bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Carcinoma Presenting During or Shortly After Pregnancy and Lactation
Authors: Shousha Sami
Published: January 2021

Context.—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

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

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 (<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

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

Objective.—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 >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

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

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

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

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

Context.—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

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

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

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

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.
c-Kit (CD117) Reactivity in Extramedullary Myeloid Tumor/Granulocytic Sarcoma
Authors: Chen Jian , Yanuck Rudolph R. , Abbondanzo Susan L. , Chu Wei-Sing , Aguilera Nadine S. I.
Published: January 2021

Context.—c-kit, a proto-oncogene, encodes the transmembrane tyrosine kinase receptor CD117 and is detected by flow cytometry in the majority of cases of acute myeloid leukemia. The prognostic significance of the presence of c-Kit in acute myeloid leukemia is debated. Recently, c-kit inhibitors have been studied as possible therapies against hematopoietic malignancies; therefore, c-Kit detection may have important implications for treatment.

Objectives.—In this study, we investigated the expression of c-Kit in granulocytic sarcoma (GS) using paraffin-embedded tissue.

Design.—Routinely formalin-fixed, paraffin-embedded tissues from 30 cases of GS were studied using immunohistochemistry. c-Kit (C-19) (a polyclonal antibody against carboxy terminal domain of c-Kit p145 or CD117) reactivity was compared with myeloperoxidase and lysozyme. The immunohistochemical panel also included CD34, CD68, CD43, Bcl-2, CD45RB, CD20, CD3, CD10, terminal deoxynucleotidyl transferase (TdT), and CD79a.

Results.—The morphologic patterns included well-differentiated (5 cases), poorly differentiated (19 cases), and blastic forms (6 cases). Clinical data were obtained from 28 of 30 patients. Granulocytic sarcoma presented in lymph nodes in 10 cases, whereas in 20 cases it presented in extranodal sites.

c-Kit reactivity was found in 87% (26/30) of the GS cases. There was no significant difference in c-Kit positivity between the nodal (90%, 9/10) and extranodal (85%, 17/20) neoplasms. c-Kit expression was not associated with the degree of the myeloid maturation. Two of 13 lymphoblastic lymphoma control cases and 1 of 28 of the large B-cell lymphomas were weakly immunoreactive with c-Kit.

Conclusions.—c-Kit reactivity can be demonstrated in a high percentage of GS cases; its presence may be useful not only in diagnosis, but also in the treatment of GS with new modalities.
Different Heparin Lots
Authors: Smythe Maureen A. , Koerber John M. , Westley Susan J. , Balasubramaniam Mamtha , Mattson Joan C.
Published: January 2021

Objective.—To assess the impact of heparin lot on the correlation between heparin concentration and activated partial thromboplastin time (aPTT), the aPTT therapeutic range, and the heparin level.

Design.—Retrospective analysis of data from 2 previous studies.

Setting.—Teaching institution with 929 beds.

Patients.—Ninety-five patients receiving heparin with 5 different lots (study 1) and 35 patients receiving heparin with 3 different lots (study 2).

Main Outcome Measures.—Laboratory-based aPTT and heparin level by anti-factor Xa analysis. Standard heparin curves were created for each lot. Each patient's heparin level was determined off each standard curve.

Results.—Correlations between heparin concentration and aPTT ranged from 0.87 to 0.89 (study 1) and 0.86 to 0.87 (study 2). Slopes of regression lines were not significantly different. Therapeutic ranges generated from lot-specific heparin levels were similar. Average bias in heparin levels from varying lots ranged from 0.005 to 0.036 units/mL.

Conclusions.—The recommendation to reevaluate the aPTT therapeutic range with each new lot of heparin requires further evaluation.
Viral Load Test Reports
Authors: Francis Diane P. , Peddecord K. Michael , Hofherr Louise K. , Astles J. Rex , Schalla William O.
Published: January 2021

Context.— Human immunodeficiency virus (HIV) RNA testing (viral load testing) is increasingly important in the care of patients infected with HIV-1 to determine when to initiate, monitor, and change antiretroviral therapy. Patient viral load testing information is communicated to the clinician through the laboratory test report.

Objectives.—To examine the format and information used in reporting viral load testing results and determine the clarity of the information provided in these reports.

Design.—Patient test reports with all personal identifiers removed were requested of viral load testing laboratories participating in a telephone survey of laboratory practices. Hospital, independent, health department, and “other type” laboratories identified as university-associated laboratories participated in the telephone survey.

Results.—Thirty-seven unique test reports were collected. All laboratories reported results in copies/mL, while 14% also reported results as “log10 copies/mL.” The test kit was identified by only 24% of the laboratories. Reportable ranges were specified by 70% of the laboratories, but there was considerable variation in terminology. One laboratory reported a viral load copy number below the manufacturer's test kit lower limit of sensitivity. The layout and format differed among reports. Some results were expressed in log10, others contained nonsignificant integers, while others contained exponential numbers. Supplemental information in some reports included previous patient test results and significance of changes from baseline. The format of some reports made it difficult to read the report information and interpret the testing results.

Conclusion.—This study emphasizes the importance of standardizing the reporting of HIV-1 viral load test results to minimize result misinterpretation and incorrect treatment.
Crystalline Inclusions in Granulocytic Sarcoma
Authors: Strauchen James A. , Gordon Ronald E.
Published: January 2021

Two cases of granulocytic sarcoma were found to contain numerous crystalline inclusions identified on hematoxylin-eosin–stained sections as clusters of pointed needlelike crystals present in foci of necrosis or within macrophages. The crystals were negative for chloroacetate esterase and myeloperoxidase. Electron microscopy demonstrated homogeneously dense, bipyramidal structures, indistinguishable from Charcot-Leyden crystals. Granulocytic sarcomas may contain crystalline inclusions similar to Charcot-Leyden crystals; these structures should be distinguished from crystalline immunoglobulin inclusions occurring in cases of plasma cell myeloma and lymphoplasmacytic lymphoma, which may have a similar appearance.
A Kaposi-like Variant of Splenic Angiosarcoma Lacking Association With Human Herpesvirus 8
Authors: Mikami Tetuo , Saegusa Makoto , Akino Fumiyuki , Machida Daisuke , Iwabuchi Keiichi , Hagiwara Shotaro , Okayasu Isao
Published: January 2021

We report the case of a Kaposi-like variant of splenic angiosarcoma in a 28-year-old woman. The tumor featured a Kaposi sarcoma–like spindle cell proliferation with slit formation and markedly dilated spongelike vascular channels filled with erythrocytes. Thirteen months following the initial splenectomy, metastatic lesions were found in the patient's liver and bone marrow. The proliferating cells were positive for factor VIII–associated antigen and CD34. The human herpesvirus 8 genome, which is regarded as a diagnostic feature of Kaposi sarcoma, was not detected by polymerase chain reaction analysis. Although the histologic findings were similar, this Kaposi-like variant of splenic angiosarcoma must be considered distinct from Kaposi sarcoma.
Dutcher Bodies in Chronic Synovitis
Authors: Gray Yulia , Schwartz Stanley
Published: January 2021

Dutcher bodies are periodic acid-Schiff–positive intranuclear pseudoinclusions found in plasma cells in mucosa-associated lymphoid tissue lymphoma, Waldenstrom macroglobulinemia, and myeloma. We describe the case of a 68-year-old woman with chronic synovitis containing multiple Dutcher bodies. The patient's workup for lymphoma was negative. Hematoxylin-eosin– and periodic acid-Schiff–stained sections of 7 cases of marked chronic synovitis selected from the files spanning a 10-year period at Memorial Hospital of Rhode Island (Pawtucket, RI) were examined, and none showed Dutcher bodies. This case illustrates that Dutcher bodies may rarely occur in benign reactive conditions, such as chronic synovitis.
Surgical Pathology Extradepartmental Consultation Practices
Authors: Azam Muhammad , Nakhleh Raouf E.
Published: January 2021

Objectives.—To document the practice parameters and case characteristics associated with personal (expert) consultations. We also examine the value, level of participant (customer) satisfaction, turnaround time, and rate of personal consultations.

Design.—We asked participants in the College of American Pathologists' Q-Probes program to document cases sent for consultation during 4 months or up to 20 cases. They documented patient and specimen characteristics, the turnaround times, and the participants' levels of satisfaction with the consultation experience.

Participants.—One hundred eighty laboratories/surgical pathology practices. One hundred seventy-two (95.6%) were from the United States; the remainder were located in Canada and Australia.

Main Outcome Measures.—Rate and turnaround time of consultations and participant level of satisfaction.

Results.—A total of 2746 consultation cases were examined for an aggregate consultation rate of 0.5% (median, 0.7%). Institutions with a higher occupied bed size and a greater number of surgical pathology cases both had lower consultation rates (P ≤ .05). The median turnaround time (defined as the interval from the date on which the case was sent to the date on which the diagnosis was received) was 6 days. Twenty-nine percent and 68% of cases had a turnaround time within 3 and 7 days, respectively. Fifty-two percent of cases were sent to nationally known experts, and 32% were sent to local experts. Skin (18.0%), hematolymphoid (11.6%), and breast (9.6%) specimens were most commonly sent for consultation. In 70.5% of cases, the consultant confirmed the referring pathologist's original diagnosis, but in 15.9% of cases, the consultant also added significant information. Satisfaction rates were higher with faster turnaround times and verbal reporting. Satisfaction rates were lower for cases in which the patient or the clinician requested the consultation and in which the consultant's diagnosis was ambiguous.

Conclusions.—This study establishes a multi-institutional consultation rate of 0.5%, defines the nature of surgical pathology consultations, and demonstrates that satisfaction with consultations is associated with a faster turnaround time and receipt of additional, clinically meaningful information.
Intratubular Embryonal Carcinoma
Authors: Rakheja Dinesh , Hoang Mai P. , Sharma Suash , Albores-Saavedra Jorge
Published: January 2021

Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and α-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.
Quality Indicators of Fresh Frozen Plasma and Platelet Utilization
Authors: Novis David A. , Renner Stephen , Friedberg Richard C. , Walsh Molly K. , Saladino Andrew J.
Published: January 2021

Objective.—To determine the normative rates of expiration and wastage for units of fresh frozen plasma (FFP) and platelets (PLTs) in hospital communities throughout the United States, and to examine hospital blood bank practices associated with more desirable (lower) rates.

Design.—In 3 separate studies, participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data retrospectively on the numbers of units of FFP and PLTs that expired (outdated) prior to being used and that were wasted due to mishandling. Participants also completed questionnaires describing their hospitals' and blood banks' laboratory and transfusion practices.

Setting and Participants.—One thousand six hundred thirty-nine public and private institutions, more than 80% of which were known to be located in the United States.

Main Outcome Measures.—Quality indicators of FFP and PLT utilization: the rates of expiration and wastage of units of FFP and PLTs.

Results.—Participants submitted data on 8 981 796 units of FFP and PLTs. In all 3 studies, aggregate combined FFP and PLT expiration rates ranged from 5.8% to 6.4% and aggregate combined FFP and PLT wastage rates ranged from 2.0% to 2.5%. Among the top-performing 10% of participants (90th percentile and above), FFP and PLT expiration rates were 0.6% or lower and FFP and PLT wastage rates were 0.5% or lower. Among the bottom-performing 10% of participants (10th percentile and below), expiration rates were 13.8% or higher and wastage rates were 6.8% or higher. We were unable to associate selected hospital characteristics or blood bank practices with lower rates of FFP and PLT utilization.

Conclusions.—The rates of FFP and PLT expiration and wastage vary greatly among hospitals in the United States. Hospital blood bank personnel are capable of achieving FFP and PLT expiration and wastage rates below 1%.
Nasal Natural Killer Cell/T-Cell Lymphoma Showing Cellular Morphology Mimicking Normal Lymphocytes
Authors: Chinen Katsuya , Kaneko Yasuhiko , Izumo Toshiyuki , Ohkura Yasuo , Matsubara Osamu , Tsuchiya Eiju
Published: January 2021

We report the autopsy case of a 34-year-old Japanese man with a nasal natural killer (NK)-cell/T-cell lymphoma. The patient developed the disease at 32 years of age, and a biopsy of the nasopharynx revealed pleomorphic lymphoma cell proliferation. Radiotherapy was performed, but the patient eventually died of respiratory failure. After radiotherapy, no histologic evidence of malignancy was obtained with biopsy materials featuring lymphocytic infiltration. Autopsy studies, including in situ hybridization for Epstein-Barr virus–encoded RNA, revealed generalized infiltration of normal lymphocyte-like, UCHL-1–positive, and Epstein-Barr virus–encoded RNA–positive lymphoma cells. Monoclonal proliferation of the Epstein-Barr virus–carrying cells was verified by means of Southern blot analysis. Retrospectively, we concluded that the normal lymphocyte-like presentation of the lymphoma cells, probably influenced by radiotherapy, prevented pathologists from recognizing the lymphoma. The utility of in situ hybridization for Epstein-Barr virus–encoded RNA in identification of tumor cells is emphasized with respect to the present case.
Natural Killer–like T-Cell Lymphoma of the Parotid in a Patient Infected With Human Immunodeficiency Virus
Authors: Cornfield Dennis B. , Papiez Joseph S. , Lynch James T. , Rimsza Lisa M.
Published: January 2021

A 42-year-old man with acquired immunodeficiency syndrome developed a mass of the right parotid gland and multiple hepatic masses. Hematoxylin-eosin–stained sections of the parotid lesion showed a diffuse infiltrate of large mononuclear cells with vesicular nuclei and prominent nucleoli, consistent with a non-Hodgkin lymphoma. Immunohistochemical stains demonstrated expression of the T-cell markers CD3 and UCHL-1, as well as latent membrane protein 1 and T-cell intracellular antigen 1. Flow cytometry showed surface expression of CD2, CD3, CD7 (dim), CD8, and CD56. CD5 was not expressed. Molecular evaluation by polymerase chain reaction demonstrated monoclonal rearrangement of the T-cell receptor γ gene. Epstein-Barr virus early RNA and human immunodeficiency virus RNA were demonstrated by in situ hybridization. To our knowledge, this is the first reported case of T-cell lymphoma of the parotid in a patient infected with human immunodeficiency virus. After 2 separate chemotherapy regimens, the patient achieved clinical remission for 1½ years; he then developed progressive pulmonary lesions and died.
Lymphoepithelioma-like Carcinoma of the Uterine Cervix
Authors: Martorell Miguel A. , Julian Jose M. , Calabuig Consuelo , García-García JoséA. , Pérez-Vallés Ana
Published: January 2021

Context.—It has been proposed that Epstein-Barr virus (EBV) plays a role in the etiology of lymphoepithelioma-like carcinoma (LELC) in diverse anatomic locations. In contrast to Asian women, Western women have a low prevalence of LELC of the uterine cervix, and EBV genomes have not been identified.

Objective.—To assess the presence of EBV in LELC of the uterine cervix in 4 white Western women.

Design.—We collected 4 cases of LELC of the uterine cervix between 1990 and 2000. We performed histologic and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. We amplified tumor DNA with polymerase chain reaction to detect EBV, human papillomavirus, and simian virus 40 DNAs.

Results.—Immunohistochemically, tumor cells were positive for cytokeratins and showed strong expression of p53 and MIB-1. Staining for the oncoprotein c-Erb-B2 was focally positive, and staining for Bcl-2 and progesterone receptors was negative. Only one case showed focal nuclear staining for estrogen receptors. All cases had a dense infiltrate of mature lymphocytes expressing T-cell antigens CD45RO, CD3, and CD8. Polymerase chain reaction analysis did not detect EBV, human papillomavirus, or simian virus 40 DNA sequences in any of the 4 cases. One case had positive serologic results for anti-EBV antibodies, indicating a mild or chronic infection.

Conclusions.—LELC of the uterine cervix shows the immunohistochemical profile of an aggressive tumor in spite of its good prognosis, in which CD8 cytotoxic suppressor lymphocytes could play an important role. Based on our results, the role of EBV, human papillomavirus, or simian virus 40 in the pathogenesis of LELC of the uterine cervix in Western women remains unclear.
Metastatic Carcinoid to the Conducting System—Is It a Rare or Merely Unrecognized Manifestation of Carcinoid Cardiopathy?
Authors: Shehata Bahig M. , Thomas Jean E. , Doudenko-Rufforny Irina
Published: January 2021

We report a unique case of carcinoid cardiopathy. The patient, a 59-year-old white woman with a known carcinoid tumor of the terminal ileum, presented with complete heart block and subsequently died. Because of her clinical presentation, we examined the conducting system at autopsy. The atrioventricular node was heavily infiltrated by metastatic carcinoid. The tumor was also seen in the surrounding atrial myocardium. No other metastatic lesions were seen in the heart. Carcinoid cardiopathy in the form of right-sided endocardial and valvular thickening has been well documented in the literature, and we found these features in our case as well. To our knowledge, carcinoid has never been documented in the cardiac conducting system until now. We found 2 cases of possible involvement of the conducting system reported in the literature. Unfortunately, the conducting system was not examined postmortem in either of these cases. If conducting system involvement is not unique to the present case, patients with metastatic carcinoid and cardiac problems may require different management. We hope that this case will stimulate further postmortem study of the conducting system in patients with metastatic carcinoid tumor.
Malignant Ameloblastoma, Spindle Cell Variant
Authors: Zarbo Richard J. , Marunick Mark T. , Johns Robert
Published: January 2021

In this report, we document the histologic and clinical features of a previously undefined spindle cell variant of ameloblastoma that eventually behaved in a malignant fashion during a protracted course. The predominant histologic pattern was a well-differentiated, cellular, spindled epithelial proliferation arising in the maxilla of a 14-year-old African American girl. Over 19 years, the patient experienced numerous local recurrences, metastases to distant bones after 15 years, and finally bulky local recurrence with intracranial extension resulting in death. This ameloblastic malignancy histologically simulates a low-grade true sarcoma or an ameloblastic sarcoma, but differs in that the extensive spindle cell proliferation is epithelial, characterized by strong cytokeratin immunoreactivity and negative vimentin staining.
Angiosarcoma Masquerading as Embryonal Carcinoma in the Metastasis From a Mature Testicular Teratoma
Authors: Sahoo Sunati , Ryan Christopher W. , Recant Wendy M. , Yang Ximing J.
Published: January 2021

Sarcoma can arise within a germ cell tumor (GCT) from a malignant transformation of teratomatous elements or as late sequelae to radiation therapy. Angiosarcoma as a malignant component in testicular GCTs has rarely been reported and is often misdiagnosed as embryonal carcinoma. We report the case of a 23-year-old man with mature teratoma of the testis and retroperitoneal metastasis exhibiting components of mature teratoma intermingled with high-grade angiosarcoma. It is important to recognize the presence of a high-grade sarcomatous component within a GCT because of its aggressive clinical behavior and different response to therapy.
Characterization of 4 Mantle Cell Lymphoma Cell Lines
Authors: Amin Hesham M. , McDonnell Timothy J. , Medeiros L. Jeffrey , Rassidakis Georgios Z. , Leventaki Vasiliki , O'Connor Sean L. , Keating Michael J. , Lai Raymond
Published: January 2021

Context.—Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by t(11;14)(q13;q32) and cyclin D1 overexpression. The pathogenesis of MCL has not been comprehensively studied, which can be attributed in part to the paucity of well-characterized MCL cell lines.

Objectives.—We collected 4 previously developed MCL cell lines and performed extensive characterization, including the susceptibly of these cell lines to transduction by adenovirus vectors. Our aim was to facilitate the establishment of an in vitro model that can be reliably used to study the pathogenesis of MCL.

Methods.—Standard techniques were used to compare the morphologic, immunophenotypic, and cytogenetic features of the 4 cell lines. In addition, Western blotting was used to investigate the presence of several cell cycle- and apoptosis-related proteins. TP53 DNA sequencing was also performed on the cell lines. The adenoviral transduction efficiency was assessed using an adenoviral vector carrying the gene encoding for the green fluorescence protein (Ad-GFP).

Results.—All cell lines demonstrated evidence of t(11;14)(q13;q32) and overexpression of cyclin D1. Cyclin D2 was not detectable in all cell lines, whereas cyclin D3 was weakly expressed in JeKo-1 and SP-53. Other abnormalities of the cell cycle G1 phase regulatory pathway were detected, including loss of expression of p53 (JeKo-1) and p16INK4a (SP-53 and Granta 519), as well as TP53 mutation (Mino). All cell lines express high levels of cyclin E, c-Myc, Bcl-2, Bax, Bcl-xL, and Mcl-1. Retinoblastoma protein is hyperphosphorylated in all cell lines. With the exception of Mino, MCL cell lines are highly transducible with adenoviral vectors.

Conclusion.—These cell lines are representative of MCL and can be used as an in vitro model to further explore the pathogenesis of this disease. The susceptibility of these cell lines to gene transfer provides opportunities to evaluate the importance of various oncogenes and tumor suppressor genes that may have an impact on developing effective therapeutic regimens for MCL.
Myxoma of the Small Bowel in a 47-Year-Old Woman With a Left Atrial Myxoma
Authors: Wang Yuanhong , Sharkey Francis E.
Published: January 2021

Although atrial myxoma is the most common primary tumor of the heart, the synchronous occurrence of myxomas of the intestine and the heart has not been reported in the English literature. We report a case of a 47-year-old woman who presented with small bowel obstruction by a pedunculated mass that was found to be a myxoma after resection. A left atrial mass was found incidentally by a computed tomographic scan, and a diagnosis of atrial myxoma was confirmed after a second surgery. The cardiac myxoma showed classic histologic features, with tumor cells layered around vascular channels in an abundant myxoid matrix, while the small bowel lesion was less cellular. Immunohistochemical stains yielded identical results in both. No vascular involvement was noted at either site. This case supports the recommendation that a search for a cardiac lesion should be performed when a myxoma is identified at an unusual location.