Showing papers in "American Journal of Clinical Pathology in 2006"
TL;DR: This review summarizes the anatomic and histologic variations of osteosarcoma and offers a schema for its subclassification.
Abstract: Osteosarcoma is the most common primary tumor of bone, yet its absolute incidence among malignant tumors is low. Within its strict histologic definition, osteosarcoma comprises a family of lesions with considerable diversity in histologic features and grade. Its prognosis is dependent not only on these parameters, but also on its anatomic site. It may occur inside the bones (in the intramedullary or intracortical compartment), on the surfaces of bones, and in extraosseous sites. Information of diagnostic or prognostic significance has not been elucidated from studies of its cytogenetics. This review summarizes the anatomic and histologic variations of osteosarcoma and offers a schema for its subclassification.
384 citations
TL;DR: The concept of sessile serrated adenoma was introduced at the Roger C. Haggitt Gastrointestinal Pathology Society Forum presented in Vancouver, Canada, as part of the annual meeting of the United States-Canadian Academy of Pathology as discussed by the authors.
Abstract: Serrated polyps of the large intestine, including traditional hyperplastic polyps, traditional serrated adenomas, and more recently described sessile serrated adenomas, have gained increased recognition in recent years because of growing evidence that one of these lesions, the sessile serrated adenoma, might be the precursor lesion for some cases of microsatellite unstable colorectal carcinoma. Nevertheless, there has been some reluctance to embrace the concept of sessile serrated adenoma, and numerous diagnostic challenges exist. This article, which grew out of the Roger C. Haggitt Gastrointestinal Pathology Society Forum presented in Vancouver, Canada, March 6, 2004, as part of the annual meeting of the United States–Canadian Academy of Pathology, reviews the morphologic and molecular evidence for the concept of various polyps in the general category of serrated polyps of the large intestine, in particular the lesion known as the sessile serrated adenoma, and provides a conceptual framework for diagnosis of these lesions.
306 citations
TL;DR: Transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.
Abstract: Numerous published guidelines encourage appropriate use of fresh frozen plasma (FFP). However, adherence is documented as poor. Therefore, we sought to determine the laboratory effect of FFP administration to patients with an international normalized ratio (INR) less than 1.6 (prothrombin time <1.6 times normal). We found minimally prolonged INRs decreased with treatment of the underlying disease alone. Adding FFP to the treatment failed to change the decrease in INR over time. In addition, we observed that the change in the INR per unit of FFP transfused can be predicted by the pretransfusion INR (INR change = 0.37 [pretransfusion INR] – 0.47; r 2 = 0.82). With an observed analytic variation of 3.2%, a significant amount of change in the INR following FFP transfusion is expected at an INR of more than 1.7. Indeed, only 50% of patients with an INR of 1.7 showed a significant change in INR with FFP transfusion. Therefore, transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.
251 citations
TL;DR: New studies are needed based on adequate liver biopsy samples to provide reliable estimation of grading and staging in chronic liver disease and studies of sampling heterogeneity and intraobserver and interobserver variability also used inadequate specimens by present standards.
Abstract: Characteristics for an optimal liver biopsy specimen were recently defined as 20 to 25 mm long and/or containing more than 11 complete portal tracts (CPTs). A systematic review of percutaneous liver biopsy (PLB) and transjugular liver biopsy (TJLB) series yielded only 32 PLB studies in which these characteristics were evaluated: mean ± SD length, 17.7 ± 5.8 mm and number of CPTs, 7.5 ± 3.4; and 15 TJLB studies: mean ± SD length, 13.5 ± 4.5 mm and number of CPTs, 6.8 ± 2.3. Studies of sampling heterogeneity and intraobserver and interobserver variability also used inadequate specimens by present standards. Only 11 (5.3%) of 207 therapeutic studies for chronic hepatitis B and C documented length and/or number of CPTs. Of the current 12 studies evaluating noninvasive fibrosis tests, only 8 documented length or number of CPTs, and only 1 documented length and number of CPTs. New studies are needed based on adequate liver biopsy samples to provide reliable estimation of grading and staging in chronic liver disease.
229 citations
TL;DR: Transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.
Abstract: Numerous published guidelines encourage appropriate use of fresh frozen plasma (FFP). However, adherence is documented as poor. Therefore, we sought to determine the laboratory effect of FFP administration to patients with an international normalized ratio (INR) less than 1.6 (prothrombin time <1.6 times normal).
We found minimally prolonged INRs decreased with treatment of the underlying disease alone. Adding FFP to the treatment failed to change the decrease in INR over time. In addition, we observed that the change in the INR per unit of FFP transfused can be predicted by the pretransfusion INR (INR change = 0.37 [pretransfusion INR] – 0.47; r 2 = 0.82).
With an observed analytic variation of 3.2%, a significant amount of change in the INR following FFP transfusion is expected at an INR of more than 1.7. Indeed, only 50% of patients with an INR of 1.7 showed a significant change in INR with FFP transfusion. Therefore, transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.
218 citations
TL;DR: This study offers additional strong evidence that SSA is truly a precursor to at least a subset of sporadic microsatellite-unstable colorectal cancer.
Abstract: Sessile serrated adenomas (SSAs) show serrations typical of hyperplastic polyps but display architectural differences and lack traditional dysplasia. SSAs with foci of low- (LGD) or high-grade dysplasia (HGD) or early invasive carcinoma are seldom biopsied and, thus, are not well studied. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 (mismatch repair gene products) was performed on colon biopsy specimens from 11 patients (age range, 54-87 years; 4 men and 7 women) showing SSA with LGD (n = 1), HGD (n = 5), or focal invasive carcinoma (n = 5). All 11 cases showed intact nuclear staining for MSH2 and MSH6 in the SSA component; in foci of LGD, HGD, or carcinoma; and in background normal mucosa. In contrast, there was tandem loss of MLH1 and PMS2 in zones of LGD (1/1) or HGD (3/5) and early carcinoma (2/4; with concordant loss in associated HGD) but retention in SSA areas (11/11) and normal mucosa (11/11). No patient was known to have hereditary nonpolyposis colorectal cancer/Lynch syndrome. This study offers additional strong evidence that SSA is truly a precursor to at least a subset of sporadic microsatellite-unstable colorectal cancer.
159 citations
TL;DR: All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%.
Abstract: The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age (P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (
157 citations
TL;DR: HRMA of archived cytological specimens of advanced NSCLC is suggested to be useful for detecting EGFR mutations in clinical practice by establishing and validated an easy, inexpensive, and rapid method for detecting DEL and L858R from cytologic material by high-resolution melting analysis.
Abstract: Mutations of the epidermal growth factor receptor (EGFR), particularly deletional mutations (DEL) in exon 19 and L858R in exon 21, are reportedly correlated with clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving the EGFR tyrosine kinase inhibitors gefitinib and erlotinib, suggesting that detection of EGFR mutations would have an important role in clinical decision making. We established and validated an easy, inexpensive, and rapid method for detecting DEL and L858R from cytologic material by high-resolution melting analysis (HRMA). Dilution for sensitivity studies revealed that DEL and L858R were detectable in the presence of at least 10% and 0.1% EGFR-mutant cells, respectively. We analyzed 37 archived cytological slides of specimens from 29 patients with advanced NSCLC and compared the results with direct sequencing data obtained previously. Of 37 samples, 34 (92%) yielded consistent results with direct sequencing, 2 were false negative, and 1 was indeterminate. The sensitivity of this analysis was 90% (19/21) and specificity, 100% (15/15). These results suggest that HRMA of archived cytologic specimens of advanced NSCLC is useful for detecting EGFR mutations in clinical practice.
151 citations
TL;DR: It is suggested that those factors might have a decisive role in the development of lymphocytic esophagitis.
Abstract: A novel histologic phenotype of chronic esophagitis, ie, lymphocytic esophagitis, is reported in 20 patients. Lymphocytic esophagitis is characterized by high numbers of intraepithelial lymphocytes (IELs) gathered mainly around peripapillary fields and by none (n = 12) to occasional (n = 8) CD15+ intraepithelial granulocytes. IELs expressed CD3, CD4 (42%), CD8 (36%), and granzyme B (0.2%), whereas T-cell intracytoplasmic antigen (TIA) 1 was not expressed. Of the 20 patients, 11 (55%) were 17 years or younger. Of 20 patients, 5 had no symptoms in the upper gastrointestinal tract. Only 4 (20%) of 20 patients had symptoms of gastroesophageal reflux disease and 6 (30%) of gastroduodenitis; 2 (10%) had celiac disease; 4 (20%) had carcinoma of the esophagus (1) or elsewhere (3); 1 (5%) each had hiatus hernia, gastric ulcer/asthma/blood hypertension, Hashimoto thyroiditis, and cirrhosis/diabetes; and 8 (40%) had Crohn disease. Hence, a novel histologic phenotype of chronic esophagitis called lymphocytic esophagitis is reported. Because phenotype is defined as the visible features resulting from the interaction between the genetic makeup and the environment, it is suggested that those factors might have a decisive role in the development of lymphocytic esophagitis.
148 citations
TL;DR: The serrated neoplasia pathway has its underpinnings in a recently characterized molecular mechanism that eventuates in microsatellite unstable-high (MSI-high) colorectal adenocarcinomas, which may provide insight into several current issues that are the subject of active debate.
Abstract: Eight sessile serrated adenoma (SSA), right colon polypectomies with focal invasive adenocarcinoma or high-grade dysplasia were studied to identify features indicating a high risk of transformation and characterize the morphologic features of serrated dysplasia; 6 cases had invasive adenocarcinoma; 2 were high-grade dysplasia. All 8 were microsatellite unstable-high and had absent hMLH1 nuclear immunoreactivity. The mean patient age at polypectomy was 69.5 years (range, 57.1-83.9 years). Mean polyp maximum dimension was 8.5 mm (range, 6-12 mm). The majority of each polyp was nonmalignant SSA. All 8 cases had an abrupt transition from benign to high-grade in situ or invasive malignancy. In the 6 invasive adenocarcinomas, the neoplasm extended directly down into the submucosa without lateral intramucosal spread. The mean maximum dimension of the invasive adenocarcinoma was 2.9 mm (range, 2-4 mm). All 8 cases had high-grade serrated-type dysplasia. The nonmalignant SSAs had marked expansion of the proliferative zone. Crypts adjacent to malignancy had moderately enlarged nuclei, irregular nuclear membranes, and overly prominent nucleoli. SSA crypts were lined by a variety of gastric-type cells; no cell type predominated. Foci of adjacent crypts had similar cytologic features. Small proximal SSAs can transform into adenocarcinoma without a component of adenomatous dysplasia.
145 citations
TL;DR: The data suggest that COPD exhibits increased bronchial deposition of ECM proteins that contribute to deteriorated lung function and airway remodeling.
Abstract: Remodeling of airways and blood vessels is an important feature in chronic obstructive pulmonary disease (COPD). By using immunohistochemical analysis, we examined bronchial expression patterns of various extracellular matrix (ECM) components such as collagens (subtypes I, III, and IV), fibronectin, and laminin β2 in patients with COPD (forced expiratory volume in 1 second [FEV1] ≤75%; n = 15) and without = COPD (FEV1 =≥85%; n = 16) and correlated expression data with lung function. Quantitative analysis revealed enhanced levels ( P < .01) of total collagens I, III, and IV in surface epithelial basement membrane (SEBM) and collagens I and III in bronchial lamina propria ( P < .02) and adventitia ( P < .05) in COPD. Distinct and increased ( P < .05) vascular expression of fibronectin accounts for intimal vascular fibrosis, whereas laminin β2 (P < .05) was elevated in airway smooth muscle (ASM). FEV1 values inversely correlated with collagens in the SEBM, fibronectin in bronchial vessels, and laminin in the ASM. Our data suggest that COPD exhibits increased bronchial deposition of ECM proteins that contribute to deteriorated lung function and airway remodeling.
TL;DR: HBME1, galectin-3, cytokeratin (CK)19, and a new anti-CITED1 antibody can have a confirmatory role in distinguishing the follicular variant of PTC and FA and for FL/QPTC, these antibodies are helpful in some cases, their limitation perhaps suggesting the biologic ambiguity of these lesions.
Abstract: We evaluated HBME1, galectin-3 (GAL3), cytokeratin (CK)19, and a new anti-CITED1 antibody in 127 follicular adenoma (FA) and papillary thyroid carcinoma (PTC) cases The findings were used to evaluate 11 diagnostically challenging encapsulated follicular lesions with questionable features of PTC (FL/QPTC) All 4 markers showed higher expression in PTC than FA HBME1 was the most specific (96%), whereas CK19 was the most sensitive (96%) In addition, 100% specificity was seen with coexpression of HBME1/CK19 Negative expression of all 4 markers was 97% specific for FA GAL3 and CITED1, less useful individually, could help in selective cases FL/QPTC showed heterogeneous, often intermediate, staining patterns, implying that some FL/QPTCs may be biologically borderline lesions or represent a biologic spectrum of PTC These antibodies can have a confirmatory role in distinguishing the follicular variant of PTC and FA For FL/QPTC, these antibodies are helpful in some cases, their limitation perhaps suggesting the biologic ambiguity of these lesions
TL;DR: Chemokine receptors are expressed widely on leukocytes but rarely on carcinoma cells in ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in this malignancy.
Abstract: We studied the clinical role of leukocyte infiltration and chemokine receptor expression in ovarian carcinoma effusions. Expression of leukocyte markers (CD3, CD4, CD8, CD4/CD8 ratio, CD16, CD19, and CD14) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 73 effusions by using flow cytometry. CXCR4, CCR5, and CCR7 were expressed abundantly on leukocytes, but all receptors were expressed rarely on cancer cells. The presence of natural killer cells (P = .042) and International Federation of Gynecology and Obstetrics (FIGO) stage IV disease (P = .024) predicted worse overall survival (OS). A higher percentage of CD19+ cells (P = .015) and stage IV disease (P = .008) predicted poor survival for patients with postchemotherapy effusions. Only FIGO stage retained significance as a predictor of OS (P = .035) in multivariate analysis. Chemokine receptors are expressed widely on leukocytes but rarely on carcinoma cells in ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in this malignancy. Immune response parameters in ovarian cancer effusions are weak predictors of outcome.
TL;DR: The key clinical findings were as follows: The presence of an Xp11.2 (TFE3) translocation frequently is associated with advanced stage at initial examination, and all patients who underwent complete, partial nephrectomy with clear margins were alive and relapse-free at last follow-up.
Abstract: We describe the clinical features, outcome, pathology, cytogenetics, and molecular aspects of 13 pediatric papillary renal cell carcinomas during a 19year period. Seven cases (54%) had translocations involving Xp11.2 (TFE3). They were identified by cytogenetic, molecular, and/or immunohistochemical analyses. All Xp11.2+ translocations were TFE3+ by immunostaining. Cytogenetic and/or polymerase chain reaction analyses identified 3 cases with t(X17) and 1 case with t(1;17), and all had additional translocations. Histologic features in common in TFE3+ tumors also were present in some TFE3– tumors. One TFE3– tumor had complex cytogenetic abnormalities, 55XY,+2, del(3)(p14),+7,+8,+12,+13,+16,+17,+20[11], and 2 cases had normal karyotypes. None had t(6;11)/TFEB+ immunostaining. Five cases had focal, weak MITF tumor immunostaining. The key clinical findings were as follows: (1) The presence of an Xp11.2 (TFE3) translocation frequently is associated with advanced stage at initial examination. (2) All patients who underwent complete, partial nephrectomy with clear margins (adequate only for stage 1) and resection of metastases were alive and relapse-free at last follow-up. (3) The mean ± SD eventfree survival and overall survival rates at 5 years were both 92% ± 7.4%. (4) One patient with a TFE3+ and MITF+ tumor and 66-87,XXY,der(1)t(1;8)del(4)(q?) der(11)t(11;15)der17t(X;17) abnormalities died 9 months after diagnosis. Renal cell carcinoma (RCC) is a rare childhood tumor constituting fewer than 0.3% of all tumors and 2.6% of renal neoplasms in children and adolescents younger than 15 years, 1 and, given its rarity, it has been difficult to determine whether pediatric RCC differs from its adult counterpart. However, reports suggest that the clinical and pathologic features of pediatric RCC are different from those seen in older adolescents and young adults. 2 In children, most cases consist of papillary histologic features, 3 whereas among the 4 types of RCC (clear cell, papillary, chromophobe, and collecting duct), the clear cell type predominates in adults (75%); in younger adults (1845 years), Cao et al 4 found that 53% were clear cell, 12% were papillary, 8% were chromophobe, 2% were oncocytoma, and 26% were in a miscellaneous group (that comprised Xp11.2 translocation carcinoma, renal medullary carcinoma, primitive neuroectodermal tumor, cystic nephroma, metanephric biphasic tumor, and mucinous tubular and spindle cell carcinoma). Cytogenetic and molecular studies have suggested that abnormalities in the Xp11.2 region involving the TFE3 gene might account for a significant proportion of pediatric RCC, with these tumors representing a subset of papillary RCC. Therefore, RCC associated with Xp11.2 translocations/TFE3 gene fusion is listed as a separate entity in the World Health Organization (WHO) classification of tumors of the urinary system. 5 Moreover, multiple chromosomal translocation partners can be fused to TFE3 at Xp11.2 in this subset of RCCs. The 2 most common forms are the t(X;17)(p11.2;q25) translocation that fuses the transcription factor gene TFE3 with the ASPL gene on 17q25, 6-15 and the t(X;1)(p11.2;q21)
TL;DR: This LC-MS/MS method provides a rapid, accurate, sensitive, and cost-effective alternative to other methods for detection of 25-hydroxyvitamin D(2) and 25(OH)D(3) at nanomolar concentrations.
Abstract: Serum levels of 25-hydroxyvitamin D are important in establishing true vitamin D levels in humans. The purposes of this study were to develop a sensitive, specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of 25-hydroxyvitamin D(2) and D(3) and establish reference intervals for these analytes. Chromatographic separation of 25(OH)D(2) and 25(OH)D(3) was achieved after adding deuterated Delta(9)-tetrahydrocannabinol (D(9)-THC-D(3)) and organic extraction. The 3 ions were ionized using positive electrospray ionization and detected in the multiple-reaction monitoring mode using mass (m)/charge (z) transitions of 318.15 > 196.20 (Delta(9)-THC-D(3)), 401.15 > 365.2 (25(OH)D(3)), and 413.15 > 355.20 (25(OH)D(2)). Reference interval study results were compared with current 25(OH)D recommendations. Elution of 25(OH)D(2), 25(OH)D(3), and Delta(9)-THC-D(3) was achieved after 3.0 minutes (total run time, 6.0 minutes). Within- and between-run coefficients of variation were less than 11%. Deming regression of radioimmunoassay and LC-MS/MS methods for total 25(OH)D levels yielded a slope of 0.97 (95% confidence interval, 0.88-1.05) and y-intercept of -1.74 ng/mL. Reference intervals were less than recommended levels (D(2), 0.0-12.1; D(3), 5.5-41.4; total vitamin D, 6.0-43.5 ng/mL [0-30, 14-103, 15-109 nmol/L, respectively]) with no statistically significant differences in race, age, or sex. This LC-MS/MS method provides a rapid, accurate, sensitive, and cost-effective alternative to other methods for detection of 25(OH)D(2) and 25(OH)D(3) at nanomolar concentrations.
TL;DR: The analytic quality of laboratory tests requires improvement in measurement performance and more intensive quality control monitoring than the CLIA minimum of 2 levels per day.
Abstract: To assess the analytic quality of laboratory testing in the United States, we obtained proficiency testing survey results from several national programs that comply with Clinical Laboratory Improvement Amendments (CLIA) regulations. We studied regulated tests (cholesterol, glucose, calcium, fibrinogen, and prothrombin time) and nonregulated tests (international normalized ratio [INR], glycohemoglobin, and prostate-specific antigen [PSA]). Quality was assessed on the σ scale with a benchmark for minimum process performance of 3 σ and a goal for world-class quality of 6 σ. Based on the CLIA criteria for acceptable performance in proficiency testing (allowable total errors [TE a ]), the national quality of cholesterol testing (TE a = 10%) estimated σ values as 2.9 to 3.0; glucose (TE a = 10%), 2.9 to 3.3; calcium (TE a = 1.0 mg/dL), 2.8 to 3.0; prothrombin time (TE a = 15%), 1.8; INR (TE a = 20%), 2.4 to 3.5; fibrinogen (TE a = 20%), 1.8 to 3.2; glycohemoglobin (TE a = 10%), 1.9 to 2.6; and PSA (TE a = 10%), 1.2 to 1.8. The analytic quality of laboratory tests requires improvement in measurement performance and more intensive quality control monitoring than the CLIA minimum of 2 levels per day. What is the quality of laboratory tests today? Studies of laboratory errors have documented that a higher percentage of errors occur in the preanalytic and postanalytic processes than in analytic processes. 1-3 The figures often quoted are 45% for errors in preanalytic processes, 10% for analytic errors, and 45% for postanalytic errors (actual estimates, 45.5%, 7.3%, and 47.2%, respectively) based on a study done in 1988 1 before the implementation of the current Clinical Laboratory Improvement Amendments (CLIA) regulations. As a consequence of this expected distribution of errors, laboratories are urged to focus their attention on preanalytic and postanalytic processes to improve patient safety. 4
TL;DR: The data suggest that expression of CXCL8 and CXCR2 contributes to aggressive growth and metastasis in human malignant melanoma, consistent with the transition from radial to vertical growth phase melanoma.
Abstract: We examined the expression of CXCL8 (interleukin8), its receptors, CXCR1 and CXCR2, and vessel density in human melanoma by immunohistochemical analysis of tumors from different Clark levels, depths, and thicknesses. Expression of CXCL8 and CXCR2 was lower in Clark level I and II specimens than in level III through V specimens and metastases. CXCR1 expression was observed ubiquitously in the majority of human melanoma tumor specimens irrespective of disease state, with the highest intensity in Clark level III specimens. We observed a significant difference in CXCL8 and CXCR2 expression between thin (≤0.75 mm) and thick (>0.75 mm) melanomas and between thin and metastatic lesions. Positive correlations were observed between Clark level and CXCL8 or CXCR2 and between thickness and CXCR2 expression. We found no correlation between vessel density and Clark level or thickness. Our data suggest that expression of CXCL8 and CXCR2 contributes to aggressive growth and metastasis in human malignant melanoma. Consistent with the transition from radial to vertical growth phase melanoma, expression of CXCL8 and its receptor, CXCR2, may be key in the switch to an aggressive, more metastatic phenotype.
TL;DR: Critical value reporting is evaluated by test, laboratory specialty, patient type, clinical care area, time of day, and critical value limits, and approaches to improving this important operational and patient safety issue are described.
Abstract: Reporting of laboratory critical values has become an issue of national attention as illustrated by recent guidelines described in the National Patient Safety Goals of the Joint Commission on Accreditation of Healthcare Organizations. Herein, we report the results of an analysis of 37,503 consecutive laboratory critical values at our institution, a large urban academic medical center. We evaluated critical value reporting by test, laboratory specialty, patient type, clinical care area, time of day, and critical value limits. Factors leading to delays in critical value reporting are identified, and we describe approaches to improving this important operational and patient safety issue.
TL;DR: The densities and positions of HIV-1 target cells in the foreskin tissue of these Kenyan men indicate that the inner mucosal surface of the human foreskin contains cells that make it highly susceptible to HIV infection.
Abstract: Numerous epidemiologic studies have found significant associations between lack of circumcision and HIV-1 acquisition in men. To our knowledge, this is the first study of human foreskin tissue that examines biologic mechanisms that increase susceptibility of uncircumcised African men to HIV-1. Foreskin specimens from 20 men with and 19 men with no history of sexually transmitted infections were examined for HIV-1 target cells. Most Langerhans cells were found in the epithelium; most CD4+ T cells and macrophages were in the submucosa. There were no differences in HIV-1 target cells between men with and those without history of sexually transmitted infections. However Langerhans cells and macrophages were more abundant in the group with a history of infection. The densities and positions of HIV-1 target cells in the foreskin tissue of these Kenyan men indicate that the inner mucosal surface of the human foreskin contains cells that make it highly susceptible to HIV infection.
TL;DR: This review addresses the genetic mutations and cell signaling pathway alterations in colorectal premalignant polyps, focusing on the link between molecular changes and morphologic features.
Abstract: This review addresses the genetic mutations and cell signaling pathway alterations in colorectal premalignant polyps, focusing on the link between molecular changes and morphologic features. Biallelic APC (adenomatous polyposis coli) mutations are directly responsible for the specific and characteristic cytologic features of dysplastic cells in conventional tubular adenomas. Sessile serrated adenomas (SSAs) are the precursor lesions of the serrated neoplasia pathway. The BRAF activating mutation and hypermethylation of SLC5A8, which mediates short chain fatty acid transport, may be the important events in the genesis of SSAs. Intracellular butyrate inhibits histone deacetylase, allowing histone hyperacetylation and, eventually, transcriptional activation of specific genes. Decreased p21(WAF1/CIP1) and activation of the mitogen-activated protein kinase pathway may be the key intermediary alterations. Progressive loss of cell cycle control and decreased and altered cytoplasmic differentiation produce the characteristic constellation of morphologic changes of SSAs and traditional serrated adenomas.
TL;DR: After an inpatient phlebotomy-laboratory test request audit for 2 general inpatient wards identified 5 tests commonly ordered on a recurring basis, a multidisciplinary committee developed a proposal to minimize unnecessaryphlebotomies and laboratory tests by reconfiguring the electronic order function to limit phlebots to occur singly or to recur within one 24-hour window.
Abstract: After an inpatient phlebotomy–laboratory test request audit for 2 general inpatient wards identified 5 tests commonly ordered on a recurring basis, a multidisciplinary committee developed a proposal to minimize unnecessary phlebotomies and laboratory tests by reconfiguring the electronic order function to limit phlebotomy–laboratory test requests to occur singly or to recur within one 24-hour window. The proposal was implemented in June 2003. Comparison of fiscal year volume data from before (2002–2003) and after (2003–2004) implementation revealed 72,639 (12.0%) fewer inpatient tests, of which 41,765 (57.5%) were related directly to decreases in the 5 tests frequently ordered on a recurring basis. Because the electronic order function changes did not completely eliminate unnecessary testing, we concluded that the decrease in inpatient testing represented a minimum amount of unnecessary inpatient laboratory tests. We also observed 17,207 (21.4%) fewer inpatient phlebotomies, a decrease sustained in fiscal year 2004–2005. Labor savings allowed us to redirect phlebotomists to our understaffed outpatient phlebotomy service.
TL;DR: Factor XI activity levels correlate with factor XI antigen levels by Deming regression analysis and a lack of correlation of both with hs-CRP suggests that factor XI is not an acute phase reactant, and the findings suggest an association between elevated factor XI activity and stroke.
Abstract: High levels of factor XI have been implicated as a risk factor for deep venous thrombosis and possibly cardiovascular disease; however, the relationship between elevated factor XI activity and stroke has yet to be established. We retrospectively evaluated factor XI activity, factor XI antigen, and high-sensitivity C-reactive protein (hs-CRP) values in samples from 65 patients with stroke, 13 with transient ischemic attack (TIA), and 17 with venous thrombosis, younger than 55 years with normal prothrombin and partial thromboplastin times who underwent evaluation for a hypercoagulable state. Factor XI activity levels were more than normal in 22% of patients with stroke or TIA and 18% of patients with venous thrombosis, producing odds ratios of 5.3 and 4.1 for stroke or TIA and venous thrombosis, respectively. Factor XI activity levels correlate with factor XI antigen levels by Deming regression analysis (slope, 1.3; R = 0.667) and a lack of correlation of both with hs-CRP suggests that factor XI is not an acute phase reactant. Our findings suggest an association between elevated factor XI activity and stroke.
TL;DR: 11 new PMD cases are presented and a meta-analysis of the associated IUGR and fetal death rates are provided, finding that females represented 82% of cases and PMD is associated with high IugR and IUFD/neonatal death rates and disproportionally affects females.
Abstract: Placental mesenchymal dysplasia (PMD) is a rare condition of placentomegaly and abnormal chorionic villi often clinically mistakenly as partial hydatidiform mole. However, it is clinicopathologically distinct with high incidence of intrauterine growth restriction (IUGR) and fetal death. This study presents 11 new PMD cases and provides a meta-analysis of the associated IUGR and fetal death rates. The cases were identified between 1971 and 2005, mostly from consultation files. To our knowledge, 71 PMD cases have previously been reported; 15 of these were associated with Beckwith-Wiedemann syndrome (BWS). With the addition of our new results, among all cases without BWS, 50% had IUGR and 43% had intrauterine fetal demise (IUFD) or neonatal death. Females represented 82% of cases. Thus, PMD is associated with high IUGR and IUFD/neonatal death rates and disproportionally affects females. The cause and pathogenesis are yet unknown. The current understanding and hypotheses involving PMD are discussed.
TL;DR: Terminal ileum (TI) sections from 250 ulcerative colitis (UC) total colectomy specimens resected during 3 periods and endoscopic TI biopsy specimens from 100 contemporary chronic UC and 100 Crohn disease patients were reviewed, finding the activity level of BWI correlated with level of cecal UC.
Abstract: Terminal ileum (TI) sections from 250 ulcerative colitis (UC) total colectomy specimens resected during 3 periods and endoscopic TI biopsy specimens from 100 contemporary chronic UC and 100 Crohn disease (CD) patients were reviewed. The respective proportions of cases resected during the 3 periods with moderately or markedly active cecal UC were 72%, 34%, and 2% and with moderate or marked backwash ileitis (BWI), 21%, 18%, and 0%. The activity level of BWI correlated with level of cecal UC. In contemporary initial endoscopic TI biopsy specimens, 6% of chronic UC patients had BWI, all with moderately to markedly active cecal chronic UC. In CD cases, 75% had chronic or active enteritis, consisting of patchy lamina propria edema containing mildly active inflammation, crypt disarray, and focally blunted or flattened villi. Mucous gland metaplasia was present in 27% of CD biopsy specimens. BWI should be restricted to active enteritis that involves the ileum in a contiguous pattern from the cecum that has a similar or greater degree of active inflammation. Mild BWI predominantly involves the superficial mucosa in a contiguous pattern. Focal isolated ileal erosions, mucous gland metaplasia, or patchy edema with mild active inflammation are features of CD.
TL;DR: In this paper, a study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples.
Abstract: This study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples. Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were stained for clusterin-beta, MUC4, survivin, and mesothelin. For each biomarker, the staining patterns in adenocarcinoma and in reactive ductal epithelium were evaluated and compared. Clusterin-beta stained reactive ductal epithelium significantly more frequently than pancreatic adenocarcinoma (P < .001). In comparison, MUC4 and mesothelin were expressed more frequently in pancreatic adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P < .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin-beta (90% vs 7%; P < .001) were noted significantly more frequently in adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-beta and MUC4 can help distinguish reactive ductal epithelial cells from the cells of pancreatic adenocarcinoma in FNA samples.
TL;DR: The hypothesis that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors is hypothesized and it is suggested that current smoking obscures intrinsically higher expression in COPD.
Abstract: Smoking may affect epithelial repair and differentiation differentially in smokers with and without chronic obstructive pulmonary disease (COPD). We hypothesized that epithelial repair is disturbed in patients with COPD owing to higher expression of epidermal growth factor (EGF)-like factors and/or receptors. We studied epithelial expression of EGF, transforming growth factor a, amphiregulin, heregulin (HRG), betacellulin (BTC), and their receptors, EGFR, HER-2, and HER-3, by immunohistochemical analysis in resected bronchial tissue from 20 subjects with (forced expiratory volume in 1 second [FEV(1)] 85% predicted value) COPD. All subjects underwent surgery for lung cancer. The proportion of intact, damaged, goblet, or squamous metaplastic epithelium was similar in subjects with and without COPD. Regardless of smoking status, HRG expression was higher in intact epithelium of patients with COPD than in those without. Subgroup analysis showed higher EGFR expression in intact epithelium (1.4 times; P pound .04) and higher EGF, BTC, and HRG expression in damaged epithelium (1.4-1.8 times; P
TL;DR: Evaluated epidermal growth factor receptor (EGFR) protein expression by immunohistochemical analysis and EGFR gene amplification by fluorescence in situ hybridization in 199 consecutive newly diagnosed and surgically treated patients with primary non-small cell lung carcinoma (NSCLC) and correlated results with clinicopathologic findings.
Abstract: We evaluated epidermal growth factor receptor (EGFR) protein expression by immunohistochemical analysis and EGFR gene amplification by fluorescence in situ hybridization in 199 consecutive newly diagnosed and surgically treated patients with primary non-small cell lung carcinoma (NSCLC) and correlated results with clinicopathologic findings. EGFR protein expression was more common in squamous cell carcinoma (SCC; 17 [26.2%]) than in adenocarcinoma (14 [11.1%]; (P = .0076) and more frequently associated with EGFR amplification (8 [14.5%] vs 4 [3.6%] cases; P = .0208). Poor differentiation was associated with a higher average number of EGFR gene copies per cell (mean, 4.18; P = .0322) and a higher EGFR/chromosome 7 ratio (mean, 1.84; P = .0324). N0 disease showed a higher number of EGFR gene copies (mean, 4.196; P = .0163). SCCs demonstrated a higher EGFR/chromosome 7 ratio than adenocarcinomas (mean, 1.95 vs 1.47; P = .0324), particularly T1 tumors (mean, 1.79; P = .0243). Statistical analysis failed to show correlation between outcome and EGFR protein expression and gene amplification in early NSCLC. EGFR protein expression was uncoupled from gene amplification in most cases, although good correlation occurred in a subset of SCCs.
TL;DR: This first step of an Agency for Healthcare Research and Quality patient safety project measured the performance metrics of thyroid gland fine-needle aspiration, performed root cause analysis to determine the causes of error, and proposed error-reduction initiatives to address specific errors.
Abstract: Scant published data exist on redesigning pathology practice based on error data. In this first step of an Agency for Healthcare Research and Quality patient safety project, we measured the performance metrics of thyroid gland fine-needle aspiration, performed root cause analysis to determine the causes of error, and proposed error-reduction initiatives to address specific errors. Eleven cytologists signed out 1,543 thyroid gland aspirates in 2 years, and surgical pathology follow-up was obtained in 364 patients. Of the 364 patients, 91 (25.0%) had a false-negative diagnosis and 36 (9.9%) a false-positive diagnosis. Root cause analysis showed that major sources of error were preanalytic (poor specimen quality) and analytic (interpretation of unsatisfactory specimens as nonneoplastic and lack of diagnostic category standardization). We currently are evaluating the effectiveness of error reduction initiatives that target preanalytic and analytic portions of the diagnostic pathway.
TL;DR: Eight sessile serrated adenoma, right colon polypectomies with focal invasive adenocarcinoma or high-grade Dysplasia were studied to identify features indicating a high risk of transformation and characterize the morphologic features of serrated dysplasia.
Abstract: Eight sessile serrated adenoma (SSA), right colon polypectomies with focal invasive adenocarcinoma or high-grade dysplasia were studied to identify features indicating a high risk of transformation and characterize the morphologic features of serrated dysplasia; 6 cases had invasive adenocarcinoma; 2 were high-grade dysplasia. All 8 were microsatellite unstable-high and had absent hMLH1 nuclear immunoreactivity. The mean patient age at polypectomy was 69.5 years (range, 57.1–83.9 years). Mean polyp maximum dimension was 8.5 mm (range, 6–12 mm). The majority of each polyp was nonmalignant SSA. All 8 cases had an abrupt transition from benign to high-grade in situ or invasive malignancy. In the 6 invasive adenocarcinomas, the neoplasm extended directly down into the submucosa without lateral intramucosal spread. The mean maximum dimension of the invasive adenocarcinoma was 2.9 mm (range, 2–4 mm). All 8 cases had high-grade serrated-type dysplasia. The nonmalignant SSAs had marked expansion of the proliferative zone. Crypts adjacent to malignancy had moderately enlarged nuclei, irregular nuclear membranes, and overly prominent nucleoli. SSA crypts were lined by a variety of gastric-type cells; no cell type predominated. Foci of adjacent crypts had similar cytologic features. Small proximal SSAs can transform into adenocarcinoma without a component of adenomatous dysplasia.
TL;DR: The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.
Abstract: We aimed to study the expression and localization of the molecular components of enterocyte junctions in celiac disease together with the level of tyrosine phosphorylation, a phenomenon known to affect their cellular distribution and function, and to explore the influence of proinflammatory cytokines. Duodenal biopsy specimens from patients with celiac disease and control subjects were used for immunoprecipitation, immunoblotting, and immunolocalization by using antioccludin, anti-zonula occludens (ZO)-1, anti-E-cadherin, anti-beta-catenin, and antiphosphotyrosine antibodies. The same procedures were carried out on filter-grown Caco-2 cells incubated in the absence or presence of interferon g and tumor necrosis factor a. In active celiac disease, the absence of a phosphorylated ZO-1 and the extensive phosphorylation of beta-catenin might be responsible for the absence of membranous localization of occludin and E-cadherin, respectively. The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.