bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing Pseudoepitheliomatous Hyperplasia From Squamous Cell Carcinoma in Mucosal Biopsy Specimens From the Head and Neck
Authors: Zarovnaya Elena , Black Candice 
Published: February 2021

Abstract
Context.—The differentiation of pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma is a difficult and frequently encountered distinction, especially in biopsy specimens from head and neck mucosa. The problem is compounded by inflamed and often poorly oriented tissue sections.
Objective.—To distinguish pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma, utilizing a panel of antibodies to various epithelial and stromal elements (p53, matrix metalloproteinase 1, E-cadherin, and collagen IV) that has been shown to be useful in differentiating intestinal adenomas with invasive adenocarcinoma from displaced adenomatous epithelium.
Design.—Thirty-three archival specimens (16 squamous cell carcinoma [12 with invasion and 4 with microinvasion] and 17 pseudoepitheliomatous hyperplasia) from head and neck mucosal locations were immunostained and examined by the authors.
Results.—We found increased nuclear staining of the invasive tumor cells with p53. There was decreased staining within invasive tumor nests with E-cadherin. There was highly significant increased staining within tumor cells and adjacent stroma with matrix metalloproteinase 1 (P &lt; .001). The only antibody in our panel that did not show a reliable staining pattern was collagen IV. It appeared fragmented in benign inflamed and malignant areas and therefore was not useful.
Conclusions.—p53, matrix metalloproteinase 1, and E-cadherin showed significant staining trends independent of inflammation and suboptimal tissue orientation. Although a properly oriented hematoxylin-eosin–stained section was our gold standard, we found this immunoperoxidase panel useful as a diagnostic adjunct in difficult cases.
Primitive Neuroectodermal Tumor of the Stomach
Authors: Soulard Raoulin , Claude Valère , Camparo Philippe , Dufau Jean-Philippe , Saint-Blancard Patrick , Gros Philippe 
Published: February 2021

Abstract
Ewing sarcoma/primitive neuroectodermal tumor is classically a tumor of the soft tissue or bone in children and young adults, but several cases have been described in patients of all ages. Within the last decade, the clinicopathologic spectrum of Ewing sarcoma/primitive neuroectodermal tumor has been markedly expanded by recognition that the tumor may also have a visceral origin. We describe a case of primitive neuroectodermal tumor arising in the stomach of a 66-year-old woman. The neoplasm was excised using a radical surgical procedure. Microscopically, the tumor was made up of solid nests and sheets of round cells. Immunohistochemically, the tumor cells showed immunoreactivity for CD99, S100, neuron-specific enolase, and vimentin. A multiplex real-time polymerase chain reaction assay detected an EWS-ERG fusion. To our knowledge, this is the first description of a primitive neuroectodermal tumor arising in the stomach.
CDX2 Is a Useful Marker of Intestinal-Type Differentiation: A Tissue Microarray–Based Study of 629 Tumors From Various Sites
Authors: De Lott Lindsey B. , Morrison Carl , Suster Saul , Cohn David E. , Frankel Wendy L. 
Published: February 2021

Abstract
Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas.
Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas.
Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2.
Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2.
Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.
Overcoming the Limitations of Integrated Clinical Digital Imaging Solutions
Authors: Sinard John H. , Mattie Mark E. 
Published: February 2021

Abstract
Context.—Digital imaging is increasingly common in medicine. Vendors of anatomic pathology software have addressed this need by integrating digital image acquisition and storage into their products. While offering a number of advantages, these solutions cannot be easily adapted to accommodate the existing work flow for many pathology departments.
Objective.—To describe a novel solution that maintains the advantages of these integrated solutions but offers many additional flexibilities, making it more compatible with the work flow in most clinical departments.
Design.—This solution involves separating the image acquisition step from the image archiving process and creating dual-image storages for greater usability. Software needed to deploy this modular and scalable solution is described.
Results.—We have deployed this solution at our institution and achieved widespread acceptance and use, with minimal training required. Deployment in the surgical pathology gross specimen room, in particular, has resulted in a significant increase in the number of photographs taken and the percentage of cases documented photographically.
Conclusions.—The complete clinical digital imaging solution described herein is an effective, scalable solution for pathology imaging at a departmental level. Although developed and implemented in an anatomic pathology department, the method described is generally applicable to digital imaging in any large multiuser environment.
Evaluation of Stroma in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome–Affected Bone Marrows and Correlation With CD4 Counts
Authors: O'Malley Dennis P. , Sen Joy , Juliar Beth E. , Orazi Attilio 
Published: February 2021

Abstract
Context.—Little is known about cellular and extracellular composition of fibrosis in bone marrows in the context of human immunodeficiency virus/acquired immunodeficiency syndrome.
Objective.—To evaluate the stromal composition of bone marrows affected by human immunodeficiency virus/ acquired immunodeficiency syndrome and to correlate this with laboratory parameters including CD4 lymphocyte counts.
Design.—We evaluated extracellular matrix and stromal cell composition in bone marrows and correlated these results with hematologic parameters. Extracellular matrix, stromal cells, and smooth muscle differentiation were evaluated by immunohistochemistry for collagen type IV expression and reticulin staining, an antibody directed against low-affinity nerve growth factor receptor (a marker of adventitial reticular cells), and actin staining, respectively. Concurrent laboratory information was collected, including white blood cell count, hemoglobin, platelet count, CD4 count, CD8 count, CD4/CD8 ratio, and absolute lymphocyte count.
Patients.—Bone marrows of 35 patients with human immunodeficiency virus/acquired immunodeficiency syndrome were evaluated.
Main Outcome Measures.—Correlation of reticulin, low-affinity nerve growth factor receptor, actin, and collagen IV staining with hematologic parameters.
Results.—More than half of the bone marrows showed moderate to severe reticulin fibrosis. The degree of reticulin fibrosis was correlated with the degree of low-affinity nerve growth factor receptor expression (P = .048). Actin expression was identified in only 3 of 35 cases and collagen IV in only 5 of 35 cases. No statistical relationship between degree of fibrosis and CD4 count was identified. Lower levels of low-affinity nerve growth factor receptor expression were associated with CD4 counts of &gt;100 (P = .04). Marrow fibrosis was present in almost all cases studied (97%), and the staining of adventitial reticular cells correlated with the degree of reticulin fibrosis.
Conclusions.—There does not appear to be a correlation between CD4 count and degree of fibrosis, suggesting that the mechanism of fibrosis is independent of disease status.
A Simple, Focused, Computerized Query to Detect Overutilization of Laboratory Tests
Authors: Weydert Jamie A. , Nobbs Newell D. , Feld Ronald , Kemp John D. 
Published: February 2021

Abstract
Context.—Although there is nearly universal agreement that laboratory tests are overutilized, the degree of overutilization in a given institution is difficult to quantify and monitor across time.
Objective.—To detect and clearly document repetitive daily ordering of a commonly ordered laboratory test (serum sodium) by employing a simple, focused, computerized query of a test result database followed by chart review and validation.
Design.—A retrospective computerized query of our clinical data repository was performed to find inpatients who displayed normal serum sodium test results on 4 or more consecutive days, without any abnormal values during the same admission. The search was limited to a 1-month period. A subset of these patients was selected for chart review.
Results.—One hundred sixteen patients met our criteria, and the tests ordered for those patients comprised 5.1% of the monthly volume of serum sodium tests ordered in our institution. Chart review revealed a consistent lack of documentation of medical necessity for repeat testing as well as persistence of repeat serum sodium orders until the end of the patients' hospital course.
Conclusions.—We conclude that a focused query of data derived from a clinical data repository can detect and document overutilization of a common laboratory test in a convincing fashion within a given institution.
Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Gene Defect in the Kuwaiti Population
Authors: AlFadhli Suad , Kaaba Salim , Elshafey Alaa , Salim Matra , AlAwadi Anwar , Bastaki Layla 
Published: February 2021

AbstractContext.—Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human enzyme deficiencies. More than 130 different molecular abnormalities have been described worldwide, with considerable variation in the enzyme among various racial groups. Data from Kuwaiti populations are scarce, and the studies available are the result of screening male blood donors who may not be truly representative of the Kuwaiti population.Objective.—The objective of this study was to investigate the mutation spectrum of the G6PD gene among Kuwaiti Arabs.Design.—DNA was extracted from 82 G6PD-deficient Kuwaiti subjects (75 men and 7 women) and screened for gene mutations using polymerase chain reaction/restriction fragment length polymorphism and polymerase chain reaction/single-strand conformation polymorphism followed by direct sequencing. A total of 1209 randomly selected Kuwaiti adult subjects of both sexes were then screened for any characterized mutation.Results.—G6PD Mediterranean563C→T, and A−202G→A,376A→G genotypes were characterized as the most common variants among the G6PD-deficient population, representing 0.742 and 0.124 allele frequencies, respectively. The 2 previously described mutations, G6PD Chatham1003G→A and Aures143T→C, were found at lower frequencies (0.101 and 0.034, respectively). The allele frequencies for these 4 G6PD variants among the randomly selected Kuwaitis were 0.035, 0.0074, 0.0046, and 0.0023 for Mediterranean, A−, Chatham, and Aures, respectively.Conclusion.—This study has characterized the molecular heterogeneity of G6PD variants among ethnic Kuwaitis. The findings suggest that gene flow from the Indian subcontinent, sub-Saharan African, and other parts of the Mediterranean may have contributed to the observed G6PD mutations seen in the Kuwaiti population.
Intraoperative Assessment of the Breast: Guidelines and Potential Pitfalls
Authors: Laucirica Rodolfo 
Published: February 2021

Abstract
Context.—Intraoperative evaluation of breast tissue has changed as newer imaging techniques and surgical approaches to the treatment of breast cancer have placed the pathologist in a pivotal role in the management of this disease. Assessment of the index lesion and surgical margins are but two of the many tasks we face when the specimen arrives in the surgical pathology laboratory. We are also called on to correlate changes in the mammogram with the gross pathology, particularly in those cases in which the lesion is nonpalpable. More recently, pathologists have been asked to analyze 1 or more sentinel lymph nodes at the time of frozen section to look for metastatic disease. This review discusses many of these issues and also provides a simplified approach to the differential diagnosis of a variety of breast lesions one may encounter intraoperatively.
Objective.—To provide guidelines for and address potential pitfalls in the intraoperative management of the breast.
Data Sources.—Author's experience and pertinent literature.
Conclusions.—Careful assessment of the gross specimen coupled with prudent utilization of frozen sections is pivotal to reducing intraoperative error rates and preventing needless anxiety for the patient.
Intraoperative Pathology Consultation for Kidney and Urinary Bladder Specimens
Authors: Truong Luan D. , Krishnan Bhuvaneswari , Shen Steven S. 
Published: February 2021

AbstractContext.—Intraoperative pathology consultation for kidney and urinary bladder specimens is relatively infrequent. Scant literature is devoted to this topic.Objective.—The clinical indications and diagnostic usefulness and pitfalls of intraoperative pathology consultation of kidney and urinary bladder specimens will be reviewed, based on literature and personally encountered cases.Data Sources.—The indications for intraoperative pathology consultation for renal lesions included (1) surgical margins in partial nephrectomy specimens, (2) solid renal mass in unusual clinical or radiologic settings, (3) synchronous renal and extrarenal masses, (4) cystic renal lesions, (5) ureteral surgical margin for transitional cell carcinoma, (6) multiple renal masses, (7) solid mass in a diffusely cystic kidney, and (8) evaluation of renal injury. The indications for urinary bladder included (1) status of the surgical margins, (2) diagnosis of bladder tumor biopsy, (3) diagnosis of extravesical tumors with vesical extension, (4) diagnosis of extravesical mass, including pelvic lymph nodes encountered during cystectomy, and (5) status of bladder neck margin during radical prostatectomy for cancer. The frequent problematic areas for the kidney included misdiagnosis or incorrect classification of cystic tumors or spindle cell tumors, and confusion of clear cell renal cell carcinoma with inflammatory lesions. The problematic areas for urinary bladder included the differential diagnoses of high-grade dysplasia/carcinoma in situ with reactive changes at the ureteral or urethral surgical margins.Conclusions.—Distinctive indications and diagnostic pitfalls are recognized for intraoperative consultation of renal or urinary bladder lesions. Awareness of the pertinent problems should improve diagnostic accuracy and facilitate the proper management of these lesions.
Pitfalls in Salivary Gland Fine-Needle Aspiration Cytology: Lessons From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology
Authors: Hughes Jonathan H. , Volk Emily E. , Wilbur David C. 
Published: February 2021

Abstract
Context.—We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to identify common diagnostic errors in salivary gland fine-needle aspiration (FNA).
Objective.—To identify salivary gland FNA cases with poor performance characteristics in the Nongynecologic Cytology Program surveys, so that the most common diagnostic pitfalls can be avoided.
Design.—A retrospective review of the College of American Pathologists Nongynecologic Cytology Program's cumulative data from 1999 to 2003 revealed the most common false-positive and false-negative interpretations on FNA for common salivary gland lesions. Slides that performed poorly were then reviewed to identify the cytologic characteristics that may have contributed to their poor performance.
Results.—A total of 6249 participant responses with general interpretations of benign (n = 4642) or malignant (n= 1607) were reviewed. The sensitivity and specificity of the participant responses for correctly interpreting the cases as benign or malignant were 73% and 91%, respectively. Benign cases with the highest false-positive rates were monomorphic adenoma (53% false-positive), intraparotid lymph node (36%), oncocytoma (18%), and granulomatous sialadenitis (10%). Malignant cases with the highest false-negative rates were lymphoma (57%), acinic cell carcinoma (49%), low-grade mucoepidermoid carcinoma (43%), and adenoid cystic carcinoma (33%). Selected review of the most discordant individual cases revealed possible explanations for some of the interpretative errors.
Conclusions.—These data confirm the difficulty associated with interpretation of salivary gland FNA specimens. Cytologists should be aware of the potential false-positive and false-negative interpretations that can occur in FNAs from this organ site in order to minimize the possibility of diagnostic errors.
Total Long-term Within-Laboratory Precision of Cortisol, Ferritin, Thyroxine, Free Thyroxine, and Thyroid-Stimulating Hormone Assays Based on a College of American Pathologists Fresh Frozen Serum Study: Do Available Methods Meet Medical Needs for Precision?
Authors: Steele Bernard W. , Wang Edward , Palmer-Toy Darryl E. , Killeen Anthony A. , Elin Ronald J. , Klee George G. 
Published: February 2021

AbstractContext.—It is important that the total long-term precision of laboratory methods meet the medical needs of the patients being served.Objectives.—To determine the long-term within- and between-laboratory variation of cortisol, ferritin, thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using commonly available methods and to determine if these variations are within accepted medical needs.Design.—Two vials of pooled frozen serum were mailed 6 months apart to laboratories participating in 2 separate College of American Pathologists surveys. The data from those laboratories that analyzed an analyte in both surveys were used to determine for each method the total variance and the within- and between-laboratory components.Setting.—The study included the A mailing of the 2003 College of American Pathologists Ligand Survey and the C mailing of the Chemistry Survey.Main Outcome Measures.—For each analyte, total variance was partitioned into within- and between-laboratory components for each analytic method. The within-laboratory variations were then compared with imprecision criteria based on biological variation.Participants.—The laboratories that reported results on the same analyte using the same method in both surveys.Results.—For each analyte, the median of the long-term within-laboratory variances of each peer group was 78% to 95% of its total-survey variance, and the median long-term within-laboratory coefficients of variation varied from 5.1% to 7.6%. The number of methods that met within-laboratory imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7 for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid-stimulating hormone.Conclusions.—For all analytes tested, the total within-laboratory component of variance was the major source of variability in this study. In addition, there are several methods, especially for thyroxine and free thyroxine, that may not meet analytic goals in terms of their imprecision.
Comparison of Fresh Frozen Serum to Proficiency Testing Material in College of American Pathologists Surveys: α-Fetoprotein, Carcinoembryonic Antigen, Human Chorionic Gonadotropin, and Prostate-Specific Antigen
Authors: Schreiber William E. , Endres David B. , McDowell Geraldine A. , Palomaki Glenn E. , Elin Ronald J. , Klee George G. , Wang Edward 
Published: February 2021

Abstract
Context.—Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS).
Objective.—To compare the performance of an FFS pool to standard PTM for measurement of α-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA).
Design.—One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for α-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys.
Participants.—The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey).
Main Outcome Measures.—Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means.
Results.—The FFS specimen gave significantly higher imprecision than PTM for the analytes α-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the α-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM.
Conclusions.—Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.