bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Interstitial Cells of Cajal in the Internal Anal Sphincter of Patients With Internal Anal Sphincter Achalasia and Hirschsprung Disease
Authors: Piotrowska Anna Piaseczna , Solari Valeria , Puri Prem 
Published: February 2021

Abstract
Context.—Interstitial cells of Cajal (ICCs) are pacemaker cells in the smooth muscles of the gut. The internal anal sphincter (IAS) is the most caudal part of gastrointestinal tract. It has the important function of maintaining fecal continence. It has been proposed that ICCs in the IAS mediate the inhibitory innervation of the recto-anal reflexes.
Objective.—To investigate the distribution of ICCs in the normal IAS and in the IAS of children diagnosed with internal anal sphincter achalasia (IASA) and Hirschsprung disease (HD).
Methods.—At the time of IAS myectomy, specimens of the IAS were taken from 8 patients with IASA, 4 patients with HD, and 4 normal controls. All specimens were examined using anti–c-Kit and antiperipherin antibodies; immunolocalization was detected with light microscopy. Density of the ICCs was graded by computerized image analysis.
Results.—There was strong peripherin immunoreactivity in the ganglia cells and nerve fibers in the normal IAS. The number of peripherin-positive nerve fibers was markedly reduced in the IAS in patients with IASA. In HD patients, there was lack of peripherin immunoreactivity in the IAS, but hypertrophic nerve trunks stained strongly. Many c-Kit–positive ICCs were present among the muscle fibers and between the muscle bundles in the normal IAS. In HD and IASA patients, ICCs were absent or markedly reduced.
Conclusion.—Altered distribution of ICCs in the internal sphincter in IASA and HD may contribute to motility dysfunction in these patients.
Lyme-Associated Parkinsonism: A Neuropathologic Case Study and Review of the Literature
Authors: Cassarino David S. , Quezado Martha M. , Ghatak Nitya R. , Duray Paul H. 
Published: February 2021

Abstract
Neurological complications of Lyme disease include meningitis, encephalitis, dementia, and, rarely, parkinsonism. We present a case of striatonigral degeneration, a form of multiple system atrophy, in Lyme-associated parkinsonism. A 63-year-old man presented with erythema migrans rash, joint pains, and tremors. Serum and cerebrospinal fluid antibodies and polymerase chain reaction for Borrelia burgdorferi were positive. Clinical parkinsonism was diagnosed by several neurologists. Despite treatment, the patient continued to decline, with progressive disability, cognitive dysfunction, rigidity, and pulmonary failure. At autopsy, the brain showed mild basal ganglia atrophy and substantia nigra depigmentation, with extensive striatal and substantia nigral neuronal loss and astrogliosis. No Lewy bodies were identified; however, ubiquitin-positive glial cytoplasmic inclusions were identified in striatal and nigral oligodendroglia. There were no perivascular or meningeal infiltrates, the classic findings of neuroborreliosis. To our knowledge, this is the first report of striatonigral degeneration in a patient with B burgdorferi infection of the central nervous system and clinical Lyme-associated parkinsonism.
Molecular Genetic Analysis Excludes Implantation Metastasis of Basal Cell Carcinomas
Authors: Hafner Christian , Hartmann Arndt , Knuechel Ruth , Dietmaier Wolfgang , Landthaler Michael , Vogt Thomas 
Published: February 2021

Abstract
Basal cell carcinoma (BCC) of the skin is the most common tumor in the white population. A 66-year-old man developed 2 BCCs at the left parietal region of the head and at the helix of the left ear. The 2 lesions matched exactly when pressing the ear against the head, suggesting an implantation metastasis mechanism. Molecular genetic techniques were used to confirm or exclude such a mechanism in this rare clinical constellation. Tumor tissues were precisely microdissected for DNA isolation. Exons 5–9 of the p53 tumor suppressor gene were directly sequenced. In addition, loss of heterozygosity analysis of chromosome 9q was performed using 5 polymorphic microsatellite markers. The BCC of the ear revealed a p53 mutation at codon 273, whereas the other one lacked this mutation. In addition, the smaller BCC of the ear showed loss of heterozygosity at 9q33.3, in contrast with the larger BCC. Interestingly, histologically normal skin of the ear distant from the small BCC had the same deletion, indicating a field defect of this skin patch at 9q33.3. Molecular genetic analysis clearly demonstrated different genetic alterations of the two BCCs and therefore most likely excludes a mechanism of implantation metastasis.
Comparison of Epstein-Barr Virus Presence in Hodgkin Lymphoma in Pediatric Versus Adult Argentine Patients
Authors: De Matteo Elena , Barón AnahíVijnovich , Chabay Paola , Porta José , Dragosky Marta , Preciado María Victoria 
Published: February 2021

Abstract
Context.—In developed countries and high socioeconomic groups, Hodgkin lymphoma has an initial peak in young adulthood, whereas in undeveloped countries and low socioeconomic groups, it shows an early childhood peak. In developing countries, 90% of children are infected with the Epstein-Barr virus (EBV) by the age of 6 years, but in developed countries, only 30% to 40% are seropositive by that age. Early childhood EBV infection in 75% of Argentine patients was demonstrated.
Objective.—To explore the epidemiology of Hodgkin lymphoma and its relationship with EBV in Argentine patients.
Methods.—The presence of EBV was assessed by Epstein-Barr encoded RNA in situ hybridization and latent membrane protein 1 immunohistochemistry. We studied 92 pediatric and 42 adult Hodgkin lymphoma cases from a public center as well as 39 adult cases from a private center.
Results.—The mixed cellularity Hodgkin lymphoma had a prevalence of 52% in the pediatric group, while similar frequencies of both nodular sclerosis Hodgkin lymphoma (47%) and mixed cellularity Hodgkin lymphoma (44%) were observed in adults. As for Epstein-Barr encoded RNAs, 55% of the pediatric cases and 31% of the adult cases were positive. Among adult EBV+ cases, 38% were from the public hospital, and 23% were from the private center. EBV was present in 77% of the pediatric mixed cellularity Hodgkin lymphoma cases when compared with the other histologic subtypes of Hodgkin lymphoma. EBV was mainly detected in mixed cellularity cases (39% in the adult group).
Conclusion.—Our findings strengthen the argument that EBV is involved in the pathogenesis of Hodgkin lymphoma in most children younger than 10 years. Our findings of EBV prevalence, along with both childhood and second-decade peaks as well as comparable frequencies for Hodgkin lymphomas of mixed cellularity and nodular sclerosis, distinguish our population from others in developing countries.
Latent Membrane Protein 1, Tumor Necrosis Factor Receptor–Associated Factor (TRAF) 1, TRAF-2, TRAF-3, and Nuclear Factor Kappa B Expression in Posttransplantation Lymphoproliferative Disorders
Authors: Ramalingam Preetha , Chu Wei-Sing , Tubbs Raymond , Rybicki Lisa , Pettay James , Hsi Eric D. 
Published: February 2021

AbstractContext.—Most posttransplantation lymphoproliferative disorders (PTLDs) are associated with Epstein-Barr virus (EBV) infection. The EBV latent membrane protein 1 (LMP-1) is important in the transformation of B lymphocytes through its interaction with intracellular tumor necrosis factor receptor–associated factors (TRAFs) that, in turn, can activate transcription factors such as nuclear factor kappa B (NFκB) and Jun-N-kinase. Of the 6 members of the TRAF family, TRAF-1, TRAF-2, and TRAF-3 are most commonly associated with LMP-1. Recently, it has been suggested that LMP-1–induced TRAF activation is important in the pathogenesis of PTLDs.Objective.—To characterize the expression patterns of these proteins in PTLDs, we studied a series of well-characterized cases for expression of LMP-1, TRAF-1, TRAF-2, TRAF-3, and NFκB by immunohistochemical analysis.Methods.—A total of 27 specimens from 25 patients were analyzed for LMP-1, TRAF-1, TRAF-2, TRAF-3, and NFκB (active form) by immunohistochemical analysis. Expression of EBV-encoded RNA (EBER) was evaluated by in situ hybridization. Correlation between the expression of the different markers was performed using the Mantel-Haenszel χ2 test. Cox proportional hazards analysis and Kaplan-Meier analysis with log-rank testing were used to analyze antigen expression and clinical outcome.Results.—Ninety-six percent of PTLDs expressed NFκB, 74% to 84% expressed TRAFs, 78% expressed EBER, and 77% expressed LMP-1. TRAF-1, TRAF-2, and TRAF-3 expression did not correlate with either EBER or LMP-1 expression. TRAF-2, but not TRAF-1 or TRAF-3, expression correlated with NFκB expression (P = .02).Conclusions.—These results suggest that TRAF molecules and active NFκB are expressed in PTLDs regardless of EBV positivity. Given the association of TRAF-2 and active NFκB expression, TRAF-2 may play an important role in regulating this transcription factor in PTLD.
Fatal Dural Sinus Thrombosis Associated With Heterozygous Factor V Leiden and a Short Activated Partial Thromboplastin Time
Authors: Stephan Christina L. , SantaCruz Karen , May Corrie , Wilkinson Steve B. , Cunningham Mark T. 
Published: February 2021

Abstract
Inherited thrombophilia is a risk factor for dural sinus thrombosis (DST). To our knowledge, this is the first description with autopsy findings of a patient with DST associated with heterozygous factor V Leiden and a short activated partial thromboplastin time (aPTT). A 51-year-old woman presented with a 3-day history of headache, nausea, right-sided weakness, and focal motor seizure; she died 3 days after admission. At autopsy, a gross examination showed hemorrhage of bilateral parietal lobes and left primary motor cortex, uncal and tonsillar herniation, and pulmonary embolus of the right upper lobe. A microscopic examination of the brain showed an organizing thrombus in the superior sagittal sinus, diffuse cerebral edema, and extensive venous congestion. Laboratory studies showed heterozygous factor V Leiden by polymerase chain reaction and a very short aPTT of 17 seconds (reference range, 22–30 seconds). The combination of a heterozygous factor V Leiden mutation and a short aPTT may have contributed to the fatal DST in this patient.
Severe Hemolysis Due to Passenger Lymphocyte Syndrome After Hematopoietic Stem Cell Transplantation From an HLA-Matched Related Donor
Authors: Reed Maria , Yearsley Martha , Krugh Dave , Kennedy Melanie S. 
Published: February 2021

Abstract
A 61-year-old white man (group A, Rh-positive) was allotransplanted for acute myelogenous leukemia from his HLA-matched related sister (group O, Rh-positive) in 2 separate infusions. Three days after the second graft infusion, the patient's front blood type converted to O Rh-positive, with a negative direct antiglobulin test and elevated anti-A1 titer. Severe hemolysis developed, and the patient expired 14 days posttransplantation.
Combined Serous Microcystic Adenoma and Well-Differentiated Endocrine Pancreatic Neoplasm: A Case Report and Review of the Literature
Authors: Slukvin Igor I. , Hafez G. Reza , Niederhuber John E. , Warner Thomas F. 
Published: February 2021

Abstract
We report a case of combined microcystic adenoma and pancreatic endocrine neoplasm of the pancreas in a 53-year-old male patient. The pancreatic tumor was an incidental computed tomography scan finding and was not accompanied by gastrointestinal symptoms. The tumor was located in the head of the pancreas and was composed of numerous small cysts lined by uniform clear cells with a centrally located solid endocrine component. Four cases of similar neoplasm have recently been reported, exclusively in women. Literature review and case analysis indicate that combined microcystic adenoma and pancreatic endocrine neoplasm is characterized by the presence of pancreatic endocrine neoplasm within microcystic adenoma in the head of the pancreas, affects women more often than men, and presents at a younger age when compared to microcystic adenoma.
Carcinoembryonic Antigen Elevation Due to Bowel Sequestration With Mucocele Formation Following Colonic Resection
Authors: Haber Marian M. , Leon Marino E. , Bakker Jennifer E. , Nagle Deborah 
Published: February 2021

Abstract
Carcinoembryonic antigen (CEA) is recommended as a serologic marker to monitor colorectal carcinoma recurrence. Elevations of CEA due to causes other than carcinoma exist and may lead to a misdiagnosis of recurrent carcinoma. We report a case of bowel sequestration with mucocele formation at the site of previous colo-colic anastomosis causing a mild elevation in CEA. The patient exhibited increasing CEA levels 6 years after resection of a sigmoid colon carcinoma with end-to-end anastomosis. Subsequently, computed tomographic and positron emission tomographic scans documented the presence of a cystic mass showing increased uptake at the anastomotic site. At exploratory laparotomy a mass lesion with mucus-filled protrusions was resected. Pathologic examination documented the presence of sequestration of a segment of the bowel wall with a mucocele and no overlying defect at the mucosal anastomotic site by demonstrating the presence of all bowel layers. After resection of the lesion, the CEA level normalized.
Intraoperative Testing for Parathyroid Hormone: A Comprehensive Review of the Use of the Assay and the Relevant Literature
Authors: Carter Alexis Byrne , Howanitz Peter J. 
Published: February 2021

AbstractObjective.—The rapid intraoperative parathyroid hormone assay is transforming the parathyroidectomy procedure. We present a review of the literature on the use of the assay as an adjunct to surgery. To our knowledge, this is the first review of the literature to encompass and compare all known primary studies of this assay in parathyroidectomy patients.Data Sources.—Articles were collected by searching MEDLINE databases using relevant terminology. The references of these articles were reviewed for additional studies. Supplementary articles pertinent to the parathyroidectomy procedure, preoperative parathyroid localization studies, and intraoperative parathyroid hormone assay development also were examined.Study Selection and Data Extraction.—One hundred sixty-five references were analyzed and categorized separately into groups.Data Synthesis.—The primary studies of intraoperative data on patients undergoing parathyroidectomy were compared when possible. Studies were analyzed by type of assay used, where performed, turnaround time, and efficiency of use. Reviews of the types of parathyroid surgery and preoperative localization were included for educational purposes.Conclusions.—The intraoperative parathyroid hormone assay is a useful adjunct to preoperative imaging and parathyroid surgery because of its unique ability to detect an occult residuum of hyperfunctioning parathyroid tissue. Use of this assay will obviate the need for frozen section in most routine cases. The test facilitates minimally invasive parathyroidectomy for single parathyroid adenomas, which, in turn, improves cost-effectiveness and cosmetic outcome. Its use in patients with known preoperative multiglandular disease is promising but requires further study.
HER-2/neu Status in Breast Cancer Metastases to the Central Nervous System
Authors: Lear-Kaul Kelly C. , Yoon Hye-Ryoung , Kleinschmidt-DeMasters Bette K. , McGavran Loris , Singh Meenakshi 
Published: February 2021

Abstract
Context.—Breast cancer is lethal when it metastasizes; one frequent site for spread is the central nervous system (CNS). Approximately 15% to 30% of breast cancers overexpress the protein HER-2/neu at the primary site, but there are few data on whether metastases from these tumors overexpress HER-2/neu and might be responsive to the potentially toxic anti–HER-2/neu immunotherapy (trastuzumab [Herceptin]) used in patients with disseminated disease.
Objective.—To assess CNS breast cancer metastases for HER-2/neu protein overexpression by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH) and to compare the status in primary and metastatic sites in the same patient, whenever possible.
Design.—Central nervous system breast cancer metastases (n = 53) from 33 patients and corresponding primary breast cancer specimens in a subset of these patients (n = 12) were retrospectively identified in surgical pathology and autopsy databases. Fluorescence in situ hybridization analysis using PathVysion probes for HER-2/neu and chromosome enumeration probe 17 (CEP 17) and immunohistochemistry using the c-Erb-B2 antibody (Dako A0485) were compared. Immunohistochemical sections were evaluated by both visual and image analysis techniques.
Results.—Of 31 cases assessable by FISH, 26% showed gene amplification. One hundred percent concordance for HER-2/neu status was detected between the primary and CNS metastatic lesions in 10 of 10 patients analyzed by FISH; lesser concordance was noted in 12 cases compared by immunohistochemistry. In 9 patients with multiple CNS metastases, FISH showed concordance among different lesions within the same patient.
Conclusions.—When FISH is the detection method, CNS metastases accurately reflect the HER-2/neu status of the primary tumor. Central nervous system metastases from breast cancer received as surgical specimens can therefore be used to assess HER-2/neu status in patients in whom the primary tumor is unavailable for analysis.
Interpretation of Skin Biopsies by General Pathologists: Diagnostic Discrepancy Rate Measured by Blinded Review
Authors: Trotter Martin J. , Bruecks Andrea K. 
Published: February 2021

Abstract
Context.—Slide review has been advocated as a means to reduce diagnostic error in surgical pathology and is considered an important component of a total quality assurance program. Blinded review is an unbiased method of error detection, and this approach may be used to determine the diagnostic discrepancy rates in surgical pathology.
Objective.—To determine the diagnostic discrepancy rate for skin biopsies reported by general pathologists.
Design.—Five hundred eighty-nine biopsies from 500 consecutive cases submitted by primary care physicians and reported by general pathologists were examined by rapid-screen, blinded review by 2 dermatopathologists, and the original diagnosis was compared with the review interpretation.
Results.—Agreement was observed in 551 (93.5%) of 589 biopsies. Blinded review of these skin biopsies by experienced dermatopathologists had a sensitivity of 100% (all lesions originally reported were detected during review). False-negative errors were the most common discrepancy, but false positives, threshold discrepancies, and differences in type or grade were also observed. Only 1.4% of biopsies had discrepancies that were of potential clinical importance.
Conclusions.—Blinded review demonstrates that general pathologists reporting skin biopsies submitted by primary care physicians have a low diagnostic error rate. The method detects both false-negative and false-positive cases and identifies problematic areas that may be targeted in continuing education activities. Blinded review is a useful component of a dermatopathology quality improvement program.
Ramipril-Associated Hepatotoxicity
Authors: Yeung Elaine , Wong Florence S. , Wanless Ian R. , Shiota Koji , Guindi Maha , Joshi Supriya , Gardiner Geoffrey 
Published: February 2021

Abstract
Context.—Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported.
Objective.—To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril.
Design.—Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor–induced liver injury reported in the literature.
Results.—The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously.
Conclusion.—Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.
Ampullary Pancreatoblastoma in an Elderly Patient: A Case Report and Review of the Literature
Authors: Du Emma , Katz Matthew , Weidner Noel , Yoder Suzanne , Moossa A. R. , Shabaik Ahmed 
Published: February 2021

AbstractPancreatoblastoma, generally regarded as a pediatric malignant tumor, is rarely found in the adult population. Only 13 adults with pancreatoblastoma, ranging in age from 19 to 68 years, have previously been reported in the world literature. A diagnosis of pancreatoblastoma relies on characteristic histologic features, including epithelial differentiation and, more importantly, squamoid differentiation. Despite aggressive therapy, adults with pancreatoblastoma have a poor outcome. We describe a 78-year-old woman who presented with painless jaundice and was found on abdominal computed tomographic scan to have a 2.7-cm ampullary mass. The patient underwent successful pancreaticoduodenectomy. Pathologic examination of the resected tumor revealed findings characteristic of pancreatoblastoma. The tumor formed acinar and glandular structures, solid areas, and contained many “squamoid corpuscles,” a defining feature of pancreatoblastoma. The tumor cells also showed acinar and ductal phenotype by immunohistochemistry. To the best of our knowledge, this case represents the oldest patient with pancreatoblastoma to be described in the literature to date and the first to occur in the ampulla of Vater. We review previously published cases and discuss the clinical and histopathologic features of adult pancreatoblastoma.