bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathology and Clinicopathologic Features of Penile Tumors
Authors: Lam King Y. , Chan Kwok W. 
Published: January 2021

AbstractObjectives.—To examine the histologic features of p21 in penile tumors and to determine the role of p21 and p53 in the pathogenesis of this group of tumors.Methods.—The clinicopathologic features of 87 patients with penile tumors were studied. The expression of p53 and p21 proteins in 49 cases was investigated by immunohistochemistry.Results.—Of the 87 tumors studied, 84 represented primary penile tumors (72 malignant and 12 benign) and 3 represented secondary tumors (2 from bladder, 1 from nasopharynx). The primary malignant penile tumors included 66 surface carcinomas with squamous differentiation (92%), 3 cases of Paget disease (4%), 1 case of Bowen disease (1%), and 2 penile urethral squamous cell carcinomas (3%). The former group was subdivided into squamous cell carcinoma (n = 50), verrucous carcinoma (n = 8), basaloid squamous cell carcinoma (n = 3), adenoid squamous cell carcinoma (n = 3), spindle cell carcinoma (n = 1), and adenosquamous carcinoma (n = 1). The benign tumors were squamous cell papillomas (n = 10) and fibromatoses (n = 2). Expression of p21 and p53 was noted in 40% and 89%, respectively, of the 47 patients with primary surface penile carcinoma with squamous differentiation. Positive p21 and p53 expression was also seen in 2 cases of Paget disease. Staining for p21 was often weak and was found in the suprabasal region of carcinomas with squamous differentiation, while p53 expression was seen in the basal region of squamous cell carcinomas. Preinvasive lesions also showed p21 and p53 expression. An inverse correlation between p53 and p21 expression (p53+/p21− or p53−/p21+) was noted in half of the squamous cell carcinomas, 4 of 5 verrucous carcinomas, 2 of 3 basaloid squamous cell carcinomas, and in 1 spindle cell carcinoma. The other cases did not show this correlation.Conclusions.—Penile tumors had different histologic variants and p21/p53 expression patterns. Expression of p21 did play a role in some tumors and could be dependent or independent of p53 expression.
Comparison of Glycoprotein Expression Between Ovarian and Colon Adenocarcinomas
Authors: Multhaupt Hinke A. B. , Arenas-Elliott Carmen P. , Warhol Michael J. 
Published: January 2021

Abstract
Objective.—Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens.
Design.—We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas.
Results.—CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities.
Conclusion.—A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.
Hoechst 33342 Induces Apoptosis in HL-60 Cells and Inhibits Topoisomerase I In Vivo
Authors: Zhang Xinbo , Chen Jenn , Davis Bruce , Kiechle Frederick 
Published: January 2021

Abstract
Context.—Bisbenzimides (Hoechst 33342 and Hoechst 33258) are cell-permeable, adenine-thymine–specific dyes that bind to the minor groove of DNA and stain DNA. Hoechst 33342 induces apoptosis in BC3H-1 myocytes and hepatoma cells.
Objective.—To determine if Hoechst 33342 or Hoechst 33258 induces apoptosis in human promyelocytic leukemia cells (HL-60) and inhibits topoisomerase I activity.
Design.—A variety of methods were used to detect apoptosis: cell viability (trypan blue exclusion), nuclear fluorescence staining (Hoechst 33342 or Hoechst 33258 stained for 10 minutes), flow cytometric quantitation of annexin binding to phosphatidylserine, and DNA fragmentation (agarose gel electrophoresis). Topoisomerase I activity was determined by a plasmid unwinding assay.
Setting.—A large teaching hospital and research laboratories.
Patients.—None.
Intervention.—None.
Main Outcome Measurements.—Apoptosis is characterized by decreased cell viability, condensation of nuclear chromatin, increased phosphatidylserine translocation, and DNA fragmentation into oligonucleosomes composed of multiples of 180 to 200 base pairs. Inhibition of endogenous nuclear topoisomerase I is detected by the absence of plasmid unwinding from a tightly coiled to relaxed form.
Results.—Hoechst 33342, but not Hoechst 33258, induced apoptosis in the HL-60 cells in a time- and dose-dependent manner. Endogenous nuclear topoisomerase I activity in HL-60 cells was inhibited by treatment with Hoechst 33342 but not Hoechst 33258.
Conclusion.—Hoechst 33342–induced HL-60 cell apoptosis may be related to the dye's inhibition of topoisomerase I activity.
An Optimized Strategy for Choosing the Number of Platelet Concentrates to Pool
Authors: Hoeltge Gerald A. , Shah Amrik , Miller John P. 
Published: January 2021

Abstract
Context.—The number of platelet concentrates (PCs) pooled per dose varies widely. The number should be based on quality control statistics.
Objective.—To determine the optimal number of PCs per pool that will achieve a target dose.
Design.—The population statistics of PC cell counts were obtained from routine quality control records. A target value of 3.00 × 1011 cells was chosen. A theoretical model to predict the probability of achieving this target cell count was developed.
Main Outcome Measures.—The calculated probability was tested in a Monte Carlo simulation.
Results.—The mean of a sequential series of 100 PC counts (obtained from routine quality control records) was 9.08 × 1010, and the standard deviation was 2.70 × 1010. Platelet loss during pooling was measured at 8.3%, so that the pooling of 3.27 × 1011 cells is required to deliver a dose of 3.00 × 1011 cells. The pooling of 4 PCs from this data set predicts an average pool cell count of 3.63 ± 2.30 × 1011. Using standard tables for normal distribution, the probability of achieving a minimal pool dose of 3.00 × 1011 cells is estimated to be greater than 0.76. Similarly, the probability of achieving the target value by pooling 5 PCs is greater than 0.99. In a Monte Carlo simulation selecting 4 PCs, 76.5% of the trials were successful, and for 5 PCs, 99.5% were successful (estimated P values of .77 and .99, respectively).
Conclusion.—Five PCs per pool are necessary and sufficient to achieve the chosen target value given the cell count characteristics of our PC supply.
Multifocal Granular Cell Tumor of the Esophagus and Proximal Stomach With Infiltrative Pattern
Authors: David Odile , Jakate Shriram 
Published: January 2021

Abstract
The granular cell tumor is a solitary painless nodule that arises most commonly on the skin or the tongue. The vast majority are benign. Approximately 5% to 9% of granular cell tumors have been reported in the gastrointestinal tract, most commonly in the esophagus. We report a case of a 45-year-old African American woman with multifocal granular cell tumors of the esophagus and proximal stomach. Two lesions within the distal esophagus and proximal stomach were characteristic nodular granular cell tumors. Within the mid esophagus there was poorly defined transmural involvement by benign-appearing granular cells. This pattern of infiltration by benign cells is uncharacteristic. A review of the literature with emphasis on the determination of malignancy is also presented.
Muscular Dystrophy
Authors: Hoffman Eric P. 
Published: January 2021

Abstract
The application of cloned genes and their protein products to molecular diagnostics has been an increasingly important area of pathology. The first gene to be identified by positional cloning was the Duchenne muscular dystrophy gene, mutations of which cause one of the most common and most devastating human inherited conditions. The identification of the responsible gene and the encoded dystrophin protein has resulted in a large series of studies concerning the other components of the membrane cytoskeleton of myofibers and their involvement in different forms of muscular dystrophy. Through the study of patients deficient in specific components of the muscle fiber, much is being learned about normal myofiber structure and function and dysfunction in disease states. A new frontier is the application of the normal genes and proteins toward patient therapeutics (gene therapy). Although highly experimental, delivery of therapeutic genes promises to become an important medical practice.
Impact of Molecular (DNA) Testing on Determination of Parentage
Authors: Polesky Herbert F. 
Published: January 2021

Abstract
Objective.—To examine changes in parentage testing practices since the introduction of DNA polymorphisms.
Methods.—Comparison of data from American Association of Blood Banks (AABB) annual questionnaires and the responses of participants to AABB–College of American Pathologists proficiency test panels.
Results.—DNA polymorphisms have led to a complete change in the technical methods used by parentage testing laboratories.
Conclusions.—The widespread use of DNA methods has increased the power of the information routinely provided to the courts in cases of disputed paternity, to agencies needing information about relatedness, and to the individuals who are tested.
Financial Determinants of Outcomes in Molecular Testing
Authors: Ross Jeffrey S. 
Published: January 2021

Abstract
For the benefits of molecular pathology to outweigh its inherent costs, testing procedures must be integrated into total disease assessment to realize the true financial impact. Major financial benefits are achievable from molecular testing because the tests reduce the use of less sensitive and less specific tests, unnecessary diagnostic procedures, and ineffective therapies. In this review, the financial determinants of outcomes for molecular-based testing for disease predisposition, screening, early detection, and directed therapy are presented.
Implementation of a Practical Digital Imaging System for Routine Gross Photography in an Autopsy Environment
Authors: Belanger Arthur J. , Lopes Antonio E. , Sinard John H. 
Published: January 2021

Abstract
Background.—The autopsy environment places stringent requirements on a digital imaging system. These requirements must be addressed if the system is to be functional, easy to use, and reliable.
Design.—After clearly defining the requirements for such a system, we implemented routine digital imaging in a busy academic autopsy suite.
Results.—The new technology was immediately accepted by both the resident staff and the technical staff. Although a 35-mm camera was always available for traditional photography, it was rarely used. An interesting side effect of implementing digital imaging was a nearly twofold increase in the number of images taken per autopsy case. The requirements, features, and utility of a digital imaging system are discussed.
Conclusion.—Digital imaging in an autopsy environment can be both practical and cost-effective. It provides many advantages over traditional 35-mm photography and can be the first step toward numerous additional improved services.
Atypical Epithelial Cells and Specimen Adequacy
Authors: Davey Diane D. , Woodhouse Sherry , Styer Patricia , Stastny Janet , Mody Dina 
Published: January 2021

Abstract
Context.—The Bethesda System for reporting cervical/vaginal cytologic diagnoses introduced terminology for atypical squamous and glandular cells and categories for specimen adequacy.
Objectives.—To analyze current laboratory reporting practices and compare trends to previous surveys.
Design.—Questionnaire surveys were mailed to 2000 laboratories in 1996 and 1997.
Participants.—Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.
Main Outcome Measures.—Laboratory policies, criteria, and reporting rates for Bethesda System categories.
Results.—The 1996 specimen adequacy survey had 1166 respondents, and 768 laboratories returned the 1997 questionnaire focusing on atypical squamous cells of undetermined significance (ASCUS) and glandular cells of undetermined significance (AGUS). Nearly all laboratories (92%) routinely reported specimen adequacy, an increase from the 66% rate in 1991. The median rate for unsatisfactory specimens was 0.5% (mean 0.95%), and the median rate for the satisfactory but limited category was 5.8% (mean 9.3%). The Bethesda criteria for designating a specimen unsatisfactory were used by more than 90% of laboratories. Nearly all laboratories (97%) used the term ASCUS in 1997, and more than 80% of laboratories used the Bethesda criteria for this category. Median reporting rates for epithelial abnormalities were as follows: ASCUS, 4.5%; AGUS, 0.3%; low-grade squamous intraepithelial lesion (SIL), 1.6%; and high-grade SIL, 0.5%. The median ASCUS/SIL ratio was 2.0, with 80% of laboratories reporting ratios between 0.64 and 4.23. The median ASCUS rate and ASCUS/SIL ratio were higher than 1993 survey results. Nearly all laboratories attempted follow-up studies on patients with abnormal cytology results, and midsized laboratories achieved the highest rates of follow-up. Median rates of abnormalities following an ASCUS or AGUS diagnosis were 20% and 15%, respectively. Laboratory respondents commonly used written recommendations in ASCUS/AGUS reports.
Conclusions.—Most laboratories that responded to the surveys had adopted Bethesda terminology and criteria for specimen adequacy and ASCUS/AGUS. Reporting rates for SIL and adequacy categories have remained stable, but median ASCUS rates and ASCUS/SIL ratios are higher than in 1993. The AGUS category is reported infrequently, but can be associated with significant pathology.
Role for Activation of Matrix Metalloproteinases in the Pathogenesis of Pulmonary Lymphangioleiomyomatosis
Authors: Matsui Kazuhiro , Takeda Kazuyo , Yu Zu-Xi , Travis William D. , Moss Joel , Ferrans Victor J. 
Published: January 2021

Abstract
Background.—Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined.
Objective.—To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize α-smooth muscle actin (α-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate).
Results.—Staining for α-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2–, or MT1-MMP–positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45–reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative.
Conclusions.—This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.
Intraductal Papillary Tumors of the Major Salivary Glands
Authors: Nagao Toshitaka , Sugano Isamu , Matsuzaki Osamu , Hara Hitoshi , Kondo Yoichiro , Nagao Koichi 
Published: January 2021

AbstractIntraductal papilloma is an extremely rare benign salivary gland tumor that occurs most commonly in the minor salivary glands. To our knowledge, a malignant counterpart of intraductal papilloma has not been described previously. We report one case each of benign and malignant intraductal papillary tumors. The benign tumor occurred in the sublingual gland and was a typical example of intraductal papilloma, with the exception that we found no previously published reports of this type of tumor in this location. The other patient had a left parotid gland tumor that was architecturally similar to the intraductal papilloma, with the addition of cytologic atypia, intraductal extension, microinvasion, and lymph node metastases. This tumor was diagnosed as intraductal papillary adenocarcinoma with an invasive component. Both patients were alive and well without evidence of recurrence 2 years and 6 months (case 1) and 6 years (case 2) after surgery. Immunohistochemical examination revealed that the tumor cells resembled duct luminal cells in both cases. The 2 tumors had different immunoreactivities for carcinoembryonic antigen, p53, and Ki-67. The malignant counterpart of intraductal papilloma should be considered in the differential diagnosis of salivary gland tumors with a predominantly papillary structure, even though this tumor is extremely rare.
Primary Neuroendocrine Small Cell Carcinomaof the Breast
Authors: Samli Billur , Celik Selma , Evrensel Turkkan , Orhan Bulent , Tasdelen Ismet 
Published: January 2021

Abstract
A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.
Leiomyoma of the Male Urethra
Authors: Mira Jose L. , Fan Guang 
Published: January 2021

Abstract
We describe the case of a 48-year-old quadriplegic black man with history of C4-C5 cervical spine and cord injury secondary to a fall, who presented to the University of Cincinnati Medical Center Urology Service with obstructive symptoms at urination. A bulbous urethral stricture was diagnosed and subsequently resected with primary urethral reanastomosis. On pathologic examination, the surgical specimen contained an epithelioid leiomyoma at the site of the urethral stricture. Although leiomyomas of the female urethra are relatively common, we identified only 2 previously reported cases of leiomyomas of the male urethra in the English-language medical literature. To the best of our knowledge, we describe the third case of leiomyoma of the male urethra, the first of the epithelioid type.
The Role of Clostridium septicum in Paraneoplastic Sepsis
Authors: Pelletier J. Peter R. , Plumbley Julie A. , Rouse Elizabeth A. , Cina Stephen J. 
Published: January 2021

Abstract
Context.—Clostridium septicum infections are rare but often associated with serious if not fatal outcomes. Clostridium septicum infection does not appear to be associated with a single specific defect in cellular or humoral immunity. It has been associated with multiple medical problems, including but not limited to leukemia, malignancy of the bowel, other solid tumors, cyclic neutropenia with enterocolitis, diabetes mellitus, and severe arteriosclerosis. Most cases of C septicum are associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 hours.
Objectives.—To evaluate outcomes of patients with C septicum bacteremia, whether treated medically or surgically or both, and to note associated conditions.
Design.—Retrospective evaluation of patients found to have C septicum bacteremia in the past 6 years.
Setting.—Two teaching hospitals, Brooke Army Medical Center (250 beds) and Wilford Hall Medical Center (292 beds), were the source of our patients.
Patients.—All patients found to have C septicum bacteremia during hospitalization or postmortem examination were included in the study. There were no exclusion criteria.
Main Outcome Measure.—Mortality associated with C septicum infection.
Results.—In our case series, mortality was 33%, which is slightly lower than reported in prior studies (43%–70%).
Conclusion.—Presumptive identification based on Gram stain, awareness of C septicum infection as a paraneoplastic syndrome, and prompt, clear communication between laboratory personnel and clinicians are necessary for early diagnosis of C septicum infection. Early institution of antibiotic therapy improves prognosis.
Effects of Restructuring on the Performance of Microbiology Laboratories in Alberta
Authors: Church Deirdre L. , Don-Joe Connie , Unger Barbara 
Published: January 2021

Abstract
Objective.—To evaluate the error rates of organism identification and antibiotic susceptibility proficiency testing challenges before, during, and after microbiology laboratory restructuring in Alberta.
Methods.—Alberta Health substantially reduced and redistributed laboratory funds to the regional health authorities in 1995, forcing a dramatic restructure of services. Many rural hospitals expanded their microbiology test menus, and urban centers consolidated microbiology testing into a centralized high-volume laboratory. The Laboratory Proficiency Testing Program of the College of Physicians and Surgeons of Alberta mailed regular test profile surveys to microbiology laboratories during the restructure period to determine the type and extent of changes in services. Based on the types of tests and the extent of analysis being done, most rural B-level and some C-level laboratories were reclassified to the A level. The Laboratory Proficiency Testing Program reviewed the error rates of proficiency challenges based on the performance of different levels of laboratories before and after the period of restructure.
Results.—Overall performance has improved according to the number of errors documented on identification and susceptibility challenges for laboratories that remained at the same classification (ie, A or C). The number of major identification errors for laboratories that were reclassified increased, but the rate of major susceptibility errors decreased. More reclassified laboratories do not have dedicated registered technologist(s) who perform microbiology testing and are not supervised by an on-site pathologist and/or medical microbiologist compared with laboratories that remained at the same classification.
Conclusions.—Microbiology laboratory restructuring will have adverse effects on the quality of complex testing if experienced technologists are not retained and services are not medically supervised.