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Atypical Clinical Manifestations of Cerebral Amyloid Angiopathy.
Akers C, Acosta LMY, Considine C, Claassen D, Kirshner H, Schrag M
(2019) Curr Neurol Neurosci Rep 19: 64
MeSH Terms: Aged, Alzheimer Disease, Brain, Cerebral Amyloid Angiopathy, Cerebral Hemorrhage, Cognitive Dysfunction, Diagnosis, Differential, Female, Humans, Lewy Body Disease, Male, Neuroimaging
Show Abstract · Added March 3, 2020
PURPOSE - Cerebral amyloid angiopathy is a vasculopathy caused by β-amyloid deposition in cerebral arterioles and capillaries. It is closely linked to Alzheimer's disease and predisposes elderly patients to intracerebral hemorrhage, transient focal neurological episodes, and cognitive impairment. Because of a predilection for symptomatic hemorrhage, particularly in the frontal lobes, cerebral amyloid angiopathy may also cause a dysexecutive syndrome.
RECENT FINDINGS - In this case series, we describe presentations of classic clinical dementia syndromes which are not are widely thought to be associated with cerebral amyloid angiopathy, namely logopenic variant primary progressive aphasia (n = 3), normal pressure hydrocephalus (n = 3), and Lewy body dementia (n = 2). In every case, after a clinical diagnosis was established, neuroimaging, brain biopsy, and/or autopsy confirmed the presence of cerebral amyloid angiopathy. Cerebral amyloid angiopathy has significant clinical implications, and its ability to mimic and/or contribute to other clinical dementia syndromes can complicate its diagnosis. This series of cases broadens the range of clinical scenarios associated with cerebral amyloid angiopathy.
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12 MeSH Terms
A Unilateral Facial Rash with Eye Involvement.
Buell KG, Trumbo SP, Haase VH
(2019) Am J Med 132: 823-825
MeSH Terms: Aged, Diagnosis, Differential, Exanthema, Face, Herpes Zoster, Herpes Zoster Ophthalmicus, Humans, Male
Added March 9, 2019
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8 MeSH Terms
Neuroimaging Advances in Pediatric Stroke.
Donahue MJ, Dlamini N, Bhatia A, Jordan LC
(2019) Stroke 50: 240-248
MeSH Terms: Adolescent, Anemia, Sickle Cell, Aneurysm, Dissecting, Brain, Cerebral Arteries, Cerebral Infarction, Cerebrovascular Circulation, Cerebrovascular Disorders, Child, Child, Preschool, Diagnosis, Differential, Disease Progression, Humans, Infant, Intracranial Aneurysm, Magnetic Resonance Imaging, Moyamoya Disease, Neuroimaging, Nuclear Magnetic Resonance, Biomolecular, Stroke Rehabilitation, Tomography, X-Ray Computed
Added March 24, 2020
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Discerning the Primary Carcinoma in Malignant Peritoneal and Pleural Effusions Using Imaging Mass Spectrometry-A Feasibility Study.
Schwamborn K, Weirich G, Steiger K, Zimmermann G, Schmidmayr M, Weichert W, Caprioli RM
(2019) Proteomics Clin Appl 13: e1800064
MeSH Terms: Diagnosis, Differential, Feasibility Studies, Humans, Mass Spectrometry, Molecular Imaging, Peritoneal Neoplasms, Pleural Effusion, Malignant, Tissue Array Analysis
Show Abstract · Added March 3, 2020
PURPOSE - Malignant effusions challenge diagnostic accuracy due to cytomorphologic overlaps between various malignant primaries. Workup of this material to establish a correct diagnosis is time consuming and limited by the sparsity of material. In order to circumvent these drawbacks, the use of MALDI imaging MS (IMS) as a diagnostic platform has been explored.
EXPERIMENTAL DESIGN - Cytology cell blocks from malignant effusions (serous ovarian carcinoma and several non-ovarian carcinomas including gastric adenocarcinoma) containing at least 30% neoplastic cells are selected for generation of cytology microarrays (CMA). CMA sections are transferred to conductive glass slides, subjected to on-tissue tryptic digestion, and matrix application for MALDI-IMS analysis.
RESULTS - Supervised classification analysis identifies serous ovarian carcinomas as the source of malignant effusions with a sensitivity of 85.7% when compared to samples from all other included primary sites. When compared to gastric adenocarcinoma, serous ovarian carcinoma samples can be delineated with a sensitivity of 97.3%.
CONCLUSION AND CLINICAL RELEVANCE - These preliminary results highlight that MALDI-IMS allows subtyping of malignant effusions to identify the precise origin of neoplastic cells. While achieving similar results compared to classical approaches such as immunocytology, more material is conserved that will be available for further tests.
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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New terminology-noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) and its effect on the rate of malignancy at a single institution.
Kiernan CM, Weiss VL, Mehrad M, Ely K, Baregamian N, Solórzano CC
(2018) Surgery 163: 55-59
MeSH Terms: Adult, Carcinoma, Papillary, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Retrospective Studies, Terminology as Topic, Thyroid Cancer, Papillary, Thyroid Gland, Thyroid Neoplasms
Show Abstract · Added April 15, 2019
BACKGROUND - The cytologic qualities of noninvasive follicular neoplasm with papillary-like nuclear features mimic papillary thyroid carcinoma (PTC) on fine-needle aspiration, leading to difficulty in distinguishing the 2 preoperatively. The aim of this study was to determine the impact of reclassification of noninvasive follicular neoplasm with papillary-like nuclear features at our practice.
METHODS - We searched 1,046 patient charts for those cases with preoperative cytology and subsequent follicular-variant papillary thyroid carcinoma diagnosis on resection. Endocrine pathologists reviewed the cases to determine the reclassification of noninvasive follicular neoplasm with papillary-like nuclear features.
RESULTS - Sixty (6%) follicular-variant papillary thyroid carcinomas were identified, 4% (44) in the index nodule. Of the 44 patients, 84% (37) met the criteria for evaluation. Of these, 46% (17) were noninvasive follicular neoplasm with papillary-like nuclear features. After reclassification of noninvasive follicular-variant papillary thyroid carcinoma to noninvasive follicular neoplasm with papillary-like nuclear features, the overall cancer rate changed from 31% to 29%. Malignancy rates across Bethesda cytologic categories changed as follows: benign (n = 419) from 3.5% to 3.3%; atypia of undetermined significance/follicular lesion of undetermined significance (n = 240) from 17% to 15%; suspicious for follicular neoplasm (n = 104) from 23% to 21%; suspicious for malignancy (n = 85) from 68% to 60%, and malignant (n = 198) from 93% to 92%.
CONCLUSION - Reclassification of noninvasive follicular neoplasm with papillary-like nuclear features led to a small decrease in the overall malignancy rate. The most affected Bethesda category was suspicious for malignancy. Because the majority of noninvasive follicular neoplasm with papillary-like nuclear features will be indeterminate lesions by cytology/molecular testing, thyroidectomy will remain a common treatment modality. Noninvasive follicular neoplasm with papillary-like nuclear features classification will primarily affect decision making to avoid excessive treatment/monitoring.
Copyright © 2017 Elsevier Inc. All rights reserved.
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Diagnostic value of histone 3 mutations in osteoclast-rich bone tumors.
Nohr E, Lee LH, Cates JM, Perizzolo M, Itani D
(2017) Hum Pathol 68: 119-127
MeSH Terms: Adolescent, Adult, Aged, Alberta, Biomarkers, Tumor, Bone Cysts, Aneurysmal, Bone Neoplasms, Child, Chondroblastoma, DNA Mutational Analysis, Diagnosis, Differential, Disease-Free Survival, Female, Genetic Predisposition to Disease, Giant Cell Tumor of Bone, Histones, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Osteoclasts, Phenotype, Predictive Value of Tests, Tennessee, Time Factors, Young Adult
Show Abstract · Added November 1, 2018
Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone [GCTB], chondroblastoma [CBA], and aneurysmal bone cyst [ABC]) can be challenging, especially in small biopsies or fine-needle aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.
Copyright © 2017 Elsevier Inc. All rights reserved.
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Masquerading as Sigmoid Adenocarcinoma: A Unique Presentation of High-Grade Serous Carcinoma Arising from Endometriosis.
Johnson WR, Kensinger CD, Desai MA, Hawkins AT
(2017) Am Surg 83: e316-317
MeSH Terms: Adenocarcinoma, Aged, Biopsy, Needle, Cystadenocarcinoma, Serous, Diagnosis, Differential, Endometrial Neoplasms, Endometriosis, Female, Humans, Immunohistochemistry, Risk Assessment, Sigmoid Neoplasms, Tomography, X-Ray Computed, Treatment Outcome
Added December 14, 2017
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14 MeSH Terms
Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease.
Williams AD, Korolkova OY, Sakwe AM, Geiger TM, James SD, Muldoon RL, Herline AJ, Goodwin JS, Izban MG, Washington MK, Smoot DT, Ballard BR, Gazouli M, M'Koma AE
(2017) PLoS One 12: e0179710
MeSH Terms: Biomarkers, Biopsy, Colitis, Ulcerative, Crohn Disease, Diagnosis, Differential, Gene Expression Profiling, Humans, Immunohistochemistry, Inflammatory Bowel Diseases, Intestinal Mucosa, Muramidase, Proctocolectomy, Restorative, Retrospective Studies, alpha-Defensins
Show Abstract · Added March 14, 2018
Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.
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14 MeSH Terms
An Incidental Hypervascular Retroperitoneal Mass.
Costacurta PW, Shaver AC, Idrees K
(2017) JAMA Surg 152: 887-888
MeSH Terms: Aged, Castleman Disease, Diagnosis, Differential, Humans, Incidental Findings, Male, Retroperitoneal Neoplasms, Tomography, X-Ray Computed, Treatment Outcome
Added April 10, 2018
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Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules from Lung Adenocarcinoma.
Codreanu SG, Hoeksema MD, Slebos RJC, Zimmerman LJ, Rahman SMJ, Li M, Chen SC, Chen H, Eisenberg R, Liebler DC, Massion PP
(2017) J Proteome Res 16: 3266-3276
MeSH Terms: 5-Lipoxygenase-Activating Proteins, Adenocarcinoma, Adenocarcinoma of Lung, Adult, Aged, Antigens, CD, Arachidonate 5-Lipoxygenase, Biomarkers, Tumor, CD11 Antigens, Cell Adhesion Molecules, Diagnosis, Differential, Female, GPI-Linked Proteins, Gene Expression Regulation, Neoplastic, Glucose Transporter Type 3, Humans, Integrin alpha Chains, Lung Neoplasms, Male, Middle Aged, Neoplasm Proteins, Proteomics, Respiratory Mucosa, Solitary Pulmonary Nodule, Tandem Mass Spectrometry, Tissue Array Analysis, Transcriptome
Show Abstract · Added January 29, 2018
We hypothesized that distinct protein expression features of benign and malignant pulmonary nodules may reveal novel candidate biomarkers for the early detection of lung cancer. We performed proteome profiling by liquid chromatography-tandem mass spectrometry to characterize 34 resected benign lung nodules, 24 untreated lung adenocarcinomas (ADCs), and biopsies of bronchial epithelium. Group comparisons identified 65 proteins that differentiate nodules from ADCs and normal bronchial epithelium and 66 proteins that differentiate ADCs from nodules and normal bronchial epithelium. We developed a multiplexed parallel reaction monitoring (PRM) assay to quantify a subset of 43 of these candidate biomarkers in an independent cohort of 20 benign nodules, 21 ADCs, and 20 normal bronchial biopsies. PRM analyses confirmed significant nodule-specific abundance of 10 proteins including ALOX5, ALOX5AP, CCL19, CILP1, COL5A2, ITGB2, ITGAX, PTPRE, S100A12, and SLC2A3 and significant ADC-specific abundance of CEACAM6, CRABP2, LAD1, PLOD2, and TMEM110-MUSTN1. Immunohistochemistry analyses for seven selected proteins performed on an independent set of tissue microarrays confirmed nodule-specific expression of ALOX5, ALOX5AP, ITGAX, and SLC2A3 and cancer-specific expression of CEACAM6. These studies illustrate the value of global and targeted proteomics in a systematic process to identify and qualify candidate biomarkers for noninvasive molecular diagnosis of lung cancer.
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27 MeSH Terms