bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Apoptotic Leukocytes in Peripheral Blood Smears
Authors: Shidham Vinod B. , Swami Vanlila K.
Published: January 2021

Objectives.—Apoptosis is a phenomenon of physiological cell death in which each step is regulated, similar to the process of mitosis. We observed apoptosis in leukocytes during the review of peripheral blood smears. This study was undertaken to evaluate the morphologic features of apoptotic leukocytes in peripheral blood smears and to ascertain their clinical significance.

Design.—Sixty cases (23 males and 37 females, aged newborn to 92 years) exhibiting apoptotic leukocytes in peripheral blood smears were studied. Medical records for each case were reviewed, and patients were categorized according to their clinical diagnoses.

Results.—Neutrophils were the most common apoptotic leukocytes identified (85%), followed by lymphocytes (18%) and eosinophils (2%). The diagnosis most frequently associated with the presence of apoptotic leukocytes was infection (55%). Apoptosis in lymphocytes was comparatively less common, but when present, the most common associations were diabetes mellitus, glucocorticoid administration, and neoplastic diseases.

Conclusions.—Our findings suggest that the presence of apoptotic leukocytes in peripheral blood smears may help in the differential diagnosis and may be related to the severity of disease. We recommend further evaluation using additional special techniques for detecting apoptotic leukocytes.
Morphometric and Electron Microscopic Analyses of the Effect of Gonadotropin-Releasing Hormone Agonist Treatment on Arteriole Size in Uterine Leiomyomas
Authors: Kalir Tamara , Wu Haishan , Gordon Ronald E. , Gil Joan
Published: January 2021

Background.—Few studies have been performed on the vascular changes in leiomyomas from patients treated with gonadotropin-releasing hormone agonists (GnRHAs).

Objective.—To measure luminal diameter and wall thickness of arterioles in uterine leiomyomas using a quantitative stereologic method of analysis.

Design.—Thirty leiomyomas from 3 study groups were used: (1) patients treated with GnRHAs (10 patient samples), (2) age-matched controls (10 patient samples), and (3) postmenopausal women (10 patient samples). Measurements of arteriolar luminal diameter and wall thickness were made using a video-based, computerized system attached to the microscope, for which a morphometric ad hoc program was written. Electron micrographs were made of random arterioles from the first 2 groups (GnRHA-treated patients and age-matched controls).

Setting.—Department of Pathology, Mount Sinai School of Medicine, New York, NY.

Patients.—A total of 30 patient samples were studied, with 3 groups comprising 10 samples each, including patients treated with GnRHAs, age-matched control patients, and postmenopausal women.

Results.—Arterioles in myomas from patients treated with GnRHAs had slightly larger luminal diameters and significantly thicker walls than age-matched controls and resembled arterioles from postmenopausal women. The thickening was due to smooth muscle cell hyperplasia in the muscularis media.

Conclusions.—Treatment with GnRHAs causes a thickening of the walls of intramyomatous arterioles, which resemble those of postmenopausal women. This thickening may play a role in the decreased flow of blood reported in GnRHA treatment.
Prostate Elastosis
Authors: Billis Athanase , Magna Luis A.
Published: January 2021

Background.—Elastosis of the prostate may be seen on needle biopsy and radical prostatectomy specimens, but its significance is unknown. Prostatic atrophy (or postatrophic hyperplasia) is one of the most frequent mimics of prostatic adenocarcinoma.

Objective.—To observe the frequent occurrence of elastosis of the prostate stroma in areas of postatrophic hyperplasia.

Design.—A step-section method was used to cut the posterior lobe (or peripheral zone) in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsy specimens of men older than 40 years. Elastosis was detected because of a basophilic tinge of the stroma on hematoxylin-eosin stain and confirmed using elastic fiber stains. Presence of elastosis correlated with the following variables: age, prostatic atrophy (simple, hyperplastic, or sclerotic), local arteriosclerosis, histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. For statistics, a stepwise linear regression method adjusted for age was used.

Results and Conclusions.—Elastosis was found in 65 of the prostates examined and was significantly more frequent with increasing age (P < .001), prostatic atrophy (P < .001), and local arteriosclerosis (P < .02). There was no significant relation to histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. The correlation with local arteriosclerosis favors a possible role of ischemia to its etiopathogenesis. The absence of correlation to neoplastic and preneoplastic lesions and the striking spatial relationship of elastosis to prostatic atrophy (or postatrophic hyperplasia) add a new microscopic feature for the diagnosis of this latter lesion, helping in the differential diagnosis with prostate adenocarcinoma.
An Algorithm to Aid in the Investigation of Thalassemia Trait in Multicultural Populations
Authors: Kiss Thomas L. , Ali Mahmoud A. M. , Levine Mitchell , Lafferty John D.
Published: January 2021

Context.—The differentiation between iron deficiency and a thalassemia syndrome is an important consideration in the investigation of microcytic anemia.

Objective.—An established statistical method was used to demonstrate the importance of considering ethnic background in combination with mean cell volume (MCV) in the investigation of β-thalassemia trait in a multicultural urban population.

Design.—Posttest probabilities for β-thalassemia trait were calculated using likelihood ratios for various microcytic MCV ranges in conjunction with published pretest probabilities for β-thalassemia trait based on ethnic background.

Setting.—Regional hemoglobinopathy laboratory, St Joseph's Hospital, Hamilton, Ontario, Canada.

Patients.—Patient data were derived from a previously published study. The original study cohort consisted of 789 patients aged 18 years or older who had an MCV less than 80 fL and were referred for routine complete blood count during a 6-month period.

Main Outcome Measures.—Posttest probabilities.

Results.—Simplified tables for the determination of posttest probabilities for β-thalassemia trait in individual patients based on ethnic background and MCV are provided. An algorithm to assist in determining when thalassemia investigations are indicated is presented.

Conclusions.—A high index of suspicion based on ethnic background and low MCV can provide increased sensitivity and specificity for the detection of thalassemia trait in centers with multicultural populations similar to the study population.
Performance Characteristics of the Becton Dickinson ProbeTec System for Direct Detection ofChlamydia trachomatisandNeisseria gonorrhoeaein Male and Female Urine Specimens in Comparison With the Roche Cobas System
Authors: Chan Edward L. , Brandt Ken , Olienus Karen , Antonishyn Nick , Horsman Greg B.
Published: January 2021

Objective.—The Becton Dickinson BDProbeTec ET System is a new semiautomated system using strand displacement amplification technology that simultaneously amplifies and detects Chlamydia trachomatis and Neisseria gonorrhoeae DNA. The strand displacement amplification products are hybridized with a fluorescent detector probe and are captured by a chemiluminescent assay in a microwell format. An amplification control is also included to monitor assay inhibition. This study evaluated the performance of the BDProbTec ET system in detecting C trachomatis and N gonorrhoeae in male and female urine specimens, calculated its ability to process large volumes of specimens, and determined the inhibition rate.

Materials and Methods.—Eight hundred twenty-five male and 399 female urine specimens were tested for both C trachomatis and N gonorrhoeae with the BDProbeTec ET system, and results were compared with those of the Roche Amplicor Cobas system. All urine specimens were processed on both assays on the same day they were received, according to the manufacturers' instructions. Discrepant results were resolved by in-house polymerase chain reaction assays. Internal or amplification controls were also used in each specimen assay to monitor inhibition. The throughput of the BDProbTec ET system was further tested with 150 urine specimens on an 8-hour shift for 2 days.

Results.—The overall sensitivity, specificity, positive predicative value, and negative predicative value for for detection of chlamydia were 95.3%, 99.3%, 95.9%, and 99.2% for strand displacement amplification and 95.9%, 98.3%, 90.6%, and 99.3% for the Roche Amplicor system. For detection of gonorrhea, these values were 100%, 99.7%, 88.2%, and 100% and 96.7%, 98.9%, 69%, and 99.9%, respectively. The overall inhibition rates for both strand displacement amplification and Roche Amplicor were less than 3.5%. The BDProbTec ET system was able to produce 150 results each for chlamydia and gonorrhea and the internal control within the 8-hour shift.

Conclusions.—The performance characteristics of the BDProbeTec ET assay are similar to those of the Roche Amplicor polymerase chain reaction for detection of chlamydia and gonorrhea in male and female urine specimens. The system was able to produce 300 results in an 8-hour shift.
Acute Fulminant Hepatic Failure in a Woman Treated With Phenytoin and Trimethoprim-Sulfamethoxazole
Authors: Ilario Marius J-M. , Ruiz Jose E. , Axiotis Constantine A.
Published: January 2021

Massive hepatic necrosis following exposure to phenytoin and trimethoprim-sulfamethoxazole is a rare occurrence and to the best of our knowledge has not been reported previously. Acute hepatic failure following administration of trimethoprim-sulfamethoxazole has rarely been seen, and only 4 cases have been well documented pathologically. We report a case of acute liver failure in a 60-year-old woman following ingestion of phenytoin and trimethoprim-sulfamethoxazole concomitantly over a 9-day period. Autopsy findings revealed acute fulminant hepatic failure. This case demonstrates the effects of chemical-chemical interactions in the potentiation of hepatotoxicity of single agents and specifically illustrates the need for discontinuing trimethoprim-sulfamethoxazole in the presence of early liver injury.
Hoechst 33342–Induced Apoptosis Is Associated With Intracellular Accumulation of E2F-1 Protein in BC3H-1 Myocytes and HL-60 Cells
Authors: Zhang Xinbo , Kiechle Frederick L.
Published: January 2021

Context.—Hoechst 33342 induces apoptosis, inhibits topoisomerase I, and disrupts TATA box–binding protein/TATA box element binding in BC3H-1 myocytes and HL-60 cells. In contrast, Hoechst 33258 does not have any of these actions.

Objective.—To determine if Hoechst 33342 or Hoechst 33258 treatment of BC3H-1 myocytes or HL-60 cells is associated with the intracellular accumulation of the nuclear transcription factor E2F-1, known to induce apoptosis.

Methods.— The gel mobility shift assay was used to study the effect of the 2 compounds on the binding capacity of nuclear proteins extracted from the 2 cell lines to a 30–base pair double-stranded oligonucleotide that contained an E2F-1–binding element. The DNA sequence of the protein-binding region was determined by the protection footprinting method and the Maxam-Gilbert guanosine plus adenosine chemical sequencing reaction.

Results.—Nuclear extracts from each cell line treated with 26.7 μmol/L Hoechst 33342 or Hoechst 33258 for 3 to 24 hours were incubated with [32P]–labeled 30–base pair oligonucleotide (5′GGCGCGGAGACTTGGAGAAATTTGGCGCGG3′). Three protein and DNA bands were altered by Hoechst 33342, but not by Hoechst 33258: band I, increased, then decreased in both cell lines; band II (2 adjacent bands) markedly decreased in both cell lines; band III markedly increased only in HL-60 cells. Footprinting and sequencing demonstrated that the nuclear protein-binding sequence was TTTGGCGC, an E2F-1 binding site. Hoechst 33342 treatment increased the concentration of E2F-1 protein after a 3-hour incubation in both cell lines.

Conclusion.—Hoechst 33342-induced apoptosis is associated with intracellular accumulation of E2F-1 protein, another step in this specific apoptotic pathway.
Genotype and Severity of Long QT Syndrome
Authors: Towbin Jeffrey A. , Wang Zhiqing , Li Hua
Published: January 2021

Objectives.—To describe the state of the art of our understanding of the long QT syndromes and to provide the genetic correlation of clinical severity of patients with this disorder.

Date Sources.—In this review, we outline data that were obtained from work in our laboratory, as well as information reported in the literature.

Study Selection.—The information in this review spans the last decade; data were obtained from the studies that had the most impact, as well as from recent work at our laboratory.

Data Extraction.—The data reported herein were extracted from the world literature on sudden death and the clinical aspects of long QT syndrome. The genes identified to date, mutations in these genes, and the biophysical perturbations in the mutated ion channels, as well as the severity of disease, are detailed.

Data Synthesis.—The extracted data are described as a state-of-the-art review.

Conclusions.—The long QT syndromes, genetically heterogeneous disorders due to mutations in genes encoding ion channels, are relatively common causes of syncope and sudden death. The affected genes, along with the genetic background of individuals, determine the clinical severity of disease. An understanding of the mechanisms responsible for long QT syndrome is expected to enable development of specific therapies.
Molecular Techniques in Mycobacterial Detection
Authors: Woods Gail L.
Published: January 2021

Objective.—To assess the clinical utility of the commercial nucleic acid amplification (NAA) tests (ie, Amplified Mycobacterium Tuberculosis Direct Test, Gen-Probe, Inc and AMPLICOR Mycobacterium tuberculosis Test, Roche Molecular Systems, Inc) for direct detection of Mycobacterium tuberculosis complex.

Data Sources.—Review of the English-language literature.

Conclusions.—The performance of both NAA tests is excellent (sensitivity, ≥95%; specificity, 100%) when testing respiratory specimens that are smear-positive for acid-fast bacilli (AFB). Only the Gen-Probe assay is approved for testing respiratory specimens regardless of the AFB smear result. Data from 3 studies showed that the sensitivity of the Mycobacterium Tuberculosis Direct Test in smear-negative patients ranged from 83% to 85%, and that the specificity was 99%. Both NAA tests have been used to test nonrespiratory specimens; in some studies, the performance was comparable to the performance obtained for respiratory specimens, whereas in others, it was lower. The NAA tests also appear to be reliable tools for rapid detection of M tuberculosis complex in positive broth cultures of all specimen types (except blood). The impact of the NAA tests on patient outcome varies based on the result of the AFB smear. In smear-positive patients, public health and hospital infection-control resources are predominantly affected. The potential for influencing patient outcome is much greater when the AFB smear is negative. In smear-negative patients, the NAA test could provide more rapid diagnosis of tuberculosis and subsequent initiation of therapy; eliminate the need for invasive diagnostic procedures, which are both costly and pose an added risk to the patient; and allow earlier discharge of hospitalized patients. Prospective studies concerning the cost-effectiveness of the NAA tests are needed.
Interinstitutional Variation in Glycohemoglobin Monitoring and Glycemic Control of Diabetic Patients
Authors: Valenstein Paul N. , Walsh Molly K. , Pappas Alex A. , Howanitz Peter J.
Published: January 2021

Objectives.—To compare how frequently institutions monitor glycohemoglobin in diabetic patients, the level of glycemic control achieved and to identify institutional factors associated with higher rates of monitoring and lower glycohemoglobin levels.

Methods.—A total of 212 institutions retrospectively abstracted laboratory and outpatient records of up to 30 diabetic patients who had initial glycohemoglobin monitoring performed in their laboratories. Data from a cohort of 5586 diabetic patients and 17 365 assays were analyzed.

Results.—Overall, 31.3% of patients underwent glycohemoglobin monitoring at least quarterly, the frequency recommended by the American Diabetes Association (ADA) to stabilize patients at target hemoglobin A1c (HbA1c) levels. A total of 64.9% of patients were monitored at least semiannually, the ADA recommendation for patients with stable diabetes in glycemic control (final HbA1c level <7%). When we compared the top and bottom deciles of the 212 institutions, there was more than an eightfold difference in the proportion of patients monitored at least quarterly and more than a twofold difference in the proportion of patients monitored at least semiannually. Glycemic control was assessed by examining the value of the last glycohemoglobin determination on record after at least 8 months of management. For all 5586 diabetic patients, the median value of the last HbA1c assay was 7.4%. Comparing the top and bottom deciles, there was almost a fourfold difference among institutions in the proportion of diabetic patients in glycemic control. The use of reminders to order glycohemoglobin monitoring was associated with higher rates of semiannual monitoring (P < .05) and tighter glycemic control (P < .05). In addition, patients who were monitored more frequently experienced glycohemoglobin reductions of greater magnitude (P < .001). The presence of diabetes clinics and the use of rapid methods for testing glycohemoglobin were not associated with monitoring frequency or glycohemoglobin levels.

Conclusions.—There is wide interinstitutional variation in the frequency with which diabetic patients are monitored and the level of glycemic control achieved. The use of prompting systems to remind providers to order glycohemoglobin monitoring was associated with more frequent monitoring and superior glycemic control.
Pleural Posttransplantation Lymphoproliferative Disorder Following Liver Transplantation
Authors: Hoffmann Heather , Schlette Ellen , Actor Jeffrey , Medeiros L. Jeffrey
Published: January 2021

A case of posttransplantation lymphoproliferative disorder (PTLD) involving the pleura is reported. The patient was a 57-year-old man who underwent liver transplantation 2 years prior to the development of PTLD. The PTLD was pleural-based and was first detected by radiologic studies as a pleural effusion. Transbronchial biopsy and cytologic examination of 2 pleural fluid specimens were nondiagnostic. Subsequent open-wedge biopsy revealed a monomorphic PTLD, composed of large immunoblasts with plasmacytoid differentiation. Immunohistochemical studies demonstrated B-cell lineage with expression of monotypic cytoplasmic immunoglobulin κ light chain and CD79a, and absence of T-cell antigens. Immunohistochemical and in situ hybridization studies demonstrated Epstein-Barr virus protein and RNA, respectively. No evidence of human herpesvirus 8 DNA was detected by polymerase chain reaction. We report this case because pleural-based PTLD is rare. The diagnosis of this entity is made more difficult by the fact that PTLD is often underrepresented in pleural fluid cytology samples.
Aneurysmal Bone Cyst of the Larynx Presenting With Hypoglottic Obstruction
Authors: Libera Duilio Della , Redlich Gillian , Bittesini Lucia , Falconieri Giovanni
Published: January 2021

We report a new case of aneurysmal bone cyst of the larynx occurring in a 22-year-old man. The lesion manifested with progressive breathing discomfort and appeared as a polypoid pedunculated mass attached to the subglottic mucosa. Microscopically, it featured numerous mononuclear and multinucleated giant cells surrounding cavernous spaces filled with blood. Foci of proliferating spindle cells and mature osteoid tissue could be recognized. There was no apparent relationship with the cricoid perichondrium. Clinical follow-up was negative for local recurrence. Based on this report and a review of the literature, we conclude that aneurysmal bone cyst of the larynx is phenotypically comparable to its bone homologue; however, its microscopic recognition may be difficult, especially on small biopsy fragments. Since it can be confused with several lesions, including telangiectatic osteosarcoma, awareness of this rare appearance of aneurysmal bone cyst is important to avoid unnecessary radical surgery.
Composite Nodular Lymphocyte-Predominance Hodgkin Disease and γ-Heavy-Chain Disease
Authors: Hudnall S. David , Alperin Jack B. , Petersen John R.
Published: January 2021

The association of Hodgkin disease with monoclonal gammopathy has rarely been reported. We present a case of a 48-year-old woman with a history of autoimmune hemolytic anemia and Graves disease who presented with hepatosplenomegaly and a γ-heavy-chain paraprotein. Histopathology of lymph node and bone marrow revealed nodular lymphocyte-predominance Hodgkin disease, while examination of the spleen revealed plasmacytosis consistent with γ-heavy-chain disease. Following splenectomy, the patient has remained in complete remission for both conditions with no further treatment. To our knowledge, this is the first report of a patient with both γ-heavy-chain disease and nodular lymphocyte-predominance Hodgkin disease. Given recent data indicating the B-cell nature of this form of Hodgkin disease, the authors propose that in this unique case there may be a clonal relationship between these 2 concurrent B-cell lymphoproliferative processes.
National Practice Characteristics and Utilization of Pathologists' Assistants
Authors: Grzybicki Dana Marie , Reilly Thomas L. , Hart Alison R. , Galvis Colleen O. , Raab Stephen S.
Published: January 2021

Objective.—To obtain descriptive information regarding the practice characteristics and utilization of US pathologists' assistants.

Design.—A self-administered, mailed, voluntary, anonymous questionnaire was distributed to a cross-sectional sample of 515 US pathologists' assistants registered as members of the American Association of Pathologists' Assistants. The questionnaire contained items relating to subject demographics, practice characteristics, specific task performance, and amount of time spent per day on the performance of specific tasks. Descriptive statistics were used to describe the data in terms of measures of central tendency and dispersion.

Results.—The response rate was 66.8%. The majority of questionnaires sent and received were from East Coast regions. Of all respondents, 46.6% were women, 57.6% were less than 40 years old, and 60.0% had been practicing 10 years or less. Over half (54.0%) had a master's degree. Almost the entire sample reported working 30 or more hours per week, with 43.4% reporting working more than 40 hours per week. The majority reported earning annual salaries between $56 000 and $75 000. Although task analysis of responses revealed a wide range of responses, the majority of the sample reported spending most of their daily time performing surgical specimen gross examinations (median 300 min/d). Approximately half of respondents also reported spending up to 90 minutes per day on nonspecific tasks such as logging specimens and answering the phone. Most respondents reported spending more daily time on such nonspecific tasks than on autopsy prosection or research.

Conclusions.—To our knowledge, this national survey provides the first description of pathologists' assistants across the United States. These data provide a useful tool for tracking changes in the profession.
Infantile Hemangioendothelioma of the Liver in an Adult
Authors: Diment Judith , Yurim Oded , Pappo Orit
Published: January 2021

Hepatic infantile hemangioendothelioma (IHE) is a rare benign vascular tumor of the liver found mostly in infancy and early childhood. We describe herein a tumor of the liver, morphologically indistinguishable from IHE, that presented in an adult. The patient is a 56-year-old woman with a history of ductal carcinoma in situ of the left breast and a mass in the liver. The patient underwent resection of the tumor, and after 23 months of follow-up she is alive with no evidence of expansion of the liver tumor.
Pseudosarcomatous Myofibroblastic Tumor and Myosarcoma of the Urogenital Tract
Authors: Watanabe Kazuo , Baba Keiich , Saito Atsuko , Hoshi Nobuo , Suzuki Toshimitsu
Published: January 2021

Objective.—Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis.

Methods.—We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, α-smooth muscle actin, high-molecular-weight caldesmon, and myogenin.

Results.—Desmin, muscle-specific actin, and α-smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas.

Conclusion.—High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.
Cytokeratin-Positive, CD45-Negative Primary Centroblastic Lymphoma of the Adrenal Gland
Authors: Donner Ludvik R. , Mott Frank E. , Tafur Isaac
Published: January 2021

We report a case of cytokeratin-positive, CD45-negative primary polymorphic centroblastic lymphoma of the adrenal gland. Additional immunostaining, which demonstrated positivity for CD20 and κ light chain, as well as detection of the monoclonal rearrangement of the immunoglobulin heavy chain gene, helped to establish the diagnosis of lymphoma and to rule out an initially favored diagnosis of poorly differentiated carcinoma.
Vibrio vulnificus Septicemia in a Patient With the Hemochromatosis HFE C282Y Mutation
Authors: Gerhard Glenn S. , Levin Kimberly A. , Goldstein Jennifer Price , Wojnar Margaret M. , Chorney Michael J. , Belchis Deborah A.
Published: January 2021

Vibrio vulnificus is an extremely invasive gram-negative bacillus found in marine waters that causes overwhelming bacteremia and shock that is associated with high mortality. Impaired iron metabolism has been implicated in the susceptibility to V vulnificus bacterial infections. We report a case of fatal V vulnificus sepsis in a 56-year-old man who died within 1 to 3 days after consuming raw seafood. At autopsy, he was found to have micronodular cirrhosis and iron overload. Postmortem genetic analysis revealed the presence of the hemochromatosis gene (HFE) C282Y mutation. To our knowledge, this is this first documented fatal case of V vulnificus infection in a patient proven to carry the HFE C282Y mutation. Because this patient was heterozygous for the major hereditary hemochromatosis mutation and was not previously diagnosed with clinical iron overload, the spectrum of clinical susceptibilities to V vulnificus infection may include carriers of the C282Y mutation.
An Unusual Presentation of Calciphylaxis Due to Primary Hyperparathyroidism
Authors: Mirza Imran , Chaubay Damanjeet , Gunderia Himanshu , Shih Winston , El-Fanek Hani
Published: January 2021

We present the case of a 69-year-old woman with calciphylaxis due to primary hyperparathyroidism. A 0.5-g parathyroid adenoma was surgically removed, which resulted in complete recovery of the patient. Review of the literature revealed 7 other cases of calciphylaxis due to primary hyperparathyroidism and showed that prompt surgical removal of the autonomous parathyroid gland lesion results in clinical recovery of calciphylactic skin lesions.
Necrotic Seminoma of the Testis
Authors: Florentine Barbara D. , Roscher Arno A. , Garrett Jerry , Warner Nancy E.
Published: January 2021

We describe an infarcted mass in the testis containing “ghost” cells suspicious for neoplasm. The entire lesion was necrotic. A Masson trichrome stain greatly improved nuclear and cytologic detail, confirming the suspicion of neoplasm. Placental alkaline phosphatase revealed specific membrane staining of the neoplastic cells and established a diagnosis of seminoma. Masson trichrome plus selected immunostains offer a promising approach to the diagnosis of certain necrotic neoplasms.
Splenic Marginal Zone Lymphoma
Authors: Depowski Peter L. , Dunn Harry , Purdy Sheila , Ross Jeffrey S. , Nazeer Tipu
Published: January 2021

Splenic marginal zone lymphoma is a recently described primary splenic lymphoproliferative disorder that mainly affects older individuals. We report the case of a 22-year-old woman with morphologic and immunophenotypic findings consistent with splenic marginal zone lymphoma. This woman is one of the youngest patients ever described with this disease. The patient presented with complaints of left-sided abdominal fullness and was noted to have splenomegaly on physical examination. Laboratory evaluation revealed pancytopenia and a serum M component. The spleen was removed and weighed 1550 g. Histology showed prominent white pulp with an expanded marginal zone. The neoplastic cells were marginal zone–type cells with small to intermediate-sized nuclei with occasional conspicuous nucleoli and moderate amounts of pale to amphophilic cytoplasm. Immunophenotypic analysis revealed a B-cell population (CD20 positive) with κ-light-chain restriction. The patient was treated with adjuvant therapy, but developed progressive disease less than 2 years after initial diagnosis.
The Microbiology Laboratory's Role in Response to Bioterrorism
Authors: Robinson-Dunn Barbara
Published: January 2021

Context.—Bioterrorism has existed since before the 14th century; however, the specter of such an attack is much greater today than ever before. Technical expertise in microbiology and molecular testing, combined with the rapidity of worldwide air travel, has ensured that no geographic area would be untouched in a widespread attack. Clinical microbiology laboratories will play a pivotal role in the detection of attacks involving weapons of mass destruction.

Objective.—To identify and discuss the microorganisms most likely to be used as agents of bioterrorism.

Data Sources.—Data were obtained from literature searches from 1997 through June 2001 using the subject headings of bioterrorism, biological weapons, biological warfare, anthrax, brucellosis, tularemia, smallpox, plague, and botulism. In addition, information was obtained from publications of the Center for Civilian Studies, Johns Hopkins University, the Centers for Disease Control and Prevention, American Society for Microbiology, and the United States Army Medical Research Institute of Infectious Diseases.

Data Extraction and Synthesis.—Findings obtained from these studies and publications were analyzed for the most likely microorganisms that would be involved in a bioterrorist attack and the most efficient means by which they could be identified. In all instances, the guidelines from the Centers for Disease Control and Prevention for Level A laboratories were observed.

Conclusions.—The most likely microorganisms to be utilized as biological weapons include Bacillus anthracis (anthrax), Brucella species (brucellosis), Clostridium botulinum (botulism), Francisella tularensis (tularemia), Yersinia pestis (plague), and variola major (smallpox). While knowledge of the potential of these microorganisms is critical, clinical microbiologists and medical technologists possess the basic tools to rule out the suspected pathogens or to refer these isolates to public health laboratories for identification and susceptibility testing.
Pulmonary Neuroendocrine Carcinomas
Authors: Huang Qin , Muzitansky Alona , Mark Eugene J.
Published: January 2021

Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC.

Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications.

Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995.

Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded.

Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.
Gynecomastia With Marked Cellular Atypia Associated With Chemotherapy
Authors: Yang Yi Jun
Published: January 2021

Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy. The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized.
Laboratory Critical Values Policies and Procedures
Authors: Howanitz Peter J. , Steindel Steven J. , Heard Nan V.
Published: January 2021

Context.—Critical values lists have been used for many years to decide when to notify physicians and other caregivers of potentially life-threatening situations; however, these lists have not been studied widely.

Objectives.—To investigate critical values lists in institutions participating in the College of American Pathologists Q-Probes program and to provide suggestions for improvement.

Setting.—A total of 623 institutions voluntarily participating in the Q-Probes program.

Design.—A multipart study in which participants responded to information from preprinted lists, collected information about current practices, completed a questionnaire, monitored critical values calls, reviewed patients' medical records, and surveyed nursing supervisors and physicians about critical values.

Main Outcome Measures.—Defining critical values systems, including lists, personnel, costs, processes, usefulness, and related medical outcomes.

Results.—Critical values lists were determined for routine chemistry and hematology analytes and were found to vary widely among participants. In contrast, more than 95% of participants reported positive blood cultures, cerebrospinal fluid cultures, and toxic therapeutic drug levels as critical values. Based on more than 13 000 critical values, participants' data showed that most critical values reports (92.8%) were made by the person who performed the test, and that 65% of reports for inpatients were received by nurses. For outpatients, physicians' office staff received the largest percentage (40%) of reports. The majority of participants (71.4%) had no policy on how repeat critical calls should be handled. On average, completion of notification required about 6 minutes for inpatients and 14 minutes for outpatients. Slightly greater than 5% of critical value telephone calls were abandoned, with the largest percentage abandoned for outpatients. More than 45% of critical values were unexpected, and 65% resulted in a change in therapy. Although only 20.8% of 2301 nursing supervisors thought critical values lists were helpful, 94.9% of 514 physicians found critical values lists valuable.

Conclusions.—Critical values systems were medically important, highly variable, but also costly practices for participants. We propose a number of recommendations for improvement, including that the critical values list should be approved by the medical staff, each laboratory should develop a written policy for handling initial and repeat critical values reports, a foolproof policy should be established to report results from calls abandoned, and efforts at automating the process should become widespread.
Altered Cytoskeleton in Smooth Muscle of Aganglionic Bowel
Authors: Nemeth Laszlo , Rolle Udo , Puri Prem
Published: January 2021

Context.—Intestinal motility is under the control of smooth muscle cells, enteric plexus, and hormonal factors. In Hirschsprung disease (HD), the aganglionic colon remains spastic or tonically enhanced and unable to relax. The smooth muscle cell's cytoskeleton consists of proteins or structures whose primary function is to link or connect protein filaments to each other or to the anchoring sites. Dystrophin is a subsarcolemmal protein with a double adhesion property, one between the membrane elements and the contractile filaments of the cytoskeleton and the other between the cytoskeletal proteins and the extracellular matrix. Desmin and vinculin are functionally related proteins that are present in the membrane-associated dense bodies in the sarcolemma of the smooth muscle cells.

Objective.—To examine the distribution of the cytoskeletal proteins in the smooth muscle of the aganglionic bowel.

Design.—Bowel specimens from ganglionic and aganglionic sections of the colon were collected at the time of pull-through surgery from 8 patients with HD. Colon specimens collected from 4 patients at the time of bladder augmentation acted as controls. Anti-dystrophin, anti-desmin, and anti-vinculin antibodies were used for fluorescein immunostaining using confocal laser scanning microscopy.

Results.—Moderate to strong dystrophin immunoreactivity was observed at the periphery of smooth muscle fibers in normal bowel and ganglionic bowel from patients with HD, whereas dystrophin immunoreactivity was either absent or weak in the smooth muscle of aganglionic colon. Moderate to strong cytoplasmic immunostaining for vinculin and desmin was seen in the smooth muscle of normal bowel and ganglionic bowel from patients with HD, whereas vinculin and desmin staining in the aganglionic colon was absent or weak.

Conclusion.—This study demonstrates that the cytoskeletal proteins are abundant in the smooth muscle of normal bowel, but are absent or markedly reduced in the aganglionic bowel of HD. As cytoskeletal proteins are required for the coordinated contraction of muscle cells, their absence may be responsible for the motility dysfunction in the aganglionic segment.
Primary Carcinoid Tumor Arising in a Mature Teratoma of the Kidney
Authors: Yoo Jinyoung , Park Sonya , Lee Hee Jung , Kang Seok Jin , Kim Byung Kee
Published: January 2021

Primary carcinoid tumor, especially that arising in a mature teratoma of the kidney, is extremely rare; only 3 cases have been reported in the world literature to date. Because of the rarity of the lesion, its histogenesis and prognosis are unknown. We report a case of primary renal carcinoid tumor occurring in a mature teratoma in a 30-year-old woman. A computed tomographic scan of the abdomen revealed a mass in the left kidney containing dense calcification with minimal contrast enhancement. Histologically, the tumor was composed of trabecular and anastomosing ribbonlike nests, identical to the features of carcinoid tumors of other sites. Immunohistochemical stainings were positive for cytokeratin, neuron-specific enolase, and chromogranin. In addition, there were mature teratoid tissues, such as columnar epithelium, smooth muscle, and bone. The carcinoid tumor was under and closely apposed to the lining of the cysts. The patient did not have clinical manifestations of the carcinoid syndrome and had an uneventful recovery.
β-Catenin Accumulation and Gene Mutation in Exon 3 in Dedifferentiated Liposarcoma and Malignant Fibrous Histiocytoma
Authors: Sakamoto Akio , Oda Yoshinao , Adachi Toshisada , Saito Tsuyoshi , Tamiya Sadafumi , Iwamoto Yukihide , Tsuneyoshi Masazumi
Published: January 2021

Context.—β-Catenin is an adhesion molecule that also plays a role in the Wnt signaling pathway.

Objective.—To analyze β-catenin mutation and accumulation in a series of liposarcomas and malignant fibrous histiocytomas.

Design.—β-Catenin mutation in exon 3 was studied using polymerase chain reaction–single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30 formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12 dedifferentiated liposarcomas, characterized by both high-grade anaplastic components and well-differentiated liposarcoma components, plus 18 well-differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2 components of dedifferentiated liposarcomas were analyzed independently. β-Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell-proliferation marker, MIB-1 labeling index) were examined immunohistochemically. Nine storiform-pleomorphic–type malignant fibrous histiocytomas were also studied.

Results.—Dedifferentiated liposarcomas showed mutation in 2 cases (17%) and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a mutation in the well-differentiated component; this mutation was silent. The other case had mutations that differed between the 2 components. In well-differentiated liposarcomas, mutation was not seen in any of the cases (0/18; 0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8; 63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases, respectively, without any exact correlation between the cases. Cases with accumulation had a higher MIB-1 labeling index than those without, among both the sclerosing-type well-differentiated liposarcomas (P < .05) and the malignant fibrous histiocytomas.

Conclusions.—Our results suggest the possible involvement of β-catenin activation caused by β-catenin mutation in liposarcoma and malignant fibrous histiocytoma, but the contribution would seem to be different, depending on the tumor type. β-Catenin accumulation is also thought to be related to cell proliferation in some of the cases.
Merkel Cell Carcinoma
Authors: Idowu Michael O. , Contos Melissa , Gill Satinder , Powers Celeste
Published: January 2021

Merkel cell carcinoma (MCC) is an uncommon, highly aggressive cutaneous neoplasm of neuroendocrine differentiation with a poor prognosis. MCC most often presents as a painless, firm, raised lesion in sun-exposed sites of the head and neck region of the elderly. We report a case of a metastatic MCC to the stomach presenting as upper gastrointestinal bleeding. To our knowledge, this is the second reported case of MCC presenting as upper gastrointestinal bleeding and the first case confirmed by the newer immunohistochemical techniques. The literature is reviewed.
An Unusual Case of Recurrent Loffler Endomyocarditis of the Aortic Valve
Authors: Gudmundsson G. Steinar , Ohr Joseph , Leya Ferdinand , Jacobs William R. , Godwin John E. , Schwartz Jeffrey
Published: January 2021

Idiopathic hypereosinophilic syndrome is a rare systemic disease with an unexplained elevated eosinophil count. Loffler endomyocarditis is hypereosinophilic syndrome with endocardial fibrosis and restrictive cardiomyopathy. The atrioventricular valves are frequently involved, causing valvular regurgitation. Previously, there has been one case report of combined aortic and mitral valve involvement with Loffler endomyocarditis that was treated with bivalvular replacement. We describe a previously healthy 50-year-old man diagnosed with Loffler endomyocarditis complicated by peripheral thromboembolism and severe aortic regurgitation due to valve fibrosis and fibrotic vegetation on the aortic valve. He underwent embolectomy and aortic valve replacement in addition to treatment for his hypereosinophilia. He later presented with cardiomyopathy with severe aortic insufficiency due to the destruction of the aortic valve prosthesis by sterile fibrinous vegetation. To our knowledge, this is the second case in the literature in which Loffler endomyocarditis involves the aortic valve and the first patient in whom only the aortic valve is involved.