bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Human Chorionic Gonadotropin– Related Components in Fresh Frozen Serum With the Proficiency Testing Material Used by the College of American Pathologists
Authors: Knight George J. , Palomaki Glenn E. , Klee George G. , Schreiber William E. , Cole Lawrence A.
Published: February 2021

Context.—As part of a College of American Pathologists (CAP) proficiency testing survey, a comparison is made between human chorionic gonadotropin (hCG) results from an actual patient pool and a similarly targeted artificial sample. The goal is to gain insight into the possible source(s) of bias attributable to the proficiency testing material (PTM) with a view toward creating more appropriate survey materials.

Objective.—To compare hCG and related variants in a pool of fresh frozen sera (FFS) with that found in PTM.

Design.—The 2003 CAP K/KN-A Survey included a FFS specimen along with admixtures of PTM. The FFS (K-02) and 1 PTM admixture (K-01) had similar mean hCG values. Five hCG-related analytes were measured on these 2 samples by a reference laboratory.

Participants.—Approximately 1800 clinical laboratories and diagnostic test kit manufacturers participated in the K/ KN-A Survey.

Main Outcome Measures.—Method imprecision (coefficient of variation) and method bias (relative difference between peer group mean and all-method median) were computed for the 2 samples. Differences were evaluated with respect to hCG-related analytes levels.

Results.—All-method hCG results were 12.9 mIU/mL (12.9 IU/L) for the PTM material and 21.6 mIU/mL (21.6 IU/L) for the FFS material. Method biases for 14 manufacturers were greater for PTM than for FFS (−40% to +35% and −16% to +23%). Twelve of 14 methods had higher coefficients of variation on PTM. Total hCG and free β hCG measurements by the reference laboratory were 14.1 mIU/ mL (14.1 IU/L) for the PTM material and 18.5 mIU/mL (18.5 U/L) for the FFS material (FFS), and 2.4 (PTM) and 0.7 (FFS) mIU/mL (2.4 and 0.7 IU/L), respectively. On a molar basis, free β represented 17% and 4% of the total hCG, respectively. Levels of hyperglycosylated hCG, nicked hCG, and β core fragment were not measurable in either sample.

Conclusions.—It is unlikely that the hCG added to the PTM is the source of the increased bias and variability. The main difference is a 3-fold increase in free β found in the PTM, but methods previously found to strongly react with free β were not systematically elevated. The biases between manufacturers found for the FFS specimen are likely attributable to calibration differences.
The Openings of Uteroplacental Vessels With Villous Infiltration at Different Gestational Ages
Authors: Fujikura Toshio
Published: February 2021

Context.—The number of uteroplacental vessels flowing into the intervillous space in mature placentas has been reported in some studies to increase and in others to decrease. Both villous infiltration and proliferation in the vessels have been neglected in histologic examinations and need to be studied.

Objective.—To clarify these conflicting findings regarding villous infiltration and proliferation in the uteroplacental vessels.

Design.—A retrospective study was done using placental sections of different gestational ages. The openings of the vessels in each section were counted, noting if they were with or without villous infiltration. The frequency of openings per section was calculated, and the findings were grouped by gestational age.

Results.—The frequency of total openings was significantly lower in the 41 to 37 weeks group (1.2) than in the 36 to 30 weeks group (2.0), the 29 to 20 weeks group (2.2), and the 19 to 13 weeks group (2.4) (P < .001). The frequency of openings with villous infiltration decreased similarly in mature placentas. Chorionic villi infiltrated the openings and proliferated in uteroplacental vessels. Differentiation between arteries and veins was difficult in the basal plate, because all vessels had veinlike structures.

Conclusions.—This decreasing frequency of openings in mature placentas suggests that the amount of intervillous blood flow is limited in full-term and postterm pregnancy. Villous infiltration into the vessels is considered a normal finding with gestation and can provide trophoblast for uteroplacental arteries. The relationship between placental development and villous proliferation in the vessels is presented.
Putative Precursors of Gallbladder Dysplasia: A Review of 400 Routinely Resected Specimens
Authors: Mukhopadhyay Sanjay , Landas Steve K.
Published: February 2021

Context.—Dysplasia is thought to be a precursor of invasive gallbladder carcinoma, but it is unsettled whether dysplasia arises from other precursor lesions.

Objective.—To ascertain the presence and nature of precursors of dysplasia in the gallbladder.

Design.—Four hundred consecutive cholecystectomy specimens were processed and stained routinely for diagnosis. We retrospectively reviewed these cases to look for the presence of epithelial changes, including antral-type metaplasia, intestinal metaplasia, and dysplasia.

Results.—Antral-type metaplasia, intestinal metaplasia, and dysplasia were found in 238 (59.5%), 39 (9.8%), and 20 (5.0%) cases, respectively. The mean patient age was 47.7 years (range, 15–93 years). The mean ages for patients with antral-type metaplasia, intestinal metaplasia, and dysplasia were 49.4, 50.9, and 52.6 years, respectively. Statistically significant associations were found between antral-type metaplasia and intestinal metaplasia (P = .007, χ2 test) and between intestinal metaplasia and dysplasia (P < .001, χ2 test).

Conclusion.—These associations, along with the age gradient from antral-type metaplasia to dysplasia, suggest a progression from antral-type metaplasia to dysplasia via intestinal metaplasia.
Collision Tumor of the Stomach: A Rare Case of an Adenocarcinoma and Carcinoid Tumor
Authors: Morishita Yukie , Sugitani Masahiko , Sheikh Aleemuzzaman , Nemoto Norimichi , Fujii Masashi , Takayama Tadatoshi
Published: February 2021

We report a rare case of gastric collision tumor composed of moderately differentiated tubular adenocarcinoma and carcinoid in an 84-year-old woman. On endoscopic examination, an invasive tumor was noted at the cardia of the stomach, and a pathologic examination of the biopsy specimen revealed adenocarcinoma. After total gastrectomy, a thorough histopathologic examination of the resected tumor revealed the concurrent presence of moderately differentiated adenocarcinoma and a typical carcinoid tumor, which had a colliding pattern of tissue proliferation. There was no intermixing or transition area between the 2 components. The final pathologic diagnosis was collision tumor of the adenocarcinoma and carcinoid tumor. The presence of either tumor individually would not be especially noteworthy, but this collision-type tumor of both histopathologic types in the stomach is, to our knowledge, only the sixth such case in the literature.
Kidney and Urinary Tract Polyomavirus Infection and Distribution: Molecular Biology Investigation of 10 Consecutive Autopsies
Authors: Boldorini Renzo , Veggiani Claudia , Barco Diana , Monga Guido
Published: February 2021

Context.—Distinct human polyomavirus genotypes cause different diseases in patients with renal transplants: BK virus (BKV) causes tubulointerstitial nephritis and ureteral stenosis, whereas both JC virus (JCV) and BKV are responsible for hemorrhagic cystitis. These findings could result from a selective infection of kidney and urinary tract segments by JCV or BKV.

Objective.—To verify this hypothesis, 10 complete, unselected, consecutive autopsies from 9 immunocompetent patients and 1 patient affected by acquired immunodeficiency syndrome were investigated.

Design.—Samples from kidneys (n = 80), renal pelvis (n = 20), ureter (n = 40), and urinary bladder (n = 30) obtained from 10 consecutive autopsies were investigated by means of multiplex nested polymerase chain reaction to detect polyomavirus DNA and to distinguish different species of the Polyomavirus genus. In situ hybridization and immunohistochemistry were also carried out to define the viral status of the infected tissues.

Results.—Polyomavirus DNA was detected in all of the subjects (positive samples ranging from 2 to 7 samples), for a total of 43 of 170 samples (25.3%), distributed as follows: urinary bladder (10/30, 33%), renal pelvis (6/20, 30%), ureter (10/40, 25%), and kidney tissue (17/80, 21%). We found that JCV was most frequently detected overall (23/43 samples, 53.5%) and was also detected most frequently within the kidney (8/17 positive samples, 47%), the renal pelvis (5/6 positive samples, 70%), and the ureter (7/10 positive samples, 70%), whereas BKV was found in 14 samples (32.5%), and it was the prevailing genotype in urinary bladder (6/10 positive samples, 60%). Coinfection of BKV-JCV was found in 6 samples (14%). Immunohistochemistry and in situ hybridization returned negative results.

Conclusions.—The viruses JCV and BKV latently persist randomly in kidney and urinary tract. Distinct diseases induced by them could be related more closely to molecular viral rearrangements than to the topographic distribution of latent viruses.
Measurement of Organochlorines in Commercial Over-the-Counter Fish Oil Preparations: Implications for Dietary and Therapeutic Recommendations for Omega-3 Fatty Acids and a Review of the Literature
Authors: Melanson Stacy Foran , Lee Lewandrowski Elizabeth , Flood James G. , Lewandrowski Kent B.
Published: February 2021

Context.—The consumption of fish high in omega-3 fatty acids is advocated by the American Heart Association to decrease the risk of coronary artery disease. However, fish contain environmental toxins such as mercury, polychlorinated biphenyls, and organochlorine pesticides, which may negate the beneficial cardiovascular effects of fish meals. Toxin levels vary depending on both the fish source and the specific toxin, and neither farm-raised nor wild fish are toxin free. Fish oil supplements also prevent the progression of coronary artery disease and reduce cardiovascular mortality. However, only sparse data exist on the level of toxins in fish oil. In a previous study we showed that the amount of mercury in 5 over-the-counter brands of fish oil was negligible.

Objective.—To determine the concentrations of polychlorinated biphenyls and other organochlorines in 5 over-the-counter preparations of fish oil.

Design.—The contents of 5 commercial fish oil brands were sent for organochlorine analysis.

Results.—The levels of polychlorinated biphenyls and organochlorines were all below the detectable limit.

Conclusions.—Fish oil supplements are more healthful than the consumption of fish high in organochlorines. Fish oils provide the benefits of omega-3 fatty acids without the risk of toxicity. In addition, fish oil supplements have been helpful in a variety of diseases, including bipolar disorder and depression.
The Internet for Pathologists: A Simple Schema for Evaluating Pathology-Related Web Sites and a Catalog of Sites Useful for Practicing Pathologists
Authors: Talmon Geoffrey , Abrahams Neil A.
Published: February 2021

Context.—With the increasing popularity of the Internet as a primary medical information source, it is critical for pathologists to be able to use and evaluate both general medical- and pathology-related Web sites. Several published models for evaluating Web sites prove cumbersome to use and often involve computer- or statistic-based algorithms.

Objectives.—To develop a simple group of scoring criteria to objectively evaluate medical Web sites and provide a list of the highest-scoring pathology-related sites that will be useful to the practicing pathologist.

Design.—Using 11 commonly used Internet search engines, the top 50 “hits” retrieved from the search term websites for pathologists were scored using 5 criteria, including accuracy, ease of navigation, relevance, updates, and completeness. A possible 6 to 12 points per area were awarded, and the total score was summated.

Results.—Scores obtained ranged from 12 to 21. Thirty-five Web sites, all scoring 15 or higher based on these criteria, were listed as most useful.

Conclusion.—A simple, easy-to-use, 5-category scoring system can prove useful in evaluating pathology- and medical-related Web sites.
Distinguishing Fibrovascular Septa From Vasculogenic Mimicry Patterns
Authors: Lin Amy Y. , Maniotis Andrew J. , Valyi-Nagy Klara , Majumdar Dibyen , Setty Suman , Kadkol Shri Hari , Leach Lu , Pe'er Jacob , Folberg Robert
Published: February 2021

Context.—Molecular analyses indicate that periodic acid–Schiff (PAS)–positive (laminin-rich) patterns in melanomas are generated by invasive tumor cells by vasculogenic mimicry. Some observers, however, consider these patterns to be fibrovascular septa, generated by a stromal host response.

Objective.—To delineate differences between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas.

Design.—Frequency distributions, associations with outcome, and thicknesses of trichrome-positive and PAS-positive looping patterns were determined in 234 primary uveal melanomas. Sequential sections of 13 additional primary uveal melanomas that contained PAS-positive/trichrome-negative looping patterns were stained for type I and type IV collagens, laminin, and fibronectin. Real-time quantitative polymerase chain reaction was performed on RNA from cultured uveal melanoma cells for the expression of COL1A1, COL4A2, and fibronectin.

Results.—Trichrome-positive loops were encountered less frequently than PAS-positive loops (10% vs 56%, respectively). Death from metastatic melanoma was strongly associated with PAS-positive (P < .001) but not with trichrome-positive (P = .57) loops. Trichrome-positive loops were significantly thicker than PAS-positive loops (P < .001). The PAS-positive patterns stained positive for laminin, type I and type IV collagens, and fibronectin. Type I collagen was detected within melanoma cells and focally within some PAS-positive patterns. Real-time quantitative polymerase chain reaction revealed 3-fold, 25-fold, and 97-fold increases, respectively, in expression of COL4A2, fibronectin, and COL1A1 by invasive pattern-forming primary melanoma cells compared with poorly invasive non– pattern-forming cells.

Conclusions.—Fibrovascular septa are rare and prognostically insignificant in uveal melanomas, whereas vasculogenic mimicry patterns are associated with increased mortality. Type I collagen, seen focally in some vasculogenic mimicry patterns, may be synthesized by tumor cells, independent of a host stromal response.
Ectopic Decidua of Pelvic Lymph Nodes: A Potential Diagnostic Pitfall
Authors: Wu Debbie C. , Hirschowitz Sharon , Natarajan Sathima
Published: February 2021

Ectopic decidua is one of several benign lymph node inclusions that have been increasingly documented in the literature, most often in postmortem examinations of pregnant woman and recently in pregnant women with cervical squamous cell carcinoma. Although lacking clinical significance of its own, the major diagnostic implication would be misdiagnosis as metastatic carcinoma in the lymph node. Intraoperative frozen sections are often performed prior to radical hysterectomy, leading to a potential alteration of therapy if metastatic carcinoma is identified in the lymph nodes. We report such a case of a pregnant woman with cervical squamous cell carcinoma requiring lymphadenectomy and hysterectomy, in which the intraoperative frozen section of a pelvic lymph node with ectopic decidual change was mistakenly identified as metastatic carcinoma. Its histologic resemblance to carcinoma and location within subcapsular sinuses, compounded with the fact that ectopic lymph node decidua is not commonly seen in routine practice, can lead to this diagnostic pitfall. We review the literature regarding ectopic decidua, its presence in lymph nodes, and its pathogenesis, as well as review the literature on benign lymph node inclusions.
Epithelioid Angiosarcoma Involving the Lungs
Authors: Lund Lidiya , Amre Ramila
Published: February 2021

Diffuse lung involvement by metastatic tumor from an unknown primary site often constitutes a diagnostic dilemma. Although cytologic features and pattern of metastatic spread can guide in narrowing the list of possible primary neoplasms, immunohistochemistry remains pivotal in determining the phenotype of metastatic disease. We report a case with extensive involvement of lung parenchyma by a metastatic epithelioid neoplasm exhibiting a variety of distinctive patterns with a predominance of intra-arterial and lymphangitic spread. Immunohistochemical studies showed no evidence of epithelial, melanocytic, or lymphoid differentiation. The neoplastic cells were strongly positive for vimentin and CD31 but negative for CD34 and factor VIIIR:Ag. Electron microscopy of formalin-fixed tissue revealed multiple Weibel-Palade bodies and pinocytosis, supporting the diagnosis of epithelioid angiosarcoma. Doppler studies performed after pathologic diagnosis was rendered demonstrated 2 discrete hypoechoic masses within the medial aspect of the left proximal calf musculature, suggestive of solid soft tissue neoplasm—a possible source of pulmonary metastatic disease.
Gastric Toxoplasmosis as the Presentation of Acquired Immunodeficiency Syndrome
Authors: Merzianu Mihai , Gorelick Steven M. , Paje Voltaire , Kotler Donald P. , Sian Corazon
Published: February 2021

We report a case of a 39-year-old West African man with unknown human immunodeficiency virus status diagnosed with gastric toxoplasmosis as the presenting manifestation of acquired immunodeficiency syndrome. Toxoplasma gondii is common in severely immunosuppressed patients and most frequently involves the central nervous system, followed by the eye, myocardium and skeletal muscle, lungs, bone marrow, and peripheral blood. For unclear reasons, gastrointestinal involvement is exceedingly rare and occurs in the context of severe immunosuppression and disseminated disease. To our knowledge, this is the first report in the English literature of a patient with isolated, manifest gastric toxoplasmosis without evidence of concomitant cerebral or extracerebral involvement. It is important for both the clinician and the pathologist to maintain a high index of suspicion for toxoplasmosis in immunosuppressed patients presenting with nonspecific symptoms of gastritis and radiologic and endoscopic presence of thickened gastric folds with or without ulceration.
Robustness of Validation Criteria in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Walsh Molly K. , Blond Barbara , Moriarty Ann T. , Mody Dina R. , Colgan Terence J.
Published: February 2021

Context.—Field validation of slides used in gynecologic cytology proficiency testing has surfaced as an important issue. Although the precision of diagnoses in peer-reviewed educational programs has been examined, the robustness of the validation criteria for specific types of interpretations used in proficiency testing has not been previously studied.

Objective.—To evaluate the robustness of validation criteria for slides entering an educational slide program.

Design.—We reviewed the results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology and compared the robustness of validation criteria for different reference diagnoses, using a total of 16 948 circulating slides.

Results.—Validation criteria could be divided into 2 significantly different groups. The criteria for herpes, Trichomonas, squamous cell carcinoma, and adenocarcinoma were significantly more robust than the diagnoses of unsatisfactory; negative for intraepithelial lesion and malignancy, not otherwise specified; low-grade squamous intraepithelial lesion; and high-grade squamous intraepithelial lesion (P < .001).

Conclusions.—The validation criteria used in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology show 2 different levels of robustness or redundancy. These results have implications for the design of fair proficiency tests. Proficiency testing can be designed with the necessary number of reviews needed for slide validation.
Implementation of a Redistribution System for Near-Outdate Red Blood Cell Units
Authors: Denesiuk Lisa , Richardson Trevor , Nahirniak Susan , Clarke Gwen
Published: February 2021

Context.—Many remote hospitals keep small on-site stocks of red blood cell (RBC) units for emergency use and to support patient care programs. In Canada, the blood supplier does not accept returned units into inventory. Discard rates can, therefore, be high.

Objective.—To transport near-outdate RBC units to a high-usage hospital site, which would reduce overall discard rates, thereby increasing overall stock levels available in the blood system.

Design.—A blood transportation system was developed and validated. The validation was presented to a high-usage site that agreed to accept near-outdate RBC units transported by this system. Stocks at the remote hospitals were optimized without increasing system-wide discard rates. The redistribution program was implemented in 4 remote sites in northern Alberta, Canada. The final disposition of each transported unit was tracked. Data from the first 2 years were analyzed.

Results.—Between April 1, 2003, and March 31, 2005, 106 RBC units were successfully transported to and transfused at the high-usage site. The majority of the units were group O. None of the transfused units were involved in any reported transfusion reactions. The success rate of the transportation system varied among the sites (59%–78% successfully transported and transfused). Changes to the transport system were implemented as problems were discovered. The use of a temperature monitor in each shipment allowed for concurrent revalidation after each change.

Conclusions.—Redistribution systems can be an effective way to reduce RBC unit discard rates. Even simple transportation systems have many factors affecting the RBC unit temperature. Novel temperature stabilizing materials may make future transportation of RBC units more reliable.
Gliosarcoma With Features of Osteoblastic Osteosarcoma: A Review
Authors: Barresi Valeria , Cerasoli Serenella , Morigi Federico , Cremonini Anna Maria , Volpini Mirco , Tuccari Giovanni
Published: February 2021

Context.—Gliosarcoma is a rare tumor of the central nervous system characterized by a biphasic histologic pattern, consisting of a gliomatous and a sarcomatous component, respectively. In most instances the sarcomatous component is represented by a fibrosarcoma, but other stromal malignancies have also been described. Osteosarcomatous differentiation in gliosarcoma has been rarely reported.

Objective.—To review characteristic radiologic and histopathologic features of this rare neoplasm, to debate about possible differential diagnoses that should be taken into consideration, and to provide an overview of the potential histopathogenesis of gliosarcomas.

Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) and reference medical texts.

Conclusions.—Recent molecular studies suggest that sarcomatous and gliomatous components of gliosarcoma might be derived from a single precursor cell clone, progressing in 2 subclones with distinct morphologic features during tumor evolution. Nonetheless, events determining splitting of the original clone into 2 histologic populations remain to be investigated.
Concomitant Epstein-Barr Virus–Negative Large B-Cell Lymphoma (Richter Syndrome) and Epstein-Barr Virus– Positive B-Cell Lymphoproliferation After Treatment With Fludarabine and Cyclophosphamide in a Patient With B-Cell Chronic Lymphocytic Leukemia
Authors: Compérat Eva , Delmer Alain , Le Tourneau Agnes , Molina Thierry J. , Diebold Jacques , Audouin Josée
Published: February 2021

We report the case of a patient treated with a combination of fludarabine and cyclophosphamide after suffering from B-cell chronic lymphocytic leukemia for 10 years. Three months after treatment, the patient presented with an unusual association, not previously reported in the literature: Richter syndrome (monotypic Epstein-Barr virus– negative large B-cell lymphoma) with the proliferation of Epstein-Barr virus–positive B cells secreting a polytypic immunoglobulin A. The Epstein-Barr virus–positive lymphoproliferation can be accounted for by the type of immunosuppression induced by the treatment.
Pleuropulmonary Desmoid Tumors: Immunohistochemical Comparison With Solitary Fibrous Tumors and Assessment of β-Catenin and Cyclin D1 Expression
Authors: Andino Lizmarie , Cagle Philip T. , Murer Bruno , Lu Li , Popper Helmut H. , Galateau-Salle Francoise , Sienko Anna E. , Barrios Roberto , Zander Dani S.
Published: February 2021

Context.—Desmoid tumors arising in the lung and pleura are extremely rare and can resemble other, more common neoplasms native to these sites. Alterations of the adenomatous polyposis coli/β-catenin pathway have been detected in sporadic desmoid tumors and have been associated with nuclear accumulation of β-catenin and overexpression of cyclin D1.

Objective.—To analyze the expression of β-catenin and cyclin D1 in desmoid tumors and solitary fibrous tumors (SFTs), and to compare the utilities of these substances for distinguishing between these entities with those of other, more commonly used stains.

Design.—Formalin-fixed, paraffin-embedded sections of 4 desmoid tumors (1 pulmonary, 1 pleural, 2 pleural/chest wall), and 5 benign and 6 malignant SFTs of the pleura were immunostained for β-catenin, cyclin D1, ALK1, CD34, vimentin, desmin, smooth muscle actin, muscle-specific actin, S100, and pancytokeratin. Staining intensity and the percentage of stained tumor cells were assessed semiquantitatively.

Results.—Diffuse moderate or strong nuclear staining for β-catenin was found in all desmoid tumors, 4 of 5 benign SFTs, and 2 of 6 malignant SFTs. All cases except 1 benign SFT showed concurrent cytoplasmic staining. Nuclear and cytoplasmic cyclin D1 staining was increased in all groups. The best distinction between desmoid tumors and SFTs was provided by CD34 (desmoid tumors, 0/4; SFTs, 8/11) and smooth muscle actin (desmoid tumors, 4/4; SFTs, 0/11).

Conclusions.—Our findings suggest that alterations in the adenomatous polyposis coli/β-catenin pathway and cyclin D1 dysregulation may contribute to the pathogenesis of pleuropulmonary desmoid tumors and SFTs. CD34 and smooth muscle actin stains are particularly useful for differentiating between pleuropulmonary desmoid tumors and SFTs.
The Variability of Results Between Point-of-Care Testing Glucose Meters and the Central Laboratory Analyzer
Authors: Khan Adil I. , Vasquez Yolanda , Gray Jacquelyn , Wians Jr Frank H. , Kroll Martin H.
Published: February 2021

Context.—Point-of-care testing glucose meters are strongly recommended in the management of diabetes and are increasingly being used for making therapeutically important decisions. Thus, it is essential that their results correlate well with those of laboratory analyzers.

Objectives.—To test the reliability of point-of-care testing glucose meters.

Design.—Two studies were performed: (1), an in-house study comparing accuracy of point-of-care testing glucose meters with a reference analyzer using fresh whole blood specimens (2), a real-time comparison of (a) 2 successive glucose meter readings and (b) glucose meter reading to central laboratory analyzer reading.

Setting.—(1), Seven glucose meters from 4 manufacturers were compared with the Yellow Springs YSI 2300 blood glucose analyzer using whole blood without preservative. (2), (a) Whole blood samples were read within 5 minutes of each other using Accu-Chek meters and (b) between a glucose meter and a Hitachi laboratory analyzer.

Results.—(1) Within the Accu-Chek group of glucose meters, fresh, preservative-free whole blood samples showed the lowest bias. (2) At the hypoglycemic level, successive glucose meter readings agreed well, but there was considerable disagreement between glucose meter and central laboratory values. Because laboratory analyzers are of proven accuracy, they are used as the reference. In the glucose meter–central laboratory analyzer correlation, for both hypoglycemic and hyperglycemic values, readings in which the differences were greater than 10% occurred more than 61% of the time. In the hypoglycemic range, differences greater than 20% occurred 57% of the time.

Conclusions.—One should scrutinize point-of-care testing glucose meter readings at the hypoglycemic and hyperglycemic levels and whenever possible to corroborate these clinical results with central laboratory analyzers.
Thin Basement Membrane Nephropathy: Diffuse and Segmental Types
Authors: Ivanyi Bela , Pap Robert , Ondrik Zoltan
Published: February 2021

Context.—Diffuse thinning of the glomerular basement membrane (GBM) is the ultrastructural diagnostic criterion of thin basement membrane nephropathy (TBMN). However, there is no consensus regarding what diagnosis should be made if the attenuation is segmental.

Objective.—To develop a diagnostic approach to TBMN in cases with segmental GBM thinning.

Design.—We compared the diagnostic sensitivities of 2 methods used for the quantitative expression of GBM width in a consecutive series of renal biopsies from 26 patients (median age, 36 years; range, 15 to 59 years) with dysmorphic hematuria (a variable degree of proteinuria in 19 patients), a thin GBM, and absence of other renal disease. The harmonic GBM width was determined from orthogonal intercepts, and the actual width in the thinnest loops was obtained by direct measurement. The GBM attenuation was categorized into diffuse or segmental types by conventional inspection.

Results.—Segmental TBMN accounted for one third of the series. In neither type did the male patients have a higher harmonic mean GBM width than the female patients. Focal-global glomerulosclerosis was more common in diffuse TBMN. The laborious orthogonal intercept method proved insensitive for the verification of segmental TBMN, whereas the much simpler direct measurement technique captured all the cases.

Conclusions.—A considerable number of patients with TBMN display segmental GBM attenuation. Because the routine criterion excludes these cases from the diagnosis, we propose to define TBMN as a clinicopathologic entity of dysmorphic hematuria and a diffusely or segmentally thinned GBM confirmed by the direct measurement technique.
The Impact of the World Health Organization Classification and Clonality Assessment of Posttransplant Lymphoproliferative Disorders on Disease Management
Authors: Mourad Walid A. , Tulabah Asma , Al Sayed Adher , Raja Madras , Khafaga Yasser , El Gamal Hazem , Al Shabanah Mohamed , Al Meshari Khaled , Al Shaibani Khaled , Ezzat Adnan
Published: February 2021

Context.—The World Health Organization classification of posttransplant lymphoproliferative disorders divides them into 4 main categories.

Objective.—To classify cases of posttransplant lymphoproliferative disorders diagnosed in our institution according to the World Health Organization scheme and correlate the classification and clonality with clinical data.

Design.—Cases of posttransplant lymphoproliferative disorders were reviewed. They were classified according to the World Health Organization scheme. Clonality was determined by flow cytometry and/or polymerase chain reaction. Patients' charts were reviewed.

Results.—Thirty-one cases were identified. Median age was 33 years. There were 19 cases of kidney, 8 cases of liver, and 4 cases of bone marrow transplant. Immunosuppression consisted of cyclosporin A and prednisone (N = 24) or FK506 and prednisone (N = 7). Twenty cases (63%) were World Health Organization type 3, 7 cases (23%) type 2, 3 cases (6.4%) type 1, and 1 case type 4 posttransplant lymphoproliferative disorder. Ten patients received chemotherapy, 20 patients had reduction of immunosuppression, and 1 had no treatment. Follow-up was available on 25 patients. Seven (43.75%) of 16 with type 3 lesions with available follow-up died of their disease. Five of these patients received reduction of immunosuppression alone. Only 2 of 9 patients with type 3 disease who received chemotherapy died of disease. Two patients with type 2 disease died of unrelated causes. One patient is alive with disease; the remaining patients with types 1 and 2 disease are alive with no disease.

Conclusions.—The World Health Organization classification of posttransplant lymphoproliferative disorders is valuable in the identification of subtypes. It helps identify early lesions (1 and 2) requiring reduction of immunosuppression and type 3 disease, which requires chemotherapy from the outset.
Paratesticular Mucinous Cystadenoma Arising From an Oviduct-Like Müllerian Remnant: A Case Report and Review of the Literature
Authors: Uschuplich Vedran , Hilsenbeck John R. , Velasco Claude R.
Published: February 2021

A mucinous cystadenoma of the paratestis arising from an unequivocal oviduct-like structure in an 18-year-old man is reported. Mucinous cystadenomas of the testis and paratestis are extremely rare benign tumors of controversial origin. The diagnosis may be challenging and is of clinical importance because these lesions may mimic a teratoma, and teratomas in postpubertal males carry a malignant potential regardless of the degree of maturation. A few case reports and reviews of testicular and paratesticular mucinous neoplasms resembling ovarian tumors have suggested the possibility of a müllerian origin of these tumors. However, no histologic evidence has been found to support such a histogenesis. The current case demonstrates a clear transition from müllerian-type tubal epithelium to intestinal-type mucinous epithelium. This finding, in conjunction with immunophenotypic studies, strongly supports a derivation from a paratesticular müllerian remnant. To our knowledge this represents the first substantial evidence that, in at least some cases, mucinous cystadenomas of the testis and paratestis are of müllerian derivation.
An In-depth Look at Krukenberg Tumor: An Overview
Authors: Al-Agha Osama M. , Nicastri Anthony D.
Published: February 2021

Krukenberg tumor is an uncommon metastatic tumor of the ovary. This article provides an overview of the major pathologic manifestations of Krukenberg tumor, patient characteristics, clinical and laboratory features of the disease, prognostic factors, and current knowledge about its pathogenesis. Pathologists have to be familiar with the diagnostic histopathologic features of the tumor and its principal differential diagnoses. Awareness of the diagnostic manifestations of the tumor leads to the correct diagnosis and prevents tumor misclassification, thus avoiding improper clinical management. The article also addresses the potential clinical utility of serum CA 125 in patients with Krukenberg tumors. Prognosis of Krukenberg tumor is still very poor but our review of the literature reveals several factors that appear to have an impact on survival. There is no established treatment for Krukenberg tumors. A national registry and prospective studies are needed to set a therapeutic approach for Krukenberg tumors in the hope of improving the survival rate.
Gene Rearrangement and Comparative Genomic Hybridization Studies of Classic Hodgkin Lymphoma Expressing T-Cell Antigens
Authors: Aguilera Nadine S. I. , Chen Jian , Bijwaard Karen E. , Director-Myska Alison E. , Barekman Carol L. , Millward Carl , Lichy Jack , Abbondanzo Susan L.
Published: February 2021

Context.—Reed-Sternberg cells in classic Hodgkin lymphoma are enigmatic and difficult to study because they are so sparse. Tissue microdissection allows for the isolation of single Reed-Sternberg cells. Isolated Reed-Sternberg cells show clonal immunoglobulin gene rearrangement indicating a B-cell origin. Rarely, Reed-Sternberg cells in classic Hodgkin lymphoma express T-cell antigens, suggesting a possible T-cell origin.

Objective.—To determine whether there is a difference in genotype between classic Hodgkin lymphoma and classic Hodgkin lymphoma expressing T-cell antigens and to document T-cell clonality.

Design.—We studied 4 cases of Hodgkin lymphoma with a characteristic phenotype and immunoreactivity for CD2 and CD3. Single CD30+ Reed-Sternberg cells from each case were isolated by laser capture microdissection for immunoglobulin heavy chain and T-cell receptor-γ genes by polymerase chain reaction studies. Comparative genomic hybridization was performed in all cases.

Results.—Two of 4 cases showed clonal rearrangement of the T-cell receptor-γ; none showed immunoglobulin heavy chain rearrangement. Two control cases were negative for T cell receptor-γ but 1 showed immunoglobulin heavy chain rearrangement. Comparative genomic hybridization analysis revealed significant overlap in genomic alteration in Hodgkin lymphoma cases regardless of genotype or phenotype and several regions of imbalance specific to CD3+ Hodgkin lymphoma cases. All patients are alive with no evidence of disease from 10 to 44 months.

Conclusions.—Our findings suggest that a T-cell phenotype classic Hodgkin lymphoma can be supported by genotypic studies and that there may be cytogenetic differences between classic Hodgkin lymphoma and Hodgkin lymphoma expressing T-cell antigens.
Myelopoiesis in the Liver of Stillborns With Evidence of Intrauterine Infection
Authors: Miranda Roberto N. , Omurtag Kenan , Castellani William J. , De Las Casas Luis E. , Quintanilla Norma M. , Kaabipour Emad
Published: February 2021

Context.—Chorioamnionitis is the maternal and fetal response to an ascending intrauterine infection. The fetal response is manifested by funisitis and chorionic vasculitis, or as neutrophils within pulmonary spaces. Human hematopoiesis occurs in the liver primarily during the 6th to 22nd weeks of gestation.

Objective.—To establish the relationship between the presence of an intrauterine infection and the degree of fetal hepatic myelopoiesis in second- and third-trimester fetuses.

Design.—Liver and lungs from 49 fetal autopsies, 20 to 41 weeks of gestational age, and their associated placentas and membranes were analyzed for evidence of intrauterine infection and hepatic myelopoiesis. Hematoxylin-eosin– stained sections from fixed tissues were evaluated for the presence of amnionic fluid infection, defined by the presence of acute chorioamnionitis or funisitis. The degree of portal hematopoiesis, myelopoiesis and intra-alveolar neutrophils was assessed semiquantitatively with hematoxylin-eosin–stained sections and immunohistochemically with antimyeloperoxidase. The Kruskal-Wallis 1-way analysis of variance and the Wilcoxon-Mann-Whitney test were used to determine the significance of any observed difference.

Results.—The degree of portal and lobular myelopoiesis was significantly greater with the presence of inflammation in both the membranes and umbilical cord, and correlated with the presence of intra-alveolar neutrophils (P < .001). A high correlation between the hematoxylin-eosin and immunohistochemistry assessment of myeloid cells was noted.

Conclusions.—There is increased portal and lobular myelopoiesis in 20-week to 41-week gestational age fetal livers that is associated with intrauterine ascending infection. The presence of increased portal or lobular myelopoiesis suggests the presence of an active fetal response to an intrauterine ascending infection.
Interference of Blood Cell Lysis on Routine Coagulation Testing
Authors: Lippi Giuseppe , Montagnana Martina , Salvagno Gian Luca , Guidi Gian Cesare
Published: February 2021

Context.—Preanalytical factors influencing the reliability of laboratory testing are commonplace. It is traditionally accepted that hemolytic samples are unsuitable for coagulation assays because of the release of hemoglobin, intracellular components, and thromboplastic substances from damaged blood cells.

Objective.—To evaluate the influence of blood cell lysis on routine coagulation testing.

Design.—Twelve aliquots prepared by serial dilutions of homologous lysated samples collected from 10 different subjects, and displaying a final percentage of lysis ranging from 0% to 9.1%, were tested for prothrombin time, activated partial thromboplastin time, fibrinogen, and dimerized plasmin fragment D. Lysis was achieved by subjecting citrated whole blood to a freeze-thaw cycle.

Outcome Measures.—Interference from blood cell lysis on routine coagulation testing.

Results.—Statistically significant increases in prothrombin time and dimerized plasmin fragment D were observed in samples containing final lysate concentrations of 0.5% and 2.7% respectively, whereas significant decreases were observed in activated partial thromboplastin time and fibrinogen in samples containing a final lysate concentration of 0.9%. The current analytical quality specifications for desirable bias are ±2.0% for prothrombin time, ±2.3% for activated partial thromboplastin time, and ±4.8% for fibrinogen. Percent variations from the baseline values exceeding the current analytical quality specifications for desirable bias were achieved for lysate concentrations of 0.9% (prothrombin time and activated partial thromboplastin time) and 1.8% (fibrinogen), corresponding to average free plasma hemoglobin concentrations of 1.7 and 3.4 g/L, respectively.

Conclusion.—Our results confirm that, although slightly hemolyzed specimens might still be analyzable, a moderate blood cell lysis, as low as 0.9%, influences the reliability of routine coagulation testing. Because the interference in coagulation assays has a wide interindividual bias, we do not recommend lysis correction and we suggest that the most appropriate corrective measure should be free hemoglobin quantification and sample recollection.
Immunohistochemical Classification of De Novo, Transformed, and Relapsed Diffuse Large B-Cell Lymphoma Into Germinal Center B-Cell and Nongerminal Center B-Cell Subtypes Correlates With Gene Expression Profile and Patient Survival
Authors: Haarer Chadwick F. , Roberts Robin A. , Frutiger Yvette M. , Grogan Thomas M. , Rimsza Lisa M.
Published: February 2021

Context.—Diffuse large B-cell lymphoma (DLBCL) can be assigned to prognostic subgroups, including germinal center B-cell (GCB) and activated B-cell subgroups, by using gene expression profiling and, reportedly, immunohistochemistry for CD10, Bcl-6, and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4).

Objective.—To compare 2 commercial MUM1/IRF4 antibody formulations for accuracy in subtyping DLBCL against gene expression profiling, compare subtyping to patient survival, and evaluate the usefulness of GCB and non-GCB subtyping in relapsed and transformed DLBCL.

Design.—Evaluation of 2 commercial MUM1/IRF4 antibodies, ICSTAT/M17 and Mum-1p, by using 40 cases of de novo, relapsed, and transformed DLBCL; and comparison of the results obtained with gene expression profiling and survival.

Results.—Immunohistochemistry predicted the gene expression profiling subtype 71.8% and 69.2% of the time overall with use of the Mum-1p and ICSTAT/M17 antibodies, respectively, and 100% and 91.7% of the time when MUM1/IRF4 expression determined subtype. Gene expression profiling and immunohistochemistry revealed nearly identical 5-year overall survival rates for the GCB vs non-GCB subtypes (68.0% for GCB vs 24.7% for non-GCB with use of gene expression profiling [P = .03] and 70.2% vs 18.4%, respectively, with use of immunohistochemistry [P < .001]). When de novo, transformed, and relapsed cases were analyzed separately, 5-year overall survival rates were also significantly different.

Conclusions.—Immunohistochemistry can be used to subclassify DLBCL, including a very small series of transformed and relapsed cases, into GCB and non-GCB subtypes and predict survival rates similar to those predicted by use of gene expression profiling. The 2 MUM1/IRF4 antibodies performed similarly.
BRCA1 and BRCA2 Mutation Screening Using SmartCycler II High-Resolution Melt Curve Analysis
Authors: Dufresne Scott D. , Belloni Dorothy R. , Wells Wendy A. , Tsongalis Gregory J.
Published: February 2021

Context.—Real-time polymerase chain reaction technologies have replaced many of the more labor-intense methods in the molecular diagnostics laboratory. Similarly, melt curve analysis can provide a rapid means of mutation screening.

Objective.—To determine if real-time polymerase chain reaction and melt curve analysis using the SmartCycler II could be used as a screening tool for 3 common mutations in BRCA1 and BRCA2.

Design.—Real-time polymerase chain reaction amplification with SYBR Green I detection was performed on DNA from cell lines known to carry the 185delAG or 5382insC mutation in BRCA1 or the 6174delT mutation in BRCA2. The melting temperatures and the melt curves were analyzed for differences between wild-type DNA and cell lines that were heterozygous for each mutation.

Results.—Significant differences were present in the melt curves for each of the mutations compared with those of the wild-type sequences. The melt curve for the 185delAG mutation showed a separate peak at a lower temperature, which represented the melting temperature of the heteroduplex. For the 6174delT mutation, the melt curve had a shoulder at a lower temperature, while the melt curve for the 5382insC mutation was shifted to the left and was broader than that for the wild-type sequences.

Conclusions.—High-resolution melt curve analysis is a quick, reliable method for identifying mutations due to small deletions or insertions. As a proof of principle, we used this assay to identify the 3 most common BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population.
Prostatic Glands and Urothelial Epithelium in a Seminal Vesicle Cyst: Report of a Case and Review of Pathologic Features and Prostatic Ectopy
Authors: Aslan Deniz L. , Pambuccian Stefan E. , Gulbahce H. Evin , Tran Michael L. , Manivel J. Carlos
Published: February 2021

We report a case of a seminal vesicle cyst containing prostatic glands and urothelial epithelium in a patient with no other urogenital anomalies. The detection of prostatic tissue, which is of endodermal origin, in a seminal vesicle cyst, a mesonephric duct derivative, is unusual. We review the pathologic features of seminal vesicle cysts and discuss the histogenesis of prostatic and urothelial tissue.
Cytologic Features of Adenocarcinoma, Not Otherwise Specified, in Conventional Smears: Comparison of Cases That Performed Poorly With Those That Performed Well in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology
Authors: Renshaw Andrew A. , Schwartz Mary R. , Wang Edward , Haja Jennifer , Hughes Jonathan H.
Published: February 2021

Context.—Characteristic cytologic features have been identified that distinguish cases that are consistently identified from those that are sometimes missed in the College of American Pathologists Gynecologic Cytology Program for a variety of different lesions and preparations.

Objectives.—To compare the cytologic features of cases of adenocarcinoma, not otherwise specified (NOS), in conventional smears that perform poorly and well.

Design.—The cytologic features of 21 conventional smear cases of adenocarcinoma, NOS, that performed poorly in the College of American Pathologists Interlaboratory Comparison Program were compared with 17 cases that performed extremely well.

Results.—Cases that performed well were significantly more likely to have greater than 1000 abnormal cells (P = .006), greater than 100 large abnormal cells (P = .006), large nuclei (P < .001), marked nuclear atypia (P = .02), and hyperchromasia (P = .02). Repair-like features were rare in both groups and were not significant (P = .71).

Conclusion.—Conventional smears with a diagnosis of adenocarcinoma that were consistently identified were significantly more likely to have more abnormal cells, larger abnormal cells, larger nuclei, marked atypia, and hyperchromasia than cases that performed poorly.