bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter Hypermethylation of the p16 Gene and Loss of Its Protein Expression Is Correlated With Tumor Progression in Extrahepatic Bile Duct Carcinomas
Authors: Hong Seung-Mo , Choi Jene , Ryu Kyueun , Ro Jae Y. , Yu Eunsil 
Published: February 2021

Abstract
Context.—The p16 gene is one of the tumor suppressor genes, and its inactivation results in abnormal regulation of the cell cycle in human neoplasms. Promoter hypermethylation, a mechanism of p16 gene inactivation, has been reported to play an important role in tumorigenesis and to be related to patient prognosis in several carcinomas.
Objective.—To determine the role of the p16 gene in extrahepatic bile duct (EBD) carcinomas.
Design.—We examined promoter hypermethylation of the p16 gene using a methylation-specific polymerase chain reaction and the expression of the p16 protein using an immunohistochemical staining method in 90 cases of EBD carcinomas. We then compared the data with various clinicopathologic parameters, including survival rate.
Results.—Promoter hypermethylation was observed in 69 (77%) of the 90 cases. Of 69 hypermethylated cases, 32 (46%) demonstrated loss of p16 expression. Promoter hypermethylation of the p16 gene was more commonly observed in tumors with vascular invasion (22 [92%] of 24 cases) than without vascular invasion (71%, P = .03). Furthermore, p16 promoter hypermethylation with loss of p16 expression was more frequently observed in cases with lymph node metastasis (P = .006) and higher tumor stage group (P = .04). However, there was no significant difference in survival rate according to the status of p16 promoter methylation and/or p16 expression.
Conclusion.—Promoter hypermethylation is an important mechanism in the inactivation of the p16 gene in EBD carcinogenesis. Furthermore, the loss of p16 expression, with or without p16 gene promoter hypermethylation, is closely related to the tumor progression in EBD carcinomas.
The Use of Virtual Microscopy for Proficiency Testing in Gynecologic Cytopathology: A Feasibility Study Using ScanScope
Authors: Marchevsky Alberto M. , Khurana Renu , Thomas Premi , Scharre Karen , Farias Paul , Bose Shika 
Published: February 2021

Abstract
Context.—ScanScope software can digitize entire cytology slides.
Objective.—To test the feasibility of using virtual microscopy methods and “virtual Papanicolaou tests” for proficiency testing (PT) in gynecologic cytopathology.
Design.—Two PT exercises were conducted using virtual microscopy. Five cytopathologists and 1 cytotechnologist interpreted images using 2 different schema as follows: (1) the College of American Pathologists graded diagnostic codes (CAP-GDCs) and (2) the Center for Medicare and Medicaid Services test scoring categories (CMS-TSCs). The number of diagnostic errors using the CAP-GDCs and the CMS-TSCs, the mean length of time spent diagnosing each case, and the impressions by the users regarding the facility of the technology and image quality were studied.
Results.—In the first PT exercise, the participants provided incorrect diagnoses in 4 to 8 of the 10 test cases using the CAP-GDCs and in 1 to 4 of the 10 test cases using the CMS-TSCs. In the second PT exercise, the number of errors decreased to 1 to 6 using the CAP-GDCs and to 0 to 6 using the CMS-TSCs. The results did not achieve statistical significance. The mean time of 9.4 minutes spent per case in the second PT exercise was significantly shorter than the 14.4 minutes spent per case in the first PT exercise (P &lt; .001). The ease of use of the software and the image quality were scored by all participants as 3+ or as 4+.
Conclusions.—This preliminary study shows that virtual microscopy and virtual Papanicolaou tests prepared using ScanScope may provide effective tools for PT. Technical issues that require further investigation are discussed.
Metastatic Basal Cell Carcinoma: Four Case Reports, Review of Literature, and Immunohistochemical Evaluation
Authors: Ionescu Diana N. , Arida Muammar , Jukic Drazen M. 
Published: February 2021

Abstract
Context.—Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported.
Objective.—To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs.
Design.—We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2.
Results.—In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases.
Conclusions.—Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.
Adequacy of Physician Documentation of Red Blood Cell Transfusion and Correlation With Assessment of Transfusion Appropriateness
Authors: Friedman Mark T. , Ebrahim Amber 
Published: February 2021

Abstract
Context.—A major function of the hospital transfusion service is to assess the appropriateness of blood transfusion. Inadequate documentation of transfusions may hamper this assessment process.
Objective.—To correlate the level of physician documentation of transfusion with the ability to justify transfusion.
Design.—Retrospective review of red blood cell transfusions in adult patients in 2 hospital facilities during 1-week audit periods of each month from April 2001 to March 2003. Assessment forms were used to classify the level of physician documentation of transfusions into 3 groups: adequately, intermediately, and inadequately documented. Transfusions were deemed justified or not via comparison with hospital transfusion guidelines.
Results.—There were 5062 audited red blood cells transfused to 2044 adult (≥18 years) patients. Medical records from 154 patients transfused with 257 units of red blood cells during 172 transfusion events were reviewed after initial screenings of hemoglobin/hematocrit values failed to justify the transfusions. Nine percent of adequately documented, 50% of intermediately documented, and 73% of inadequately documented transfusion events could not be justified. Transfusion events with suboptimal (intermediate and inadequate) documentation accounted for 49% of all medical record–reviewed transfusion events and 62% could not be justified. The correlation between inadequate documentation and failure to justify transfusion was significant (P &lt; .001), as was the correlation between suboptimal documentation and failure to justify transfusion (P = .03).
Conclusions.—There is a significant correlation between suboptimal documentation and failure to justify transfusions. Educating clinicians to improve documentation along with appropriate indications for transfusions may enhance efficiency of blood utilization assessment and lead to reduced rates of unjustifiable transfusions.
Use of Microsatellite Analysis in Detection of Tumor Lineage as a Cause of Death in a Liver Transplant Patient
Authors: Cankovic Milena , Linden Michael D. , Zarbo Richard J. 
Published: February 2021

Abstract
Malignant tumors are a significant cause of long-term morbidity and mortality in allograft recipients. Most solid tumors in transplant recipients are assumed to arise de novo in the setting of chronic immunosuppressive therapy; however, there have been instances in which malignant tumors have been transplanted in donated tissue from apparently healthy donors. We report a case of a 49-year-old liver transplant patient who presented with metastatic melanoma 9 months after transplantation for hepatocellular carcinoma and who later succumbed to the disease. To investigate the possibility that melanoma was derived from the donor liver, we used a commercially available polymerase chain reaction–based microsatellite marker assay to perform tissue identity testing. The genetic profiles of the patient's original hepatocellular carcinoma and the melanoma from the autopsy specimen were compared with the profile of the normal donor liver tissue, which was still available for testing. The pattern of microsatellite allelic expression strongly suggested that the melanoma detected at autopsy originated from the transplanted liver.
Concurrent Herpes Simplex Viral Lymphadenitis and Mantle Cell Lymphoma: A Case Report and Review of the Literature
Authors: Pilichowska Monika E. , Smouse Jason H. , Dorfman David M. 
Published: February 2021

Abstract
We report a case of localized herpes simplex virus lymphadenitis in a patient with mantle cell lymphoma (MCL). A 43-year-old woman with a 2-month history of lymphadenitis and peripheral lymphocytosis received a diagnosis of stage IV MCL based on histologic, flow cytometric, and immunohistochemical findings. One week after completion of chemotherapy, she presented with rapidly enlarging bilateral cervical lymph nodes, a retropharyngeal mass, and incipient respiratory compromise. Multiple biopsies of the cervical nodes and oropharynx that were submitted for morphologic, flow cytometric, and immunohistochemical studies revealed involvement by MCL with superimposed herpes simplex virus lymphadenitis. The recognition of herpes simplex virus infection with MCL is important for treatment as well as to rule out transformation of MCL to a higher-grade lesion.
Medicolegal Aspects of Error in Pathology
Authors: Troxel David B. 
Published: February 2021

Abstract
Objective.—To discuss the various ways error is defined in surgical pathology. To identify errors in pathology practice identified by an analysis of pathology malpractice claims.
Design.—Three hundred seventy-eight pathology malpractice claims were reviewed. Nuisance claims and autopsy claims were excluded; 335 pathology claims remained and were analyzed to identify repetitive patterns of specimen type and diagnostic category.
Setting.—All pathology malpractice claims reported to The Doctors Company of Napa, Calif, between 1998 and 2003.
Results.—Fifty-seven percent of malpractice claims involved just 5 categories of specimen type and/or diagnostic error, namely, breast specimens, melanoma, cervical Papanicolaou tests, gynecologic specimens, and system (operational) errors. Sixty-three percent of claims involved failure to diagnose cancer, resulting in delay in diagnosis or inappropriate treatment.
Conclusion.—A false-negative diagnosis of melanoma was the single most common reason for filing a malpractice claim against a pathologist. Nearly one third involved melanoma misdiagnosed as Spitz nevus, “dysplastic” nevus, spindle cell squamous carcinoma, atypical fibroxanthoma, and dermatofibroma. While breast biopsy claims were a close second to melanoma, when combined with breast fine-needle aspiration and breast frozen section claims, breast specimens were the most common cause of pathology malpractice claims. Cervical Papanicolaou test claims were third in frequency behind melanoma and breast; 98% involved false-negative Papanicolaou tests. Forty-two percent of gynecologic surgical pathology claims involved misdiagnosed ovarian tumors, and 85% of these were false-negative diagnoses of malignancy. The most common cause of system errors was specimen “mix-ups” involving breast or prostate needle biopsies.
Comparing Methods to Measure Error in Gynecologic Cytology and Surgical Pathology
Authors: Renshaw Andrew A. 
Published: February 2021

Abstract
Context.—Both gynecologic cytology and surgical pathology use similar methods to measure diagnostic error, but differences exist between how these methods have been applied in the 2 fields.
Objective.—To compare the application of methods of error detection in gynecologic cytology and surgical pathology.
Data Sources.—Review of the literature.
Conclusions.—There are several different approaches to measuring error, all of which have limitations. Measuring error using reproducibility as the gold standard is a common method to determine error. While error rates in gynecologic cytology are well characterized and methods for objectively assessing error in the legal setting have been developed, meaningful methods to measure error rates in clinical practice are not commonly used and little is known about the error rates in this setting. In contrast, in surgical pathology the error rates are not as well characterized and methods for assessing error in the legal setting are not as well defined, but methods to measure error in actual clinical practice have been characterized and preliminary data from these methods are now available concerning the error rates in this setting.
9-Color and 10-Color Flow Cytometry in the Clinical Laboratory
Authors: Wood Brent 
Published: February 2021

Abstract
Context.—The development of commercial flow cytometers capable of detecting more than 10 simultaneous fluorescent signals presents opportunities for improved diagnosis and monitoring of patients with leukemia and lymphoma.
Objective.—To describe instrument and reagent characteristics necessary for successful 9-color and 10-color flow cytometry in a clinical setting.
Design.—Systematic review of issues related to instrument settings, reagent performance, and general principles of panel construction.
Results.—Nine-color and 10-color flow cytometry offers the possibility for increased accuracy in population identification, the ability to obtain detailed information from paucicellular specimens, improved laboratory efficiency, and the means to consistently detect abnormal populations at low levels. Careful attention to details of instrument and reagent performance allows for the development of panels suitable for screening of samples for leukemia and lymphoma in a clinical setting.
Conclusions.—The characteristics of this technique are particularly well suited to the analysis of leukemia and lymphoma and have the potential to revolutionize and standardize this type of analysis in the clinical laboratory.
Juxtaglomerular Cell Tumor of Kidney With CD34 and CD117 Immunoreactivity: Report of 5 Cases
Authors: Kim Hyun-Jung , Kim Chul Hwan , Choi Yeong-Jin , Ayala Alberto G. , Amirikachi Mojgan , Ro Jae Y. 
Published: February 2021

Abstract
Context.—Juxtaglomerular cell tumor is a rare renal neoplasm. Renin immunohistochemistry and electron microscopic documentation of rhomboid crystals are the primary methods of diagnosing this benign tumor.
Objectives.—In this retrospective study, we evaluated the morphologic, immunohistochemical, and ultrastructural features of 5 cases of juxtaglomerular cell tumor to determine the effectiveness of CD34 and CD117 immunohistochemistry for the diagnosis of this tumor.
Design.—We reviewed 5 cases with clinical, histologic, immunohistochemical, and ultrastructural aspects.
Results.—Three women and 2 men with a mean age of 37.8 years (range, 16–60 years) were included in this study. All patients presented with severe hypertension. All tumors were well circumscribed and ranged from 1.5 cm to 8.5 cm (mean, 4.4 cm). On light microscopic examination, we found solid sheets and nests of tumor cells with oval-to-round nuclei and eosinophilic cytoplasm. Low-power microscopic examination disclosed a hemangiopericytic vascular pattern. Immunohistochemistry results were as follows: vimentin (positive), renin (weakly positive), smooth muscle actin (focal immunoreactivity), and cytokeratin (negative). All 5 tumors were immunoreactive for CD34 and CD117. Electron microscopy revealed rhomboid crystals in the cytoplasm. Postoperatively, 4 patients were normotensive and 1 patient experienced persistent mild hypertension.
Conclusions.—Our findings indicate that immunohistochemistry for CD34 and CD117 are effective at diagnosing juxtaglomerular cell tumor. Juxtaglomerular cell tumor should be considered in the diagnosis of any renal tumors with epithelioid cells and negative initial cytokeratin immunohistochemistry.
An Overview of Inflicted Head Injury in Infants and Young Children, With a Review of β-Amyloid Precursor Protein Immunohistochemistry
Authors: Dolinak David , Reichard Ross 
Published: February 2021

Abstract
Context.—Inflicted traumatic brain injury of infants and young children results in a complex array of autopsy findings. In many cases, immunostains for β-amyloid precursor protein are used to detect axonal injury. Interpretation of the gross, microscopic, and immunostaining results requires the integration of the many facets of the individual case.
Objective.—In this article we review the gross and microscopic findings associated with inflicted traumatic brain injury. The application and interpretation of β-amyloid precursor protein immunostains are discussed and photomicrographs are used to illustrate immunostaining patterns.
Data Sources.—The pertinent literature is integrated into a review of the subject.
Conclusions.—Inflicted traumatic brain injury often results in subdural, subarachnoid, retinal, and optic nerve sheath hemorrhage. These findings must be interpreted within the entire context of the case. β-Amyloid precursor protein immunostains may be helpful in illustrating the traumatic nature of the injuries in some cases.
Synchronous Pulmonary Carcinoma and Pleural Diffuse Malignant Mesothelioma
Authors: Allen Timothy Craig , Moran Cesar 
Published: February 2021

Abstract
Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16 000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.
Asphyxiation Caused by Giant Fibrovascular Polyp of the Esophagus
Authors: Sargent Rachel L. , Hood Ian C. 
Published: February 2021

Abstract
Giant fibrovascular polyps of the esophagus are rare, benign, “tumorlike” lesions that typically present as large pedunculated growths arising in the cervical esophagus. The predominant histologic component of these lesions is variable, often resulting in misdiagnosis. Clinically, these polyps present with nonspecific symptoms and are often undiagnosed or misdiagnosed until they are significant in size. Diagnosis is best made by upper endoscopic evaluation; surgical excision is the definitive treatment. Although rare, asphyxia resulting from obstruction of the glottis is the most serious complication. We describe a case of asphyxiation caused by laryngeal occlusion by a giant esophageal polyp and we provide a review of the literature.
The CD117 Immunohistochemistry Tissue Microarray Survey for Quality Assurance and Interlaboratory Comparison: A College of American Pathologists Cell Markers Committee Study
Authors: Dorfman David M. , Bui Marilyn M. , Tubbs Raymond R. , Hsi Eric D. , Fitzgibbons Patrick L. , Linden Michael D. , Rickert Robert R. , Roche Patrick C. 
Published: February 2021

Abstract
Context.—We have developed tissue microarray-based surveys to allow laboratories to compare their performance in staining predictive immunohistochemical markers, including proto-oncogene CD117 (c-kit), which is characteristically expressed in gastrointestinal stromal tumors (GISTs). GISTs exhibit activating mutations in the c-kit proto-oncogene, which render them amenable to treatment with imatinib mesylate. Consequently, correct identification of c-Kit expression is important for the diagnosis and treatment of GISTs.
Objective.—To analyze CD117 immunohistochemical staining performance by a large number of clinical laboratories.
Design.—A mechanical device was used to construct tissue microarrays consisting of 3 × 1-mm cores of 10 tumor samples, which can be used to generate hundreds of tissue sections from the arrayed cases, suitable for large-scale interlaboratory comparison of immunohistochemical staining.
Results.—An initial survey of 63 laboratories and a second survey of 90 laboratories, performed in 2004 and 2005, exhibited &gt;81% concordance for 7 of 10 cores, including all 4 GIST cases, which were immunoreactive for CD117 with &gt;95% staining concordance. Three of the cores achieved less than 81% concordance of results, possibly due to the presence of foci of necrosis in one core and CD117-positive mast cells in 2 cores of CD117-negative neoplasms.
Conclusions.—There was good performance among a large number of laboratories performing CD117 immunohistochemical staining, with consistently higher concordance of results for CD117-positive GIST cases than for nonimmunoreactive cases. Tissue microarrays for CD117 and other predictive markers should be useful for interlaboratory comparisons, quality assurance, and education of participants regarding staining nuances such as the expression of CKIT by nonneoplastic mast cells.