Showing papers in "Archives of Pathology & Laboratory Medicine in 2003"

Human papillomavirus: epidemiology and public health.

Abstract: Approximately 15 types of human papillomavirus (HPV) infection cause virtually all cases of cervical cancer. Human papillomavirus 16 is the major type, accounting for approximately 50% of cases. The major steps of cervical carcinogenesis include HPV infection, viral persistence and progression to precancer (as opposed to viral clearance), and invasion. Human papillomavirus is the most common sexually transmitted infection. However, most HPV infections become undetectable by even sensitive HPV DNA testing within 1 to 2 years. The prevalence of infection peaks at young ages and declines thereafter, perhaps as the result of HPV type-specific acquired immunity. Most HPV infections are neither microscopically evident nor visible, making HPV DNA detection the diagnostic reference standard. Poorly defined immunologic factors are the major determinants of viral outcome. Smoking, multiparity, and long-term oral contraceptive use increase the risk of persistence and progression. Other sexually transmitted infections (eg, Chlamydia trachomatis), chronic inflammation, and nutritional factors might also play a role. Overt, long-term viral persistence in the absence of precancer is uncommon. New prevention strategies can be derived from the evolving knowledge of HPV carcinogenesis. Human papillomavirus vaccination is the ultimate prevention strategy, and large-scale trials are already underway. In the meantime, HPV DNA diagnostics are more sensitive although less specific than cytology, permitting a consideration of lengthened screening intervals. In terms of public health education, clinicians and patients will need to shift discussions of the mildly abnormal Papanicolaou test to consideration of HPV infection as a common sexually transmitted infection that rarely causes cervical cancer.

Findings to date from the ASCUS-LSIL Triage Study (ALTS).

Abstract: Controversy exists in the United States regarding the proper evaluation and management of low-grade squamous intraepithelial lesion (LSIL) and equivocal (atypical squamous cells of undetermined significance [ASCUS, now ASC-US]) cervical cytologic interpretations. To address this issue, the National Cancer Institute initiated the ASCUS-LSIL Triage Study (ALTS). ALTS is a multicenter, randomized clinical trial designed to evaluate 3 alternative methods of management, namely, immediate colposcopy, cytologic follow-up, and triage by human papillomavirus (HPV) DNA testing. This article summarizes the major findings of ALTS that have been published to date. Patients with ASCUS (n = 3488) or LSIL (n = 1572) were randomly assigned to research arms between November 1996 and December 1998, and were monitored for 2 years. The disease outcome was histologic cervical intraepithelial neoplasia (CIN) 3/cancer. The prevalence of oncogenic HPV was too high to permit effective triage of LSIL using HPV DNA testing by Hybrid Capture 2. However, for the women referred with a cytologic interpretation of ASCUS, HPV triage proved useful, with sensitivity equivalent to immediate colposcopy and a halving of colposcopic referrals. Among older women with ASCUS, HPV testing remained sensitive for detecting CIN 3 and cancer, but the referral percentage was dramatically lower compared to younger women. ALTS yielded insight into the performance of cytology and histopathology; experienced pathologists differed significantly in their interpretations of cervical abnormalities, especially histologic CIN 1 and cytologic ASCUS. Nonetheless, it was possible to distinguish a relatively uncommon type of ASCUS, equivocal for high-grade squamous intraepithelial lesion, that has a high positive predictive value for identifying women with underlying high-grade CIN. Many additional analyses are underway.

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases.

Abstract: Context.—Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) share many clinical features and have been difficult to separate into distinct entities. Histologic examination of organs from autopsied patients suggested that TTP and HUS have dissimilar lesions of different severity and distribution. Objective.—To perform a retrospective observational review of autopsied patients with TTP or HUS to compare the nature and severity of the lesions found. Design.—To examine the pathologic features of these conditions, we reviewed all cases among 51 350 indexed autopsies at The Johns Hopkins Hospital (Baltimore, Md) diagnosed with TTP or HUS, and included those showing multiple arteriolar thrombi or their sequela. Results.—The 56 cases that met the inclusion criteria fell into 2 distinct groups, based on distribution and severity of arteriolar lesions. In 25 patients classified as having TTP, platelet-rich thrombi were present—in decreasing severity—in heart, pancreas, kidney...

Implementation of a point-of-care satellite laboratory in the emergency department of an academic medical center. Impact on test turnaround time and patient emergency department length of stay.

Abstract: Context.—Emergency department (ED) overcrowding has reached crisis proportions in the United States. Many hospitals are seeking to identify process reengineering efforts to reduce crowding and ED patient length of stay (LOS). Objectives.—To investigate the impact of a point-of-care testing (POCT) satellite laboratory in the ED of a large academic medical center. Setting.—The ED of the Massachusetts General Hospital, Boston, Mass. Design and Outcome Measures.—Evaluation of physician satisfaction, turnaround time (TAT), and ED LOS before and after implementation of a POCT laboratory. ED LOS was measured by patient chart audits. TAT was assessed by manual and computer audits. Clinician satisfaction surveys measured satisfaction with test TAT and test accuracy. Results.—Blood glucose, urine human chorionic gonadotropin, urine dipstick, creatine kinase–MB, and troponin tests were performed in the ED POCT laboratory. Test TAT declined an average of 87% after the institution of POCT. The ED LOS decrease...

Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs.

Abstract: Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.

Human papillomavirus testing methods.

Abstract: Testing for human papillomavirus (HPV) relies exclusively on techniques of molecular biology using nucleic acid probes. Tests for HPV using nucleic acid probes have been commercially available since the late 1980s, but early tests were cumbersome, involving the use of nucleic acid probes labeled with radioactive phosphorus (32P). These early HPV tests did not achieve widespread use because they did not detect all oncogenic HPV genotypes. The current commercial HPV detection kit, Digene's Hybrid Capture 2 kit, detects virtually all high-risk oncogenic HPV types, as well as most low-risk nononcogenic HPV genotypes. The Hybrid Capture 2 test format is a proprietary nucleic acid hybridization signal amplification system owned by Digene Corporation. Virtually all test formats for DNA sequence analysis are amenable to applications intended to detect and perhaps quantify the various HPV genotypes. These methods can involve direct hybridization with complementary DNA probes, such as Southern blotting or in situ hybridization, signal amplification, such as the Hybrid Capture 2 method or target nucleic acid amplification, most notably the polymerase chain reaction (PCR). Polymerase chain reaction has been used for HPV detection, genotyping, and viral load determination. General or consensus primer-mediated PCR assays have enabled screening for a broad spectrum of HPV types in clinical specimens using a single PCR reaction. Following amplification using consensus primers, individual HPV genotypes are identified using a variety of methods. Using consensus primers in a test format known as real-time quantitative PCR (RQ-PCR), it is possible to generate viral load (concentration) data from reaction curves generated by monitoring PCR reaction kinetics in real time.

Solitary fibrous tumors in the central nervous system. A clinicopathologic review of 18 cases and comparison to meningeal hemangiopericytomas.

Abstract: Context.—Solitary fibrous tumors (SFTs) of the central nervous system are rare neoplasms that usually present as dura-based masses and clinically resemble meningiomas. Histologically, they can be similar to fibrous meningioma or hemangiopericytoma (HPC). In particular, densely cellular regions seen in some SFTs can be indistinguishable from HPC. Little is known about the biological behavior of SFTs, although most seem amenable to total resection. Objectives.—To define the clinicopathologic spectrum of SFTs in the central nervous system and to outline their differences from HPC and meningioma. Design.—We present the clinicopathologic features of 18 patients with SFT and compare them with those of an age- and sex-matched cohort of HPCs. Results.—Eleven SFTs were supratentorial, 3 were infratentorial, and 4 were intraspinal. Four of the 18 tumors were intra-axial (2 in the lateral ventricles and 2 within the spinal cord). Histologically, SFTs were similar to their soft tissue counterparts. Six tumor...

Male versus female breast cancers. A population-based comparative immunohistochemical analysis.

Abstract: Context The rate of male breast cancer is a small fraction of that observed in females, thus severely limiting our understanding of the pathogenesis of this condition. It remains unclear whether the biological behavior and tumor progression associated with male breast cancer parallel that of the female form. Objectives To evaluate the immunohistochemical profile of male breast carcinomas and to compare this profile with that of stage-matched female breast cancers. Design Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970-1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue blocks available for the purposes of this study. All cases were reviewed and a standardized modified Bloom-Richardson grading criterion was applied. Estrogen receptor status, progesterone receptor status, c-Erb-B2 expression, p53 expression, and Bcl-2 expression were evaluated by immunohistochemistry. Results from 240 consecutive cases of stage-matched female breast cancers analyzed in the same laboratory were used as a standard set for comparison. Results Male breast cancers tended to be high grade (85% grade 3) in comparison with the female breast cancers (50% grade 3). In descriptive analysis across all stages of disease, male carcinomas were more frequently estrogen receptor positive (81% vs 69%) than their female counterparts. Despite their high grade, they were less likely to overexpress p53 (9% vs 28%) and Erb-B2 (5% vs 17%) than the female counterparts. There was no significant difference in either progesterone receptor (63% vs 56%) or Bcl-2 (79% vs 76%) overexpression. Stratified analysis by stage-matched controls showed no statistically significant differences among the men and women with stage I disease. However, in stage II-matched samples, statistically significant differences were observed between the 2 groups. The male cancers were more likely to overexpress estrogen receptor (81.6% vs 64.4%, P = .04), progesterone receptor (71.1% vs 47.5%, P = .01), and Bcl-2 (78.9% vs 69.4%, P = .20). They also showed statistically significant lower expression of p53 (7.9% vs 36.3%, P = .001) and Erb-B2 (5.3% vs 23.8% P = .01). Conclusion Male breast cancers display distinct immunophenotypic differences from those occurring in women, implying a different pathogenesis in the evolution and progression of this disease. Such differences may play key roles in therapeutic management, warranting different treatment strategies in comparison to female breast cancers.

Innate Immune-Related Receptors in Normal and Psoriatic Skin

Abstract: Context.—A precise role for the innate immune system in psoriasis remains to be determined. Surface receptors, including Toll-like receptors (TLRs) that recognize bacterial ligands and CD91, which recognizes heat shock proteins (HSPs), are implicated in both innate and adaptive immunity. Objective.—Since skin is exposed to various exogenous stimuli, which can provoke or exacerbate psoriasis, we characterized expression and function of TLRs, CD91, and HSPs in normal and psoriatic skin. Design.—A variety of skin-derived cells and blood-derived cells were analyzed both in vivo and in vitro; samples were obtained from 24 different individuals for innate immune-related receptor expression and function. By comparing and contrasting individuals with healthy skin and psoriatic patients, several specific differences were identified. Results.—Immunohistochemistry-based expression profiling revealed TLR1 expression in epidermal dendritic cells (DCs) and dermal dendritic cells (DDCs) in normal skin, as well ...

Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data.

Abstract: Context.—Acute leukemia displays characteristic patterns of surface antigen expression (CD antigens), which facilitate their identification and proper classification and hence play an important role in instituting proper treatment plans. In addition to enzyme cytochemical analysis, multiparameter flow cytometric analysis has become commonplace in most laboratories for that purpose. The essential role and caveats of flow cytometry in that regard, however, have received little scrutiny. Objective.—To evaluate the expression of commonly used immunomarkers and patterns in various acute leukemias to help define the best use and role of multiparameter flow cytometry in the diagnosis and proper classification of acute leukemias. Design.—We have retrospectively analyzed the immunophenotypic data from 508 de novo adult and pediatric acute leukemia patients, as studied using multiparameter flow cytometry in addition to routine morphologic and enzyme cytochemical analysis. Cytogenetic and/or molecular data ...

Characterization of 4 Mantle Cell Lymphoma Cell Lines

Abstract: Context.—Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by t(11;14)(q13;q32) and cyclin D1 overexpression. The pathogenesis of MCL has not been comprehensively studied, which can be attributed in part to the paucity of well-characterized MCL cell lines. Objectives.—We collected 4 previously developed MCL cell lines and performed extensive characterization, including the susceptibly of these cell lines to transduction by adenovirus vectors. Our aim was to facilitate the establishment of an in vitro model that can be reliably used to study the pathogenesis of MCL. Methods.—Standard techniques were used to compare the morphologic, immunophenotypic, and cytogenetic features of the 4 cell lines. In addition, Western blotting was used to investigate the presence of several cell cycle- and apoptosis-related proteins. TP53 DNA sequencing was also performed on the cell lines. The adenoviral transduction efficiency was assessed using an adenoviral vector carrying...

Allergic transfusion reactions: an evaluation of 273 consecutive reactions.

Abstract: Context.-Allergic reaction to transfusion is common. However, the review of a large series of allergic transfusion reactions has not been performed. Objective.-To review a large series of allergic transfusion reactions. Design.-A retrospective review of all reported and evaluated transfusion reactions during a 9-year period at 1 institution was performed. Associated clinical signs and symptoms were evaluated. Setting.-Large, tertiary-care teaching hospital. Results.-A total of 1613 adverse reactions to transfusion were evaluated. Allergic transfusion reactions accounted for 17% (273 of 1613) of the transfusion reactions. Severe allergic reactions (anaphylaxis, anaphylactoid signs and symptoms, and/or hypotension) were observed in 21 patients (7.7% of allergic reactions, or 1.3% of all transfusion reactions). Serum tryptase, a marker for anaphylaxis, was measured in 1 patient and determined to be borderline elevated. Five patients experienced allergic transfusion reactions to autologous red cell transfusions. One patient experienced hives during the transfusion of a major ABO mismatched red blood cell. A wide variety of skin manifestations were observed, but 26 (9.5%) patients did not have skin manifestations. Allergic transfusion reactions were estimated to occur in approximately 1 in 4124 blood components transfused, or 1 in 2338 transfusion episodes. Severe allergic reactions occurred in approximately 1 in 30281 transfusions. No deaths directly attributable to transfusion were observed in this patient group. Conclusions.-The clinical presentation of allergic transfusion reactions was quite variable, and the pathophysiology remains unclear. Recommendations for clinical evaluation and therapy remain problematic and often empirical.

Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract.

Abstract: Objective.—Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor. Methods.—Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa. Results.—The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P = .008) and were more frequently amelanotic (14 vs 12, P = .04...

Male Versus Female Breast Cancers

Abstract: Context.—The rate of male breast cancer is a small fraction of that observed in females, thus severely limiting our understanding of the pathogenesis of this condition. It remains unclear whether the biological behavior and tumor progression associated with male breast cancer parallel that of the female form. Objectives.—To evaluate the immunohistochemical profile of male breast carcinomas and to compare this profile with that of stage-matched female breast cancers. Design.—Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970–1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue blocks available for the purposes of this study. All cases were reviewed and a standardized modified Bloom-Richardson grading criterion was applied. Estrogen receptor status, progesterone receptor status, c-Erb-B2 expression, p53 expression, and Bcl-2 expression were evaluated by immunohistochemistry...

Comparison of polymerase chain reaction with histopathologic features for diagnosis of tuberculosis in formalin-fixed, paraffin-embedded histologic specimens.

Abstract: Objective.-To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.-We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.-Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.-TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.

Pulmonary sclerosing hemangioma with lymph node metastases: report of 4 cases.

Abstract: Context.-Sclerosing hemangioma is an unusual pulmonary tumor. Previously, 4 patients with pulmonary sclerosing hemangioma and lymph node metastases have been described in the literature. objective.-To report 4 additional cases of metastatic sclerosing hemangioma. Design.-Retrospective review of the authors' consultation files and review of histologic sections of pulmonary tumors and lymph node metastases. Results.-Four cases of a morphologically benign pulmonary sclerosing hemangioma with regional lymph node metastases (including hilar, peribronchial, and interlobar metastases) were identified. The patients (3 female, 1 male) had a mean age of 39 years (range, 10-56 years). The tumors ranged in size (greatest dimension) from 1.5 to 4.7 7 cm (mean, 3.1 cm). The pulmonary tumors were typical circumscribed sclerosing hemangiomas without mitotic activity, angiolymphatic invasion, or necrosis. One tumor had focal cytologic atypia. The metastases were identified in hilar lymph nodes that were removed at operation for the lung nodule. One patient received adjuvant chemotherapy for adenocarcinoma. All of the patients are alive. No recurrences or residual disease has been detected at a mean follow-up of 4.7 years (range, 2.3-10 years). Conclusions.-on the basis of case data from the 4 patients described here and the 4 patients described previously, metastases to regional lymph nodes from pulmonary sclerosing hemangioma may occur but are rare and do not appear to affect prognosis.

Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish?

Abstract: Context—Fish consumption has been associated with a decreased risk of coronary artery disease Recent studies have illustrated that the high mercury content in cold-water fish may negate the cardiovascular benefits of fish meals Fish oils have similar antiatherogenic properties to fish, and similar studies should be performed to determine the level of mercury in fish oils Objective—To determine the concentration of mercury in 5 over-the-counter brands of fish oil Results—The levels of mercury in the 5 different brands of fish oil ranged from nondetectable (<6 μg/L) to negligible (10–12 μg/L) The mercury content of fish oil was similar to the basal concentration normally found in human blood Conclusions—Fish are rich in omega-3 fatty acids, and their consumption is recommended to decrease the risk of coronary artery disease However, fish such as swordfish and shark are also a source of exposure to the heavy metal toxin, mercury The fish oil brands examined in this manuscript have neglig

Interobserver and intraobserver variability using the Fuhrman grading system for renal cell carcinoma

Abstract: Context.—Histologic grading of renal cell carcinoma has been shown to be second to staging in prognostic significance. A 4-tier grading scheme proposed by Fuhrman et al and based on nuclear features is the system used most frequently in North America. There are, however, very few studies in the literature assessing the interobserver variability for this system, and to our knowledge, none addressing intraobserver variability. Objective.—To assess the interobserver and intraobserver agreement among 4 pathologists using the Fuhrman nuclear grading scheme for renal cell carcinoma. Design.—Representative hematoxylin-eosin–stained slides of 99 consecutive primary renal cell carcinoma cases diagnosed between 1994 and 1999 at St Joseph's Hospital, Hamilton, Ontario, were independently graded by 4 pathologists on 2 occasions with a minimum period of 3 months separating the 2 readings. Results.—Intraobserver κ values ranged from 0.29 to 0.62 (mean = 0.45), and interobserver κ values ranged from 0.19 to 0.3...

Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 [correction of hMLH6] immunostaining.

Abstract: Context Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard. Objective The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI. Methods In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters. Results Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases. Conclusions These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.

Allergic Transfusion Reactions

Abstract: Context.—Allergic reaction to transfusion is common. However, the review of a large series of allergic transfusion reactions has not been performed. Objective.—To review a large series of allergic transfusion reactions. Design.—A retrospective review of all reported and evaluated transfusion reactions during a 9-year period at 1 institution was performed. Associated clinical signs and symptoms were evaluated. Setting.—Large, tertiary-care teaching hospital. Results.—A total of 1613 adverse reactions to transfusion were evaluated. Allergic transfusion reactions accounted for 17% (273 of 1613) of the transfusion reactions. Severe allergic reactions (anaphylaxis, anaphylactoid signs and symptoms, and/or hypotension) were observed in 21 patients (7.7% of allergic reactions, or 1.3% of all transfusion reactions). Serum tryptase, a marker for anaphylaxis, was measured in 1 patient and determined to be borderline elevated. Five patients experienced allergic transfusion reactions to autologous red cell t...

Hantaviruses A Short Review

Abstract: ○ Objective-Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases of humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) This article presents a concise review of hantavirus biology, the medical features of HFRS and HPS, and tests for the detection of hantavirus infections in humans Data Synthesis-Hemorrhagic fever with renal syndrome is a disease found outside the Americas and denotes a group of clinically similar illnesses that vary in severity relative to the causative agent Hantavirus pulmonary syndrome is associated with higher mortality than HFRS, was first recognized as a hantavirus disease in 1993, and occurs within the American continents Recent genetic studies show that both Old and New World hantavirus species co-evolved with specific rodent hosts The list of distinct hantaviruses associated with HPS is growing The burgeoning human population is causing disruption of natural habitats as more and more land is cleared for commercial and residential purposes Many rodents readily adapt to life in human settlements, where they generally benefit from reduced predation and where they sometimes proliferate to high numbers Conclusions-Although often referred to as emerging pathogens, HPS-associated hantaviruses emerge through increased exposure of humans to rodents and their excreta, not through genetic drift or reassortment of the viral genome Based on current human population growth and development trends, hantavirus diseases will become more common in the near future unless public health measures are taken to curtail or eliminate rodents from human communities

Mammaglobin expression in lymph nodes is an important marker of metastatic breast carcinoma.

Abstract: Context.—Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member of the uteroglobin family, is known to be overexpressed in human breast cancer. Objective.—We investigated mammaglobin A expression in metastatic carcinomas of lymph nodes from the breast and various other organs and its usefulness in identifying metastatic carcinoma of the breast. For comparative purposes, we also investigated BRST-1 and BRST-2 expression. Design.—We produced recombinant mammaglobin and polyclonal antimammaglobin antibodies. Mammaglobin expression was analyzed by immunohistochemical staining using a tissue microarray and by reverse transcription–polymerase chain reaction in 210 carcinomas, including those of the breast (n = 70), lung (n = 30), stomach (n = 30), colorectum (n = 25), hepatobiliary tract (n = 20), urinary tract (n = 10), thyroid gland (n = 10), ovary and endometrium (n = 10), and salivary gl...

Development and validation of a molecular beacon probe-based real-time polymerase chain reaction assay for rapid detection of methicillin resistance in Staphylococcus aureus.

Abstract: Context.—A rapid, real-time, duplex, fluorescent molecular beacon probe–based polymerase chain reaction (PCR) assay was recently developed for the detection of methicillin-resistant Staphylococcus aureus. Objective.—To describe the development and validation of this unique assay. Design.—Prospective laboratory analysis. Setting.—Urban health region/centralized diagnostic microbiology laboratory. Bacterial Strains.—One hundred eighty-one previously characterized clinical and American Type Culture Collection isolates, including 50 strains each of methicillin-resistant and methicillin-sensitive S aureus, plus 50 strains of coagulase-negative staphylococci and 31 nonstaphylococcal isolates to ensure assay specificity. Intervention.—Assays were performed on purified genomic DNA extracted from growing bacterial colonies. Two sets of oligonucleotide primers were used to specifically amplify the mecA and nuc genes, followed by detection of amplicons using fluorophore-labeled molecular beacon probes. Assa...

Anaplastic large cell lymphoma arising in a silicone breast implant capsule: a case report and review of the literature.

Abstract: Anaplastic large cell lymphoma is a rare type of primary breast lymphoma. We report a case of anaplastic large cell lymphoma, T-cell phenotype, occurring in the periprosthetic capsule of a silicone breast prosthesis 9 years after implantation for augmentation mammoplasty. This case is unique for its unusual presentation.

Concept-match medical data scrubbing. How pathology text can be used in research.

Abstract: Context.—In the normal course of activity, pathologists create and archive immense data sets of scientifically valuable information. Researchers need pathology-based data sets, annotated with clinical information and linked to archived tissues, to discover and validate new diagnostic tests and therapies. Pathology records can be used for research purposes (without obtaining informed patient consent for each use of each record), provided the data are rendered harmless. Large data sets can be made harmless through 3 computational steps: (1) deidentification, the removal or modification of data fields that can be used to identify a patient (name, social security number, etc); (2) rendering the data ambiguous, ensuring that every data record in a public data set has a nonunique set of characterizing data; and (3) data scrubbing, the removal or transformation of words in free text that can be used to identify persons or that contain information that is incriminating or otherwise private. This article ...

Schwannoma of the sinonasal tract: a clinicopathologic and immunohistochemical study of 5 cases.

Abstract: Context.—Peripheral nerve sheath tumors are soft tissue neoplasms rarely encountered in the nasal cavity and paranasal sinuses. Objective.—To describe the clinicopathologic and immunohistochemical features of a series of schwannomas of the sinonasal tract. Design.—Surgical pathology files were searched for the diagnosis “sinonasal schwannoma.” All histologic documents and clinical data were reviewed. Immunohistochemistry was performed on paraffin-embedded tissue with antibodies to S100 protein, epithelial membrane antigen, CD34, and MIB-1. Results.—Five cases of sinonasal schwannoma were retrieved; patients included 3 women and 2 men, aged 20 to 56 years. Three cases were located in the ethmoid sinus. Clinical symptoms were nonspecific (nasal obstruction, epistaxis, and anosmia). All tumors were treated with conservative surgical resection. Pathologic examination showed a spindle cell proliferation without encapsulation in all cases. No cytologic atypia was seen, and the mitotic activity was low ...

The Relationship Between p63 and p53 Expression in Normal and Neoplastic Breast Tissue

Abstract: Context—p63 is a recently described p53 homologue Despite structural homology, they have different activities Objectives—To obtain new insights into the role of p63 in normal and neoplastic breast tissue and to verify the possible association between p63 and p53 in breast carcinomas Design—Immunohistochemistry in 85 breast carcinomas using p63, smooth muscle actin (1A4), p53, estrogen receptor, and progesterone receptor The p63-positive cases were submitted to a double-immunolabeling study using p63 with 1A4, cytokeratin 7, and 34βE12 Clinical data were retrieved from medical files Results—p63, like 1A4, stained a single and continuous layer surrounding normal breast ductal and alveolar epithelium In carcinomas, p53 was expressed in 2117% of carcinomas, whereas p63 was expressed only in poorly differentiated ductal carcinomas (1176% of cases) p63-positive cells coexpressed 1A4 and 34βE12, but not cytokeratin 7 Expression of p63 correlated with pathologic staging, tumor size, histol

Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature.

Abstract: Objective.—The rapid intraoperative parathyroid hormone assay is transforming the parathyroidectomy procedure. We present a review of the literature on the use of the assay as an adjunct to surgery. To our knowledge, this is the first review of the literature to encompass and compare all known primary studies of this assay in parathyroidectomy patients. Data Sources.—Articles were collected by searching MEDLINE databases using relevant terminology. The references of these articles were reviewed for additional studies. Supplementary articles pertinent to the parathyroidectomy procedure, preoperative parathyroid localization studies, and intraoperative parathyroid hormone assay development also were examined. Study Selection and Data Extraction.—One hundred sixty-five references were analyzed and categorized separately into groups. Data Synthesis.—The primary studies of intraoperative data on patients undergoing parathyroidectomy were compared when possible. Studies were analyzed by type of assay u...

Propionic Acidemia: A Neuropathology Case Report and Review of Prior Cases

Abstract: Propionic acidemia is a disorder of branch-chain amino acid and odd-chain fatty acid metabolism. The clinical features typically begin shortly after birth, with rare cases presenting in young adulthood. This disorder most commonly is characterized by episodic decompensations with dehydration, lethargy, nausea, and vomiting as well as a risk for neurologic sequelae. The defect is in the propionyl-CoA carboxylase enzyme with a resultant accumulation of toxic organic acid metabolites. Neuropathologic findings in this inborn error of metabolism have not been extensively characterized but include white matter spongiosis in neonates and a variable appearance in older children. We describe the pertinent literature on the neuropathology of propionic acidemia and a case report of a 4-year-old girl who had widespread gray matter vacuolization at postmortem examination. Although a previously unreported finding in propionic acidemia, diffuse gray matter vacuolization has been described in other fatty acid metabolic disorders.

Chromosomal translocations involved in non-Hodgkin lymphomas.

Abstract: Context.—The discovery that recurrent chromosomal translocations are involved in the pathogenesis of non-Hodgkin lymphomas has greatly improved our understanding of these diseases and revolutionized their diagnosis. Objective.—To review the mechanisms by which chromosomal translocations occur and contribute to the pathogenesis of various types of non-Hodgkin lymphomas and to review the utility of molecular genetic methods for the assessment of these translocations. Data Sources and Study Selection.—Primary research studies and reviews published in the English language that focus on chromosomal translocation and non-Hodgkin lymphomas. Data Extraction and Synthesis.—Chromosomal translocations, which usually result in oncogene activation, occur in many types of B- and T-cell lymphoma, and their detection is helpful for establishing an accurate diagnosis and monitoring disease following therapy. However, the precise mechanisms that explain how translocations occur remain unknown, although for some ty...