bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Carcinoma Presenting During or Shortly After Pregnancy and Lactation
Authors: Shousha Sami 
Published: January 2021

AbstractContext.—Much has been written about the clinical management and prognosis of breast carcinomas presenting during pregnancy and lactation, yet little is known about the detailed histopathology of these tumors.Objective.—To determine whether these carcinomas have any specific diagnostic features.Design.—A detailed histologic and immunohistochemical study of 14 cases of breast carcinoma presenting during or shortly after pregnancy or lactation was conducted. The findings were compared with a control group of 13 tumors developing in age-matched women with no recent history of pregnancy or lactation.Setting.—The histopathology department of a tertiary referral teaching hospital.Results.—Tumors in the pregnancy/lactation group had a significantly higher incidence of cancerization of lobules (79% vs 15%) and of grade III invasive ductal carcinomas (80% vs 33%). Tumors occurring during lactation were either totally or partly mucinous and were MUC2 positive. Tumors occurring during pregnancy, but not during lactation, were mostly estrogen and progesterone receptor negative (4/5 and 5/5, respectively). All tumors occurring during pregnancy and lactation that were tested for c-erbB-2 overexpression were negative, whereas all 4 tumors tested that occurred shortly after delivery or cessation of lactation were positive for c-erbB-2 overexpression. The incidence of axillary lymph node metastasis was high in both the study and control groups, although it was slightly higher in the control group (78% and 90%, respectively).Conclusions.—Although breast carcinomas diagnosed during or shortly after pregnancy and lactation have features in common with those developing in women of similar ages, particularly with respect to a high incidence of lymph node metastasis, the findings of this study suggest that they may also have distinct morphologic and immunohistochemical features of their own. Such features may vary according to whether the patient was pregnant, lactating, or had recently terminated her pregnancy or lactation at the time of surgical excision. Examination of more cases would help confirm these findings.
Prevalence and Pathogenesis of Pancreatic Acinar Tissue at the Gastroesophageal Junction in Children and Young Adults
Authors: Popiolek Dorota , Kahn Ellen , Markowitz James , Daum Fredric 
Published: January 2021

Abstract
Background.—Pancreatic acinar tissue (PAT) at the gastroesophageal junction (GEJ) has been reported in 3% of adults with Barrett esophagus (BE) and in 24% of healthy subjects. The pathogenesis of this ectopic tissue is controversial. Both an acquired metaplastic process in the setting of BE and a congenital abnormality have been suggested in adults.
Objective.—To clarify the origin of PAT at the GEJ.
Methods.—We reviewed material obtained from the GEJ in 69 children and young adults. Each specimen was evaluated by 3 levels stained with hematoxylin-eosin for the presence of PAT, BE, esophagitis, and gastritis. Selected cases were also examined with immunohistochemical stains for lipase, trypsin, and amylase.
Results.—In 16% of the study population, PAT was present at the GEJ and was not associated with BE. The prevalence of esophagitis and/or gastritis did not vary significantly between patients with and without PAT.
Conclusions.—Our data suggest that PAT at the GEJ develops independently of inflammation and is, therefore, likely to be congenital.
Selective Demonstration of Mural Nerves in Ganglionic and Aganglionic Colon by Immunohistochemistry for Glucose Transporter-1
Authors: Kakita Yutaka , Oshiro Kiyohiko , O'Briain D. Sean , Puri Prem 
Published: January 2021

Abstract
Objective.—Hypertrophic nerves have long been considered a histopathologic feature of the aganglionic segment in Hirschsprung disease, but they remain incompletely explained. The purpose of this study was to define the nature and diagnostic importance of hypertrophic nerves in Hirschsprung disease and to clarify their relation to nearby smaller nerve fibers.
Methods.—We used an immunoperoxidase staining technique to compare the distribution of 2 nerve markers—erythrocyte-type glucose transporter (GLUT-1), a marker of perineurium, and nerve growth factor receptor, a marker of both nerve fibers and perineurium—in aganglionic tissue (12 resected specimens and 4 rectal biopsies) and control tissue (6 autopsy specimens and 17 rectal biopsies) of children.
Results.—In control ganglionic tissue, the myenteric and submucosal areas contained only occasional GLUT-1–positive nerves (usually less than 50 μm in diameter), but extramural extrinsic (serosal) nerves were invariably positive for GLUT-1. In aganglionic tissue, GLUT-1–positive nerves in the myenteric and submucosal areas were frequent and included both large (50–150 μm) and small (&lt;50 μm) diameter nerves. Nerve growth factor receptor–positive fibers were frequent in all layers of all tissue studied. In aganglionic bowel, a distinct perineurium could be identified in the largest nerves, but nerve growth factor receptor had poor discrimination for small perineurium-sheathed nerves.
Conclusion.—Most nerves, of both large and small diameter, in the myenteric and submucosal plexus of aganglionic bowel are GLUT-1 positive. Serosal extrinsic nerves stain identically, supporting the interpretation that the mural nerves are of extrinsic origin. Mural GLUT-1–positive nerves, when they are multiple and especially when they are greater than 50 μm in diameter (a figure which may be used as a threshold for hypertrophic nerves), are suggestive of Hirschsprung disease.
Evaluation of the Extent of Nonlinearity in Reportable Range Studies
Authors: Kroll Martin H. , Præstgaard Jens , Michaliszyn Ellen , Styer Patricia E. 
Published: January 2021

Abstract
Objectives.—To extend the polynomial method for evaluating linearity in 2 ways. First, we developed a screen to ascertain whether the data were precise enough to permit a reliable evaluation of linearity and therefore eliminate findings of linearity due to low statistical power. Second, we assessed whether the degree of nonlinearity detected by the polynomial method was clinically relevant using a statistically rigorous method.
Methods.—Because we assessed linearity relative to a clinically determined level of importance instead of the default value of zero, we used sampling theory based on the noncentral χ2 distribution. Using statistical power calculations, we incorporated a screen for imprecision that guarantees that the probability of correctly identifying nonlinear methods is at least 80%.
Results.—With the described methods, we achieved a sensitivity of at least 80% and a specificity of at least 95%. When the data were too imprecise to achieve a sensitivity of 80%, no determination of linearity was made. This procedure mimics the practice in manual inspection of flagging data that appear imprecise by visual inspection and halting the evaluation.
Conclusions.—Formal statistical tests for precision and amount of nonlinearity are advantageous because they allow us to quantify and limit classification errors. By formalizing these various aspects of linearity assessment, we maintain some of the complex features of manual methods while making the linearity assessment feasible to apply to a high volume of assessments and removing the between-analyst variability.
Neonatal Bilirubin Testing Practices
Authors: Dale Jane C. , Hamrick Harvey J. 
Published: January 2021

AbstractObjective.—To characterize laboratory practices for neonatal bilirubin testing and to identify opportunities for improvement.Design.—A voluntary self-assessment questionnaire was used to assess the laboratory practices of 312 laboratories subscribing to the College of American Pathologists (CAP) Excel Chemistry Proficiency Testing Program.Results.—A range of preanalytic and analytic practices were reported. The most notable problems identified were the use of overly long capillary puncture devices (17.8%), failure to protect the specimen from light prior to analysis (3.4%), failure to use a control containing &gt;171 μmol/L bilirubin (26.1%), use of single-level control (4.2%), and lack of established linearity limits (7.0%).Conclusion.—Opportunities exist to improve specimen collection, processing, and analysis for some physician-office and small-hospital laboratories.
Histologic Changes of the Gastric Mucosa Associated With Primary Gastric Lymphoma in Endoscopic Biopsy Specimens
Authors: Arista-Nasr Julián , Herrera-Goepfert Roberto , Lazos-Ochoa Minerva , Pichardo Raúl 
Published: January 2021

Abstract
Context.—Recently, we have observed intestinal metaplasia, atrophy, and dysplasia in the mucosa adjacent to primary gastric lymphoma (PGL) in gastrectomy specimens.
Objective.—To determine the frequency and type of epithelial disorders at the histopathologic level in the mucosa adjacent to PGL in endoscopic specimens.
Design.—We studied 54 endoscopic biopsies from patients harboring PGL. We searched for the following morphologic changes in the gastric mucosa: intestinal metaplasia; atrophy; dysplasia; epithelial erosion; and atypical regeneration of the glandular epithelium. Other nonepithelial findings such as lymphoid follicles, Helicobacter pylori, and lymphoma grade, were also recorded. For comparative purposes, 50 endoscopic biopsies with gastric adenocarcinoma and 50 biopsies with chronic gastritis associated with H pylori infection were also studied.
Results.—The 54 biopsies included 28 (52%) low-grade and 26 (48%) high-grade PGLs. We found intestinal metaplasia in 32 biopsies (59%), atrophy in 20 biopsies (37%), dysplasia in 2 biopsies (4%), erosion of the epithelium in 33 biopsies (61%), and atypical regenerative changes of the glandular epithelium in 10 biopsies (19%). Lymphoid follicles were found in 21 biopsies (39%), and H pylori was demonstrated in 31 biopsies (57%). When groups were compared, the frequency of epithelial changes in biopsies from patients with PGL and adenocarcinoma was similar. Intestinal metaplasia or atrophy were present in only 10% of biopsies from patients with gastritis, and dysplastic glands were not identified.
Conclusions.—Biopsies from patients with PGL showed chronic damage of the gastric mucosa at diagnosis, including precancerous conditions. Intestinal metaplasia and atrophy were among the most frequent disorders, but dysplasia was also occasionally present. Endoscopists and pathologists must be acquainted with such changes and look for them in the initial biopsy, as well in subsequent samples. This practice is particularly important when reviewing biopsies from patients with low-grade mucosa-associated lymphoid tissue (MALT)-lymphomas who are eligible for eradication treatment for H pylori.
Molecular Characterization of Colorectal Neoplasia in Translational Research
Authors: Grizzle William E. , Manne Upender , Jhala Nirag C. , Weiss Heidi L. 
Published: January 2021

Abstract
Objective.—To present recent advances in the use of molecular markers in diagnosis, in prognosis, in early detection, in novel therapies, and in understanding the molecular pathogenesis of colorectal neoplasia.
Data and Literature Sources.—A review of studies of molecular markers in colorectal neoplasia, published in English and available on MEDLINE and BioMednet, indicates that molecular markers are being increasingly studied to predict clinical outcomes in patients with colorectal adenocarcinoma (CRC). We have used this resource, together with our published and unpublished observations at the University of Alabama at Birmingham, to provide an overview of translational research related to molecular markers in colorectal neoplasia.
Conclusions.—Currently, the prognosis of patients with CRC is predicted primarily on the basis of clinicopathologic staging; however, pathologists and oncology surgeons have recently begun to investigate the use of molecular markers to diagnose and/or understand the progression of CRC. In recent years, much has been learned about the molecular events responsible for the development of CRC. Also, several studies have reported the implication of some molecular markers in metastasis and tumor aggression and their usefulness in predicting clinical outcome. In this article, we discuss the use of specific molecular markers, including tumor-associated glycoprotein 72 (TAG-72), carcinoembryonic antigen (CEA), and oncofetal tumor antigens (Lewis X and Y) in diagnosis and as targets for novel therapies, as well as the phenotypic expression of bcl-2, mucin antigens (MUC1 and MUC2), and nuclear accumulation of p53 in predicting the clinical outcome of patients with CRC. We also review the ways in which molecular markers may aid the early detection of colorectal neoplasia and promote our understanding of the earliest changes in colorectal neoplasia.
Quality Improvement on an Academic Autopsy Service
Authors: Sinard John H. , Blood Deborah J. 
Published: January 2021

Abstract
Context.—Autopsy rates continue to decline in the United States.
Objective.—Although many of the causes of this decline are external to pathology departments, we hypothesized that intradepartmental efforts to improve the quality of the service we provide to our clinical colleagues could increase our autopsy rate.
Method.—We developed a multifaceted quality improvement program for our autopsy service aimed at increasing the visibility of the service, improving the service's reporting, and increasing the amount and quality of data available from the service.
Setting.—A large academic medical center that performs approximately 250 autopsies each year.
Results.—After implementation of our quality improvement program, the decline in our autopsy rate has not only stopped, but rates have even begun to increase. Additionally, physician satisfaction surveys conducted before and after implementation of our quality improvement initiatives showed an across-the-board improvement in clinician perception of the service.
Conclusion.—Pathologists can and should be proactive in addressing the declining autopsy rate, rather than viewing it as someone else's problem or hoping that someone else will protect this important quality assurance tool for medical care.
Vulvar Keratinizing Squamous Cell Carcinoma in a 26-Year-Old Woman
Authors: Echeverri Carolina , Stoler Mark H. , Valente Philip T. 
Published: January 2021

Abstract
A 26-year-old Hispanic woman complaining of “itching” and “herpetic lesions” on the vulva for 9 months was seen at a university hospital. On physical examination, multiple vulvar masses were noted. Biopsies taken from these lesions showed invasive keratinizing squamous cell carcinoma. The vulvectomy specimen revealed 4 tumor masses, the largest located on the mons pubis. Although the incidence of vulvar intraepithelial neoplasia has increased in recent years, only very few cases of invasive carcinoma have been reported in young women. The tumors that occur at a younger age characteristically have basaloid or warty histology, in contrast to those occurring in older women, which usually are well-differentiated keratinizing carcinomas. We believe this is an unusual case of vulvar squamous cell carcinoma. In addition to our patient's young age, her tumor had a histologic profile usually found in lesions of an elderly woman. The tumor was negative for human papillomavirus by polymerase chain reaction analysis and was positive for p53 by immunohistochemistry.
Approach to the Diagnosis of Thin Basement Membrane Nephropathy in Females With the Use of Antibodies to Type IV Collagen
Authors: Lajoie Ginette 
Published: January 2021

AbstractContext.—Thin basement membrane nephropathy is recognized by a diffusely thin glomerular basement membrane (GBM) ultrastructurally. In contrast to Alport syndrome (AS), there is no GBM thickening, lamellation, or granular inclusions. Morphologically, there is overlap between thin basement membrane nephropathy and AS in female patients in whom there might be only thin GBM and no pathognomonic findings of AS.Objective.—To determine if the use of antibodies to collagen IV is helpful in making the distinction between thin basement membrane nephropathy and AS in female patients with primarily thin GBMs.Design.—We examined renal biopsies from 9 adult female patients with thin GBMs for the presence of α1, α3, α4, and α5 chains of type IV collagen by immunofluorescence.Results.—In 2 patients with segmental GBM staining, no suggestion for AS was found on physical examination or in their family history. In the remaining 7 patients with normal GBM staining, 4 had family members with end-stage renal disease of unknown etiology, raising the suspicion of X-linked or autosomal-recessive AS. Three patients were presumed to have thin basement membrane nephropathy.Conclusion.—Segmental GBM staining for α3, α4, and α5 chains of type IV collagen raises the suspicion of AS in the presence of adequate controls and other supporting evidence. Normal GBM staining for α3, α4, and α5 chains of type IV collagen, however, does not exclude AS.
Neck Needle Foreign Bodies
Authors: Hutchins Kenneth D. , Williams A. Wayne , Natarajan Geetha A. 
Published: January 2021

Abstract
The risk to pathologists of contracting diseases due to cuts or needles punctures while performing autopsies is well known. An additional risk is an accidental needle puncture due to retained needle fragments within the subcutaneous tissues or internal organs of intravenous drug addicts. We report 4 cases of drug addicted patients infected with human immunodeficiency virus who came to autopsy and had retained needle fragments within their cervical-clavicular soft tissues. The presence of retained needle fragments increases the risk to the autopsy pathologist of accidental needle puncture and exposure to disease. Because of this phenomenon, the pathologist should take precautions in addition to those currently prescribed when performing autopsies on possible drug abusers.
Characterization of Microorganism Identification in the United States in 1996
Authors: Steindel Steven J. , Simon Marianne K. 
Published: January 2021

Abstract
Context.—The National Inventory of Clinical Laboratory Testing Services (NICLTS) was designed to give an unbiased estimate of all patient testing performed by laboratories registered under the Clinical Laboratory Improvement Amendments in 1996.
Objective.—Survey data were used to develop a profile of laboratory testing primarily intended to identify microorganisms or antibodies to these microorganisms.
Design.—Estimates of the extent of microorganism identification were derived from the NICLTS database by identifying associated tests and methods. The volumes for tests performed at locations that primarily prepared blood components for distribution were excluded. Organisms of public health importance were identified from the National Notifiable Disease list maintained by the Centers for Disease Control and Prevention.
Participants.—Laboratories that were enrolled in the 1996 Online Certification Survey and Reporting System, maintained by the US Health Care Finance Administration, and that performed laboratory testing in 1996.
Outcome Measure.—Estimated volumes and associated confidence limits by test, method, specimen type, public health importance, and testing location.
Results.—Excluding testing of the blood supply, 315 million tests (95% confidence limits, 280–354 million tests) were performed in the United States for microorganism identification. Those tests for which public health consensus requires national reporting represented 38% of this total. Although hospitals performed 46% of all microorganism identification, they only performed 33% of the testing for microorganisms of public health importance. Independent and specialty laboratories performed 38% of all testing but 65% of the testing for microorganisms of public health importance. Direct methods (methods not involving culture) were used in 77% of the tests for microorganisms of public health importance and in 42% of all identification tests.
Conclusions.—The distribution of microorganism identification testing found using NICLTS data is consistent with plans to modernize the public health surveillance system in the United States.
Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen Immunostaining in Benign Multicystic Mesothelioma of the Peritoneum
Authors: Holtzman Robert N. N. , Heymann A. Douglas , Bordone Fausto , Marinoni Gianfilippo , Barillari Paolo , Wahl Samuel J. 
Published: January 2021

Abstract
A 58-year-old Italian man was incidentally discovered to have an elevated carbohydrate antigen 19-9 (CA-19-9) level of 132 U/mL on routine blood testing. Multisystem imaging studies revealed multiple benign-appearing cysts of the liver and single cysts in the pancreas and kidney parenchyma. Throughout 14 months, fluctuations were observed in the elevated serum CA-19-9 levels from 99 to 450 U/mL. Serum carcinoembryonic antigen (CEA) and other tumor markers were normal. Laparoscopy disclosed multiple cystic lesions on the surface of the liver, on the serosal surface of the ileum, and in the mesentery. Electron microscopy characterized the cells as mesothelial. The pathologic diagnosis was benign multicystic mesothelioma of the peritoneum (BMMP). Aspirated fluid from the liver cyst revealed CA-19-9 levels at 28 500 U/mL, strongly linking the elevated serum CA-19-9 levels with mesothelial cyst secretion. Immunostaining was positive for CA-19-9, CEA, and cancer antigen 125 (CA-125). We believe this is the first documented instance of CA-19-9 and CEA secretion in BMMP.
Expression of Protein Gene Product 9.5 in Epithelioid and Conventional Malignant Peripheral Nerve Sheath Tumors
Authors: Hoang Mai P. , Sinkre Prasanna , Albores-Saavedra Jorge 
Published: January 2021

Abstract
Context.—Due to the frequent lack of S100 protein expression in malignant peripheral nerve sheath tumors (MPNSTs), especially the epithelioid variant, these tumors are difficult to diagnose without the aid of electron microscopy or a clinical history of neurofibromatosis.
Methods.—Protein gene product 9.5 (PGP9.5), a broad neural marker, is expressed in nerve fibers and neurons of both the peripheral and central nervous systems. We compared its expression to that of S100 protein in 16 cases of MPNST. As controls, 6 monophasic synovial sarcomas, 9 leiomyosarcomas, and 5 dermatofibrosarcoma protuberans were included.
Results.—Expression of PGP9.5 was seen in 15 MPNSTs, with 3 to 4+ positivity in the majority of the cases. Ten cases, 2 epithelioid and 8 conventional MPNSTs, were reactive with PGP9.5, but were negative for S100 protein. Five cases were immunoreactive for both S100 protein and PGP9.5. One case was negative for PGP9.5 but demonstrated focal S100 protein positivity. Expression of PGP9.5 was seen in 4 of 6 synovial sarcomas, 3 of 9 leiomyosarcomas, and none of 5 dermatofibrosarcoma protuberans.
Conclusion.—Although PGP9.5 is not a specific marker for MPNST, it is a more sensitive marker than S100 protein (94% vs 38%). When there is a lack of S100 protein expression and a broad panel of immunostains, such as cytokeratin, epithelial membrane antigen, and smooth muscle actin, yields only focal or equivocal staining, PGP9.5 is a useful diagnostic adjunct in confirming the neural origin of a spindle cell sarcoma.