bluuebunny/crossref_metadata_2025 huggingface dataset:
Carcinoid Tumors of the Urinary Tract and Prostate
Authors: Murali Rajmohan , Kneale Kenneth , Lalak Nestor , Delprado Warick
Published: February 2021

Context.—Carcinoid tumors are exceedingly rare in the genitourinary tract and may occur in the kidney, urinary bladder, urethra, or prostate.

Objective.—To review the clinical and pathologic features of carcinoid tumors occurring in the urinary tract and prostate.

Data Sources.—We searched the English language literature using MEDLINE and Ovid.

Conclusions.—Carcinoid tumors of the urinary tract and prostate share similar morphologic features with their counterparts in other organs. The differential diagnosis includes metastatic carcinoid tumor, paraganglioma, and nested variants of urothelial and prostatic carcinomas. Correlation of the clinical presentation and histopathologic features (including the immunohistochemical profile) will ensure accurate diagnosis of these rare tumors.
Hyperleptinemia as a Risk Factor for High Blood Pressure in the Elderly
Authors: Mendoza-Núñez Víctor Manuel , Correa-Muñoz Elsa , Garfias-Cruz Elsa A. , Sánchez-Rodriguez Martha A. , Galván-Duarte Rosa Elba , Retana-Ugalde Raquel
Published: February 2021

Context.—Studies have demonstrated that high serum leptin levels are associated with aging. However, we do not know whether hyperleptinemia is a relevant risk factor for high blood pressure (HBP) in the elderly.

Objective.—To determine the relationship between hyperleptinemia and HBP in the elderly.

Design.—A comparative cross-sectional study was carried out in a convenience sample of 70 healthy elderly persons comprising 46 women (mean age, 67 ± 5.8 years) and 24 men (mean age, 73 ± 7.5 years), and a group of 91 elderly persons with HBP, comprising 62 women (mean age, 67 ± 8.2 years) and 29 men (mean age, 70 ± 0.3 years). We measured serum leptin levels through the radioimmunoassay method.

Results.—The elderly subjects with HBP had significantly higher leptin levels than the healthy elderly subjects (P = .02). Furthermore, in female elderly subjects we observed a statistically significant correlation between systolic blood pressure and leptin (r = 0.37, P = .003), as well as systolic blood pressure and age (r = 0.29, P = .02), but not with diastolic blood pressure. In male elderly subjects, there was no correlation between leptin and systolic blood pressure or leptin and diastolic blood pressure. However, hyperleptinemia as risk factor for HBP was nearly 5 times higher in men than in women (men, odds ratio = 18.0, 95% confidence interval 3.2–100.9, P < .001 vs women, odds ratio = 3.33, 95% confidence interval 1.4–7.4, P = .003).

Conclusions.—Our data suggest that hyperleptinemia was a significant risk factor for HBP elderly individuals, mainly in men.
Flow Cytometric Analysis of Lymphomas: Current Status and Usefulness
Authors: Kaleem Zahid
Published: February 2021

Context.—Immunophenotyping has become a routine practice in the diagnosis and classification of most cases of non-Hodgkin lymphoma, and flow cytometry is often the method of choice in many laboratories. The role that flow cytometry plays, however, extends beyond just diagnosis and classification.

Objective.—To review and evaluate the current roles of flow cytometry in non-Hodgkin lymphoma, to compare it with immunohistochemistry, and to discuss its potential future applications in the molecular diagnostic era.

Data Sources.—The information contained herein is derived from peer-reviewed articles on the subject published in the English-language medical literature during the years 1980 to 2005 that were identified using PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi, 1980–2005) search, various books and other sources on flow cytometry, and the author's personal experience of more than 10 years with flow cytometric analysis of lymphomas and leukemia using Becton-Dickinson (San Jose, Calif) and Beckman-Coulter (Miami, Fla) flow cytometers.

Study Selection.—Studies were selected based on adequate material and methods, statistically significant results, and adequate clinical follow-up.

Data Extraction.—The data from various sources were compared when the methods used were the same or similar and appropriate controls were included. Most of the studies employed 2-color, 3-color, or 4-color flow cytometers with antibodies from Becton-Dickinson, Beckman-Coulter, or DakoCytomation (Carpinteria, Calif). Results were evaluated from studies utilizing the same or similar techniques and flow cytometers. Only objective data analyses from relevant and useful publications were included for reporting and discussion.

Data Synthesis.—Flow cytometry serves a variety of roles in the field of lymphoma/leukemia including rapid diagnosis, proper classification, staging, minimal residual disease detection, central nervous system lymphoma detection, evaluation of prognostic markers, detection of target molecules for therapies, ploidy analysis of lymphoma cell DNA, and evaluation of multidrug-resistance markers. It offers many advantages in comparison to immunohistochemistry for the same roles and provides uses that are either not possible or not preferable by immunohistochemistry such as multiparameter evaluation of single cells and detection of clonality in T cells.

Conclusions.—By virtue of its ability to evaluate not only surface but also cytoplasmic and nuclear antigens, flow cytometry continues to enjoy widespread use in various capacities in lymphoma evaluation and treatment. Additional roles for flow cytometry are likely to be invented in the future and should provide distinctive uses in the molecular era.
Epithelioid Trophoblastic Tumor: Review of a Rare Neoplasm of the Chorionic-Type Intermediate Trophoblast
Authors: Allison Kimberly H. , Love Jason E. , Garcia Rochelle L.
Published: February 2021

We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0–9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-α is typically expressed, as well as focal, more variable expression of other trophoblastic markers including β-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.
Interactions Between Leukotriene C4 and Interleukin 13 Signaling Pathways in a Mouse Model of Airway Disease
Authors: Chavez Jaime , Young Hays W. J. , Corry David B. , Lieberman Michael W.
Published: February 2021

Context.—During an asthmatic episode, leukotriene C4 (LTC4) and interleukin 13 (IL-13) are released into the airways and are thought to be central mediators of the asthmatic response. However, little is known about how these molecules interact or affect each other's signaling pathway.

Objective.—To determine if the LTC4 and IL-13 signaling pathways interact with each other's pathways.

Design.—We examined airway responsiveness, cysteinyl LTs (Cys-LTs), and Cys-LT and IL-13 receptor transcript levels in wild-type mice and in mice that were deficient in γ-glutamyl leukotrienase (an enzyme that converts LTC4 to LTD4), STAT6 (signal transducer and activator of transcription 6 [a critical molecule in IL-13 signaling]), and IL-4Rα (a subunit of the IL-13 receptor).

Results.—Wild-type (C57BL/129SvEv) and γ-glutamyl leukotrienase–deficient mice showed increased airway responsiveness after intranasal instillation of IL-13; similar results were observed after intranasal instillation of IL-13 or LTC4 in a second wild-type strain (BALB/c). Interleukin 13 treatment reduced levels of Cys-LTs in bronchoalveolar lavage fluid. This change was unaccompanied by changes in other arachidonic acid metabolites or in RNA transcript levels of enzymes associated with Cys-LT synthesis. Interleukin 13 treatment also increased transcript levels of the Cys-LT 1 and Cys-LT 2 receptors, while LTC4 increased transcript levels of the α1 chain of the IL-13 receptor. Furthermore, IL-4Rα–deficient mice had increased airway responsiveness to LTC4 but not to IL-13, whereas STAT6-deficient mice failed to respond to either agonist.

Conclusions.—These findings indicate that LTC4 and IL-13 are dependent on or signal through STAT6 to increase airway responsiveness and that both agonists regulate expression of each other's receptors.
Papanicolaou Tests With Mixed High-Grade and Low-Grade Squamous Intraepithelial Lesion Features: Distinct Performance in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology
Authors: Renshaw Andrew A. , Mody Dina R. , Styer Patricia , Schwartz Mary , Ducatman Barbara , Colgan Terence J.
Published: February 2021

Context.—Previous studies have shown that in gynecologic cytology, cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) perform differently on interpretive review. The performance of cases with mixed LSIL and HSIL features is unknown.

Objective.—To compare the performance of gynecologic cytology cases of “pure” LSIL and HSIL with cases showing mixed LSIL and HSIL features.

Design.—We compiled performance data from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology from the years 2003 and 2004, and compared the performance of slides showing relatively pure LSIL and HSIL (≤10% misclassification as HSIL and LSIL, respectively) with slides showing mixed LSIL or HSIL features (cases misclassified as LSIL or HSIL >10% of the time).

Results.—Interpretations from a total of 4508 cases (2452 HSIL and 2056 LSIL) were analyzed. Overall, the sensitivity of participants on slides with a reference diagnosis of HSIL was 97.3%, and of LSIL was 95.9%. Performance trends for pure versus mixed cases varied by slide type and reference diagnosis. For conventional slides, participant sensitivity on pure HSIL cases was greatest (98.0%) and on pure LSIL cases was least (95.2%), while participant performance on cases with mixed features was intermediate (97.0% for mixed HSIL and 96.7% for mixed LSIL). In contrast, participant performance on ThinPrep slides showed the greatest sensitivity for mixed LSIL slides (97.9%), while performance on mixed HSIL slides showed the lowest sensitivity (95.7%); slides with pure features had intermediate sensitivity levels (96.3% for both HSIL and LSIL). Further evaluation demonstrated that conventional pure HSIL slides performed significantly better than mixed HSIL slides (P = .006), whereas mixed LSIL slides performed better than pure LSIL slides (P = .01). For ThinPrep slides, pure HSIL cases performed similarly to mixed HSIL cases (P = .43), while mixed LSIL cases performed better than pure LSIL cases (P = .04).

Conclusion.—Slides with mixed LSIL and HSIL features have measurably distinct performance characteristics in comparison to slides with pure LSIL or HSIL features. Participant performance on conventional mixed cases is distinctly different from performance on ThinPrep mixed cases.
Origin of Chordoid Glioma of the Third Ventricle
Authors: Leeds Norman E. , Lang Frederick F. , Ribalta Teresa , Sawaya Raymond , Fuller Gregory N.
Published: February 2021

Context.—Chordoid glioma is a relatively recently described unique glial neoplasm that has been formally codified by the World Health Organization in Pathology and Genetics of Tumours of the Nervous System, in which it is included along with astroblastoma and gliomatosis cerebri under the rubric “Tumors of Uncertain Origin.” Many examples of chordoid glioma come to clinical attention only at a relatively large size and occupy a large portion of the third ventricle. Accordingly, the anatomic origin of chordoid glioma has been unclear and debated.

Objective.—To examine the regional anatomic origin of chordoid glioma.

Data Sources.—The clinical, imaging, histologic, immunophenotypic, and ultrastructural data in previously published case series and individual case reports of chordoid glioma were reviewed in conjunction with the study of a new case of chordoid glioma that presented at a relatively small size, thereby facilitating neuroanatomic localization.

Conclusions.—Chordoid glioma exhibits features of specialized ependymal differentiation on ultrastructural examination, and all examples reported in the literature to date have displayed a highly stereotypical suprasellar anatomic localization and an ovoid shape, as seen on neuroimaging studies and gross anatomy. Neuroanatomic, radiologic, and clinical evidence supports an anatomic origin for chordoid glioma from the vicinity of the lamina terminalis.
Gene Expression Profiling Data in Lymphoma and Leukemia: Review of the Literature and Extrapolation of Pertinent Clinical Applications
Authors: Dunphy Cherie H.
Published: February 2021

Context.—Gene expression (GE) analyses using microarrays have become an important part of biomedical and clinical research in hematolymphoid malignancies. However, the methods are time-consuming and costly for routine clinical practice.

Objectives.—To review the literature regarding GE data that may provide important information regarding pathogenesis and that may be extrapolated for use in diagnosing and prognosticating lymphomas and leukemias; to present GE findings in Hodgkin and non-Hodgkin lymphomas, acute leukemias, and chronic myeloid leukemia in detail; and to summarize the practical clinical applications in tables that are referenced throughout the text.

Data Source.—PubMed was searched for pertinent literature from 1993 to 2005.

Conclusions.—Gene expression profiling of lymphomas and leukemias aids in the diagnosis and prognostication of these diseases. The extrapolation of these findings to more timely, efficient, and cost-effective methods, such as flow cytometry and immunohistochemistry, results in better diagnostic tools to manage the diseases. Flow cytometric and immunohistochemical applications of the information gained from GE profiling assist in the management of chronic lymphocytic leukemia, other low-grade B-cell non-Hodgkin lymphomas and leukemias, diffuse large B-cell lymphoma, nodular lymphocyte–predominant Hodgkin lymphoma, and classic Hodgkin lymphoma. For practical clinical use, GE profiling of precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, and acute myeloid leukemia has supported most of the information that has been obtained by cytogenetic and molecular studies (except for the identification of FLT3 mutations for molecular analysis), but extrapolation of the analyses leaves much to be gained based on the GE profiling data.
Primary Choriocarcinoma of the Lung Manifesting as Diffuse Alveolar Hemorrhage
Authors: Shintaku Masayuki , Hwang Moon Hee , Amitani Ryoichi
Published: February 2021

An autopsy case of primary pulmonary choriocarcinoma that manifested as diffuse alveolar hemorrhage is reported. A 44-year-old nurse presented with fever, dry cough, hemoptysis, and progressive dyspnea, and died after a downhill course of 2 weeks. Chest radiographs showed diffuse parenchymal shadows throughout the entire lung and a nodular lesion in the right lower lobe. Findings suggestive of acute renal failure were not seen. The autopsy revealed primary pure choriocarcinoma of the right lower lobe and diffuse alveolar hemorrhage throughout the entire lung. Findings of small vessel vasculitis (“pulmonary alveolar capillaritis”) were not observed, and extensive neoplastic involvement of the pulmonary vasculature was considered the cause of the diffuse alveolar hemorrhage. Small metastatic foci were found in the liver, adrenal glands, pancreas, and ovaries. This case shows that primary pulmonary neoplasms, on rare occasions, can produce the clinical and pathologic features of diffuse alveolar hemorrhage, probably through elevated pulmonary venous pressure caused by extensive destruction of the vasculature.
Hodgkin Lymphoma–like Posttransplantation Lymphoproliferative Disorder
Authors: Semakula; Barbara , Rittenbach Jon V. , Wang Jun
Published: February 2021

Posttransplantation lymphoproliferative disorders (PTLD) are a heterogeneous group of monoclonal or polyclonal lymphoproliferative lesions that occur in immunosuppressed recipients following solid organ or bone marrow transplantation, including 4 categories: (1) early lesions (reactive plasmacytic hyperplasia, and infectious-mononucleosis–like PTLD), (2) polymorphic PTLD, (3) monomorphic PTLD (including B-cell neoplasms and T-cell neoplasms), and (4) Hodgkin lymphoma (HL) and HL-like PTLD in the current World Health Organization classification. Although HL-like PTLD has been grouped with classic HL PTLD, controversy remains as to whether it is truly a form of HL or whether it should be more appropriately considered as a form of B-cell PTLD. The current available literature data indicate the presence of important immunophenotypic, molecular genetic, and clinical differences between HL PTLD and HL-like PTLD, suggesting that HL-like PTLD is in fact most often a form of B-cell PTLD. Distinction from true HL may be important for clinical management and prognosis.
Risk of Oral Nonmalignant Lesions Associated With Human Papillomavirus Infection, Betel Quid Chewing, and Cigarette Smoking in Taiwan: An Integrated Molecular and Epidemiologic Study
Authors: Chen Paul Chih-Hsueh , Pan Chin-Chen , Kuo Chih , Lin Chih-Pei
Published: February 2021

Context.—In contrast to previous studies about the association of oral squamous cell carcinoma with human papillomavirus (HPV) 16/18, the associations between nonmalignant oral lesions (chronic inflammation, submucous fibrosis, leukoplakia, and squamous papilloma) and HPV are much less well understood.

Objective.—We conducted this study using an in situ polymerase chain reaction in situ hybridization assay, which is one of the most sensitive methods for in situ viral detection. Other known oral cancer risk factors, including betel quid chewing and cigarette smoking, were also analyzed.

Design.—Oral specimens from 23 patients with submucous fibrosis, 36 patients with leukoplakia, 22 patients with squamous papilloma, and 21 patients without significant lesions were analyzed for the presence of HPV DNA. Their betel quid chewing and cigarette smoking histories were reviewed.

Results.—HPV-16 and HPV-18 were frequently identified in all 3 oral lesions (61.5% and 42.1%), while HPV-6 and HPV-11 were seen only in squamous papilloma (21.1% and 5.0%). HPV-18, betel quid chewing, and smoking were significantly associated with leukoplakia and squamous papilloma, while only betel quid chewing and smoking were significantly associated with submucous fibrosis. Multivariate analysis showed that the betel quid chewing habit remained an independent factor for leukoplakia and squamous papilloma.

Conclusions.—Our data indicated that betel quid chewing and smoking habits are 2 important risk factors for these nonmalignant or premalignant oral lesions, while for high-risk HPV, only HPV-18—not HPV-16—is a significant risk factor for leukoplakia and squamous papilloma.
Errors in Surgical Neuropathology and the Influence of Cognitive Biases: The Psychology of Intelligence Analysis
Authors: McLendon Roger E.
Published: February 2021

Context.—A significant difficulty that pathologists encounter in arriving at a correct diagnosis is related to the way information from various sources is processed and assimilated in context.

Objective.—These issues are addressed by the science of cognitive psychology. Although cognitive biases are the focus of a number of studies on medical decision making, few if any focus on the visual sciences.

Data Sources.—A recent publication authored by Richards Heuer, Jr, The Psychology of Intelligence Analysis, directly addresses many of the cognitive biases faced by neuropathologists and anatomic pathologists in general. These biases include visual anticipation, first impression, and established mindsets and subconsciously influence our critical decision-making processes.

Conclusions.—The book points out that while biases are an inherent property of cognition, the influence of such biases can be recognized and the effects blunted.
Neutrophil CD64 Is an Improved Indicator of Infection or Sepsis in Emergency Department Patients
Authors: Davis Bruce H. , Olsen Stephen H. , Ahmad Ejaz , Bigelow Nancy C.
Published: February 2021

Context.—Sepsis, affecting millions of individuals annually with an associated high mortality rate, is among the top 10 causes of death. In addition, improvements in diagnostic tests for detecting and monitoring sepsis and infection have been limited in the last 25 years. Neutrophil CD64 expression has been proposed as an improved diagnostic test for the evaluation of infection and sepsis.

Objective.—To evaluate the diagnostic performance of a quantitative flow cytometric assay for leukocyte CD64 expression in comparison with the standard tests for infection/sepsis in an ambulatory care setting.

Design.—Prospective analysis of 100 blood samples from patients from an emergency department setting in a 965-bed tertiary care suburban community hospital was performed for neutrophil CD64 expression, C-reactive protein, erythrocyte sedimentation rate, and complete blood count. The laboratory findings were compared with a clinical score for the likelihood of infection/sepsis, which was obtained by a blinded retrospective chart review.

Results.—The diagnostic performance, as gauged by the clinical score, varied with neutrophil CD64 (sensitivity 87.9%, specificity 71.2%, efficiency 76.8%) and outperformed C-reactive protein (sensitivity 88.2%, specificity 59.4%, efficiency 69.4%), absolute neutrophil count (sensitivity 60.0%, specificity 50.8%, efficiency 53.8%), myeloid left shift (sensitivity 68.2%, specificity 76.3%, efficiency 73.3%), and sedimentation rate (sensitivity 50.0%, specificity 65.5%, efficiency 61.0%).

Conclusion.—Neutrophil CD64 expression quantitation provides improved diagnostic detection of infection/sepsis compared with the standard diagnostic tests used in current medical practice.
p16 Expression in Keratoacanthomas and Squamous Cell Carcinomas of the Skin: An Immunohistochemical Study
Authors: Kaabipour Emad , Haupt Helen M. , Stern Jere B. , Kanetsky Peter A. , Podolski Victoria F. , Martin Anne-Marie
Published: February 2021

Context.—Distinguishing between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is not an uncommon histologic diagnostic dilemma.

Objective.—To determine if p16 expression is useful in the differential diagnosis of SCC and KA.

Design.—We studied the expression of p16 by immunohistochemistry in 24 KAs, 24 infiltrating SCCs of the skin, 4 histologically indeterminate lesions, and 8 nonmalignant keratoses.

Results.—A range of immunohistochemical p16 expression was seen in KAs and SCCs in terms of the thickness of lesional staining and the percentage of cells staining. No significant difference in measures of p16 expression was identified among the KAs, the SCCs, the indeterminate lesions, or the benign keratoses.

Conclusions.—These findings suggest that p16 is not a useful marker to distinguish between KA and SCC, supporting the similarity between the 2 lesions; p16 alterations appear to play a role in the pathogenesis of both KA and SCC.
Thin Glomerular Basement Membrane Nephropathy: Incidence in 3471 Consecutive Renal Biopsies Examined by Electron Microscopy
Authors: Haas Mark
Published: February 2021

Context.—Thin glomerular basement membrane (GBM) nephropathy is often equated with benign familial hematuria, although it may occur sporadically and may not always be benign. Thin GBM nephropathy is reported to occur in at least 1% of the population, although its reported incidence varies considerably in different studies because there are presently no uniform criteria for its diagnosis by electron microscopy (EM).

Objective.—To determine the incidence of thin GBM nephropathy in a large sample of renal biopsies using a basic methodology that can easily be applied in any diagnostic EM laboratory.

Design.—Direct measurements of GBM thickness were made from electron micrographs at 3 specified points along each of 10 randomly selected glomerular capillaries to determine an average GBM thickness for each of 50 males and 50 females, ages 9 to 80 years, with minimal-change nephropathy or acute interstitial nephritis, without hematuria. The means of the average GBM thickness values were 330 ± 50 (SD) nm in the males and 305 ± 45 nm in the females; normal ranges for each sex were defined as being within 2 SD of these means. The average GBM thickness was then similarly determined for renal biopsies with suspected thin GBMs examined from January 2000 to December 2004; a total of 3471 renal biopsies were examined by EM during this period.

Setting.—Academic medical center renal pathology/EM laboratory.

Results.—Excluding biopsies with immunoglobulin A nephropathy, which is known to be frequently associated with thin GBMs, and biopsies with Alport syndrome, 67 biopsies (1.9% of total) had an average GBM thickness below the sex-specific normal range. Of these, 37 biopsies were performed specifically because of hematuria and had an average GBM thickness of 121 to 215 nm (mean, 185 ± 20 nm). The remaining 30 (0.9%) biopsies, with average GBM thicknesses of 143 to 227 nm (mean, 190 ± 20 nm), represent cases of incidentally discovered thin GBM nephropathy.

Conclusions.—Based on the frequency of incidentally discovered cases and taking into account excluded cases and biopsies (eg, with diabetic nephropathy) in which diagnosis of incidental thin GBM nephropathy by EM is not possible, the incidence of thin GBM nephropathy in our population is estimated to be between 1% and 2%. Diseases most often associated with incidental thin GBM nephropathy were focal segmental glomerulosclerosis (10 cases) and minimal-change nephropathy (5 cases).
Desmoplastic Small Round Cell Tumors: Cytologic, Histologic, and Immunohistochemical Features
Authors: Chang Fuju
Published: February 2021

Desmoplastic small round cell tumor (DSRCT) is a recently recognized clinicopathologic entity that has a predilection for adolescent males and usually affects the abdominal cavity. Due to its uncommon nature, many pathologists lack experience with this tumor. The literature regarding DSRCT is reviewed with special attention to its histologic and cytologic diagnosis. Morphologic features of DSRCT and its immunohistochemical and cytogenetic profile are summarized and differential diagnosis with other small round cell tumors is discussed. As observed by both histologic and cytologic examinations, small round blue cells and fibrosclerotic stroma are the striking morphologic features of DSRCT. The typical immunohistochemical profile is characterized by coexpression of epithelial, mesenchymal, myogenic, and neural markers. Cytogenetically, this tumor harbors a specific karyotypic abnormality, namely t(11;22)(p13;q12). These features distinguish DSRCT from other members of the family of small round cell tumors.
Performance Accuracy of Antibacterial and Antifungal Susceptibility Test Methods: Report From the College of American Pathologists Microbiology Surveys Program (2001–2003)
Authors: Pfaller Michael A. , Jones Ronald N.
Published: February 2021

Context.—The College of American Pathologists Microbiology Surveys Program provides external proficiency samples that monitor the performance of nearly 3000 laboratories that perform and report antimicrobial susceptibility tests.

Objective.—To summarize results obtained with bacterial and yeast challenge samples (2001 through 2003).

Design.—One organism every 4 months was tested by surveys participants against antibacterials/antifungals by routinely used methods. Reports were graded by interpretive category (susceptible, intermediate, resistant) based on an 80% consensus of referees/participants.

Results.—The most common antibacterial test methods/ systems were Vitek (38%–43%), MicroScan (39%–43%), and the disk diffusion test (14%–15%), although Etest was most used for fastidious species. YeastOne was the dominant antifungal test (50%–55%). Antifungal results demonstrated continuous, improved accuracy (83%–88%), highest for YeastOne (96%) and broth microdilution (95%) methods. Antibacterial test accuracy was consistently greater than 97% against gram-positive organism challenges and greater than 98% against gram-negative challenges. For gram-negative strains with well-characterized resistance mechanisms, the accuracy by method was disk diffusion greater than broth microdilution greater than automated systems. Major problems identified were (1) Haemophilus influenzae control ranges require re-evaluation, (2) overuse of β-lactamase tests, (3) errors among Enterococcus faecium against penicillins (Vitek 2, MicroScan), (4) false-susceptible results with trimethoprim/sulfamethoxazole against coagulase-negative staphylococci (MicroScan), (5) macrolide false-susceptibility for β-hemolytic streptococcus (MicroScan), (6) flawed reporting for antimicrobials not active at the infection site, (7) use of outdated interpretive criteria, and (8) failure to follow Clinical and Laboratory Standards Institute testing/reporting recommendations.

Conclusions.—Susceptibility tests were generally performing satisfactorily as measured by the surveys, but serious errors were identified with some drug/organism combinations that may require action by the Clinical and Laboratory Standards Institute and/or the Food and Drug Administration.
No Residual Cancer on Radical Prostatectomy After Positive 10-Core Biopsy: Incidence, Biopsy Findings, and DNA Specimen Identity Analysis
Authors: Trpkov Kiril , Gao Yuan , Hay Robert , Yimaz Asli
Published: February 2021

Context.—It is uncertain whether extensive prostate-specific antigen (PSA) testing and extended biopsies currently performed will increase the incidence of no residual cancer on subsequent prostatectomy.

Objective.—To identify the incidence of cases with no residual cancer on prostatectomy after a positive 10-core biopsy and to review the clinical, biopsy, and prostatectomy findings and the results of specimen identity analysis.

Design.—We identified 9 patients with no residual cancer in 1351 consecutive prostatectomies and we reviewed the clinical, biopsy, and prostatectomy data from our institutional database. In 6 cases encountered after 2003, we also performed a polymerase chain reaction–based microsatellite analysis on formalin-fixed tissue to confirm the identity of the biopsies and prostatectomies.

Results.—All patients had positive biopsies in 1 or 2 cores: 1 in 7 and 2 in 2 patients (1 each, unilateral and bilateral). Mean total cancer length on biopsy measured 2.5 mm, which represented 1.7% of the total biopsy tissue. Gleason score 6 was found in 8 of 9 patients and 1 patient had Gleason score 9. Patients' age was 60.3 years, preoperative PSA was 6.0 ng/mL, and PSA density was 0.1 (all means). In 6 cases tested for microsatellite identity, the patient identity was confirmed.

Conclusions.—Incidence of no residual cancer on prostatectomy of 0.67% after 10-core positive biopsy is higher than previously reported. In most cases, finding no residual cancer on prostatectomy after exhaustive work-up may indicate minimal patient disease. Microsatellite analysis provides a useful and cost-effective test in establishing specimen identity.
Myeloid Sarcoma of the Urinary Bladder and Epididymis as a Primary Manifestation of Acute Myeloid Leukemia With inv(16)
Authors: Al-Quran Samer Z. , Olivares Adriana , Lin Pei , Stephens Tanya W. , Medeiros L. Jeffrey , Abruzzo Lynne V.
Published: February 2021

Myeloid sarcoma (MS) of the lower urinary tract is rare. We describe a 47-year-old man with hematuria, who was subsequently found to have MS involving bladder and epididymis. The neoplasm was composed predominantly of blasts that expressed CD68, CD117, myeloperoxidase, and lysozyme, with occasional immature eosinophils. Although blood and bone marrow examinations showed no morphologic evidence of leukemia, conventional cytogenetic studies of marrow demonstrated inv(16)(p13q22) in 4 of 20 metaphases; fluorescence in situ hybridization of the bladder neoplasm also showed inv(16). Following chemotherapy, the patient has been in complete remission for 32 months. In our literature review, we identified 7 cases of MS involving bladder, only 3 without evidence of an associated myeloid neoplasm in marrow, none with cytogenetic data. A high index of suspicion is required to establish the diagnosis of MS involving bladder. Cytogenetic analysis is useful for both demonstrating minimal marrow disease and classifying MS in paraffin-embedded tissue sections.
Proximal-Type Epithelioid Sarcoma With Elevated Serum CA 125: Report of a Case With CA 125 Immunoreactivity
Authors: Lee Hyang-Im , Kang Kil Hyun , Cho Young Mee , Lee Oak-Jun , Ro Jae Yoon
Published: February 2021

Proximal-type epithelioid sarcoma is a recently described rare soft tissue neoplasm. It is commonly found in the pelvic, perineal, and genital areas in middle-aged or older adults, as compared with the classic type of epithelioid sarcoma, which arises in the distal portion of the extremities in adolescents and young adults. Proximal-type epithelioid sarcoma has a more aggressive clinical behavior than the classic type of epithelioid sarcoma. Proximal-type epithelioid sarcoma is histologically characterized by a diffuse proliferation of epithelioid cells with prominent rhabdoid feature. Recently, a few cases have been reported of epithelioid sarcoma with elevated serum CA 125 level and CA 125 immunoreactivity in neoplastic cells. These cases raise the possibility that serum CA 125 and CA 125 immunoreactivity could be a useful tumor marker for diagnosing and monitoring epithelioid sarcoma. We describe a case of proximal-type epithelioid sarcoma with elevated serum CA 125 level (up to 3395 U/mL [reference range, <35 U/mL]) in a 12-year-old girl who presented with a huge pelvic mass measuring 12 cm in greatest dimension. The serum CA 125 level dropped to 452 U/mL after a debulking operation of the mass. Immunostaining for CA 125 demonstrated a positive immunoreactivity in the neoplastic cells. She received one cycle of chemotherapy and died of the disease 2 months after diagnosis. This case represented a rare example of proximal-type epithelioid sarcoma with elevated serum CA 125 and immunoreactivity for CA 125 in the tumor cells. Based on the previous reported cases and the current case, serum CA 125 as well as immunohistochemical stain for CA 125 may be a useful tumor marker of proximal-type epithelioid sarcoma.
Renal Cell Carcinoma With Rhabdoid Features: An Aggressive Neoplasm With Overexpression of p53
Authors: Leroy Xavier , Zini Laurent , Buob David , Ballereau Charles , Villers Arnauld , Aubert Sebastien
Published: February 2021

Context.—Adult renal cell carcinoma (RCC) with rhabdoid features is a recently recognized morphologic variant of kidney carcinoma. To date, only very few studies have been published on this subject and p53 was not previously studied.

Objective.—To evaluate clinical attributes, morphology, and immunohistochemistry in RCC with rhabdoid component.

Design.—Reviewing a consecutive series of 310 RCCs, we identified 14 cases of RCC with rhabdoid features. All cases were reviewed and subjected to detailed clinical and pathologic studies with immunohistochemical evaluation of p53.

Results.—All tumors were clear RCCs with rhabdoid component representing from 5% to 50% of the tumor volume. Rhabdoid cells were large with a central eosinophilic intracytoplasmic inclusion and an eccentric atypical nucleus. Tumor necrosis was common (13/14) and sometimes extensive. Nine of 14 tumors were staged pT3, 4 of 14 were pT2, and only 1 tumor was pT1. On immunohistochemistry, rhabdoid cells were positive for vimentin (14/ 14), epithelial membrane antigen (11/14), and cytokeratin (9/14). Desmin and smooth muscle actin were always negative. p53 was positive in 10 of 14 tumors in the rhabdoid areas (5%–50% of tumor cells stained) but only in 5 of 14 cases in usual clear renal cell areas. In the follow-up, 10 of 14 patients developed metastases and 6 of 14 died of the disease. The median of survival was 8 months.

Conclusions.—We showed that RCC with rhabdoid features is a very aggressive neoplasm with a poor prognosis. We observed an overexpression of p53 in the rhabdoid component that may be implicated in the tumor dedifferentiation.
Differential Expression of Kinase Genes in Primary Hyperparathyroidism: Adenoma Versus Normal and Hyperplastic Parathyroid Tissue
Authors: Schachter Pinhas P. , Ayesh Suhail , Matouk Imad , Schneider Tamar , Czerniak Abraham , Hochberg Abraham
Published: February 2021

Context.—Differentiation between adenoma and hyperplasia or even normal parathyroid tissue is difficult and based mainly on the surgeon's skill. Exploration of genes that express differentially in these various tissues using microarrays and other sophisticated research tools will enable identification and perhaps development of new methods of perioperative diagnosis.

Objective.—To assemble a panel of kinase genes to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue.

Design.—RNA was extracted from adenoma, hyperplasia, and normal parathyroid tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis. Semiquantitative reverse transcriptase polymerase chain reaction analysis of sample genes was performed, up-regulated or down-regulated, to validate the microarray results.

Results.—The ratio values considered significant (<0.5 or >1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for blood vessel angiogenesis and genes belonging to the cyclin-dependent kinase inhibitor groups. Genes down-regulated in parathyroid adenoma are related to cellular growth and apoptosis—genes from the mitogen-activated protein kinase group and DNA-dependent protein kinase group. An interesting gene down-regulated in the parathyroid adenoma samples is related to the serine/threonine protein kinases that exert a key function in calcium handling. A panel of 5 genes was defined: p19, p21 and the gene for vascular endothelial growth factor from the up-regulated group, and the gene for protein kinase C and SGK from the down-regulated group. Reverse transcriptase polymerase chain reaction confirmed the microarray results for these genes.

Conclusions.—The kinase genes panel presented can be used to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue in particular when histopathology fails to provide a decisive diagnosis.
Primary Peritoneal Serous Borderline Tumors
Authors: Hutton, MC C. P. T. Robert L. , Dalton, MC M. A. J. Scott R.
Published: February 2021

Context.—Primary peritoneal serous borderline tumor is a rare epithelial proliferation that can present as an incidental finding at laparotomy and raises concern for a primary ovarian tumor with peritoneal implants.

Objective.—To present a brief history of this condition and describe its distinctive histology and clinical presentation, as well as to review the chief differential diagnostic considerations, to include mesothelial proliferations, endosalpingiosis, endometriosis, high-grade primary peritoneal papillary serous carcinoma, and implants from primary ovarian serous neoplasms.

Data Sources.—Relevant articles indexed in PubMed (National Library of Medicine) between 1966 and 2005, references thereof, and reference surgical pathology texts.

Conclusions.—Primary peritoneal serous borderline tumor should be considered in the differential diagnosis of an epithelial proliferation with prominent psammoma bodies on the peritoneal surface of specimens submitted for nongynecologic complaints.
Critical Leadership and Management Skills for Pathology Practice
Authors: Brimhall Bradley B. , Wright Louis D. , McGregor Kelli L. , Hernandez James S.
Published: February 2021

Context.—Managed care has changed the nature of medical practice. The practice of pathology has also changed and is likely to undergo further modification. Additional skills in leadership and management are needed to perform optimally in the current medical marketplace.

Objective.—To determine whether pathologists view business and informatics skills as being important and valuable in their practices.

Design.—A survey was sent electronically (via e-mail) to 2566 pathologists and pathology administrators.

Results.—Two hundred sixteen survey recipients (8.4%) responded to the survey. The response rate to individual questions ranged from 86% to 99% (186 to 214 of 216 total respondents). Most who took the survey ranked communication (203/209; 97%), leadership skills (165/209; 79%), and systems thinking skills (155/209; 74%) as either “very important” or “essential.” Fewer respondents were willing to offer salary premiums for marketing (108/196; 55%), business or finance (92/196; 47%), or staff leadership (95/196; 48%) skills unless the candidate had a track record of measurable achievement using these skills. Those practicing in academia as well as those making hiring decisions by themselves were more likely to value leadership and management skills. Fewer than 1% of respondents in any category considered current pathology residency training in leadership and management to be adequate.

Conclusions.—Prospective employers value leadership and management skills. Pathology residency programs must include meaningful training in pathology practice management and informatics to satisfy the demand for these skills in the modern pathology marketplace.
Atherogenic Lipid Phenotype in a General Group of Subjects
Authors: Van Joanne , Pan Jianqiu , Charles M. Arthur , Krauss Ronald , Wong Nathan , Wu Xiaoshan
Published: February 2021

Context.—The atherogenic lipid phenotype is a major cardiovascular risk factor, but normal values do not exist derived from 1 analysis in a general study group.

Objective.—To determine normal values of all of the atherogenic lipid phenotype parameters using subjects from a general study group.

Design.—One hundred two general subjects were used to determine their atherogenic lipid phenotype using polyacrylamide gradient gels.

Results.—Low-density lipoprotein (LDL) size revealed 24% of subjects express LDL phenotype B, defined as average LDL peak particle size 258 Å or less; however, among the Chinese subjects, the expression of the B phenotype was higher at 44% (P = .02). For the total group, mean LDL size was 265 ± 11 Å (1 SD); however, histograms were bimodal in both men and women. After excluding subjects expressing LDL phenotype B, because they are at increased cardiovascular risk and thus are not completely healthy, LDL histograms were unimodal and the mean LDL size was 270 ± 7 Å. A small, dense LDL concentration histogram (total group) revealed skewing; thus, phenotype B subjects were excluded, for the rationale described previously, and the mean value was 13 ± 9 mg/dL (0.33 ± 0.23 mmol/L). High-density lipoprotein (HDL) cholesterol histograms were bimodal in both sexes. After removing subjects as described previously or if HDL cholesterol levels were less than 45 mg/dL, histograms were unimodal and revealed a mean HDL cholesterol value of 61 ± 12 mg/dL (1.56 ± 0.31 mmol/L). HDL 2, HDL 2a, and HDL 2b were similarly evaluated.

Conclusions.—Approximate normal values for the atherogenic lipid phenotype, similar to those derived from cardiovascular endpoint trials, can be determined if those high proportions of subjects with dyslipidemic cardiovascular risk are excluded.
Epstein-Barr Virus Infection and Single Nucleotide Polymorphisms in the Promoter Region of Interleukin 10 Gene in Patients With Hodgkin Lymphoma
Authors: da Silva Glenda Nicioli , Bacchi Maura Moscardi , Rainho Cláudia Aparecida , de Oliveira Deilson Elgui
Published: February 2021

Context.—Hodgkin lymphoma is a neoplastic disease in which the immune system plays a major role in its pathogenesis. Interleukin 10 (IL-10), an immunosuppressive cytokine actively produced in patients with Hodgkin lymphomas, favors the survival of the Hodgkin/Reed-Sternberg cells. Individual variations in IL-10 levels may be due, in part, to the presence of single nucleotide polymorphisms in the IL10 gene promoter.

Objective.—To evaluate whether particular single nucleotide polymorphisms in the IL10 gene are found more frequently in Hodgkin lymphoma cases associated with Epstein-Barr virus infection.

Design.—The identification of single nucleotide polymorphisms at positions -1082 and -819/-592 in the IL10 gene was performed by polymerase chain reaction and restriction length fragment polymorphisms analysis in 65 cases of Hodgkin lymphoma and 50 cases of reactive benign follicular lymphoid hyperplasia (non-Hodgkin lymphoma control group).

Results.—The frequency of the genotype GG at position -1082 was found to be significantly higher in patients with Epstein-Barr virus–positive Hodgkin lymphoma compared with Epstein-Barr virus–negative cases.

Conclusions.—The results suggest that the presence of specific single nucleotide polymorphisms in the IL10 gene, notably those associated with high IL-10 production, may play a role in the susceptibility to Epstein-Barr virus–positive Hodgkin lymphoma development.
Nested Variant of Urothelial Carcinoma
Authors: Dhall Deepti , Al-Ahmadie Hikmat , Olgac Semra
Published: February 2021

Nested variant of urothelial carcinoma is a rare neoplasm that is histologically characterized by large numbers of small, closely packed, haphazardly arranged, poorly defined, confluent irregular nests of bland-appearing urothelial cells infiltrating the lamina propria and the muscularis propria. Due to the cells' deceptively bland appearance, the tumors are sometimes misdiagnosed as benign lesions, leading in some cases to a significant delay in establishing the correct diagnosis and thus contributing to this neoplasm's advanced stage. Nested variant of urothelial carcinoma must be differentiated from the benign proliferative lesions of urothelium, such as von Brunn nests, cystitis cystica, cystitis glandularis, nephrogenic adenoma, inverted papilloma, and paraganglioma.