bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status.
Authors: Maeda T , Matsumura S , Hiranuma H , Jikko A , Furukawa S , Ishida T , Fuchihata H
Published: January 2009

AIMS: To correlate vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma with the clinicopathological characteristics and prognosis; and to assess whether p53 gene status is associated with VEGF expression in human cancers. METHODS: Tumour specimens from 45 patients with oral squamous cell carcinomas were examined. Expression of VEGF was determined using an immunohistochemical method, and a tumour was considered positive when more than 5% of the neoplastic cells showed VEGF immunoreactivity. The p53 gene status was screened using a polymerase chain reaction--single strand conformation polymorphism analysis. RESULTS: VEGF positive staining was detected in 19 (42.2%) of the 45 cases. VEGF immunoreactivity did not correlate with the histological degree of tumour differentiation, clinical stages, or lymph node metastasis. The patients with VEGF positive tumours had a significantly worse prognosis than those with VEGF negative tumours. The five year overall survival rate of the VEGF negative patients was 76.5%, as compared with 48.8% for the VEGF positive patients. No significant association between VEGF expression and the p53 gene status of the tumours was found. CONCLUSIONS: VEGF is a good prognostic indicator of the survival of patients with oral squamous cell carcinoma. The p53 gene status does not seem to be associated with VEGF expression in these cancers.
The role of alternative splicing of the adhesion molecule, CD44, in lymphoid malignancy.
Authors: Irving J A , Cain G , Howard M , Angus B , Taylor P R , Cattan A R
Published: January 2009

AIM: To investigate the expression of CD44 isoforms containing variant exon 6 (v6) in a well characterised cohort of patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), and to correlate this with phenotype and disease course. METHODS: Cryostat sections of OCT embedded diagnostic nodal material from NHL patients and cryopreserved mononuclear preparations from CLL patients were used as sources of RNA. After reverse transcription, PCR was carried out with amplimers positioned at either side of the variant exon insertion site to amplify all possible CD44 isoforms. Those isoforms containing v6 were identified after Southern blotting and hybridisation with a radiolabelled oligonucleotide. RESULTS: Of 32 NHL samples analysed, 16 did not express CD44 isoforms containing v6, six expressed an isoform containing exon v6 alone, and 10 expressed v6 long isoforms which contained exon v6 in addition to other variant exons. These data did not correlate with lymphoma classification, disease staging, or the presence or absence of extranodal disease. However, those patients expressing v6 long CD44 isoforms had a worse overall survival than those that did not. The plateau of the survival curves was 50% compared with 82%. No v6 long isoforms were detected in the 21 CLL samples investigated. CONCLUSIONS: The expression of v6 long CD44 isoforms is associated with aggressive disease in NHL, independent of grade, stage, or presence of extranodal disease.
Expression of extracellular matrix proteins in cervical squamous cell carcinoma--a clinicopathological study.
Authors: Goldberg I , Davidson B , Lerner-Geva L , Gotlieb W H , Ben-Baruch G , Novikov I , Kopolovic J
Published: January 2009

AIM: To evaluate the intracellular and peritumoral expression of matrix proteins in squamous cell carcinoma of the uterine cervix using immunohistochemistry. METHODS: 71 squamous cell carcinomas and 10 controls were stained for laminin, fibronectin, and collagen IV. Cytoplasmic staining in tumour cells and peritumoral deposition of matrix proteins were evaluated. The association between staining results and patient age, tumour stage, histological grade, and survival was studied. RESULTS: Positive cytoplasmic staining for laminin, fibronectin, and collagen IV was observed in 17 (23.9%), 27 (38%), and 10 (14.1%) cases, respectively. Staining for laminin was most pronounced in the invasive front of tumour islands, while for fibronectin and collagen IV it appeared to be diffuse. Peritumoral staining for laminin and collagen IV was detected in 12 cases (16.9%). Early stage (Ia1-Ia2) tumours were uniformly negative for all three proteins. Cytoplasmic staining for laminin correlated with positive staining for fibronectin and collagen IV, and with the presence of a peritumoral deposition of collagen IV and laminin. There was no correlation with any of the three markers between staining results and patient age, stage, grade, or survival. CONCLUSIONS: Expression of extracellular matrix proteins in some cervical squamous cell carcinomas might reflect the enhanced ability of these tumours to modify the peritumoral stroma. This ability seems to be absent in early stage tumours. The correlation between intracytoplasmic and peritumoral expression of matrix proteins supports the evidence of their synthesis by tumour cells. However, this property did not correlate with disease outcome in this study.
Fatal Serratia marcescens meningitis and myocarditis in a patient with an indwelling urinary catheter.
Authors: Johnson J S , Croall J , Power J S , Armstrong G R
Published: January 2009

Serratia marcescens is commonly isolated from the urine of patients with an indwelling urinary catheter and in the absence of symptoms is often regarded as a contaminant. A case of fatal Serratia marcescens septicaemia with meningitis, brain abscesses, and myocarditis discovered at necropsy is described. The patient was an 83 year old man with an indwelling urinary catheter who suffered from several chronic medical conditions and from whose urine Serratia marcescens was isolated at the time of catheterisation. Serratia marcescens can be a virulent pathogen in particular groups of patients and when assessing its significance in catheter urine specimens, consideration should be given to recognised risk factors such as old age, previous antibiotic treatment, and underlying chronic or debilitating disease, even in the absence of clinical symptoms.
In situ hybridisation and direct fluorescence antibodies for the detection of Chlamydia trachomatis in synovial tissue from patients with reactive arthritis.
Authors: Berlau J , Junker U , Groh A , Straube E
Published: January 2009

BACKGROUND: Chlamydia trachomatis is associated with Reiter's syndrome and reactive arthritis but the form in which the organism survives in synovial cells is unclear. AIM: To compare in situ hybridisation with direct fluorescence in the detection of inapparent chlamydial infection in synovial tissue. METHODS: Synovial tissue from four patients with reactive arthritis patients was examined using biotin labelled probes for chlamydial DNA and fluorescein isothiocyanate (FITC) labelled monoclonal antibodies against the major outer membrane protein. RESULTS: In two of the four patients, evidence of chlamydial infections was detected by in situ hybridisation in parallel sections but not with FITC labelled monoclonal antibodies. CONCLUSIONS: Detection of chlamydial DNA by in situ DNA hybridisation may be a better way to identify chlamydial infection in synovial tissue than phenotype targeting with FITC conjugated antibodies, which is used as a standard procedure for screening clinical specimens for chlamydia.
Detection of cytomegalovirus in upper gastrointestinal biopsies from heart transplant recipients: comparison of light microscopy, immunocytochemistry, in situ hybridisation, and nested PCR.
Authors: Muir S W , Murray J , Farquharson M A , Wheatley D J , McPhaden A R
Published: January 2009

AIM: To establish the diagnostic value of in situ hybridisation and the nested polymerase chain reaction (PCR) in detecting clinically relevant cytomegalovirus (CMV) infection in upper gastrointestinal biopsies from heart transplant patients. METHODS: Test sensitivity and specificity for detection of CMV early gene RNA by in situ hybridisation and CMV intermediate early gene by PCR were established and then compared with haematoxylin and eosin (H&E) and immunocytochemical detection of CMV in order to establish the best pathological diagnostic approach. All investigations were carried out on formalin fixed, paraffin embedded tissue. RESULTS: Nested PCR had the highest test sensitivity, followed by in situ hybridisation and immunocytochemistry with the same sensitivity; H&E had the lowest. H&E and immunocytochemistry were the most specific but both had a significant false negative rate which was less of a problem with PCR. However, PCR gave no other diagnostic information, and in situ hybridisation was no better than immunocytochemistry. Both in situ hybridisation and PCR were technically complex and more expensive. CONCLUSIONS: H&E and immunocytochemistry represent the best initial screen for CMV and other diseases in upper gastrointestinal biopsies from heart transplant patients. If H&E and immunocytochemistry were negative, nested PCR could significantly increase the diagnostic yield of clinically relevant CMV infection. In situ hybridisation appeared to have no advantages and some drawbacks compared with immunocytochemistry and PCR.
Chlamydia pneumoniae in atheroma: consideration of criteria for causality.
Authors: Shor A , Phillips J I , Ong G , Thomas B J , Taylor-Robinson D
Published: January 2009

AIMS: (1) To seek evidence of the existence of Chlamydia pneumoniae in a spectrum of atheromatous lesions in different types of arteries from individuals of different ages, using a polymerase chain reaction (PCR) assay supported by electron microscopy and immunocytochemistry; (2) to use electron microscopy to examine interactions between C pneumoniae and the cells present in the arterial tissue; (3) to assess the extent to which the data fulfil the criteria for causality. METHODS: At necropsy examination, 35 arterial specimens were taken from 25 subjects. The grade of atheroma was determined macroscopically and microscopically and the tissues coded and examined by the three techniques. RESULTS: Of the 35 specimens, 24 had macroscopic or microscopic atheromatous lesions of varying degree. Twenty two of the 35 specimens were examined by electron microscopy, C pneumoniae-like bodies being found in 11 (50%); seven specimens were examined by the immunocytochemical method, positive staining being detected in three; and all specimens were examined by the PCR technique, 15 (43%) being PCR positive. Overall, of the 24 specimens with lesions, 17 (71%) were positive by at least one of the three tests, whereas of the 11 specimens without lesions, only one was positive. The positive specimens comprised 10 of 19 aortas, three of six iliac arteries, and one coronary and one pulmonary artery. C pneumoniae was detected in four of six specimens in which there were early changes and in a 20 year old subject. Concerning the 25 subjects, of 17 who had atheromatous arteries, 14 (82%) were C pneumoniae positive and of the eight who had normal arteries, none was positive. CONCLUSIONS: There is a strong correlation between C pneumoniae and arterial atheromatous lesions. The organism may contribute to the disease process by damaging smooth muscle cells.
Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile.
Authors: Ceccarelli C , Santini D , Chieco P , Taffurelli M , Gamberini M , Pileri S A , Marrano D
Published: January 2009

AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive breast tumours and compare its expression with the major biopathological prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival paraffin embedded tissues from 153 consecutive primary breast carcinomas. METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were identified by immunohistochemistry and score values were recorded by image cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb scores correlated strongly with proliferation activity as determined by Ki-67 staining. Positive relations were also observed between pRb scores, tumour size, nuclear and histological grade, and oestrogen receptor/progesterone receptor content, while abnormal p53 accumulation was not associated with pRb expression. Among the high proliferating carcinomas it was possible to identify 13 cases with loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative activity in the majority of breast carcinomas examined, suggesting that in these cases the protein behaves normally in regulating the cell cycle. Conversely in cases with loss of pRb immunostaining, the combined expression of specific highly aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone receptor negative status, and high K67) seems to characterise a more aggressive phenotype showing growth advantage and cellular "progression" rather than significant nodal involvement.
Study of the cell biology and biochemistry of cherubism.
Authors: Southgate J , Sarma U , Townend J V , Barron J , Flanagan A M
Published: January 2009

AIMS: To establish whether the multinucleate cells in lesions of patients with cherubism are also osteoclasts and if this is the case whether they were responsive to calcitonin; to carry out cytogenetic studies on two members of the same family affected by cherubism in an attempt to identify any major chromosomal defects; and to perform an in-depth modern biochemical study of four children in the same family. SUBJECTS AND METHODS: Four related children with cherubism were studied. Tissue taken from one of the children at elective decompression of an optic nerve was submitted to in vitro bone resorption studies. Cytogenetic studies were done on two of the children and biochemical studies on all four. RESULTS: The multinucleate cells in the cherubic lesions were shown to be osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed the vitronectin receptor, and resorbed bone. Bone resorption by the cultured multinucleate cells was significantly inhibited by calcitonin. High resolution cytogenetic studies failed to detect any chromosomal abnormalities in two children with cherubism. The biochemistry profile of all four children with cherubism showed that serum calcium, parathyroid hormone, parathyroid related hormone, calcitonin, and alkaline phosphatase were within normal levels. Urine analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and calcium in relation to urine creatinine were measured to assess bone resorption in these children, and the values were at the upper end of the normal range in all four. CONCLUSIONS: Further studies are required to determine whether calcitonin treatment will control this grossly deforming disease until the time when the physiological changes that occur at puberty rectify the pathology. It is not recommended that biochemical markers of bone resorption are used in isolation to monitor the activity of cherubism in individuals because the results are based on a small number of children and because of reports of marked interindividual variation in the levels of these markers, particularly in children.
Schwannoma with features mimicking neuroblastoma: report of two cases with immunohistochemical and ultrastructural findings.
Authors: Bhatnagar S , Banerjee S S , Mene A R , Prescott R J , Eyden B P
Published: January 2009

OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET). METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by tinctorial stains and immunohistochemistry, and the tissue retrieved from formalin was examined by electronmicroscopy in one case. RESULTS: The tumours were small and subcutaneous. Both showed features of benign schwannoma; one had a multinodular plexiform pattern. In addition, rosette-like structures consisting of collagenous cores surrounded by small round cells or slightly larger epithelioid cells were present. Tumour cells were positive for S100 protein, Leu7, and in one case GFAP, but were negative for neurofilament protein, synaptophysin, and MIC2. Type IV collagen surrounded individual cells. Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes) and failed to show features of neuroblastoma (neuroendocrine granules). CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only and eliminated neuroblastoma/PNET. These uncommon variants should be recognised by practising histopathologists to avoid erroneous diagnoses and inappropriate treatment.
How to improve low lymph node recovery rates from axillary clearance specimens of breast cancer. A short-term audit.
Authors: Cserni G
Published: January 2009

AIM: To implement an audit scheme to increase the lymph node yield from axillary clearance specimens. METHODS: Two pathologists cut up each specimen after weighing it. The number of nodes and the dimensions of the largest and smallest nodes were recorded, together with the number of non-lymph node structures recovered. Fifty consecutive audited cases were compared with 50 consecutive cases assessed before the audit process. RESULTS: It proved possible to increase the median number of lymph nodes from 10 to 22. There was an obvious learning period, during which the number of nodes recovered during the second pathologist's cut-up gradually decreased, while the total number remained relatively constant. The increase in lymph node yield resulted from the recovery of smaller nodes. The identification of lymph nodes also improved, and fewer non-lymph node structures were recovered by the end of the study. CONCLUSIONS: Such an audit scheme can be recommended for all institutions where the lymph node yield of axillary clearance specimens seems suboptimal. The relevance of recovering more nodes remains to be determined; from this small series, it seems to have no clinical impact.
The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study.
Authors: Retera J M , Leers M P , Sulzer M A , Theunissen P H
Published: January 2009

AIMS: To investigate the expression of beta-catenin in non-small-cell lung cancer (NSCLC) and its clinical significance. METHODS: 101 patients were surgically treated for NSCLC by lobectomy or pneumectomy with systematic lymph node dissection. Follow up was available in all patients, ranging from 24 to 110 months. Immunostaining of tissue sections from primary tumours and (when present) their lymph node metastases was performed and evaluated using a monoclonal antibody against beta-catenin. Correlations were investigated between beta-catenin immunostaining in primary tumours and E-cadherin immunostaining (data available from a previous study), lymph node stage, and survival. RESULTS: There were significant correlations between scores for beta-catenin immunostaining and E-cadherin immunostaining in primary tumours (p = 0.007), and between the beta-catenin immunostaining score in primary tumours and in their lymph node metastases (p = 0.006). An inverse correlation was found between the beta-catenin immunostaining score in primary tumours and lymph node stage N0, N1, or N2 (p = 0.03). According to the Kaplan-Meier survival estimate, the level of beta-catenin expression in primary tumours was a statistically significant prognostic factor (p = 0.01). CONCLUSIONS: Reduced beta-catenin expression in surgically treated NSCLC is clearly associated with lymph node metastasis and an infavourable prognosis. The existence of a functional relation between E-cadherin and beta-catenin is supported by the results of this clinicopathological study.
Quantitative assessment of gastric atrophy using the syntactic structure analysis.
Authors: Zaitoun A M , al Mardini H , Record C O
Published: January 2009

AIM: To assess the topographical relation between gastric glands, using the minimum spanning tree (MST), to derive both a model of neighbourhood and quantitative representation of the tissue's architecture, to assess the characteristic features of gastric atrophy, and to assess the grades of gastric atrophy. METHODS: Haematoxylin and eosin stained sections from corporal and antral biopsy specimens (n = 139) from normal patients and from patients with nonatrophic gastritis and atrophic gastritis of grades 1, 2, and 3 (Sydney system) were assessed by image analysis system (Prodit 5.2) and 11 syntactic structure features were derived. These included both line and connectivity features. RESULTS: Syntactic structure analysis was correlated with the semiquantitative grading system of gastric atrophy. The study showed significant reductions in the number of points and the length of MST in both body and antrum. The standard deviation of the length of MST was significantly increased in all grades of atrophy. The connectivity to two glands was the highest and most affected by the increased grade of atrophy. The reciprocal values of the Wiener, Randic, and Balaban indices showed significant changes in the volume of gland, abnormality in the shape of glands, and changes in irregularity and branching of the glands in both types of gastric mucosa. There was a complete separation in the MST, connectivity, and index values between low grade and high grade gastric atrophy. CONCLUSIONS: (1) Gastric atrophy was characterised by loss of the gland, variation in the volume, reduction in the neighbourhood, irregularity in spacing, and abnormality in the shape of the glands. (2) Syntactic structure analysis significantly differentiated minor changes in gastric gland (low grade atrophy) from high grade atrophy of clinical significance. (3) Syntactic structure analysis is a simple, fast, and highly reproducible technique and appears a promising method for quantitative assessment of atrophy.
Progression from colorectal adenoma to carcinoma is associated with non-random chromosomal gains as detected by comparative genomic hybridisation.
Authors: Meijer G A , Hermsen M A , Baak J P , van Diest P J , Meuwissen S G , Beliën J A , Hoovers J M , Joenje H , Snijders P J , Walboomers J M
Published: January 2009

AIMS: Chromosomal gains and losses were surveyed by comparative genomic hybridisation (CGH) in a series of colorectal adenomas and carcinomas, in search of high risk genomic changes involved in colorectal carcinogenesis. METHODS: Nine colorectal adenomas and 14 carcinomas were analysed by CGH, and DNA ploidy was assessed with both flow and image cytometry. RESULTS: In the nine adenomas analysed, an average of 6.6 (range 1 to 11) chromosomal aberrations were identified. In the 14 carcinomas an average of 11.9 (range 5 to 17) events were found per tumour. In the adenomas the number of gains and losses was in balance (3.6 v 3.0) while in carcinomas gains occurred more often than losses (8.2 v 3.7). Frequent gains involved 13q, 7p, 8q, and 20q, whereas losses most often occurred at 18q, 4q, and 8p. Gains of 13q, 8q, and 20q, and loss of 18q occurred more often in carcinomas than in adenomas (p = 0.005, p = 0.05, p = 0.05, and p = 0.02, respectively). Aneuploid tumours showed more gains than losses (mean 9.3 v 4.9, p = 0.02), in contrast to diploid tumours where gains and losses were nearly balanced (mean 3.1 v 4.1, p = 0.5). CONCLUSIONS: The most striking difference between chromosomal aberrations in colorectal adenomas and carcinomas, as detected by CGH, is an increased number of chromosomal gains that show a nonrandom distribution. Gains of 13q and also of 20q and 8q seem especially to be involved in the progression of adenomas to carcinomas, possibly owing to low level overexpression of oncogenes at these loci.
Atypical mycobacterial lymphadenitis in childhood--a clinicopathological study of 17 cases.
Authors: Evans M J , Smith N M , Thornton C M , Youngson G G , Gray E S
Published: January 2009

AIMS: To assess the clinical and pathological features of atypical mycobacterial lymphadenitis in childhood to define the salient clinical and histological features. METHODS: 17 cases were included on the basis of positive culture or demonstration of bacilli of appropriate morphology and staining characteristics. RESULTS: The mean age at diagnosis was 4.86 years. All children were systemically well, with clear chest x rays. Unilateral cervical lymphadenopathy was the commonest mode of presentation. Differential Mantoux testing played no part in diagnosis. Clinical diagnosis improved with awareness. Treatment varied with surgeons opting for excision and paediatricians adding six months antituberculous chemotherapy. Acid- and alcohol-fast bacilli were identified in nine cases. Bacterial cultures were conducted in 16 cases and were positive for atypical or nontuberculous mycobacteria in 14, the main organism being M avium-intracellulare complex (11 cases). Histologically, 12 cases had bright eosinophilic serpiginous necrosis with nuclear debris scattered throughout the necrotic foci. Langhans type giant cells featured in the majority of cases but infiltration by plasma cells and neutrophils was not consistent. CONCLUSIONS: Atypical mycobacterial lymphadenitis of childhood represents a rare but significant disease with characteristic clinical and histological features.
Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case report.
Authors: Lau G , Tan S Y , Chiang G , Poh W T
Published: January 2009

An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented as a pituitary tumour in a young adult Chinese female, who subsequently died after having undergone trans-sphenoidal resection. Metastatic cancers of the pituitary are uncommon even in necropsy series and rarely give rise to clinical symptoms. This case draws attention to the fact that, although uncommon, pituitary metastases have been noted with increasing frequency and their distinction from primary pituitary tumours is often difficult. A metastatic pituitary tumour may be the initial presentation of an unknown primary malignancy, wherein the metastatic deposits may also be limited to the pituitary gland. Clinicians and pathologists alike should consider a metastatic lesion in the differential diagnosis of a non-functioning pituitary tumour.
Breast carcinoma developing in patients on hormone replacement therapy: a histological and immunohistological study.
Authors: O'Connor I F , Shembekar M V , Shousha S
Published: January 2009

AIM: To study the histopathological features of breast carcinoma developing in postmenopausal patients on hormone replacement therapy (HRT). METHODS: The sample comprised 60 patients with invasive breast carcinoma including 31 who had received HRT at or shortly before presentation, and 29 who had not. Details concerning their tumour size, histological type and grade, lymph node status, and oestrogen and progesterone receptor status were compared. Immunoperoxidase staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of all 60 patients. The results were then statistically analysed. RESULTS: Tumours detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p = 0.0156) and of a lower histological grade (p = 0.0414) than those detected in non-HRT patients. The incidence of invasive lobular carcinoma was slightly higher in HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2 positive (compared with 79% in the control group), 29% were p53 positive (45% in the control), and 48% were E-cadherin positive (72% in the control group). Although the differences were not statistically significant there was a trend towards higher incidence of p53 negative and E-cadherin negative tumours in HRT patients. CONCLUSIONS: Breast carcinomas detected in patients on HRT have a significantly higher incidence of two favourable prognostic features (small size and a low histological grade). They also show a trend, statistically not significant, of being p53 negative and E-cadherin negative; this may be related to the slightly higher incidence of invasive lobular tumours in these patients.
Application of the principle of marginal analysis to sampling practice using prostatic chippings as a model.
Authors: Langlois N E , Donaldson C
Published: January 2009

AIMS: To demonstrate an application of health economic principles in histopathology by using the sampling of transurethral resections of prostate specimens. By demonstrating how marginal costs are calculated the aim is to illustrate that the potential opportunity cost of sampling entire specimens is much greater than would be anticipated by taking average cost, or the cost of producing a histological section alone. METHOD: A mathematical model is used with data obtained from the Aberdeen pathology department files and published estimates of the likely percentage of cancerous chippings in each specimen. RESULTS: The average cost of each cancer detected remains low, between 47 Pounds and 151 Pounds, in all the scenarios examined. However, the marginal costs can become high, exceeding 10,000 Pounds in larger specimens, if all the chippings are processed. CONCLUSIONS: This study demonstrates that there are potential opportunity cost penalties to histopathological services associated with sampling strategies. Although the results are derived from a hypothetical mathematical model using local data that applies only to histopathology, the method could be widely applied. The principles of marginal analysis should be performed by multidisciplinary teams and include outcomes as well as a broader range of costs, including those that arise subsequent to diagnosis.
Diagnosis of early acute renal allograft rejection by evaluation of multiple histological features using a Bayesian belief network.
Authors: Kazi J I , Furness P N , Nicholson M
Published: January 2009

BACKGROUND AND AIMS: The development of the Banff classification of renal transplant pathology has allowed the standardisation of approaches to transplant biopsy histology and reduced interobserver and interdepartmental variation. The usefulness of the Banff classification in the diagnosis of acute rejection has previously been tested by sending sections from 21 "difficult" biopsies to almost all of the renal transplant pathologists in the UK. Although the Banff classification improved reproducibility, the accuracy of diagnosis of early acute rejection was unchanged from the "conventional" approach. Perhaps this is because in making a diagnosis of acute rejection, the Banff classification uses only two features: tubulitis and intimal arteritis. To include more features on a systematic basis would be laborious for a human observer. Therefore, a Bayesian belief network was developed for this task. METHODS: The network was initialised with observations from 110 transplant biopsies. Its performance was then tested on 21 biopsies that had been seen by 37 different renal transplant pathologists in an earlier study. These biopsies had been selected to represent histologically difficult problems but, in retrospect, they all had clear diagnoses of rejection or non-rejection on clinical grounds. RESULTS: Using the Bayesian belief network, a relatively inexperienced pathologist made 19 of 21 correct diagnoses, better than had been achieved by any of the pathologists who had seen the same sections previously (17 of 21), and considerably better than the average proportion of correct diagnoses provided by all 37 renal transplant pathologists (65%). Application of the system by a second pathologist produced a tendency to overdiagnosis of acute rejection, illustrating the consequences of interobserver variation. CONCLUSIONS: In the diagnosis of acute rejection, further useful information can be extracted from features that are currently not considered in the Banff classification. Integration of data by a computer can give a more reliable diagnosis of early acute rejection, but routine application will require the development of a more sophisticated system that can also accommodate clinical data, perhaps one that can continue to "learn" as more data are entered.
Endometrial leucocytes: expression of steroid hormone receptors.
Authors: Stewart J A , Bulmer J N , Murdoch A P
Published: January 2009

BACKGROUND: Stromal leucocyte populations in human endometrium comprise T cells, macrophages, and phenotypically unusual endometrial granulated lymphocytes. Their proportions vary during the menstrual cycle and, in particular, endometrial granulated lymphocytes increase in number in the late secretory phase. The stimulus responsible for these cyclical changes is unknown but it is likely that the steroid hormones oestrogen and progesterone play a role. AIMS: To define further the expression of steroid hormone receptors by leucocytes in non-pregnant and pregnant human endometrium. METHODS: Frozen and paraffin wax embedded sections of endometrium from non-pregnant women and early pregnancy decidua were labelled using single and double immunohistochemical techniques with monoclonal antibodies directed against oestrogen and progesterone receptors and various leucocyte subpopulations. RESULTS: Despite the prominence of CD56 positive endometrial granulated lymphocytes in late secretory phase endometrium and early pregnancy decidua, double immunohistochemical labelling showed no evidence of expression of either progesterone or oestrogen receptors by these cells or other endometrial leucocyte populations. CONCLUSIONS: Rather than acting directly, steroid hormones are likely to influence endometrial leucocyte populations indirectly via products of endometrial stromal or epithelial cells that express steroid hormone receptors.
Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long-term, low dose azithromycin.
Authors: Dionisio D , Orsi A , Sterrantino G , Meli M , Di Lollo S , Ibba Manneschi L , Trotta M , Pozzi M , Sani L , Leoncini F
Published: January 2009

AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.
Postmortem examination of the lungs: a preservation technique for opening the bronchi and pulmonary arteries individually without transection problems.
Authors: McCulloch T A , Rutty G N
Published: January 2009

The classic methods of examining both the pulmonary arteries and bronchi postmortem partly destroy the anatomy of one of these systems. A technique is described whereby the bronchi and pulmonary arteries are dissected and preserved. The principal difference of this technique is that most of the upper lobe vasculature is opened from the hilum. The exception to this is the lingula, which because it is the embryological homologue of the right middle lobe should be treated in the same way--that is, with the vessels opened from the pleural side and the bronchi from the hilum. One general practical point is that there is a great variation in the number of pulmonary arterial branches in each lobe, particularly in the upper lobes, and especially in the left upper lobe. Furthermore, there is some variation in the local anatomic relations of the vessels and bronchi and on occasion the technique will not work as described and will require some modification. However, most of the time this technique should allow the pathologist to preserve the anatomy of the bronchial tree and pulmonary arteries for better demonstration and photographic purposes when the need arises.
Fine needle aspiration cytology in the investigation on non-Hodgkin's lymphoma.
Authors: Jeffers M D , Milton J , Herriot R , McKean M
Published: January 2009

AIMS: To assess the value of flow cytometry (FCM) in the diagnosis and classification of reactive lymphoid hyperplasia and malignant lymphoma by fine needle aspiration (FNA) cytology. METHODS: Forty six fine needle aspirates of lymphoproliferative disorders were examined by FCM as well as routine cytological assessment. An immunoglobulin light chain ratio (LCR) was calculated for clonality analysis. Additional immunophenotyping was performed in 15 cases. RESULTS: All 25 cases of reactive lymphoid hyperplasia were polyclonal by FCM (LCR < 2/1); 17 of 20 cases of B cell non-Hodgkin's lymphoma were monoclonal (LCR > 3/1). Analysis of cells based on size facilitated detection of small populations of clonal neoplastic cells. Analysis of CD5, CD10, and CD23 expression by FCM facilitated subclassification of mantle cell lymphoma, small lymphocytic lymphoma, and some lymphomas of follicle centre cell origin. One case of T cell non-Hodgkin's lymphoma was correctly classified by FCM. CONCLUSIONS: FNA cytology is a reliable method for investigation of lymphoproliferative disorders. Although excision biopsy and histopathological examination remain the gold standard for primary diagnosis and classification of non-Hodgkin's lymphoma, FNA cytology with clonality analysis and immunophenotyping by FCM is useful for distinguishing reactive from neoplastic lymphoid populations, and can facilitate lymphoma classification.
Fine needle aspiration cytology diagnosis of malignant lymphoma and reactive lymphoid hyperplasia.
Authors: Stewart C J , Duncan J A , Farquharson M , Richmond J
Published: January 2009

AIMS: To assess the diagnostic accuracy of lymph node fine needle aspiration (FNA) cytology to distinguish reactive lymphoid hyperplasia from malignant lymphoma, and to evaluate the contribution of ancillary techniques applied to cytological material. METHODS: Two hundred and seventy seven consecutive lymph node FNA specimens reported to be consistent with reactive lymphoid hyperplasia (n = 213) or suggestive/diagnostic of malignant lymphoma (n = 64) were reviewed. Follow up data were obtained by case record review or by histological correlation. The value of immunocytochemistry, in situ hybridisation for immunoglobulin light chain mRNA, and polymerase chain reaction (PCR) towards the final clinicopathological diagnosis was assessed in 92, 61, and 45 cases, respectively. RESULTS: Sixty one of 67 lymphomas and 207 of 209 reactive lymph nodes were accurately diagnosed by FNA cytology. There were six false negative aspirates including three cases of follicular lymphoma, two cases of Hodgkin's disease, and one chronic lymphocytic leukaemia. Two FNA specimens considered suspicious of lymphoma proved reactive on histology or clinical follow up. One metastatic small cell carcinoma was wrongly diagnosed as lymphoma. Ancillary studies contributed to the correct diagnosis in most cases although occasional misleading results were obtained, particularly with PCR. CONCLUSIONS: FNA cytology accurately distinguished reactive lymphoid hyperplasia from malignant lymphoma in 97% of cases. However, occasional wrong diagnoses occurred owing to sampling error or misinterpretation. Ancillary studies can be applied to cytological samples and contribute to the diagnosis in most cases.
Lymphocytic gastritis and coeliac disease: evidence of a positive association.
Authors: Feeley K M , Heneghan M A , Stevens F M , McCarthy C F
Published: January 2009

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.
CagA seropositivity associated with development of gastric cancer in a Japanese population.
Authors: Shimoyama T , Fukuda S , Tanaka M , Mikami T , Munakata A , Crabtree J E
Published: January 2009

BACKGROUND/AIMS: Infection with Helicobacter pylori strains possessing the cagA gene is associated with increased risk of gastric cancer of the intestinal type. The aims of this study were to investigate whether CagA seropositivity is associated with increasing risk of gastric cancer in a Japanese population that has a much higher incidence of gastric cancer than western populations. METHODS: Eighty one gastric cancer patients and 81 sex and age matched endoscopically evaluated controls were studied. Histologically, 62 cancers were of the intestinal type and 76 were early gastric cancer. Serum CagA IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA) using purified recombinant CagA protein as antigen. Polymerase chain reaction (PCR) analysis for cagA in H pylori isolates (n = 80) showed that the CagA ELISA had a sensitivity of 83.3% (controls) and 72.5% (cancers). RESULTS: CagA seropositivity was 60% (49 of 81) in cancer patients and 44% (36 of 81) in controls. The odds ratio for the risk of cancer if CagA seropositive was 1.93 (95% confidence interval (CI) 1.01 to 3.68; p < 0.05). In the 57 H pylori positive cancer patients and their matched H pylori positive controls, the odds ratio for the risk of cancer if CagA seropositive was 2.2 (95% CI 1.04 to 4.65; p < 0.05). CONCLUSIONS: These results suggest that CagA seropositivity is associated with increased risk of gastric cancer in Japanese populations.
Comparison of in situ hybridisation and polymerase chain reaction in the diagnosis of B cell lymphoma.
Authors: McNicol A M , Farquharson M A , Lee F D , Foulis A K
Published: January 2009

AIM: To compare the sensitivity of the detection of immunoglobulin light chain messenger RNA (mRNA) restriction by in situ hybridisation (ISH) and clonal immunoglobulin heavy chain gene rearrangements by polymerase chain reaction (PCR) in the diagnosis of B cell lymphoma. METHODS: Analyses were applied to formalin fixed, paraffin wax embedded, routine diagnostic specimens from cases with a provisional diagnosis of reactive lymph node (n = 23), B cell lymphoma (n = 21), and T cell lymphoma (n = 4). Nonisotopic ISH for kappa and lambda immunoglobulin light chain mRNA was performed using both fluorescein and digoxigenin labelled oligodeoxynucleotide probe cocktails. PCR was carried out on DNA extracted from sections using primers to framework 3 (Fr3) of the V segments and to conserved sequences from the J regions of the immunoglobulin heavy chain genes. RESULTS: All reactive lymph nodes showed a polyclonal pattern of light chain mRNA by ISH, although one showed an excess of kappa positive cells. Nineteen of 21 (90%) cases of B cell lymphoma showed light chain restriction, and a further case showed a vast excess of kappa positive cells. By PCR, 20 of 23 reactive nodes (87%) showed a polyclonal pattern. In 13 of 21 B cell lymphomas (62%) a clonal band was detected. CONCLUSION: In the diagnosis of B cell lymphoma in routinely processed diagnostic material ISH for light chain mRNA was more sensitive (90%) than PCR for heavy chain gene rearrangement using Fr3 and J region primers (62%).
Histological identification of carcinoma in 21 gauge needle tracks after fine needle aspiration biopsy of head and neck carcinoma.
Authors: Mighell A J , High A S
Published: January 2009

Six cancer resection specimens were thoroughly sectioned and microscopically examined at areas known to have been around 21 gauge fine needle aspiration (FNA) biopsy sites, in an attempt to identify needle tracks. All cases had an interval of not less than 10 days between FNA biopsy and surgery. Foci of tumour were identified histologically in needle tracks from two patients with carcinoma. This is the first instance, outside of experimental animal models, of histologically confirmed, viable tumour spread in FNA biopsy tracks. Although this complication is not common and is of unknown clinical significance, it is one that all clinicians who undertake FNA of malignant neoplasms should be aware of.
Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis.
Authors: Faller G , Steininger H , Appelmelk B , Kirchner T
Published: January 2009

Autoantibodies against gastric epithelial cells are detectable in up to 50% of patients with chronic, active Helicobacter pylori gastritis. Presence of autoantibodies against canalicular structures within human parietal cells (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has been suggested, that molecular mimicry between H pylori and the host on the level of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This study aimed at analysing whether antigastric antibodies can be absorbed to Lewis X or Y positive H pylori strains. Sera from 14 H pylori infected patients with anticanalicular autoantibodies were effectively absorbed to H pylori. Immunohistochemical studies of the absorbed sera showed no decrease of antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry lead to the formation of antigastric autoantibodies, and epitopes other than Lewis antigens are the autoimmune targets.