bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Disease Medication Use in Managed Care and Indemnity Insurance Plans
Authors: Stafford Randall S. , Davidson Stephen M. , Davidson Harriet , Miracle‐McMahill Heidi , Crawford Sybil L. , Blumenthal David
Published: December 2004

Objective. To evaluate the impact of managed care on the use of chronic disease medications.

Data Source. Claims data from 1997 from two indemnity and three independent practice association (IPA) model managed care insurance plans.

Research Design. Cross‐sectional analysis of claims data.

Data Collection. Adult patients with diabetes mellitus (DM, n=26,444), congestive heart failure (CHF, n=7,978), and asthma (n=9,850) were identified by ICD‐9 codes. Chronic disease medication use was defined through pharmacy claims for patients receiving one or more prescriptions for drugs used in treating these conditions. Using multiple logistic regression we adjusted for patient case mix and the number of primary care visits.

Principal Findings. With few exceptions, managed care patients were more likely to use chronic disease medications than indemnity patients. In DM, managed care patients were more likely to use sulfonylureas (43 percent versus 39 percent for indemnity), metformin (26 percent versus 18 percent), and troglitazone (8.8 percent versus 6.4 percent), but not insulin. For CHF patients, managed care patients were more likely to use loop diuretics (45 percent versus 41 percent), ACE inhibitors or angiotensin receptor blockers (50 percent versus 41 percent), and beta‐blockers (23 percent versus 16 percent), but we found no differences in digoxin use. In asthma, managed care patients were more likely to use inhaled corticosteroids (34 percent versus 30 percent), systemic corticosteroids (18 percent versus 16 percent), short‐acting beta‐agonists (42 percent versus 33 percent), long‐acting beta‐agonists (9.9 percent versus 8.6 percent), and leukotriene modifiers (5.4 percent versus 4.1 percent), but not cromolyn or methylxanthines. Statistically significant differences remained after multivariate analysis that controlled for age, gender, and severity.

Conclusions. Chronic disease patients in these managed care plans are more likely to receive both inexpensive and expensive medications. Exceptions included older medications partly supplanted by newer therapies. Differences may be explained by the fact that patients in indemnity plans face higher out‐of‐pocket costs and managed care plans promote more aggressive medication use. The relatively low likelihood of condition‐specific medications in both plan types is a matter of concern, however.
Patterns and Correlates of Contacting Clergy for Mental Disorders in the United States
Authors: Wang Philip S. , Berglund Patricia A. , Kessler Ronald C.
Published: December 2004

Objective. To present nationally representative data on the part played by clergy in providing treatment to people with mental disorders in the United States.

Data Sources. The National Comorbidity Survey (NCS), a nationally representative general population survey of 8,098 respondents ages 15–54.

Study Design. Cross‐sectional survey

Data Collection. A modified version of the Composite International Diagnostic Interview was used to assess DSM‐III‐R mental disorders. Reports were obtained on age of onset of disorders, age of first seeking treatment, and treatment in the 12 months before interview with each of six types of professionals (clergy, general medical physicians, psychiatrists, other mental health specialists, human services providers, and alternative treatment providers).

Principal Findings. One‐quarter of those who ever sought treatment for mental disorders did so from a clergy member. Although there has been a decline in this proportion between the 1950s (31.3 percent) and the early 1990s (23.5 percent), the clergy continue to be contacted by higher proportions than psychiatrists (16.7 percent) or general medical doctors (16.7 percent). Nearly one‐quarter of those seeking help from clergy in a given year have the most seriously impairing mental disorders. The majority of these people are seen exclusively by the clergy, and not by a physician or mental health professional.

Conclusions. The clergy continue to play a crucial role in the U.S. mental health care delivery system. However, interventions appear to be needed to ensure that clergy members recognize the presence and severity of disorders, deliver therapies of sufficient intensity and quality, and collaborate appropriately with health care professionals.
Developing and Testing a Model to Predict Outcomes of Organizational Change
Authors: Gustafson David H. , Sainfort François , Eichler Mary , Adams Laura , Bisognano Maureen , Steudel Harold
Published: December 2004

Objective. To test the effectiveness of a Bayesian model employing subjective probability estimates for predicting success and failure of health care improvement projects.

Data Sources. Experts' subjective assessment data for model development and independent retrospective data on 221 healthcare improvement projects in the United States, Canada, and the Netherlands collected between 1996 and 2000 for validation.

Methods. A panel of theoretical and practical experts and literature in organizational change were used to identify factors predicting the outcome of improvement efforts. A Bayesian model was developed to estimate probability of successful change using subjective estimates of likelihood ratios and prior odds elicited from the panel of experts. A subsequent retrospective empirical analysis of change efforts in 198 health care organizations was performed to validate the model. Logistic regression and ROC analysis were used to evaluate the model's performance using three alternative definitions of success.

Data Collection. For the model development, experts' subjective assessments were elicited using an integrative group process. For the validation study, a staff person intimately involved in each improvement project responded to a written survey asking questions about model factors and project outcomes.

Results. Logistic regression chi‐square statistics and areas under the ROC curve demonstrated a high level of model performance in predicting success. Chi‐square statistics were significant at the 0.001 level and areas under the ROC curve were greater than 0.84.

Conclusions. A subjective Bayesian model was effective in predicting the outcome of actual improvement projects. Additional prospective evaluations as well as testing the impact of this model as an intervention are warranted.
The Role of Community Involvement in Implementing Living Wage Ordinances*
Authors: LUCE STEPHANIE
Published: December 2004

Although the living wage movement has been instrumental in the passage of almost 120 ordinances in its ten‐year history, little attention has been paid to the implementation of the laws. This article analyzes the factors that can affect the success of living wage implementation. The results suggest that implementation is weaker when left solely to city administrators and more expansive when living wage advocates participate in the process. For example, involvement of advocates is more likely to lead to workplace monitoring, stricter procedures for employers to obtain a waiver, and evaluation of outcomes.
Living Wage Policies at the San Francisco Airport: Impacts on Workers and Businesses
Authors: REICH MICHAEL , HALL PETER , JACOBS KEN
Published: December 2004

This paper evaluates the costs, benefits and related impacts of living wage policies implemented at the San Francisco Airport (SFO). Unlike other living wage ordinances, the policies at SFO cover a large proportion of the low‐wage labor force in a distinct labor market. The authors find that about 73 percent of the ground‐based non‐managerial workers at SFO received substantial wage increases as a direct or indirect result of the policies; the proportion of these workers earning under $10 per hour fell from 55 percent to 5 percent, significantly reducing earnings inequality. Other benefits to workers included enhanced health benefits and an arrest of declines in quality of life indices. The costs of the policies to employers amounted to an average of 0.7 percent of fare revenue, or $1.42 per airline passenger. We observe a series of dynamic adjustments that reduced those costs, including dramatically reduced turnover, improved worker morale and greater work effort. We find some limited evidence of worker‐worker substitution, but no evidence of employment decline.
Living Wages and Retention of Homecare Workers in San Francisco
Authors: HOWES CANDACE
Published: December 2004

This study records the impact on workforce retention of the nearly doubling of wages for homecare workers in San Francisco County over a 52‐month period. Using descriptive statistics and logistic regression analysis the author finds that the annual retention rate of new providers rose from 39 percent to 74 percent following significant wage and benefit increases and that a $1 increase in the wage rate from $8 an hour—the national average wage for homecare—would increase retention by 17 percentage points. The author also shows that adding health insurance increases the retention rate by 21 percentage points.
When Do Living Wages Bite?
Authors: ADAMS SCOTT , NEUMARK DAVID
Published: December 2004

Many features of living wage laws may influence the strength of their effects on wages and employment of low‐skill individuals. Echoing past research, business assistance living wage laws generate stronger wage increases and employment reductions than contractor‐only laws. But broader enforcement or implementation and geographic concentration of living wage laws also appear to strengthen their effects. Finally, geographic concentration may be more significant than the distinction between business assistance and contractor‐only living wage laws.
Interdigitating dendritic cell sarcoma: a report of four paediatric cases and review of the literature
Authors: Pillay K , Solomon R , Daubenton J D , Sinclair‐Smith C C
Published: December 2004

Aims:  To report a series of four paediatric cases of interdigitating dendritic cell sarcoma (IDCS) and add to the known extranodal sites of occurrence for this tumour. Neoplasms derived from interdigitating dendritic cells are rare, with only 33 cases being reported in the literature (Medline search). These tumours usually occur in lymph nodes in the adult population.

Methods and results:  The patients were a 10‐year‐old girl with a large soft tissue mass bulging into the left chest, a 12‐year‐old girl with a right paraspinal mass, a 21‐month‐old boy with generalized lymphadenopathy and hepatosplenomegaly and a 6‐year‐old girl with a large bladder mass. Paraffin blocks and haematoxylin and eosin slides were available in all cases. In addition, immunohistochemistry and electron microscopy were performed. A diagnosis of IDCS was made in all cases.

Conclusion:  The diagnosis of IDCS can rarely be entertained on clinical information alone. Microscopically, there is a wide spectrum of features. Thus, immunohistochemistry and electron microscopy are crucial in making the diagnosis. The differential diagnosis includes inflammatory pseudotumour, follicular dendritic cell sarcoma, true histiocytic lymphoma, malignant Langerhans cell histiocytosis, anaplastic large‐cell lymphoma, melanoma, and a range of sarcomas. IDCS displays aggressive behaviour and approximately half of the patients die of the disease.
CD1d‐restricted T‐cell subsets and dendritic cell function in autoimmunity
Authors: Bollyky Paul L , Wilson S Brian
Published: December 2004

CD1‐restricted T cells have been shown to play a critical role in host defence, tumour surveillance, and maintenance of tolerance. However, immunologic outcomes resulting from activation of CD1d‐restricted T cells can be either beneficial or deleterious. A major mechanism by which CD1d‐restricted T cells are thought to exert immunoregulatory control is via effects on dendritic cell (DC) differentiation and migration. Important functional subsets of CD1d‐restricted T cells are also known to exist and the potential implications for preferential subset activations are discussed.
Parallels and distinctions between T and NKT cell development in the thymus
Authors: Berzins Stuart P , Uldrich Adam P , Pellicci Daniel G , McNab Finlay , Hayakawa Yoshihiro , Smyth Mark J , Godfrey Dale I
Published: December 2004

NKT cells are emerging as an extremely influential regulatory subset of T lymphocytes that are functionally and developmentally distinct from their mainstream counterparts. Like other T cells, NKT cells are thymus‐dependent but their apparently unique pathway of differentiation is poorly characterized. Given the strong association between NKT cell deficiency and increased incidences of autoimmunity and cancer it is imperative that the mechanisms by which NKT cells are generated becomes better understood. This review examines what is known about NKT cell development in the thymus and highlights elements of the pathway that differ significantly from mainstream T‐cell development. It is here that NKT cell‐specific disorders may originate and may best be addressed.
NKT cells and viral immunity
Authors: van Dommelen Serani LH , Degli‐Esposti Mariapia A
Published: December 2004

Over the past 10 years a new population of cells has been the focus of much attention. The functions of these unique lymphocytes, characterized by the concomitant expression of T‐ and NK‐cell markers and thus termed NKT cells, have been implicated in many diverse aspects of immunity, including regulation of autoimmune disorders, control of tumour growth and spread, and defence against a number of pathogens. Although much debate still remains as to the natural role of NKT cells, it is clear that these cells have the capacity, either constitutively or postactivation, to promote an amazing array of immunoregulatory responses. The involvement of NKT cells in viral immune‐surveillance and their ability to induce protection against pathogens once activated make them an attractive clinical target.
Genetic control of NKT cell numbers
Authors: Jordan Margaret A , Fletcher Julie , Baxter Alan G
Published: December 2004

NKT cells play a critical role in shaping the character and strength of a wide range of immune responses, including those against pathogens, tumours, allografts and autologous tissues. Because numbers of NKT cells affect clinical outcomes in a wide range of disease models, and this characteristic demonstrates allelic variation, the mapping of the locations and identification of the coding sequences of these genes has become a matter of significant importance. Here, we review the results to date that examine the effects of targeted deletion of a number of candidate genes, as well as the congenic and genetic linkage analyses that have attempted to localize allelic loci that affect NKT cell numbers. Although a number of candidate genes have been examined, there is no evidence that any of these contribute to variation in NKT cell numbers in natural populations. Two of the most important genetic regions controlling NKT cell numbers are Nkt1 on chromosome 1, which may contribute to lupus susceptibility, and Nkt2 on chromosome 2, which appears to contribute to diabetes susceptibility. Of great interest is a third locus on chromosome 18, identified in a novel congenic line, which can confer an absolute deficiency in this important immunoregulatory lymphocyte population.
Clinicopathological significance of hypoxia‐inducible factor‐1α expression in human pancreatic carcinoma
Authors: Kitada T , Seki S , Sakaguchi H , Sawada T , Hirakawa K , Wakasa K
Published: December 2004

Aims:  The transcription factor hypoxia‐inducible factor‐1α (HIF‐1α) plays a key role in the cellular adaptation to hypoxia and the activation of several genes that have been implicated in tumour growth. The aim of this study was to investigate the clinicopathological significance of HIF‐1α expression in pancreatic carcinoma.

Methods and results:  We investigated HIF‐1α expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF‐1α expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over‐expression of HIF‐1α was frequently (29 of 49 cases, 59.2%) detected in pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%), whereas HIF‐1α expression was almost absent in non‐cancerous pancreatic tissues. HIF‐1α expression was significantly associated with tumour size (P = 0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II versus stage IV, P = 0.027). Moreover, HIF‐1α expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo‐angiogenesis (P = 0.038), but not with apoptosis.

Conclusions:  HIF‐1α may play a critical role in the progression of pancreatic carcinoma.
The prognostic relevance of estimates of proliferative activity in early breast cancer
Authors: Offersen B V , Sørensen F B , Knoop A , Overgaard J
Published: December 2004

Aims:  Immunohistochemical estimates of cell proliferation evaluated with MIB‐1 antibody have been suggested as prognostic indicators in different types of carcinoma. This study investigates whether MIB‐1 scores add additional prognostic impact when evaluated together with classical clinicopathological parameters at diagnosis in early breast cancer patients.

Materials and methods:  Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB‐1 and evaluated under the microscope using systematic random sampling accomplished by the CAST‐grid system.

Results:  The systematic random sampling technique resulted in MIB‐1 estimates with very high interobserver and intraobserver reproducibilities (P < 0.0001). Median MIB‐1 was 16% (range 0–83%). Patients were stratified by MIB‐1 in tertiles, and increasing MIB‐1 was significantly associated with poor overall and disease‐specific survival in node‐positive patients, but not in node‐negative patients. High MIB‐1 was significantly related to large tumour size, and strongly associated with high grade, high mitotic score, negative oestrogen receptor status and young age. In multivariate analysis, both with and without malignancy grade and number of mitoses included in the analysis, MIB‐1 estimates showed no independent prognostic impact.

Conclusions:  High MIB‐1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer.
Variability in immunophenotype in diffuse large B‐cell lymphoma and its clinical relevance
Authors: De Leval L , Harris N L
Published: December 2004

Diffuse large B‐cell lymphoma (DLBCL), the single largest category of lymphoma, is a clinically and biologically heterogeneous disease entity. Clinically, patients differ in their mode of presentation and respond variably to therapy. A combination of clinical parameters can be used to predict the patient's response to therapy and survival. The pathological variability of DLBCL is expressed in morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous markers detectable by immunohistochemistry and linked to different aspects of tumour biology have been studied in DLBCL, including lineage‐associated and immune markers, proliferation and apoptosis markers, cell adhesion molecules, and more recently stage‐specific markers of B‐cell differentiation. This review summarizes these studies in regard to their clinical significance and in the light of recent advances in our understanding of the molecular pathology and histogenesis of DLBCL.
Glutamate‐L‐cysteine ligase in breast carcinomas
Authors: Soini Y , Karihtala P , Mäntyniemi A , Turunen N , Pääkkö P , Kinnula V
Published: December 2004

Aims : To investigate the immunohistochemical expression of the catalytic and regulatory subunits of γ‐glutamyl cysteine synthetase, i.e. glutamate‐L‐cysteine ligase (GLCL) in 274 invasive and in‐situ breast carcinomas. GLCL is the rate‐limiting enzyme in glutathione synthesis, which is one of the most important intracellular antioxidants participating in the detoxification reactions of several cytotoxic drugs.

Methods and results : In the tumour cells GLCL reactivity was observed in 50% and 44% of the cases for the catalytic and the regulatory subunits, respectively. There was a statistically significant association between their expression (P = 0.002). Lobular invasive carcinomas expressed the catalytic and regulatory subunits more often than other tumours (P = 0.050 and P = 0.046, respectively). Also in‐situ carcinomas expressed the catalytic subunit more often (P = 0.005). Tumours showing no immunoreactivity for the catalytic subunit had axillary metastases significantly more often (P = 0.013). Patients with tumours showing positivity for either subunit or both had a better survival (P = 0.037). No difference in survival could be observed between GCLC‐positive or ‐negative cases in the subgroup receiving chemotherapy.

Conclusions : Expression of the catalytic and regulatory subunits of GLCL is found in a substantial number of breast carcinomas and their expression is more pronounced in lobular invasive and in‐situ carcinomas. Even though the overall expression of GLCL was associated with improved survival, no such effect was observed separately in the group receiving chemotherapy.
Osteopontin: correlation with interstitial fibrosis in human diabetic kidney and PI3‐kinase‐mediated enhancement of expression by glucose in human proximal tubular epithelial cells
Authors: Junaid A , Amara F M
Published: December 2004

Aims : To examine the expression and localization of osteopontin (OPN), a secreted phosphoprotein implicated in the development of tubulointerstitial inflammation in various models of renal disease, in human diabetic kidneys, and to study the regulation of OPN expression in primary cultures of human renal proximal tubular epithelial cells (RPTEC).

Methods and results : Differential gene expression profiling through subtractive hybridization demonstrated increased renal OPN mRNA expression in a patient with diabetic nephropathy. Immunohistochemical staining of normal and diabetic human kidney samples confirmed that OPN was localized to cortical tubular, interstitial and juxtaglomerular compartments. Quantification of OPN immunostaining revealed a marked increase in the percentage of OPN‐positive tubular profiles in diabetic kidneys (47 ± 9% versus 5 ± 3%, diabetic versus minimal change disease) that correlated strongly with the degree of cortical scarring (r2 = 0.91). Results of Northern hybridization, flow cytometry and Western blotting indicated that glucose up‐regulates OPN mRNA and protein expression in primary cultures of human RPTECs. This effect was independent of the osmotic effects of glucose and independent of insulin. Finally, glucose‐stimulated OPN expression was inhibited by LY294002, an inhibitor of phosphatidylinositol 3‐kinase activity, in a dose‐dependent manner.

Conclusions : OPN is expressed in human diabetic kidneys and regulation of OPN expression is via a glucose‐mediated, phosphatidylinositol 3‐kinase‐dependent pathway.
Thymic carcinoma: a clinicopathological and immunohistological study of 19 cases
Authors: Chalabreysse L , Etienne‐Mastroianni B , Adeleine P , Cordier J‐F , Greenland T , Thivolet‐Bejui F
Published: December 2004

Aims:  To study 19 cases of primary thymic carcinoma in order to define the clinicopathological features and the precise histochemical profile of this rare and heterogeneous group of tumours of the anterior mediastinum.

Methods and results:  The study group consisted of 13 males and six females, with a mean age of 58.5 years (range 29–75 years). Superior vena cava syndrome and chest pain were the main presenting symptoms. Three patients were asymptomatic. No patient had myasthenia gravis. Six different histological types were identified: neuroendocrine tumours (six patients), epidermoid carcinoma (five patients), sarcomatoid carcinoma (three patients), lymphoepithelioma‐like carcinoma (two patients), mucoepidermoid carcinoma, clear cell carcinoma, and undifferentiated carcinoma (one patient each). The clear cell carcinoma was associated with a thymic cyst. No association with thymoma was observed. Surgical resection, performed in 10 cases, was complete in two. Sixteen patients received thoracic radiation, and 11 received systemic chemotherapy. Follow‐up information was available in 16 cases; 12 patients presented with local or metastatic relapse, and 10 patients died of their tumour. The overall 5‐year survival was 14.5%.

Conclusion:  Primary thymic carcinoma is a very heterogeneous group of tumours of the anterior mediastinum with an aggressive clinical behaviour, and a poor overall prognosis.
Angiogenesis and extracellular matrix remodelling in bronchioloalveolar carcinomas: distinctive patterns in mucinous and non‐mucinous tumours
Authors: Guedj N , Couvelard A , Arcangeli G , Dubois S , Thabut G , Lesèche G , Fournier M , Degott C , Groussard O
Published: December 2004

Aim:  Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment.

Methods and results:  In three mucinous BACs (M‐BAC) and three non‐mucinous BACs (NM‐BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M‐BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM‐BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF.

Conclusions:  In contrast to NM‐BAC, M‐BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti‐angiogenic therapeutic strategies.
Extranodal follicular lymphoma: a clinicopathological and genetic analysis of 15 cases arising at non‐cutaneous extranodal sites
Authors: Goodlad J R , MacPherson S , Jackson R , Batstone P , White J ,   on behalf of the Scotland & Newcastle Lymphoma Group
Published: December 2004

Aims:  Recent studies of primary cutaneous follicular lymphoma suggest that it represents a clinicopathological entity distinct from nodal follicular lymphoma (FL). The purpose of this study was to determine if FL arising at other extranodal sites is more closely related to FL occurring in the skin or in lymph nodes.

Methods and results:  Fifteen cases of non‐cutaneous extranodal follicular lymphoma (ENFL) were identified from the Scotland and Newcastle Lymphoma Group (SNLG) database. All were stage 1E at presentation and involved the tonsil (n = 3), palate (n = 3), skeletal muscle (n = 2), ileum (n = 2), duodenum (n = 1), stomach (n = 1), thyroid gland (n = 1), submandibular gland (n = 1) and fallopian tube (n = 1). Polymerase chain reaction for t(14;18) using primers to the major breakpoint cluster region was performed on 14 cases of ENFL and the incidence of the translocation compared with that found in 16 cases of stage 1 nodal FL. Clinical and follow‐up data were obtained from the SNLG database for the 15 cases of ENFL and 87 cases of stage 1 nodal FL, and a comparison of outcomes made. Only 2/14 cases of ENFL had detectable t(14;18) compared with 9/16 stage 1 nodal FL (P < 0.01). Freedom from progression and disease‐specific survival was similar for the 15 cases of ENFL and 87 cases of stage 1 nodal FL. However, 13/15 patients with ENFL were disease free at the end of follow‐up compared with 49/87 stage 1 nodal FL (P < 0.02).

Conclusions:  The low incidence of t(14;18) and favourable outcome encountered in ENFL in this study is similar to that previously found for primary cutaneous FL. These results support the concept of a subtype of FL lacking t(14;18) involving the major breakpoint cluster region, and with a propensity to arise at extranodal sites. Despite a high relapse rate, patients with ENFL are more likely to achieve complete remission and may ultimately have a more favourable long‐term prognosis than those with equivalent nodal disease.
The pathology of hypertrophic cardiomyopathy
Authors: Hughes S E
Published: December 2004

Sudden cardiac death (SCD) is devastating at any age, but even more so when the individual affected is young and asymptomatic, and the death is entirely unexpected. SCD is a catastrophic complication of hypertrophic cardiomyopathy (HCM) and may be the first manifestation of this disease. HCM is an inherited intrinsic disease of the myocardium characterized by left ventricular hypertophy without chamber dilatation, in the absence of either a systemic or other cardiac disease, which may cause a similar magnitude of hypertrophy. HCM may be a clinically silent disease. Indeed, the pathologist may be the first to encounter a case of HCM at autopsy. HCM has wide‐ranging implications for affected families, who will require cardiac screening and genetic counselling even if mutations are not known. Therefore, prompt and accurate diagnosis of HCM is vital. This review article will focus on the pathological diagnosis of HCM, recent advances in the genetics of this disease, and common pitfalls which may arise, leading to diagnostic uncertainty.
British Division of the International Academy of Pathology
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

Spring 2004 Symposium on Dermatopathology. Brussels, Belgium

10–15 October 2004 XXVth International Congress. Brisbane, Australia

26–27 November 2004 Symposium on Pulmonary Pathology. London, UK
Non‐alcoholic duct destructive chronic pancreatitis: a histological, immunohistochemical and in‐situ apoptosis study of 18 cases
Authors: Youssef N , Petitjean B , Bonte H , Terris B , De Saint Maur P P , Fléjou J‐F
Published: December 2004

Aims:  To assess retrospectively pancreatic changes in non‐alcoholic duct‐destructive chronic pancreatitis and to investigate the role of apoptosis in duct destruction.

Methods and results:  Eighteen patients (mean age 46 years, nine women and nine men) underwent pancreatic resection for suspected pancreatic tumour and were diagnosed as having non‐alcoholic duct‐destructive chronic pancreatitis. We performed a morphological study either semiquantitatively (fibrosis and inflammation) or quantitatively (CD3+ intraepithelial lymphocytes, M30 and TUNEL+ apoptotic cells). The results were compared with those obtained in 10 cases of chronic alcoholic pancreatitis and nine cases of chronic obstructive pancreatitis. Pancreatic changes were diffuse and heterogeneous in 14 cases, but segmental in four cases. The main pancreatic lesions were ductal epithelial alteration, periductal inflammation and fibrosis. There were no cysts or calcifications. We found a marked increase in mast cells in the infiltrate, a slight increase in TiA1+ lymphocytes and in intraepithelial lymphocytes compared with other types of chronic pancreatitis. No significant increase in ductal apoptosis was observed.

Conclusion:  Non‐alcoholic duct‐destructive chronic pancreatitis is a well‐defined pathological entity, distinct from alcoholic and obstructive chronic pancreatitis. Our results indicate that apoptosis probably does not play a major role in ductal alterations.
NK and NK‐like T‐cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status
Authors: Ko Y H , Cho E‐Y , Kim J‐E , Lee S‐S , Huh J‐R , Chang H‐K , Yang W‐I , Kim C‐W , Kim S‐W , Ree H J
Published: December 2004

Aims:  To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T‐ or NK‐cell lymphomas in different organs and to compare Epstein–Barr virus (EBV)+ and EBV– lymphoma of non‐blastoid cytomorphology.

Methods and results:  Fifty‐one cases of cCD3+ T‐cell intracellular antigen (TIA‐1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n = 10), the gastrointestinal (GI) tract (n = 13), the skin (n = 15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n = 11), the testis (n = 1), and parotid gland (n = 1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P = 0.002). The 2‐year survival rate was lowest for tumours of the GI tract (P = 0.0256). EBV– TCR– lymphoma showed less necrosis (P = 0.0133) and a better 2‐year survival rate (P = 0.0066) than EBV+ TCR– lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR– lymphoma (P = 0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P = 0.0256), EBV status (P = 0.0026), necrosis with or without perforation (P = 0.0338) and the presence of pleomorphic large tumour cells (P = 0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P = 0.018).

Conclusions:  Extranodal CD56+ EBV– lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR– lymphomas, nasal‐type NK/T‐cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.
Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases
Authors: Wang J , Weiss L M , Hu B , Chu P , Zuppan C , Felix D , Rausei‐Mills V , Chase D R
Published: December 2004

Aims:  To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs).

Methods and results:  Formalin‐fixed paraffin‐embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma.

Conclusions:  Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.
COX‐2+ myofibroblasts may play a key role in marked stromal fibrosis in strictured colorectal carcinomas
Authors: Kasamaki S , Suda K , Kamano T , Kumasaka T , Ochiai T , Haraguchi Y
Published: December 2004

Aims:  To elucidate the mechanism of marked stromal fibrosis in strictured colorectal carcinomas (SC) that cause complete ileus.

Methods and results:  Sixteen cases of SC and 29 cases of non‐strictured colorectal carcinoma (NSC) were studied. These carcinomas showed similar clinicopathological features except for bowel stricture. The stricture index (SI) showing the degree of bowel stricture was 59.8 ± 12.1% in SC versus 20.8 ± 24.6% in NSC (P < 0.001). The fibrosis index (FI), defined to reflect the extent of stromal fibrosis, was 56.3 ± 8.8% in SC versus 21.9 ± 10.6% in NSC (P < 0.001). COX‐2+ myofibroblasts were detected in 13 cases (81.3%) in SC versus eight cases (27.6%) in NSC (P < 0.01). The COX‐2+ myofibroblast density was 276.7 ± 181.1 cells/mm2 in SC versus 26.6 ± 52.7 cells/mm2 in NSC (P < 0.001). When all cases were divided into two groups with and without COX‐2+ myofibroblasts, the SI was 48.8 ± 19.1% in those with COX‐2+ myofibroblasts versus 24.8 ± 29.3% in those with COX‐2– myofibroblasts (P < 0.001).

Conclusion:  COX‐2+ myofibroblasts may play an important role in extensive bowel stricture in colorectal carcinomas.
Expression of apoptosis‐regulatory proteins in lesions of pulmonary Langerhans cell histiocytosis
Authors: Marchal J , Kambouchner M , Tazi A , Valeyre D , Soler P
Published: December 2004

Aims:  Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the presence of lesions containing numerous activated Langerhans cells (LCs). An uncontrolled immune response sustained by activated LCs seems to be involved in the pathogenesis of the disease. The aim of this study was to establish whether disruption of LC apoptosis related to the expression of the Bcl‐2 family proteins is implicated in the maintenance of PLCH lesions.

Methods:  Six patients with PLCH were evaluated by morphological and immunohistochemical techniques to explore the incidence of apoptosis in pathological LCs and to characterize the expression of Bcl‐2‐related proteins by these cells.

Results:  Very few LCs present in PLCH lesions exhibited nuclear apoptotic changes or expressed cleaved caspase‐3, whereas they all strongly expressed the anti‐apoptotic molecule Bcl‐xL. Interestingly, pulmonary LCs present in intervening lung tissue not involved by the pathological process and known to be immature dendritic cells did not express Bcl‐2 family proteins.

Conclusions:  These findings suggest that activated LCs present within PLCH lesions are poorly susceptible to apoptosis and, thus, are able to sustain the pathological process by causing continuous local stimulation of T cells. Functional studies are needed, however, to demonstrate that they are actually resistant to programmed cell death.
Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)‐like nuclear alterations express molecular markers of PTC
Authors: Prasad M L , Huang Y , Pellegata N S , De La Chapelle A , Kloos R T
Published: December 2004

Aims:  Focal papillary thyroid carcinoma (PTC)‐like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC‐like nuclear alterations in Hashimoto's thyroiditis.

Methods and results:  The expression of four genes known to be up‐regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin‐1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC‐like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin‐1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC‐like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC‐associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin‐stained sections leading to appreciation of complete PTC‐type nuclear atypia.

Conclusions:  Focal PTC‐like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.
The activation profile of tumour‐associated reactive T‐cells differs in the nodular and diffuse patterns of lymphocyte predominant Hodgkin's disease
Authors: Lin P , Medeiros L J , Wilder R B , Abruzzo L V , Manning J T , Jones D
Published: December 2004

Aims:  To compare the activation profile of T‐cells in reactive lymphoid follicles with that of tumour‐associated T‐cells in lymphocyte predominant Hodgkin's disease (LPHD) with a nodular pattern (n = 21), LPHD with partial diffuse growth pattern (n = 11) and T‐cell‐rich large B‐cell lymphoma (TCRLBCL, n = 8).

Methods and results:  Reactive germinal centres showed sparse numbers of T‐cells positive for CD134, a transient/early T‐cell activation marker, and only scattered T‐cells in the interfollicular areas positive for CD38, a marker of persistent activation. Lymphoid follicles showing progressive transformation of germinal centres (PTGC) had more numerous CD134+ T‐cells which were negative for CD38. Tumour‐associated T‐cells in nodular LPHD were frequently positive for CD134 (15 of 16 cases, 94%), but negative or only focally positive for CD38 (three of 21 cases, 14%). LPHD with diffuse areas, however, showed increased CD38+ T‐cells in the diffuse component in 10 of 11 (90%) cases, with CD134+ T‐cells being more prominent in the nodular tumour component. TCRLBCL showed strong, uniform CD38 expression in T‐cells and histiocytes in eight cases.

Conclusions:  T‐cells in nodular LPHD express markers of transient/early T‐cell activation. By contrast, T‐cells in the diffuse form of LPHD, similar to those in TCRLBCL, have an immunostaining profile consistent with persistent cellular activation. T‐cell activation may precede or accompany histological progression in nodular LPHD and immunostaining for these markers, in small samples or in difficult cases, may be useful in highlighting those cases of LPHD undergoing histological progression.
Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases
Authors: Alos L , Castillo M , Nadal A , Caballero M , Mallofre C , Palacin A , Cardesa A
Published: December 2004

Aims:  Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely.

Methods and results:  All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High‐molecular‐weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12–35 months).

Conclusions:  ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.
Prognostic impact of histological grade and vascular invasion compared with tumour cell proliferation in endometrial carcinoma of endometrioid type
Authors: Stefansson I M , Salvesen H B , Immervoll H , Akslen L A
Published: December 2004

Aims:  The relative impact of different prognostic factors is important for endometrial carcinoma patients. The aim of our study was to examine the combined value of histological grade [International Federation of Gynaecology and Obstetrics (FIGO)] and vascular invasion in comparison with tumour cell proliferation assessed by mitotic count and Ki67. The recently proposed binary architectural grade was also evaluated, in addition to age, depth of myometrial infiltration and FIGO stage in our population‐based series of 237 endometrioid carcinomas.

Methods and results:  The tumours were studied for several histological features, including FIGO grade, binary grade, vascular invasion, mitotic count, myometrial invasion and expression of Ki67. FIGO grade was significantly associated with all investigated histological features, including Ki67 expression. Vascular invasion was significantly more frequent in FIGO grade 3 tumours, and was associated with a diffusely infiltrative growth pattern, solid growth, necrosis and deep myometrial invasion. All variables showed a highly significant relationship with patient survival in univariate analysis. In multivariate models, FIGO grade, vascular invasion, and proliferation assessed by Ki67 expression all had independent prognostic influence in this population‐based study. Comparing tumour cell proliferation (Ki67) with vascular invasion as a marker of metastatic spread, the latter had a stronger survival impact.

Conclusions:  Vascular invasion and tumour cell proliferation measured by Ki67 both had independent prognostic influence, and should be considered to identify aggressive tumours of the endometrioid subtype.