bluuebunny/crossref_metadata_2025 huggingface dataset:
Autopsy Findings Following Gastric Bypass Surgery for Morbid Obesity
Authors: Melinek Judy , Livingston Edward , Cortina Galen , Fishbein Michael C.
Published: January 2021

Background.—Roux-en-Y gastric bypass, currently the most frequently performed surgical procedure for morbid obesity, has a low but significant mortality rate. There are limited data documenting the findings at necropsy in patients who have died following this procedure.

Objective.—To determine cause of death and pathologic processes present in obese subjects dying after gastric bypass surgery.

Patients.—We studied 10 patients who underwent autopsy following gastric bypass surgery for morbid obesity between the years 1994 and 2000.

Results.—There were 6 men and 4 women. The mean age of the patients was 48 years (range, 28–62 years). The mean preoperative weight was 162 kg (range, 112–245 kg), and the mean body mass index was 54 kg/m2 (range, 39–76 kg/m2), similar to all patients undergoing gastric bypass at our institution during the same period. Five deaths were directly attributable to technical complications. Five deaths were attributed to underlying comorbid conditions. One patient died of cirrhosis and one of pulmonary hemorrhage. Three patients died from pulmonary embolism. However, 8 of 10 patients had microscopic evidence of pulmonary emboli, despite prophylaxis for deep vein thrombosis. Most patients had some degree of steatohepatitis and hepatic fibrosis (80% and 70%, respectively). There were no deaths from primary cardiac events.

Conclusions.—In patients who die after Roux-en-Y gastric bypass, half die due to technical complications, whereas the other half die of complications of their obesity. Clinically, only 20% of patients were suspected to have pulmonary emboli, yet at autopsy, 80% of patients had pulmonary emboli. In morbidly obese patients undergoing Roux-en-Y gastric bypass, there is an unexpectedly high rate of clinically silent pulmonary emboli contributing to morbidity and mortality.
Mucinous Adenocarcinoma of Ectopic Breast Tissue of the Vulva
Authors: Chung-Park Moonja , Liu Cheng Zheng , Giampoli Ellen J. , Emery Jonathan D. , Shalodi Abdelwahab
Published: January 2021

Ectopic breast tissue has been described rarely in the vulva and is known to develop a variety of pathologic changes. Our review of the literature found a total of 11 reported cases of primary infiltrating ductal adenocarcinoma arising in ectopic breast tissue of the vulva. We report what we believe is the first case of primary mucinous adenocarcinoma arising in ectopic breast tissue of the vulva diagnosed by characteristic histopathologic features and immunohistochemical stain results. We discuss the criteria used in diagnosis of primary breast carcinoma of the vulva and review previously reported cases.
Desmoplastic Small Round Cell Tumor of the Lung
Authors: Syed Salahuddin , Haque Abida K. , Hawkins Hal K. , Sorensen Poul H. B. , Cowan Daniel F.
Published: January 2021

An extra-abdominal desmoplastic small round cell tumor (DSRCT) of the lung with immunohistochemical, ultrastructural, and cytogenetic evidence of multidirectional differentiation is reported. We demonstrate that DSRCTs of the lung and pleura show morphologic, molecular, genetic, and ultrastructural features similar to DSRCTs arising in other sites. The tumor showed coexpression of cytokeratins (AE1/3, epithelial membrane antigen, CAM 5.2) and mesenchymal markers (vimentin, desmin, neuron-specific enolase), as well as WT1. Ultrastructurally, intracytoplasmic whorls of intermediate filaments, similar to previous descriptions of DSRCT in nonthoracic sites, were also demonstrated in this case. EWS-WT1 gene fusion characteristic of DSRCT with the t(11;22)(q13;q12) translocation was demonstrated in this tumor.
Diagnostic Studies for Thrombophilia in Women on Hormonal Therapy and During Pregnancy, and in Children
Authors: Brenner Benjamin R. , Nowak-Göttl Ulrike , Kosch Andrea , Manco-Johnson Marilyn , Laposata Michael
Published: January 2021

Objective.—To review the role of acquired and inherited prothrombotic risk factors that increase the risk of thrombosis in oral contraceptive users, during pregnancy, and in neonates, infants, and children; and to determine by the consensus opinion of recognized experts in the field which risk factors should be determined in which individuals at which time.

Data Sources.—Review of the medical literature and current clinical practice by a panel of experts in the field of thrombophilia.

Data Extraction and Synthesis.—The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. The manuscript and recommendations were then presented at the conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.

Conclusions.—This report reviews the options for testing for thrombophilic states in women using oral contraceptives, during pregnancy, and in neonates and children. General guidelines for testing in these clinical situations are provided, along with citation of the appropriate supporting literature.
Antithrombin Deficiency
Authors: Kottke-Marchant Kandice , Duncan Alexander
Published: January 2021

Objective.—To review the current understanding of the pathophysiology of antithrombin deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing of antithrombin function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included. These recommendations specify whom, how, and when to test.

Data Sources.—Review of the published medical literature.

Data Extraction and Synthesis.—A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this article were accepted after a two-thirds majority vote by the participants.

Conclusions.—Antithrombin deficiency is an infrequent genetic abnormality that may be a significant contributing cause of thrombophilia. Antithrombin deficiency also may be observed in conjunction with other genetic or acquired risk factors. Assay of antithrombin plasma levels is appropriate in the laboratory evaluation of individuals with thrombophilia, preferably using a functional, amidolytic antithrombin assay. The diagnosis of antithrombin deficiency should be established only after other acquired causes of antithrombin deficiency, such as liver disease, consumptive coagulopathy, or heparin therapy, are excluded. A low antithrombin level should be confirmed with a subsequent assay on a fresh specimen, and family studies may be helpful to establish the diagnosis. Antigenic antithrombin assays may be of benefit in subclassification of the type of antithrombin deficiency and to confirm the decreased antithrombin level in patients with type I deficiency.
Heparin Cofactor II Deficiency
Authors: Tollefsen Douglas M.
Published: January 2021

Objectives.—To review of the state of the art relating to congenital heparin cofactor II deficiency as a potential risk factor for thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for the use of laboratory assays for assessing this thrombotic risk in individual patients.

Data Sources.—Review of the medical literature, primarily from the last 10 years.

Data Extraction and Synthesis.—After an initial assessment of the literature, including review of clinical study design and laboratory methods, a draft manuscript was prepared and circulated to participants in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. Recommendations were accepted if a consensus of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.

Conclusions.—Consensus was reached that there is insufficient evidence to recommend testing for heparin cofactor II deficiency in patients with thromboembolic disease.
Impact of Nucleic Acid Testing for Human Immunodeficiency Virus and Hepatitis C Virus on Blood Product Availability, Outdating, and Patient Safety
Authors: Sherman Laurence A.
Published: January 2021

Context.—Limited data are available about the impact of nucleic acid testing for human immunodeficiency virus and hepatitis C virus in donated blood as part of a nationwide investigational study that affected greater than 90% of the blood supply.

Objective.—To assess the impact of nucleic acid testing on supply, outdating, and patient safety.

Design.—Participants in the College of American Pathologists 2001 American Association of Blood Banks/College of American Pathologists Viral Marker C survey were asked questions about supply, outdating, and implementation of a full quarantine of blood pending nucleic acid testing results. The number of respondents for each question ranged from 197 to 219 for blood centers and from 462 to 504 for hospitals.

Results.—Shortages were more common for platelets (29% and 23% of blood centers and hospitals, respectively) than for red blood cells (13%, 11%). Similarly, outdating of platelets (13%, 11%) was more common than outdating of red blood cells; outdating of red blood cells was negligible for both blood centers and hospitals. Forty-two percent of blood centers did not meet the mid 2000 target date for quarantining red blood cells, and 18% were not quarantining as of September 2001. The hospital figures were 66% not quarantining in mid 2000 and 39% not quarantining as of September 2001. Higher proportions of centers and hospitals were not quarantining platelets at these 2 dates.

Conclusions.—Unfavorable trends in both blood shortages and outdating were attributed to nucleic acid testing. Greater effects may have been masked by delayed implementation of full quarantine nationwide. This delay meant continued patient risk, and lack of full benefit, in a trial that was in effect a national standard. In the future, added systems will be needed for similar new endeavors to ensure uniformity of care and to avoid shortages.
Chronic Lymphocytic Leukemia With t(14;18) and Trisomy 12
Authors: Sen Filiz , Lai Raymond , Albitar Maher
Published: January 2021

The chromosomal abnormality t(14;18) is most commonly associated with neoplasms of follicular center cell origin. However, t(14;18) also has been reported in rare cases of chronic lymphocytic leukemia (CLL). In 2215 cases of CLL studied by conventional cytogenetics in our institution, we identified 2 cases of CLL carrying t(14;18). Both patients were men, aged 52 and 71 years at the time of diagnosis. One patient presented with leukemia and the other primarily with nodal disease. In addition to t(14;18), trisomy 12 (+12) was identified in the same clone in both cases. Atypical morphologic features were identified: case 1 contained more than 15% lymphoid cells with cleaved nuclei, whereas case 2 contained more than 15% plasmacytoid lymphoid cells. The immunophenotype of case 2 was also unusual for CLL, showing weak CD23 expression and FMC7 positivity. We identified 6 other t(14;18)-carrying CLL cases in the literature; 2 had t(14;18) as the sole abnormality and 2 contained +12 as the additional abnormality. To conclude, cases of CLL carrying t(14;18) are exceedingly rare, and +12 appears to be the most common cytogenetic abnormality coexisting with t(14;18) in CLL.
Tissue Plasminogen Activator Plasma Levels as a Potential Diagnostic Aid in Acute Pulmonary Embolism
Authors: Flores Julio , García-Avello Angel , Flores Victor M. , Navarro JoséL. , Canseco Felipe , Pérez-Rodríguez Esteban
Published: January 2021

Context.—Pulmonary embolism (PE) is a potentially fatal and frequent complication of deep venous thrombosis, and the most reliable techniques for the diagnosis of PE are not universally available and have other limitations.

Objective.—To determine the efficacy of 4 different fibrinolysis system parameters, namely, tissue plasminogen activator (tPA), tissue plasminogen activator inhibitor type 1 (PAI-1), plasmin-antiplasmin complexes (PAP), and D-dimer, in the diagnosis of acute PE.

Setting.—A 350-bed university hospital serving an area with 280 000 inhabitants.

Patients.—Sixty-six consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on ventilation-perfusion (V/Q) lung scan in combination with clinical assessment, lower limb study, and (when required) pulmonary angiography.

Main Outcome Measures.—At the moment of clinical suspicion, a sample of venous blood was obtained to measure levels of tPA, PAI-1, PAP, and D-dimer using an enzyme-linked immunosorbent assay method.

Results.—Twenty-seven patients (41%) were classified as PE positive (high clinical probability and V/Q lung scan [n = 12], nondiagnostic V/Q lung scan and high clinical probability [n = 1], inconclusive V/Q lung scan and positive lower limb examination for deep venous thrombosis [n = 11], and positive pulmonary angiography [n = 3]), and 39 patients (59%) were classified PE negative. The sensitivity/negative predictive value for tPA, using a cutoff of 8.5 ng/mL, and PAI-1, using a cutoff of 15 ng/mL, were 100%/100% and 100%/100%, respectively. A tPA level lower than 8.5 ng/mL occurred in 13 (19.7%; all PE negative) of 66 patients with suspected PE, and PAI-1 levels were lower than 15 ng/mL in 9 (13.6%; all PE negative) of 66 patients with suspected PE. The D-dimer, using a cutoff of 500 ng/mL, showed a sensitivity and negative predictive value of 92.6% and 87.5%, respectively.

Conclusions.—Our data indicate that tPA and PAI-1 levels are potentially useful in ruling out PE, although tPA seems to be the better parameter. The sensitivity levels and negative predictive values for the rapid enzyme-linked immunosorbent assay for D-dimer used in this investigation were low compared with previous studies using the same test.
Comparison of Polymerase Chain Reaction With Histopathologic Features for Diagnosis of Tuberculosis in Formalin-Fixed, Paraffin-Embedded Histologic Specimens
Authors: Park Do Youn , Kim Jee Yeon , Choi Kyung Un , Lee Jin Sook , Lee Chang Hun , Sol Mee Young , Suh Kang Suek
Published: January 2021

Objective.—To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)–polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB.

Design.—We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB).

Results.—Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive.

Conclusions.—TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.
Posttransplant CD30+ (Ki-1) Anaplastic Large Cell Lymphoma
Authors: Lee Lisa Y. , Harpaz Noam , Strauchen James A.
Published: January 2021

Posttransplant CD30+ (Ki-1) anaplastic large cell lymphoma (ALCL) is rare. A review of the literature revealed only 3 such cases. All 3 cases were developed after single-organ transplantation. We describe CD30+ (Ki-1) ALCL in a dual-organ (liver and heart) transplantation recipient. The patient was a 68-year-old white female who underwent an orthotopic heart transplantation in 1999 and a liver transplantation in 2000. She presented with nausea and was found to have CD30+ (Ki-1) ALCL by pathologic examination of the gastric antrum biopsy specimen. To our knowledge, this patient represents the first reported case of posttransplant CD30+ ALCL following a dual-organ transplantation.
Solitary Fibrous Tumors in the Central Nervous System
Authors: Tihan Tarik , Viglione Michael , Rosenblum Marc K. , Olivi Alessandro , Burger Peter C.
Published: January 2021

Context.—Solitary fibrous tumors (SFTs) of the central nervous system are rare neoplasms that usually present as dura-based masses and clinically resemble meningiomas. Histologically, they can be similar to fibrous meningioma or hemangiopericytoma (HPC). In particular, densely cellular regions seen in some SFTs can be indistinguishable from HPC. Little is known about the biological behavior of SFTs, although most seem amenable to total resection.

Objectives.—To define the clinicopathologic spectrum of SFTs in the central nervous system and to outline their differences from HPC and meningioma.

Design.—We present the clinicopathologic features of 18 patients with SFT and compare them with those of an age- and sex-matched cohort of HPCs.

Results.—Eleven SFTs were supratentorial, 3 were infratentorial, and 4 were intraspinal. Four of the 18 tumors were intra-axial (2 in the lateral ventricles and 2 within the spinal cord). Histologically, SFTs were similar to their soft tissue counterparts. Six tumors (6/18) had densely cellular regions, and 1 tumor showed frankly anaplastic features. All but 3 patients underwent gross total resection, and there were no metastases or tumor-related mortalities during the median follow-up of 40 months. In contrast, there were 15 local recurrences (83%), 5 extracranial metastases (27%), and 4 tumor-related deaths (22%) in the HPC cohort.

Conclusions.—Our study presents the clinicopathologic features of SFT as a distinct entity from both meningioma and HPC. We also present unusual examples of anaplastic, intraventricular, and intramedullary spinal SFTs that expand the clinicopathologic spectrum of these uncommon and sometimes diagnostically difficult neoplasms.
Results of a Physician Survey on Ordering Viral Load Testing
Authors: Hofherr Louise K. , Francis Diane P. , Astles J. Rex , Schalla William O.
Published: January 2021

Objective.—To profile physicians' practices, utilization, and understanding of human immunodeficiency virus type 1 RNA (viral load) testing and the laboratory's role in this testing.

Design.—Cross sectional study using a 34-item self-report survey mailed to physicians identified as requesting viral load testing, with follow-up mailings to nonresponders.

Participants.—A sampling of US physicians specializing in infectious diseases, internal medicine, and family practice associated with high, medium, and low human immunodeficiency virus/acquired immunodeficiency syndrome incidence areas.

Results.—Most respondents using viral load results were infectious diseases specialists practicing in urban areas. The reasons most frequently given for requesting viral load testing were (1) to assist in patient follow-up or monitoring (75.4%), and (2) to initiate/guide therapy (62.5%). Respondents indicated that the interpretation and use of viral load results presented difficulty in the areas of patient treatment and in determining what change from baseline was clinically significant. Few respondents used the testing laboratory pathologist as a resource for interpreting viral load test results.

Conclusions.—Our study indicates that physicians have questions about (1) the meaning of viral load tests, (2) how often to monitor the viral load, and (3) what change from baseline of the viral load is significant. Few physicians avail themselves of the expertise available in the laboratory for testing viral loads and interpreting such results.
Histology of Gastroesophageal Junction in Fetal and Pediatric Autopsy
Authors: Park Young S. , Park Hyo Jin , Kang Gyeong Hoon , Kim Chong Jai , Chi Je G.
Published: January 2021

Context.—There is much debate over whether the gastric cardia exists from birth as a normal structure or is a metaplastic structure that develops as the result of gastroesophageal reflux disease. This question has become a matter of concern since the incidence of adenocarcinoma at the gastroesophageal junction has been increasing rapidly in the Western world for more than 2 decades. Various groups of investigators have tried to clarify this matter by examining the histology of the gastroesophageal junction in autopsy cases, and there have been striking discrepancies in their findings. In one group, it was observed that cardiac mucosa was present in all pediatric autopsies. On the contrary, another group concluded that pure cardiac mucosa was absent in 56% of their autopsy cases.

Objective.—Without regard to the definition of the cardiac mucosa, we focused on the distance between the squamocolumnar junction and the most proximal parietal cells to elucidate the histologic features of the gastroesophageal junction on the gastric side.

Design.—The entire gastroesophageal junction and the proximal part of the stomach from 23 fetal and pediatric autopsies were mapped. We measured the distance from the squamocolumnar junction to the most proximal parietal cells identified. The extent of the transitional zone, defined as the mucosa between the squamocolumnar junction and the fundic mucosa, was also evaluated.

Results.—The transitional zone was identified in 78% of cases, and it always harbored some scattered parietal cells in mucous glands. The parietal cells were consistently identified adjacent to the squamocolumnar junction in all cases. Although the transitional zone in fetal stomach was usually composed of several pits of foveolar epithelium without glandular portions, it contained glandular structures in the pediatric cases.

Conclusions.—The mucosa composed of pure mucous cells does not exist as a normal developmental structure.
Severe Gastritis Secondary to Epstein-Barr Viral Infection
Authors: Zhang Yanlong , Molot Ross
Published: January 2021

Infectious mononucleosis is usually a self-limited clinical syndrome caused by primary Epstein-Barr virus infection. It is occasionally compounded by severe complications involving many different organ systems. Predominant gastrointestinal involvement is rarely documented. We present an unusual case of acute Epstein-Barr virus infection–associated gastritis with diffuse atypical lymphoid hyperplasia in gastric mucosa. The clinical, radiographic, histopathologic, immunohistochemical, and in situ hybridization features needed for accurate diagnosis and differentiation from gastric malignancies are discussed.
Nitrergic Hyperinnervation in Appendicitis and in Appendices Histologically Classified as Normal
Authors: Nemeth Laszlo , Rolle Udo , Reen Denis J. , Puri Prem
Published: January 2021

Context.—The pathogenesis of appendicitis remains poorly understood. Despite new diagnostic techniques, appendices removed from patients with suspected appendicitis often appear histologically normal on conventional examination. There is increasing evidence of involvement of the enteric nervous system in immune regulation and in inflammatory responses in the gastrointestinal system.

Objective.—To investigate the nitrergic innervation of (a) acutely inflamed appendices, (b) appendices classified as histologically normal from patients with a clinical diagnosis of appendicitis, and (c) normal control appendix specimens, using the whole-mount preparation technique.

Patients and Design.—Full-thickness specimens were collected from 28 acutely inflamed appendices (age range, 3.2–13.4 years), 31 histologically normal appendices removed from patients (age range, 5.7–13.6 years) with suspected appendicitis, and 23 histologically normal appendices from patients (age range, newborn to 12.1 years) undergoing elective abdominal surgery (controls). Whole-mount preparation using nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and neuronal nitric oxide synthase immunohistochemistry were performed. The density of myenteric plexus was measured with a computerized analysis system.

Results.—The density of myenteric plexus in normal appendix specimens was similar to that of large bowel from the newborn period up to 3 years of age; this density decreased significantly thereafter. The myenteric plexus of normal appendix specimens from patients older than 4 years demonstrated smaller ganglia connected by thin nerve bundles, compared to larger ganglia and nerve bundles in large bowel. Significant neuronal hypertrophy was found in 55% of acutely inflamed and 41% of histologically classified normal appendix specimens. The myenteric plexus of these appendix specimens had even thicker nerve bundles connecting an increased number of ganglion cells.

Conclusions.—Differences in the architecture of the myenteric plexus in patients older than 3 years suggest an altered function and motility of appendix in the early years of life. The significant increase in neuronal components of the myenteric plexus in a high proportion of acutely inflamed and histologically normal appendix specimens is unlikely to have developed during a single acute inflammatory episode. This suggests an underlying chronic abnormality as a secondary response to chronic luminal obstruction or repeated inflammatory episodes in the histologically normal appendix.
Interobserver and Intraobserver Variability Using the Fuhrman Grading System for Renal Cell Carcinoma
Authors: Al-Aynati Maamoun , Chen Vicky , Salama Samih , Shuhaibar Hafez , Treleaven Darin , Vincic Lydia
Published: January 2021

Context.—Histologic grading of renal cell carcinoma has been shown to be second to staging in prognostic significance. A 4-tier grading scheme proposed by Fuhrman et al and based on nuclear features is the system used most frequently in North America. There are, however, very few studies in the literature assessing the interobserver variability for this system, and to our knowledge, none addressing intraobserver variability.

Objective.—To assess the interobserver and intraobserver agreement among 4 pathologists using the Fuhrman nuclear grading scheme for renal cell carcinoma.

Design.—Representative hematoxylin-eosin–stained slides of 99 consecutive primary renal cell carcinoma cases diagnosed between 1994 and 1999 at St Joseph's Hospital, Hamilton, Ontario, were independently graded by 4 pathologists on 2 occasions with a minimum period of 3 months separating the 2 readings.

Results.—Intraobserver κ values ranged from 0.29 to 0.62 (mean = 0.45), and interobserver κ values ranged from 0.19 to 0.38 and from 0.09 to 0.44 for the first and second rounds, respectively (combined mean κ value = 0.29). When combining Fuhrman grades 1 and 2 as low-grade tumors and grades 3 and 4 as high-grade tumors, the intraobserver κ values ranged from 0.4 to 0.64 (mean = 0.53) and interobserver κ values ranged from 0.28 to 0.59 and from 0.26 to 0.58 for the first and second rounds, respectively (combined mean κ value = 0.45). The admixture of 2 grades in the same tumor was observed in 53% of cases.

Conclusions.—We found only moderate intraobserver and interobserver agreement using the 4-grade Fuhrman scheme. After collapsing the diagnostic grades to 2, the intraobserver agreement changed from moderate to substantial. The collapsing of the 4-category Fuhrman grades into 2 categories is useful in improving intraobserver agreement.
Lack of Association of Lipoprotein Lipase Gene Polymorphisms With Coronary Artery Disease in the Saudi Arab Population
Authors: Abu-Amero Khaled K. , Wyngaard Carol A. , Al-Boudari Olyan M. , Kambouris Marios , Dzimiri Nduna
Published: January 2021

Context.—Previous studies reported an association of certain polymorphisms in the lipoprotein lipase (LPL) gene with the risk of coronary artery disease (CAD); however, these studies were small and inconsistent. In addition, none of these studies attempted to establish such an association in the Arab population.

Objective.—To determine whether 2 LPL polymorphisms (LPL-HindIII and LPL-PvuII located on introns 8 and 6, respectively, of the LPL gene) can be considered as independent risk factors or as predictors for CAD in Arabs.

Design.—We used polymerase chain reaction and restriction enzyme digestion to determine the distribution of the LPL-HindIII and LPL-PvuII polymorphisms among healthy blood donors of Arabic origin (BD group) and angiographically confirmed CAD patients (CAD group) with identical ethnic backgrounds.

Results.—For the HindIII genotypes, within the BD group (n = 410), the +/+ genotype was found in 206 individuals (50.2%), 173 (42.2%) carried the +/− genotype, and 31 (7.6%) carried the −/− genotype. Within the CAD group (n = 352), the +/+ genotype was found in 189 individuals (53.7%), 138 (39.2%) carried the +/− genotype, and 25 (7.1%) carried the −/− genotype. P values of .38, .45, and .92 were obtained for the +/+, +/−, and −/− genotypes, respectively. For the PvuII genotypes, within the BD group (n = 511), the +/+ genotype was found in 182 individuals (35.6%), 248 (48.5%) carried the +/− genotype, and 81 (15.9%) carried the −/− genotype. Within the CAD group (n = 431), the +/+ genotype was found in 138 individuals (32%), 225 (52.2%) carried the +/− genotype, and 68 (15.8%) carried the −/− genotype. P values of .28, .29, and .98 were obtained for the +/+, +/−, and −/− genotypes, respectively. The distribution and the allele frequency of these 2 LPL variants were similar in CAD and BD study groups and followed the Hardy-Weinberg equilibrium.

Conclusion.—There was no difference in the distribution of both LPL polymorphisms between the healthy group and the CAD group. Therefore, these 2 LPL polymorphisms cannot be considered as independent risk factors or as predictors for CAD in this population.
Age and Laboratory Costs for Hospitalized Medical Patients
Authors: Brimhall Bradley B. , Dean Troy , Hunt Edgar L. , Siegrist Richard B. , Reiquam William
Published: January 2021

Objective.—To examine the hypothesis that older hospitalized patients have higher laboratory costs than younger patients in the same severity-adjusted diagnosis-related group (DRG).

Design.—We obtained hospital case mix data sets (1995–1997) from the Massachusetts Division of Health Care Finance and Policy. We selected discharge abstracts from 4 medical DRGs, at 5 large academic hospitals (n = 15 265) and 5 midsized community hospitals (n = 10 540), for analysis. We converted laboratory and blood product charges to direct costs using the department-specific ratio of cost to charges. We adjusted diagnostic groups for severity of comorbid conditions and complications using the refined DRG method.

Main Outcome Measures.—Hospital length of stay (LOS), laboratory direct cost (LDC) per hospitalization, LDC per hospital day, and ratio of LDC to total direct cost.

Results.—Hospital LOS was longer for older patients in all comparisons. Laboratory direct cost per hospitalization was higher for older patients in some DRGs, but lower in other DRGs. Laboratory direct cost per hospital day was almost always less for older patients than for younger patients, both at academic and community hospitals. Data stratification by gender, admission status, and principal diagnosis yielded substantially the same pattern of cost differences observed within the larger data set.

Conclusions.—Older medical patients have longer hospital stays and generally higher costs. These patients also have a significantly decreased rate of laboratory resource consumption over the course of hospitalization (LDC per hospital day), as well as lower laboratory costs as a proportion of total costs. Age-specific differences in LOS and cost parameters were essentially unchanged after controlling for several potential sources of bias.
Clinical-Histopathologic Concordance of Tumors of the Nervous System at the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery in Mexico City
Authors: Velásquez-Pérez Leora , Jiménez-Marcial María Esther
Published: January 2021

Context.—When making a diagnosis, the main purpose of clinicians should not be to achieve certainty, but to decrease diagnostic uncertainty in order to make optimal therapeutic decisions. Diagnostic concordance is an essential characteristic if a measurement is to be considered scientific. In the case of tumors of the nervous system (TNS), one of the most accurate diagnostic tests is magnetic resonance imaging. However, histopathologic analyses are essential, because they refine the diagnosis, benefit the patient, and improve our understanding of the disease. By determining the clinical-histopathologic correlation of TNS in one of the main neurologic centers in Mexico, we sought to project reliable morbidity and/or mortality statistics.

Objective.—To assess clinical and histopathologic diagnostic agreement in cases involving TNS admitted to the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery between 1990 and 1999.

Design.—Cross-sectional diagnostic concordance study, including all clinical hospital records of patients with histopathologically diagnosed TNS, classified according to World Health Organization criteria.

Results.—Among 2041 TNS cases, the 3 most frequent types were those affecting the neuroepithelial tissue (32.9%), tumors of the sellar region (29.2%), and tumors of the meninges (25.6%). We found that, overall, clinical-histopathologic concordance for these 3 categories was substantial and statistically significant.

Conclusions.—Tumors of the nervous system constitute a heterogeneous group of neoplasms. In the present study, clinical diagnoses substantially agreed with pathologic diagnoses. The a priori clinical diagnosis allowed prompt treatment even before diagnostic confirmation by histopathologic analysis, which is the best way to confirm, clarify, and correct a diagnosis.
Conformity to Guidelines for Pathologic Examination of the Placenta
Authors: Spencer Michael K. , Khong T. Yee
Published: January 2021

Context.—The College of American Pathologists developed a consensual guideline for placental examination that included indications for the submission of placentas for pathologic examination. The adherence to this guideline is not known.

Objectives.—To identify the number of placentas that were and that should have been examined by a tertiary-care hospital according to the College of American Pathologists' practice guideline and to compare the indications listed by medical staff on their pathology request forms with the clinical events recorded on the hospital's databases.

Design.—Data from the hospital computer databases and from pathology request forms were collected for all 987 deliveries occurring at a tertiary-level maternity hospital from April through June 2000.

Results.—Fewer than 20% of placentas were examined, but about 50% should have been. Maternal fever and suspected neonatal infection were the indications with the lowest examination rates. Neonatal indications were infrequently listed.

Conclusions.—This hospital examined approximately one third of the placentas that should have been examined. When the placentas were examined, the medical staff often failed to appropriately list the indications on their pathology request forms.
Multiple Langerhans Cell Nodules in an Incidental Thymectomy
Authors: Novak Lea , Castro Claudia Y. , Listinsky Catherine M.
Published: January 2021

The isolated appearance of Langerhans cell histiocytosis in the thymus is quite rare. We report the finding of multiple small Langerhans cell nodules in the thymus of an 11-month-old infant who had undergone thymectomy in the course of surgical correction of tetralogy of Fallot. The subtle appearance of some of these nodules and aggregates was unlike the pattern of massive thymic infiltration seen in 7 previously reported cases of thymic Langerhans cell histiocytosis in childhood. This difference led us to consider whether these aggregates might be common in the thymus but overlooked in thymus glands removed incidental to cardiac surgery. We examined histologic material from 22 sequential thymectomy specimens removed during cardiac surgery from infants and children. None (0/22) had cohesive aggregates of Langerhans cells, as were seen in the index patient's thymus. Our patient's small thymic nodules resemble more closely a pattern found in adult patients with myasthenia gravis who have been incidentally shown to have Langerhans cell histiocytosis.
Nocardiosis With Brain Abscess Due to an Unusual Species, Nocardia transvalensis
Authors: Yorke Rebecca F. , Rouah Emilie
Published: January 2021

The identification of Nocardia transvalensis, an unusual and probably underrecognized cause of nocardial infection, is clinically significant because of this species' resistance to aminoglycosides, a standard antinocardial therapy. Diagnosis requires analytic methods available predominately in reference laboratories. We report a case of disseminated infection with N transvalensis with primary pulmonary involvement and subsequent development of brain abscesses, and review the literature to date. Familiarity with the epidemiology, pathologic findings, and clinical significance of this and other unusual Nocardia species may increase early identification and antibiotic susceptibility testing in cases of nocardial infection.
Pathology Resident Attitudes and Opinions About Pathologists' Assistants
Authors: Grzybicki Dana Marie , Vrbin Colleen M.
Published: January 2021

Context.—Changes in health care economics and organization have resulted in increased use of nonphysician providers in most health care settings. Attitudinal acceptance of nonphysician providers is important in the current health care environment.

Objectives.—To obtain descriptive information regarding pathology resident attitudes and opinions about pathologists' assistants in anatomic pathology practice and to assess the implications of resident attitudes and opinions for pathology practice and training.

Design.—A self-administered, mailed, voluntary, anonymous questionnaire was distributed to a cross-sectional sample of pathology residents in the United States (2531 pathology residents registered as resident members of one of the national pathology professional organizations). The questionnaire contained (1) items relating to resident demographics and program characteristics, (2) Likert-scale response items containing positive and negative statements about pathologists' assistants, (3) a multiple-choice item related to pathologists' assistants scope of practice, and (4) an open-ended item inviting additional comments. Both quantitative and qualitative analysis of responses was performed.

Results.—The overall response rate was 19.4% (n = 490); 50% of the respondents were women, and 77% reported use of pathologists' assistants in their program. Most respondents were 25 to 35 years old and in postgraduate years 3 through 5 of their training, and most were located in the Midwestern United States. The majority of residents expressed overall positive attitudes and opinions about pathologists' assistants and felt that pathologists' assistants enhanced resident training by optimizing resident workload. A minority (10%–20%) of residents expressed negative attitudes or opinions about pathologists' assistants. Additionally, some residents reported a lack of knowledge about pathologists' assistants' training or roles.

Conclusions.—Increased resident education and open discussion concerning pathologists' assistants may be beneficial for optimizing resident attitudes about and training experiences with pathologists' assistants.
Misdiagnosis of High-Grade Vulvar Intraepithelial Neoplasia (VIN III) as Mild Cervical Intraepithelial Neoplasia (CIN I) on Papanicolaou Tests
Authors: August Carey Z. , Ganji Masoud , Froula Evelyn
Published: January 2021

Context.—Although high-grade vulvar intraepithelial neoplasia (VIN III) is a clinically significant lesion, it can be overlooked because of nonspecific clinical findings and the fact that its cytomorphologic features mimic those of mild cervical intraepithelial neoplasia (CIN I).

Objective.—To determine if there are cytomorphologic features on Papanicolaou tests that can reliably distinguish between VIN III and CIN I.

Design.—Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven CIN I were compared with Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven VIN III but with no biopsy-proven CIN I.

Results.—None of the cytomorphologic features evaluated could reliably distinguish CIN I from VIN III.

Conclusion.—Since the Papanicolaou test cannot be used to distinguish between CIN I and VIN III, the clinician must pay careful attention to the clinical and colposcopic findings. Further research evaluating the use of ancillary studies, such as human papillomavirus typing, may be useful.
Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome Are Distinct Pathologic Entities
Authors: Hosler Gregory A. , Cusumano Ana M. , Hutchins Grover M.
Published: January 2021

Context.—Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) share many clinical features and have been difficult to separate into distinct entities. Histologic examination of organs from autopsied patients suggested that TTP and HUS have dissimilar lesions of different severity and distribution.

Objective.—To perform a retrospective observational review of autopsied patients with TTP or HUS to compare the nature and severity of the lesions found.

Design.—To examine the pathologic features of these conditions, we reviewed all cases among 51 350 indexed autopsies at The Johns Hopkins Hospital (Baltimore, Md) diagnosed with TTP or HUS, and included those showing multiple arteriolar thrombi or their sequela.

Results.—The 56 cases that met the inclusion criteria fell into 2 distinct groups, based on distribution and severity of arteriolar lesions. In 25 patients classified as having TTP, platelet-rich thrombi were present—in decreasing severity—in heart, pancreas, kidney, adrenal gland, and brain. In 31 patients with HUS, fibrin/red cell–rich thrombi were present, largely confined to the kidney and often severe, and only 6 cases showed pancreas involvement, 4 adrenal gland involvement, 2 brain involvement, and 1 heart involvement.

Conclusion.—Despite similar clinical features and therapeutic approaches, TTP and HUS each have a characteristic constellation of histopathologic findings. This observation suggests that TTP and HUS are 2 distinct disease entities with different pathophysiologies, and that they do not represent a spectrum of the same disease process.
Primary Pleural Synovial Sarcoma
Authors: Ng Siok Bian , Ahmed Qasim , Tien Sim Leng , Sivaswaren Christina , Lau Lai Ching
Published: January 2021

Synovial sarcoma (SS) is an uncommon soft tissue tumor that occurs primarily in the extremities of young adults, especially in the periarticular region. In this report, we describe the rare occurrence of primary SS of the pleura in a 15-year-old boy. Histologically, the tumor demonstrated monophasic morphologic findings and showed positive staining with vimentin and Bcl-2 and focally for cytokeratin CK7. Fluorescent in situ hybridization identified t(X;18) translocation. The patient developed recurrences 20 months following resection of the tumor. The literature on this uncommon entity is reviewed, and its histogenesis, differential diagnoses, and cytologic features are also discussed.
Primary Duodenal Carcinoma Showing Divergent Growth Patterns as Determined by Microdissection-Based Mutational Genotyping
Authors: Cheung Onki , Kandil Hossam , Moser Arthur J. , Swalsky Patricia A. , Sasatomi Eizaburo , Finkelstein Sydney D.
Published: January 2021

Primary duodenal adenocarcinoma accounts for less than 0.5% of all gastrointestinal cancers. We report a case of duodenal adenocarcinoma with highly divergent growth patterns consisting of poorly differentiated adenocarcinoma and neuroendocrine carcinoma proven to arise as a single neoplasm of monoclonal origin, as demonstrated by microdissection-based mutational profiling. Multicomponent growth patterns, as seen in this case, can occasionally be encountered in gastrointestinal malignancies and have led to speculation about the pathogenesis. The methods used to clearly establish monoclonal origin based on the unique profiling of mutational damage can address fundamental issues related to tumor development and progression, while providing cogent clinical information. Our findings confirm the great potential for intestinal epithelial cells to differentiate along different histogenetic lines during tumor progression.
Inflammatory Myofibroblastic Tumor With Bone Marrow Involvement
Authors: Hagenstad Christopher T. , Kilpatrick Scott E. , Pettenati Mark J. , Savage Paul D.
Published: January 2021

Inflammatory myofibroblastic tumor, also referred to as inflammatory fibrosarcoma, is a rare tumor composed of myofibroblastic spindle cells of uncertain etiology and disputed nosology. We report a case of inflammatory myofibroblastic tumor of the omentum with involvement of the bone marrow in an 18-year-old man. Histologic and immunohistochemical studies of the abdominal mass and bone marrow were consistent with inflammatory myofibroblastic tumor. Additionally, fluorescence in situ hybridization using a probe specific for the ALK gene showed disruption of the gene. The literature is reviewed with emphasis on the ability of inflammatory myofibroblastic tumor to recur, metastasize, and cause mortality.
CD83+ Dendritic Cells in Inflammatory Infiltrates of Churg-Strauss Myocarditis
Authors: Schoppet Michael , Pankuweit Sabine , Maisch Bernhard
Published: January 2021

Churg-Strauss syndrome (CSS) is characterized by a granulomatous vasculitis of multiple organs with the cardiovascular system being commonly affected. The initiation of the disease is not well understood, but immunologic phenomena are thought to contribute at least partially to the syndrome. We have studied endomyocardial biopsy specimens from a patient with CSS and eosinophilic myocarditis for characterization of infiltrating immune cells by immunofluorescence staining techniques and found a major population to be composed of CD83+CD14−CD19−CD56−HLA-DR+ dendritic cells (DCs). Further phenotypic characterization of infiltrating CD83+ cells in CSS myocarditis showed a surface profile reminiscent of immature DCs. In the same patient, the cytokine expression pattern of mitogen-stimulated peripheral blood mononuclear cells revealed a TH0 response as evidenced by multiplex polymerase chain reaction, and interleukin-5 levels were elevated in plasma analyzed by enzyme-linked immunosorbent assay. Thus, in this case of CSS myocarditis, we found DC-like cells in myocardial lesions, which may suggest that DCs are involved in the inflammatory process possibly triggered or sustained by an imbalance of DCs and their failure to confer tolerance to self-antigens.