bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence and Bank Soundness: Between the Devil and the Deep Blue Sea - Part 2
Authors: Ayadurai Charmele , Joneidy Sina
Published: February 2021

Banks have experienced chronic weaknesses as well as frequent crisis over the years. As bank failures are costly and affect global economies, banks are constantly under intense scrutiny by regulators. This makes banks the most highly regulated industry in the world today. As banks grow into the 21st century framework, banks are in need to embrace Artificial Intelligence (AI) to not only to provide personalized world class service to its large database of customers but most importantly to survive. The chapter provides a taxonomy of bank soundness in the face of AI through the lens of CAMELS where C (Capital), A(Asset), M(Management), E(Earnings), L(Liquidity), S(Sensitivity). The taxonomy partitions challenges from the main strand of CAMELS into distinct categories of AI into 1(C), 4(A), 17(M), 8 (E), 1(L), 2(S) categories that banks and regulatory teams need to consider in evaluating AI use in banks. Although AI offers numerous opportunities to enable banks to operate more efficiently and effectively, at the same time banks also need to give assurance that AI ‘do no harm’ to stakeholders. Posing many unresolved questions, it seems that banks are trapped between the devil and the deep blue sea for now.
An Overview on the Classification and Tectonic Setting of Neoproterozoic Granites of the Nubian Shield, Eastern Desert, Egypt
Authors: A. El Bahariya Gaafar
Published: February 2021

Granites constitute the main rock components of the Earth’s continental crust, which suggested to be formed in variable geodynamics environments. The different types of granitic rocks, their compositional characteristics, tectonic settings and magma sources are outlined. Mineralogical classification of granites includes four rock types: tonalites, granodiorites, granite (monzogranite and syenogranites) and alkali-feldspar granites. Alphabetical classification subdivided granites into: I-type, S-type, A-type and M-type granites. Moreover, formation of granitic magmas requires distinctive geodynamic settings such as: volcanic arc granite (Cordilleran); collision-related granites (leucogranites); intra-plate and ocean ridge granites. The Eastern Desert of Egypt (ED) forms the northern part of Nubian Shield. Both older and younger granites are widely exposed in the ED. Old granites (OG) comprise tonalites and granodiorites of syn- to late-orogenic granitoid assemblages. They are calcalkaline, I-type, metaluminous and display island arc tectonic setting. Younger granites (YG) on the other hand, include granites, alkali-feldspar granites and minor granodiorites. They are of I- and A-type granites and of post-orogenic to anorogenic tectonic settings. The majority of the YG are alkaline, A-type granite and of within-plate tectonic setting (WPG). The A-type granites are subdivided into: A2-type postorogenic granites and A1-type anorogenic granites. Granite magma genesis involves: (a) fractional crystallization of mafic mantle-derived magmas; (b) anatexis or assimilation of old, upper crustal rocks (c) re - melting of juvenile mafic mantle – derived rocks underplating the continental crust. Generally, older I-type granitoids were interpreted to result from melting of mafic crust and dated at approximately 760–650 Ma, whereas younger granites suggested to be formed as a result of partial melting of a juvenile Neoproterozoic mantle source. Moreover, they formed from anatectic melts of various crustal sources that emplaced between 600 and 475 Ma.
Application Technologies for Functional Finishing of Textile Materials
Authors: Omerogullari Basyigit Zeynep
Published: February 2021

Nowadays, the primary energy resources and existing water reserves in the world are gradually decreasing. Because of global warming and high consumption of energy and water, researches have focused on new technologies and methods which aim of optimum use of resources while applying functionalites to the material. When the energy and water consumption of industries is examined, it could be obviously determined that the textile industry is seen to be at a substantial level. For this reason, in this chapter broad information of application systems including conventional and low-liquor application techniques with updated versions which show notable improvements in textile industry lately, have been detailed in a way of properties, parameters and running mechanisms on textile materials.
Glypican-3 as a Useful Diagnostic Marker That Distinguishes Hepatocellular Carcinoma From Benign Hepatocellular Mass Lesions
Authors: Wang Hanlin L. , Anatelli Florencia , Zhai Qihui“Jim” , Adley Brian , Chuang Shang-Tian , Yang Ximing J.
Published: February 2021

Context.—Histopathologic distinction between hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions, particularly hepatocellular adenoma, can sometimes be challenging. The currently available ancillary tools are suboptimal in terms of sensitivity and specificity.

Objective.—To further characterize the diagnostic value of glypican-3 (GPC3), a cell surface proteoglycan that has recently been shown to be overexpressed in HCC, in the distinction between HCC and benign hepatocellular mass lesions.

Design.—A total of 221 surgically resected liver specimens were subjected to immunohistochemical staining using a monoclonal antibody specific for GPC3. These included 111 HCCs, 48 hepatocellular adenomas, 30 focal nodular hyperplasias, and 32 large regenerative nodules in the background of cirrhosis.

Results.—Cytoplasmic, membranous, and canalicular staining for GPC3 was detected in 84 (75.7%) of the 111 HCCs, among which, 61 (72.6%) of the 84 cases exhibited diffuse immunoreactivity. In contrast, none of the 110 cases of hepatocellular adenoma, focal nodular hyperplasia, and large regenerative nodule showed detectable GPC3 staining. Focal GPC3 immunoreactivity was detected in cirrhotic nodules in 11 (16.4%) of 67 HCC cases with a cirrhotic background, but no background staining was observed in the remaining 44 HCCs without cirrhosis. GPC3 expression in HCCs did not correlate with the size, differentiation, or stage of the tumors; the presence or absence of cirrhotic background; or the underlying etiologies.

Conclusions.—GPC3 is a specific immunomarker for HCC that can be used to distinguish HCC from benign hepatocellular mass lesions, particularly hepatocellular adenoma. However, the diagnosis of HCC should not rely entirely on positive GPC3 immunostaining because focal immunoreactivity can be detected in a small subset of cirrhotic nodules. In addition, GPC3 expression in HCC can also be focal, and thus, the lack of GPC3 staining does not exclude the diagnosis of HCC.
Does Nonalcoholic Fatty Liver Disease Predispose Patients to Hepatocellular Carcinoma in the Absence of Cirrhosis?
Authors: Guzman Grace , Brunt Elizabeth M. , Petrovic Lydia M. , Chejfec Gregorio , Layden Thomas J. , Cotler Scott J.
Published: February 2021

Context.—Hepatocellular carcinoma (HCC) is recognized as a complication of cirrhosis related to nonalcoholic fatty liver disease (NAFLD). Diabetes and the metabolic syndrome are also associated with HCC. However, it is not clear whether NAFLD predisposes patients to HCC in the absence of cirrhosis.

Objective.—To seek evidence that HCC can develop in NAFLD unaccompanied by cirrhosis.

Design.—Retrospective case study was performed on cases from 2004 to 2007 at the University of Illinois at Chicago Medical Center, using the key words hepatocellular carcinoma, liver explant, and liver resection. The diagnosis of HCC was identified and confirmed by hematoxylin-eosin–stained slides in 50 cases. Cause of liver disease was determined by review of liver histology, clinical history, and laboratory data.

Results.—Three patients presented with advanced HCC with features of metabolic syndrome, including an elevated body mass index. Each patient had bland steatosis on liver biopsy, without fibrosis or cirrhosis. None of the 3 patients had evidence of any cause for liver disease other than NAFLD.

Conclusions.—The cases presented here suggest that NAFLD may predispose patients to HCC in the absence of cirrhosis. Further studies are needed to confirm this potentially important observation.
Correlative Study of Microvessel Density and 5-Lipoxygenase Expression in Human Sporadic Colorectal Cancer
Authors: Barresi Valeria , Vitarelli Enrica , Tuccari Giovanni , Barresi Gaetano
Published: February 2021

Context.—5-Lipoxygenase (5-LO) is an arachidonic acid– metabolizing enzyme, which has been demonstrated to exert a role in colorectal cancer tumorigenesis. Its activity in promoting neoangiogenesis in colorectal malignancies has been also recently theorized on the basis of in vitro studies.

Objective.—To investigate whether any correlation existed between 5-LO immunoexpression amount and the quantity of neoangiogenesis, as reflected by microvessel density (MVD) in human sporadic surgically resected colorectal adenocarcinomas.

Design.—A total of 45 formalin-fixed, paraffin-embedded colorectal adenocarcinomas were submitted to the immunohistochemical procedures for 5-LO and CD105, which represent specific markers for neoangiogenesis and which were used in the assessment of MVD.

Results.—CD105-positive, intratumoral, newly formed vessels were present in 45 of 45 cases with variable MVD values. A 5-LO–positive immunohistochemical reaction was also found in 45 of 45 cases. A significantly higher MVD was evident in cases displaying a high 5-LO amount in comparison with those characterized by a low 5-LO expression (28.33 vs 19.44 vessels per mm2; P = .02). In addition, a positive significant correlation emerged between 5-LO immunoexpression amount and the MVD counts (r = 0.2986, P = .04).

Conclusions.—Our study demonstrates the existence of a relationship between 5-LO expression and the neoangiogenesis process as reflected by intratumoral MVD in human sporadic colorectal adenocarcinomas, thus suggesting that 5-LO may modulate the formation of blood vessels in these neoplasias.
Acute Myelogenous Leukemia With t(6;9)(p23;q34) and Marrow Basophilia: An Overview
Authors: Chi Yiqing , Lindgren Valerie , Quigley Sean , Gaitonde Sujata
Published: February 2021

Acute myelogenous leukemia (AML) with chromosomal translocation (6;9)(p23;q34) is a rare disease with poor prognosis and distinct clinical and morphologic features. t(6;9) results in a chimeric fusion gene between DEK (6p23) and CAN/NUP214 (9q34). FLT3-ITD mutation is one of the most frequent mutations in AML and correlates with poor clinical outcome. Prevalence of FLT3-ITD is as high as 70% among patients with t(6;9) AML, and patients with t(6;9) AML and FLT3-ITD mutations usually have higher white blood cell counts, higher bone marrow blasts, and significantly lower rates of complete remission. t(6;9) is most commonly associated with AML-FAB-M2 and is considered by some researchers to be a separate disease entity because of its distinct clinical and morphologic features and poor prognostic implication. Distinct morphologic features of this entity include marrow basophilia and myelodysplasia, and immunophenotypically, the blast cells are positive for CD9, CD13, CD33, and HLA-DR; are usually positive for CD45 and CD38; and may be positive for CD15, CD34, and terminal deoxynucleotidyl transferase.
Telomerase Activity in Effusions: A Comparison Between Telomere Repeat Amplification Protocol In Situ and Conventional Telomere Repeat Amplification Protocol Assay
Authors: Hansson Maire , Zendehrokh Nooreldin , Ohyashiki Junko , Ohyashiki Kazuma , Westman Ulla-Britt , Roos Göran , Dejmek Annika
Published: February 2021

Context.—We previously found telomere repeat amplification protocol (TRAP) in situ helpful in the diagnosis of malignancy in effusions, whereas varying sensitivities and specificities for malignancy were reported by investigators using extract-based TRAP.

Objective.—To compare the 2 methods and to elucidate the discrepancies between them.

Design.—Twenty-three effusions were analyzed. Telomerase activity of whole cell lysate was measured with a Telo TAGGG telomerase polymerase chain reaction ELISA PLUS kit with modifications to exclude polymerase chain reaction inhibitors. TRAP in situ was performed on cytospins. An estimate of total TRAP activity in the specimen was made based on the amount of positive cells, their fluorescence intensity, and the proportion of different cell types in the specimen. The estimate was compared with the level of telomerase activity in cell lysate–based TRAP.

Results.—TRAP in situ: Thirteen of 14 malignant cases and 2 of 2 equivocal cases showed moderate/strong reactivity. Five of 7 benign effusions were negative; in 2 of 7, mesothelial cells showed weak reactivity. Cell lysate–based TRAP assay: In 4 cases no internal standard was detected, indicating the presence of polymerase chain reaction inhibitors. The relative telomerase activities were 33.1 to 72.7 with a considerable overlap between malignant (48 ± 9, mean ± SD) and benign (43 ± 9) cases.

Conclusions.—The TRAP in situ results correlated to final diagnoses, whereas the cell lysate–based TRAP assay did not differentiate between malignant and benign cases. The varying proportions of positive cells and the variation in fluorescence intensity in the TRAP in situ slides explained some of the discrepancies. The problems encountered with TRAP performed on cell lysates are partly overcome using TRAP in situ.
Fascin Determination in Urothelial Carcinomas of the Urinary Bladder: A Marker of Invasiveness
Authors: Karasavvidou Foteini , Barbanis Sotirios , Pappa Dimitra , Moutzouris George , Tzortzis Vasilios , Melekos Michael D. , Koukoulis George
Published: February 2021

Context.—Invasion and the depth of invasion affect significantly the prognosis in urothelial carcinomas. The histopathologic evaluation of invasion may be problematic in some cases. Application of new immunohistochemical markers may facilitate the assessment of invasion. Fascin, one of these markers, is an actin-bundling protein involved in tumor cell migration. Fascin expression is increased in various carcinomas. Prior to this research, to our knowledge, only one study exists regarding fascin expression in urothelial carcinomas.

Objective.—To characterize the expression of fascin in additional cases of urothelial carcinoma and to verify statistically a relationship between fascin overexpression and invasiveness in these tumors.

Design.—We examined fascin immunoreactivity in 116 specimens of urothelial carcinomas obtained from 116 patients including 96 men and 20 women. Fifty-eight cases were ranked as low-grade carcinomas, pTa stage, and 58 cases were ranked as high-grade carcinomas—11 were ranked as stage pTa, 21 were ranked as pT1, and 26 were ranked as pT2 carcinomas. Fascin immunoreactivity was assessed semiquantitatively in tumor cells. In each case, we ascribed 3 immunoreactivity scores, one for extent, one for intensity, and a combined immunoreactivity score.

Results.—The combined immunoreactivity score was significantly higher in invasive carcinomas. In addition, strong staining was observed exclusively in invasive carcinomas. None of the pTa tumors demonstrated intense staining, including those ranked at the higher grade.

Conclusions.—Our results point to an association between fascin immunostaining and urothelial carcinoma invasiveness and suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas.
Reduction of Blood Loss From Laboratory Testing in Hospitalized Adult Patients Using Small-Volume (Pediatric) Tubes
Authors: Sanchez-Giron Francisco , Alvarez-Mora Francisco
Published: February 2021

Context.—Blood loss from laboratory testing (BLLT) can be significant in hospitalized patients. It is a common practice to draw full large-volume tubes of blood from adults.

Objective.—To determine whether BLLT occurred when a small-volume (pediatric) blood collection tube (SVT) was substituted for each large-volume blood collection tube and to note whether an adequate sample still was obtained.

Design.—During 2 consecutive weeks, hospital test requisitions were reviewed to collect patient demographics, tests requested, and number and type of tubes obtained. The amount of blood collected and BLLT per patient were calculated. Reduced sample requirements were calculated, and phlebotomists and ward nurses were required to use SVTs. After 2 weeks of familiarization, data were collected as previously described. Laboratory technicians logged problems related to the use of SVTs.

Results.—Baseline: 227 patients had 664 requisitions, and median BLLT per patient was 13.5 mL (interquartile range [IQR], 7.6–27.3 mL). In critical care patients, the median was 19.9 mL (IQR, 12.0–35.8 mL), and maximum BLLT was 159.8 mL. Intervention phase: 246 patients had 696 requisitions, median BLLT was 3.7 mL (IQR, 1.2–6.3 mL; P < .001). In critical care patients, the median was 5.1 mL (IQR, 2.3–10.9 mL), and maximum BLLT was 61.8 mL (P < .001). All tests requested could be performed using SVTs, and no additional blood collections were required. Use of SVTs reduced overall BLLT per patient by 73% and by 74% in critical care patients.

Conclusions.—By decreasing the size of the blood collection tube for adults, we were able to markedly reduce BLLT without noting any insufficient specimen volumes.
Definition of Reference Limits for Autoantibodies to Thyroid Peroxidase and Thyroglobulin in a Large Population of Outpatients Using an Indirect Method Based on Current Data
Authors: Tozzoli Renato , Giavarina Davide , Villalta Danilo , Soffiati Giuliano , Bizzaro Nicola
Published: February 2021

Context.—The reference limits for thyroid antibodies are generally made by measuring thyroid peroxidase and thyroglobulin antibody values in a group of healthy subjects (direct method), as proposed by the National Academy of Clinical Biochemistry.

Objective.—To define the upper reference limits of thyroid peroxidase and thyroglobulin, by using an indirect method to analyze data from a large number of outpatients that were stored in the information system of a general hospital laboratory.

Design.—Thyroid peroxidase and thyroglobulin values from 21 492 patients, who had undergone antithyroid antibody measurements, were retrieved from the laboratory information system; the upper reference limits (in the top 97.5 percentile) were calculated using the indirect Kairisto method, after exclusion of outliers.

Results.—The mean upper reference limits for females and males were 15 kIU/L and 9 kIU/L for thyroid peroxidase, and 21 kIU/L and 19 kIU/L for thyroglobulin, respectively. The upper limits showed minimal or no differences in the different age classes in either females or males.

Conclusions.—Using a vast population of patients, we demonstrated that the upper limits for thyroid antibodies are much lower than the values obtained with classic, direct methods and that they do not vary in relation to age and sex.
How Does a Pathologist Make a Diagnosis?
Authors: Pena Gil Patrus , Andrade-Filho Joséde Souza
Published: February 2021

A pathologic diagnosis is the result of a complex series of activities, mastered by the pathologist. The nature of these activities is, however, rarely talked about in depth. The medical literature occasionally discusses aspects of the pathologic diagnosis processes, generally departing from the pathologic practice. The lack of a model makes discussions about the subject a matter of preference or personal style. Educational programs are largely based on the apprenticeship model, and the development of specific abilities rests on the personal aspects of both apprentice and mentor. A model for the pathologic diagnostic process is proposed. The process of diagnosis can be viewed as an action plan, encompassing 4 domains: (1) cognitive, (2) communicative, (3) normative, and (4) medical conduct. The cognitive domain involves processes of perception, attention, memory, search, hypothesis creation, and verification, among others. Communicative skills consist of providing arguments in support of a diagnostic conclusion, with adequate clinical and relevant pathologic information. Pathologic diagnosis is also subject to technical rules (based on empirical experiences), rules of rational choice (strategies aiming at definite goals), and consensual rules among peers. Finally, the pathologic diagnosis has to be evaluated in the sphere of medical conduct, from the perspectives of both the pathologist and the referring clinician. An understanding of the diagnostic process from a theoretic perspective will benefit pathology as a science and a medical specialty because it provides the basis for understanding diagnostic variations and discrepancies. Pathologic difficulties or errors can be mapped, allowing the institution of specific remedies. This model may also enhance training and educational strategies because specific emphasis can be directed toward a particular difficulty.
Physician Satisfaction With Clinical Laboratory Services: A College of American Pathologists Q-Probes Study of 138 Institutions
Authors: Jones Bruce A. , Bekeris Leonas G. , Nakhleh Raouf E. , Walsh Molly K. , Valenstein Paul N.
Published: February 2021

Context.—Monitoring customer satisfaction is a valuable component of a laboratory quality improvement program.

Objective.—To survey the level of physician satisfaction with hospital clinical laboratory services.

Design.—Participating institutions provided demographic and practice information and survey results of physician satisfaction with defined aspects of clinical laboratory services, rated on a scale of 1 (poor) to 5 (excellent).

Results.—One hundred thirty-eight institutions participated in this study and submitted a total of 4329 physician surveys. The overall satisfaction score for all institutions ranged from 2.9 to 5.0. The median overall score for all participants was 4.1 (10th percentile, 3.6; 90th percentile, 4.5). Physicians were most satisfied with the quality/reliability of results and staff courtesy, with median values of excellent or good ratings of 89.9%. Of the 5 service categories that received the lowest percentage values of excellent/good ratings (combined scores of 4 and 5), 4 were related to turnaround time for inpatient stat, outpatient stat, routine, and esoteric tests. Surveys from half of the participating laboratories reported that 96% to 100% of physicians would recommend the laboratory to other physicians. The category most frequently selected as the most important category of laboratory services was quality/reliability of results (31.7%).

Conclusions.—There continues to be a high level of physician satisfaction and loyalty with clinical laboratory services. Test turnaround times are persistent categories of dissatisfaction and present opportunities for improvement.
Carcinomas of the Pancreas, Gallbladder, Extrahepatic Bile Ducts, and Ampulla of Vater Share a Field for Carcinogenesis: A Population-Based Study
Authors: Henson Donald Earl , Schwartz Arnold M. , Nsouli Hala , Albores-Saavedra Jorge
Published: February 2021

Context.—Carcinomas co-occur in the pancreas, extrahepatic bile ducts, and ampulla of Vater. We investigated whether cancers originating in these sites represent a field effect similar to that observed in the lung and upper aerodigestive tract.

Objective.—To determine whether a field effect for carcinogenesis exists in the ampulla of Vater, extrahepatic bile ducts, gallbladder, and pancreas.

Design.—Data were obtained from National Cancer Institute's Surveillance Epidemiology and End Results Program from 1973 through 2005. Cases were compared by age frequency density plots, age-specific incidence rates, and logarithmic plots of the age-specific incidence rates and age of diagnosis.

Results.—Incidence rates were 11.71, 1.43, 0.88, and 0.49 per 100 000 persons at risk for pancreatic, gallbladder, extrahepatic bile ducts, and ampullary carcinomas, respectively. Age frequency density plots were congruent for cancers originating in all 4 sites. Logarithmic plots of the age-specific incidence rates with age of diagnosis produced parallel linear rate patterns for the 4 sites indicative of similar populations for tumor development. However, density and logarithmic plots of pancreatic endocrine carcinomas, a tumor of different cellular differentiation and carcinogenic pathway, served as a comparison. The endocrine carcinomas showed a different age distribution and nonparallel rate patterns with ductal carcinomas.

Conclusions.—Carcinomas of the pancreas, gallbladder, extrahepatic bile ducts, and ampulla have a common embryonic cellular ancestry, differentiation pathways, mucosal histologic patterns, and population-related tumor development indicating a field effect in carcinogenesis. Parallel linear rate patterns indicate (1) the rate of cancer development is similar in all 4 sites even though the absolute incidence rates vary and (2) regardless of location, the ductal epithelium is equally susceptible to malignant transformation. If carcinogenic pathways to cancer are similar, then the different incidence rates seen clinically may depend on the relative surface area of the ductal system in these sites. Pancreatic cancers are most common because the surface area of the pancreas' ductal system is greater than that of the gallbladder, extrahepatic bile ducts, and ampulla.
Improvement of Coagulation Laboratory Practice in Thailand: The First-Year Experience of the National External Quality Assessment Scheme for Blood Coagulation
Authors: Tientadakul Panutsaya , Opartkiattikul Nisarat , Wongtiraporn Wanida
Published: February 2021

Context.—In Thailand until 2005 there had been no external quality assessment scheme at the national level for blood coagulation tests. Only a few laboratories had an external quality assessment for these tests. In the year 2005, the Thailand National External Quality Assessment Scheme for Blood Coagulation was founded.

Objectives.—To describe the establishment of the Thailand National External Quality Assessment Scheme for Blood Coagulation (including problems encountered and solutions), its progression and expansion, and the improvement of coagulation laboratory practice in Thailand during 2 trial surveys and 4 formal surveys conducted in the first 1;h1 years.

Design.—Between 2005 and 2006, the external quality assessment samples for prothrombin time/international normalized ratio and activated partial thromboplastin time were distributed to the participants as well as the instructions and suggestions for the improvement of laboratory practice. From the data collected, the all-method coefficient of variation of the international normalized ratio and activated partial thromboplastin time was calculated for each survey.

Results.—The number of participants increased during the first 1;h1 years that the surveys were conducted, from 109 to 127. Survey data demonstrate an improvement in response rate and an increase in the number of laboratories that determine their own reference ranges and repeat this for every change of reagent lot, using the appropriate anticoagulant. The increased precision of tests is indicated by the decrease of the all-method coefficient of variation of the international normalized ratio and activated partial thromboplastin time. Examples of individual laboratory improvement through feedback are also described.

Conclusions.—The improvement of coagulation laboratory practice both through the instructions provided and liaison with participants was observed during the course of this scheme.
Urine Mercury Excretion Following meso-Dimercaptosuccinic Acid Challenge in Fish Eaters
Authors: Ruha Anne-Michelle , Curry Steven C. , Gerkin Richard D. , Caldwell Kathleen L. , Osterloh John D. , Wax Paul M.
Published: February 2021

Context.—Public awareness of methylmercury in fish has caused patients to seek testing for mercury poisoning. In some patients, the diagnosis of mercury poisoning has been made based on urine mercury excretions following oral dosing of meso-dimercaptosuccinic acid (DMSA), a metal chelator. However, studies comparing urine mercury excretion following DMSA in healthy non–fish eaters with healthy fish eaters could not be located.

Objectives.—To describe urinary mercury excretion before and after DMSA in healthy fish eaters and non–fish eaters, and to determine whether urine mercury excretion after DMSA would rise above baseline levels to a greater extent in fish eaters.

Design.—A total of 24 healthy physicians were assigned to 1 of 3 groups based on fish consumption: non–fish eaters; 1 to 2 fish servings per week; and 3 or more servings per week. Blood mercury concentrations and 12-hour urine mercury and creatinine excretions were measured before and after oral ingestion of 30 mg of DMSA per kilogram of body weight.

Results.—A total of 24 subjects completed the study, and 2 subsequently were excluded. No difference in baseline urinary mercury excretion was detected between groups. All groups demonstrated an increase in urinary mercury excretion following DMSA, which was higher in fish eaters (P = .04). Multiple linear regression found that the best predictor of a rise in urine mercury excretion following DMSA challenge was the prechelation blood mercury concentration.

Conclusions.—In this study of healthy physicians, oral DMSA produced a rise in urine mercury excretion both in non–fish eaters and fish eaters. The increase in chelated mercury excretion was higher in fish eaters. A simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning.
Optimal Use of Myco/F Lytic and Standard BACTEC Blood Culture Bottles for Detection of Yeast and Mycobacteria
Authors: Kirby James E. , Delaney Meghan , Qian Qinfang , Gold Howard S.
Published: February 2021

Context.—The optimal use of dedicated fungal and mycobacterial blood culture bottles, such as the BACTEC Myco/F Lytic bottle, has not been well defined in clinical practice.

Objectives.—To compare the performance of Myco/F Lytic and standard blood culture in clinical practice in an urban tertiary care hospital setting and to implement a strategy for optimal use of Myco/F Lytic culture.

Data Sources.—Retrospective review of laboratory records.

Results.—Myco/F Lytic culture did not increase detection of yeasts. Nor did it decrease time to detection except for Candida glabrata, where mean time to positivity dropped from 2.6 ± 1.1 days in standard to 1.8 ± 0.8 days in Myco/F Lytic culture. Therefore, an algorithm was developed in which Myco/F Lytic culture was reserved primarily for detection of mycobacteria in patients with severely depressed CD4 counts. Implementation of this algorithm led to a sustained 3-fold reduction in Myco/F Lytic blood culture usage.

Conclusions.—Retrospective analysis suggests substantial clinical equivalence of standard blood and Myco/F Lytic culture for detection of yeast. A multifaceted educational approach based on this data led to a sustained change in physician ordering practices and more cost-effective use of resources.
Sino-Orbital Osteoma: A Clinicopathologic Study of 45 Surgically Treated Cases With Emphasis on Tumors With Osteoblastoma-like Features
Authors: McHugh Jonathan B. , Mukherji Suresh K. , Lucas David R.
Published: February 2021

Context.—Osteomas are limited almost exclusively to craniofacial and jaw bones. Histologically, they can be divided into ivory, mature, or mixed types. Osteomas may have osteoblastoma-like areas and distinguishing it from true osteoblastoma can be challenging. Some believe osteomas with osteoblastoma-like features behave more aggressively.

Objective.—To perform a clinicopathologic comparison of sino-orbital osteomas both with and without osteoblastoma-like features.

Design.—We studied 45 surgically excised sino-orbital osteomas. Tumors were categorized as ivory, mature, or mixed type and presence of osteoblastoma-like areas and Paget-like bone were noted. Clinical features of those with and without osteoblastoma-like areas were compared.

Results.—Men outnumbered women (3:2); median age was 37 years. Frontal sinus was the most common location (62%) followed by ethmoid and maxillary sinuses. Twelve tumors (27%) involved the orbit, 2 primarily and 10 secondarily. All cases were symptomatic with headache, sinusitis, visual changes, pain, and proptosis being most common. Seventeen tumors (38%) had osteoblastoma-like areas. Extension into an adjacent sinus/anatomic compartment was more common in osteoblastoma-like tumors (47% versus 29%), including more frequent orbital involvement (41% versus 13%). Visual changes were more frequent in the osteoblastoma-like group. Distribution of histologic subtypes and Paget-like bone were similar between the 2 groups. Osteomas with osteoblastoma-like features were more often incompletely excised (25% versus 14%). However, clinical recurrence was less common (8% versus 27%).

Conclusions.—Osteoblastoma-like features are common in sino-orbital osteomas, but it does not correlate with more adverse clinical features or worse outcome. Osteoblastoma-like areas appear to represent active remodeling within an osteoma rather than defining a distinct clinicopathologic entity. Distinguishing it from osteoblastoma may require careful histologic evaluation and radiographic correlation.
Association of Cystic Neck Metastases and Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma
Authors: McHugh Jonathan B.
Published: February 2021

Human papillomavirus is an established cause of oropharyngeal squamous cell carcinoma. Similar to cervical cancer, these cancers are usually caused by high-risk human papillomavirus types 16 and 18 and are associated with high-risk sexual behaviors. Human papillomavirus–associated oropharyngeal squamous cell carcinoma typically affects the palatine and lingual tonsils and frequently results in cystic neck metastases. The histopathology of this subset of head and neck squamous cell carcinoma is unique and typically characterized by poorly differentiated, nonkeratinizing morphology with a basaloid appearance. These tumors occur in younger patients and are more often seen in nonsmokers compared with conventional oral cavity and oropharyngeal squamous cell carcinomas. The incidence of human papillomavirus–associated squamous cell carcinoma is increasing. Recognition of this unique clinicopathologic subset of head and neck carcinoma is important because these patients typically respond more favorably to organ-sparing treatment modalities and have an improved prognosis.
Current Perspectives on the Gleason Grading of Prostate Cancer
Authors: Shah Rajal B.
Published: February 2021

Context.—Since its description in 1966 by Donald Gleason, the Gleason grading has remained a cornerstone in the diagnosis and management of prostate cancer. With widespread use of the prostate specific antigen screening, the diagnosis and management patterns of prostate cancers have dramatically changed. In addition, better understanding of the morphologic spectrum of prostate cancer and its subsequent outcome have prompted the refinement of the grading criteria and reporting practices applicable to contemporary practice management.

Objective.—To present contemporary perspectives and approaches to the Gleason grading of prostate cancer.

Data Sources.—Personal practice experience, review of medical literature, and excerpts from the 2005 International Society of Urological Pathology Consensus Statement on Gleason Grading of Prostate Cancer.

Conclusions.—This review addresses the trend in contemporary practice toward a grading shift, with rare utilization of Gleason patterns 1 and 2, and discusses the refinement of histologic criteria for Gleason patterns 3 and 4; approaches to Gleason grading in the setting of unusual variant morphologies of prostate cancer; significance of higher tertiary pattern 5; and practice recommendations for reporting in the setting of extended multiple core biopsies and multifocal prostate cancers in radical prostatectomy. Finally, the impact of consensus recommendations in current practice, its limitations and pitfalls, are also addressed.
Apocrine Ductal Carcinoma In Situ Involving a Sclerosing Lesion With Adenosis: Report of a Case
Authors: Visscher Daniel W.
Published: February 2021

Apocrine metaplasia is a ubiquitous component of the mammary fibrocystic change spectrum. Although mostly associated with cysts, apocrine metaplasia can also present as a proliferative lesion, rarely with cytologic atypism. Apocrine atypia is characterized by 3-fold nuclear enlargement, multiple nucleoli, and hyperchromatism and generally arises in florid adenosis or radial sclerosing lesions. Dramatic apocrine atypia may be very difficult to distinguish from apocrine ductal carcinoma in situ. The latter is distinguished from apocrine atypia by greater extent of the lesion (>0.4 cm) and the presence of greater nuclear pleomorphism with nuclear membrane irregularity. The clinical significance of apocrine atypia is poorly understood and reflects the lack of published outcome studies. Herein, I report a case in which apocrine ductal carcinoma in situ presented as “atypical apocrine adenosis” in a needle core breast biopsy. It illustrates the problem of assessing apocrine atypia and apocrine ductal carcinoma in situ in small samples.
Dieulafoy Disease of the Colon
Authors: Jain Richa , Chetty Runjan
Published: February 2021

Dieulafoy disease is a rare cause of upper gastrointestinal hemorrhage (usually gastric) and an even rarer cause of colonic bleeding. There is a sudden onset of catastrophic bleeding in a previously healthy individual, which cannot be managed conservatively. Although this entity can be diagnosed and treated by endoscopy and angiography, the knowledge of its existence in colon is critical to making the diagnosis because of its small size. In an era of widespread use of endoscopy, the pathologists uncommonly receive resection specimens for Dieulafoy lesions. However, the diagnosis can be missed because of the small size of the lesion and the almost normal appearance of the mucosa. Awareness of its existence will provide an answer for otherwise unexplained gastrointestinal hemorrhage.
Nephrogenic Systemic Fibrosis: A Pathologic Study of Autopsy Cases
Authors: Koreishi Aashiyana F. , Nazarian Rosalynn M. , Saenz Adam J. , Klepeis Veronica E. , McDonald Anna G. , Farris Alton Brad , Colvin Robert B. , Duncan Lyn M. , Mandal Rajni V. , Kay Jonathan
Published: February 2021

Context.—Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder initially described as a purely dermatologic process. Isolated autopsy reports have described multiorgan involvement by this disease.

Objective.—To further illustrate the varied and systemic involvement of NSF by describing the autopsy experience at the Massachusetts General Hospital.

Design.—We describe the findings in a series of 4 autopsy cases of patients diagnosed with NSF. This report describes the history of renal dysfunction, exposure to gadolinium-containing contrast agents, specific laboratory parameters, and the extent of systemic involvement identified by postmortem examination.

Results.—Causes of death included systemic thromboembolic disease (n = 3) and pneumonia (n = 1). Laboratory parameters and type, dose, or timing of gadolinium-containing contrast-agent exposure did not correlate with clinical findings and outcomes. All patients demonstrated cutaneous manifestations of the disease and nephrocalcinosis, with some exhibiting calcification and fibrosis of the dura, thyroid, and heart including the cardiac conduction system, on postmortem examination. Soft tissue calcification was associated with concurrent hyperparathyroidism or high serum parathyroid hormone levels.

Conclusions.—Thromboembolic disease can be a significant clinical complication of NSF. Patients with NSF may also develop characteristic histologic features of fibrosis and calcification in multiple organs, with significant morbidity and mortality. This autopsy series highlights the variability of systemic manifestations of NSF.
Whole-Slide Imaging Digital Pathology as a Platform for Teleconsultation: A Pilot Study Using Paired Subspecialist Correlations
Authors: Wilbur David C. , Madi Kalil , Colvin Robert B. , Duncan Lyn M. , Faquin William C. , Ferry Judith A. , Frosch Matthew P. , Houser Stuart L. , Kradin Richard L. , Lauwers Gregory Y. , Louis David N. , Mark Eugene J. , Mino-Kenudson Mari , Misdraji Joseph , Nielsen Gunnlauger P. , Pitman Martha B. , Rosenberg Andrew E. , Smith R. Neal , Sohani Aliyah R. , Stone James R. , Tambouret Rosemary H. , Wu Chin-Lee , Young Robert H. , Zembowicz Artur , Klietmann Wolfgang
Published: February 2021

Context.—Whole-slide imaging technology offers promise for rapid, Internet-based telepathology consultations between institutions. Before implementation, technical issues, pathologist adaptability, and morphologic pitfalls must be well characterized.

Objective.—To determine whether interpretation of whole-slide images differed from glass-slide interpretation in difficult surgical pathology cases.

Design.—Diagnostically challenging pathology slides from a variety of anatomic sites from an outside laboratory were scanned into whole digital format. Digital and glass slides were independently diagnosed by 2 subspecialty pathologists. Reference, digital, and glass-slide interpretations were compared. Operator comments on technical issues were gathered.

Results.—Fifty-three case pairs were analyzed. There was agreement among digital, glass, and reference diagnoses in 45 cases (85%) and between digital and glass diagnoses in 48 (91%) cases. There were 5 digital cases (9%) discordant with both reference and glass diagnoses. Further review of each of these cases indicated an incorrect digital whole-slide interpretation. Neoplastic cases showed better correlation (93%) than did cases of nonneoplastic disease (88%). Comments on discordant cases related to digital whole technology focused on issues such as fine resolution and navigating ability at high magnification.

Conclusions.—Overall concordance between digital whole-slide and standard glass-slide interpretations was good at 91%. Adjustments in technology, case selection, and technology familiarization should improve performance, making digital whole-slide review feasible for broader telepathology subspecialty consultation applications.
Alport Syndrome and Thin Glomerular Basement Membrane Nephropathy: A Practical Approach to Diagnosis
Authors: Haas Mark
Published: February 2021

Context.—Alport syndrome and thin glomerular basement membrane nephropathy (TBMN) are genetically heterogenous conditions characterized by structural abnormalities in the glomerular basement membrane and an initial presentation that usually involves hematuria. Approximately 40% of patients with TBMN are heterozygous carriers for autosomal recessive Alport syndrome, with mutations at the genetic locus encoding type IV collagen α3 [α3(IV)] and α4 chains. However, although the clinical course of TBMN is usually benign, Alport syndrome, particularly the X-linked form with mutations in the locus encoding the α5 chain of type IV collagen [α5(IV)], typically results in end-stage renal disease. Electron microscopy is essential to diagnosis of TBMN and Alport syndrome on renal biopsy, although electron microscopy alone is of limited value in distinguishing between TBMN, the heterozygous carrier state of X-linked Alport syndrome, autosomal recessive Alport syndrome, and even early stages of X-linked Alport syndrome.

Objectives.—To review diagnostic pathologic features of each of the above conditions, emphasizing the need for immunohistology for α3(IV) and α5(IV) in addition to electron microscopy to resolve this differential diagnosis on a renal biopsy. The diagnostic value of immunofluorescence studies for α5(IV) on a skin biopsy in family members of patients with Alport syndrome also is reviewed.

Data Sources.—Original and comprehensive review articles on the diagnosis of Alport syndrome and TBMN from the past 35 years, primarily the past 2 decades, and experience in our own renal pathology laboratory.

Conclusions.—Although Alport syndrome variants and TBMN do not show characteristic light microscopic findings and can be difficult to differentiate from each other even by electron microscopy, using a combination of electron microscopy and immunohistology for α3(IV) and α5(IV) enables pathologists to definitively diagnose these disorders on renal biopsy in most cases.
Renal Lesions Associated With Plasma Cell Dyscrasias: Practical Approach to Diagnosis, New Concepts, and Challenges
Authors: Herrera Guillermo A.
Published: February 2021

Context.—Patients with plasma cell dyscrasias (myeloma) may exhibit a variety of renal manifestations as a result of damage from circulating light- and heavy-chain immunoglobulin components produced by the neoplastic plasma cells. The renal alterations can occur in any of the renal compartments, and in a significant number of the cases more than one compartment is affected. Research in the laboratory has helped considerably in providing a solid conceptual understanding of how renal damage occurs.

Objectives.—To detail advances that have been made in the diagnosis of these conditions and to provide an account of research accomplishments that have solidified diagnostic criteria. The new knowledge that has been acquired serves to provide a solid platform for the future design of new therapeutic interventions aimed at ameliorating or abolishing the progressive renal damage that typically takes place.

Data Sources.—Translational efforts have substantially contributed to elucidate mechanistically the molecular events responsible for the renal damage. The spectrum of renal manifestations associated with plasma cell dyscrasias has expanded significantly in the last 10 years. Diagnostic criteria have also been refined. This information has been summarized from work done at several institutions.

Conclusions.—A number of significant challenges remain in the diagnosis of these conditions, some of which will be discussed in this article. Dealing with these challenges will require additional translational efforts and close cooperation between basic researchers, clinicians, and pathologists in order to improve the diagnostic tools available to renal pathologists and to acquire a more complete understanding of clinical and pathologic manifestations associated with these conditions.
Emerging Therapy-Related Kidney Disease
Authors: Arend Lois J. , Nadasdy Tibor
Published: February 2021

Context.—Many new therapies have emerged within the last 5 to 10 years to treat a variety of conditions. Several of these have direct or indirect renal toxicities that may go undiagnosed without careful attention of the pathologist to a patient's clinical history, particularly the addition of new medications or treatments.

Objective.—To discuss patterns of renal injury resulting from medications or therapeutic regimens that have been introduced within the last 10 years. Recognition of these patterns may allow the pathologist to alert the attending clinician to a possible drug-induced renal injury and prevent further deterioration of renal function and possible chronic kidney disease.

Data Sources.—A review of recent literature and unpublished observations of case-derived material.

Conclusions.—A number of newer therapies have emerged as agents of renal toxicity, producing a variety of pathologic changes in the kidney. The outcome can be acute or chronic glomerular, tubular, interstitial, and/or vascular injury. Some drugs will result in irreversible changes and end-stage renal disease, whereas many of the alterations can be reversed with removal of the offending agent, avoiding potential long-term kidney injury.