in appendicial mucocele. When observed, they are best regarded as part of the normal sequence in the formation of oral cavity extravasation mucocele, without attaching special importance to them.