Browsing by Author "Pathology and Laboratory Medicine, School of Medicine"
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Item 11C-PiB PET can underestimate brain amyloid-β burden when cotton wool plaques are numerous(Oxford University Press, 2022) Abrahamson, Eric E.; Kofler, Julia K.; Becker, Carl R.; Price, Julie C.; Newell, Kathy L.; Ghetti, Bernardino; Murrell, Jill R.; McLean, Catriona A.; Lopez, Oscar L.; Mathis, Chester A.; Klunk, William E.; Villemagne, Victor L.; Ikonomovic, Milos D.; Pathology and Laboratory Medicine, School of MedicineIndividuals with familial Alzheimer's disease due to PSEN1 mutations develop high cortical fibrillar amyloid-β load but often have lower cortical 11C-Pittsburgh compound B (PiB) retention than Individuals with sporadic Alzheimer's disease. We hypothesized this is influenced by limited interactions of Pittsburgh compound B with cotton wool plaques, an amyloid-β plaque type common in familial Alzheimer's disease but rare in sporadic Alzheimer's disease. Histological sections of frontal and temporal cortex, caudate nucleus and cerebellum were obtained from 14 cases with sporadic Alzheimer's disease, 12 cases with familial Alzheimer's disease due to PSEN1 mutations, two relatives of a PSEN1 mutation carrier but without genotype information and three non-Alzheimer's disease cases. Sections were processed immunohistochemically using amyloid-β-targeting antibodies and the fluorescent amyloid stains cyano-PiB and X-34. Plaque load was quantified by percentage area analysis. Frozen homogenates from the same brain regions from five sporadic Alzheimer's disease and three familial Alzheimer's disease cases were analysed for 3H-PiB in vitro binding and concentrations of amyloid-β1-40 and amyloid-β1-42. Nine sporadic Alzheimer's disease, three familial Alzheimer's disease and three non-Alzheimer's disease participants had 11C-PiB PET with standardized uptake value ratios calculated using the cerebellum as the reference region. Cotton wool plaques were present in the neocortex of all familial Alzheimer's disease cases and one sporadic Alzheimer's disease case, in the caudate nucleus from four familial Alzheimer's disease cases, but not in the cerebellum. Cotton wool plaques immunolabelled robustly with 4G8 and amyloid-β42 antibodies but weakly with amyloid-β40 and amyloid-βN3pE antibodies and had only background cyano-PiB fluorescence despite labelling with X-34. Relative to amyloid-β plaque load, cyano-Pittsburgh compound B plaque load was similar in sporadic Alzheimer's disease while in familial Alzheimer's disease it was lower in the neocortex and the caudate nucleus. In both regions, insoluble amyloid-β1-42 and amyloid-β1-40 concentrations were similar in familial Alzheimer's disease and sporadic Alzheimer's disease groups, while 3H-PiB binding was lower in the familial Alzheimer's disease than the sporadic Alzheimer's disease group. Higher amyloid-β1-42 concentration associated with higher 3H-PiB binding in sporadic Alzheimer's disease but not familial Alzheimer's disease. 11C-PiB retention correlated with region-matched post-mortem amyloid-β plaque load; however, familial Alzheimer's disease cases with abundant cotton wool plaques had lower 11C-PiB retention than sporadic Alzheimer's disease cases with similar amyloid-β plaque loads. PiB has limited ability to detect amyloid-β aggregates in cotton wool plaques and may underestimate total amyloid-β plaque burden in brain regions with abundant cotton wool plaques.Item A 2-year-old boy with hemolytic uremic syndrome and pneumocephalus(Wiley, 2012-01) Martin, Sarah E.; Allen, Steven D.; Faught, Phillip; Hawley, Dean A.; Bonnin, Jose M.; Hattab, Eyas M.; Pathology and Laboratory Medicine, School of MedicineClostridium septicum infection following hemolytic uremic syndrome is rare and carries a poor prognosis, especially when the brain is involved. We report a case of a previously healthy 2-year-old boy who presented with two days of anuria and bloody diarrhea. He was admitted to the local children's hospital with a diagnosis of hemolytic uremic syndrome, presumably secondary to E. coli O157. He soon required intubation and was noted to have fixed and dilated pupils. Head CT revealed left frontal subcortical white matter vasogenic edema and scattered pockets of pneumocephalus. The patient expired 14 hours after admission. Antemortem blood cultures grew C. septicum. Gross pathologic examination of the brain revealed a large intraparenchymal cerebral hemorrhage in the left frontal and parietal lobes. There was extensive cystic changes as well. Microscopic examination revealed vacuolization and diffuse colonization with rod-shaped bacteria, but without the expected tissue response. There have been only six previously reported cases of C. septicum infection following hemolytic uremic syndrome, four of which had brain involvement. Mortality rate is high, with the only known survivor among those with brain involvement having a brain abscess rather than diffuse pneumocephalus.Item 322. Evaluation of the BioFire® Bone and Joint Infection (BJI) Panel for the Detection of Microorganisms and Antimicrobial Resistance Genes in Synovial Fluid Specimens(Oxford University Press, 2020-12) Graue, Corrin; Schmitt, Bryan H.; Waggoner, Amy; Laurent, Frederic; Abad, Lelia; Bauer, Thomas; Mazariegos, Irving; Balada-Llasat, Joan-Miquel; Horn, Jarid; Wolk, Donna; Jefferis, Alexa; Hermans, Mirjam; Verhoofstad, Irma; Butler-Wu, Susan; Umali-Wilcox, Minette; Murphy, Caitlin N.; Cabrera, Barbara J.; Esteban, Jaime; Macias-Valcayo, Alicia; Craft, David; von Bredow, Benjamin; Leber, Amy; Everhart, Kathy; Dien Bard, Jennifer; Mestas, Jvier; Daly, Judy; Barr, Rebecca; Kensinger, Bart; Pons, Benedicte; Jay, Corinne; Pathology and Laboratory Medicine, School of MedicineBackground Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs.Item A 41-year-old woman with von Hippel-Lindau and a cerebellar lesion(Wiley, 2010-03) Martin, Sarah E.; Al-Khatib, Sohaib M.; Turner, Michael S.; Douglas-Akinwande, Annette C.; Hattab, Eyas M.; Pathology and Laboratory Medicine, School of MedicineA 41-year-old woman with a 12-year history of von Hippel-Lindau disease presented with progressive quadriparesis and difficulty swallowing. MRI revealed a well-circumscribed, partially cystic cerebellar neoplasm, consistent with hemangioblastoma. The tumor was resected and the diagnosis of hemangioblastoma confirmed. Embedded within the hemangioblastoma was a small focus of metastatic renal cell carcinoma (RCC). RCC metastatic to a CNS hemangioblastoma is the second most common type of tumor-to-tumor metastasis, which may be due to a number of factors. Proper immunostaining panels are required to clearly identify these cases since both tumor may have similar histology.Item A 61-year-old woman with osteomalacia and a thoracic spine lesion(Wiley, 2010-03) Marshall, Ann E.; Martin, Sarah E.; Agaram, Narasimhan P.; Chen, Jey-Hsin; Horn, Eric M.; Douglas-Akinwande, Annette C.; Hattab, Eyas M.; Pathology and Laboratory Medicine, School of MedicinePhosphaturic mesenchymal tumor, mixed connective tissue variant (PMT-MCT) is a rare, largely benign, mesenchymal neoplasm almost invariably associated with oncogenic osteomalacia. It is generally found in the soft tissue and bone of the extremities. We report a case of a 61-year-old female with long-standing osteomalacia who was found to have PMT-MCT of the thoracic spine. There have been very few previously reported cases of PMT involving the spinal vertebrae and neuropathologists should be aware of this lesion. Recognition of PMT-MCT is critical for optimal patient care since complete surgical resection without additional therapy is curative.Item 754. Performance Characterization of a Real Time PCR Assay for Pneumocystis jirovecii in Bronchoalveolar Lavage Fluid and Sputum(Oxford University Press, 2020-10) Bell, Drew T.; Koehlinger, Jeremy; Schmitt, Bryan H.; Pathology and Laboratory Medicine, School of MedicineBackground Pneumocystis jirovecii pneumonia (PJP) affects immunocompromised patients and contributes significantly to mortality. Outcomes depend on early treatment, making timely and accurate diagnosis critical. Typically, PJP diagnosis is through identification of trophozoite or cyst forms in bronchoalveolar lavage (BAL) fluid or sputum, a labor-intensive and insensitive process. Options for more accessible and sensitive molecular detection are limited. It is known that patients may be colonized, which can cast doubt on the clinical significance of low levels of DNA amplification in qualitative result reporting. In this study, we describe a real time (rt) PCR assay utilizing analyte specific reagent primers targeting the mtLSU gene of P. jirovecii and correlate amplification with morphological PJP identification. Methods IUHPL Clinical Microbiology assessed sputum or BAL fluid from 109 patients with clinical concern for PJP microscopically via fungal stains (GMS, calcofluor white). Comparative rtPCR was conducted as follows. First, 2µL of residual specimen or control were mixed with an 8µL combination of rtPCR mastermix, control DNA, and primer pairs (Simplexa). No nucleic acid extraction was performed. Real time PCR was executed and analyzed on the LIAISON MDX (DiaSorin) platform. Qualitative amplification results and cycle threshold (CT) values were correlated with microscopic methods to establish performance. Chart review was performed to assess the clinical impact of this assay. Results P. jirovecii was microscopically detected in 26% (29/109) of samples, while 31.1% (34/109) exhibited amplification by rtPCR. Agreement between the two methods was 95.4%; rtPCR demonstrated 100% sensitivity and 93.8% specificity in comparison. Conclusion Our results indicate that this assay has exceptional negative predictive value (100%), and therefore may be valuable as a screening test. Considering this data alone, the positive predictive value is lower (85.3%). Further examination of the data, however, revealed that 80% (4/5) of discrepant results demonstrated CT values of >34, while the highest CT for a microscopically positive sample was 31.2. Further clinical correlation may establish a CT cutoff that will reduce false positive and potentially clinically insignificant cases.Item A deep learning framework for automated classification of histopathological kidney whole-slide images(Elsevier, 2022-04-18) Abdeltawab, Hisham A.; Khalifa, Fahmi A.; Ghazal, Mohammed A.; Cheng, Liang; El-Baz, Ayman S.; Gondim, Dibson D.; Pathology and Laboratory Medicine, School of MedicineBackground: Renal cell carcinoma is the most common type of malignant kidney tumor and is responsible for 14,830 deaths per year in the United States. Among the four most common subtypes of renal cell carcinoma, clear cell renal cell carcinoma has the worst prognosis and clear cell papillary renal cell carcinoma appears to have no malignant potential. Distinction between these two subtypes can be difficult due to morphologic overlap on examination of histopathological preparation stained with hematoxylin and eosin. Ancillary techniques, such as immunohistochemistry, can be helpful, but they are not universally available. We propose and evaluate a new deep learning framework for tumor classification tasks to distinguish clear cell renal cell carcinoma from papillary renal cell carcinoma. Methods: Our deep learning framework is composed of three convolutional neural networks. We divided whole-slide kidney images into patches with three different sizes where each network processes a specific patch size. Our framework provides patchwise and pixelwise classification. The histopathological kidney data is composed of 64 image slides that belong to 4 categories: fat, parenchyma, clear cell renal cell carcinoma, and clear cell papillary renal cell carcinoma. The final output of our framework is an image map where each pixel is classified into one class. To maintain consistency, we processed the map with Gauss-Markov random field smoothing. Results: Our framework succeeded in classifying the four classes and showed superior performance compared to well-established state-of-the-art methods (pixel accuracy: 0.89 ResNet18, 0.92 proposed). Conclusions: Deep learning techniques have a significant potential for cancer diagnosis.Item A large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information(Springer Nature, 2024-02-29) Ramakrishnan, Divya; Jekel, Leon; Chadha, Saahil; Janas, Anastasia; Moy, Harrison; Maleki, Nazanin; Sala, Matthew; Kaur, Manpreet; Cassinelli Petersen, Gabriel; Merkaj, Sara; von Reppert, Marc; Baid, Ujjwal; Bakas, Spyridon; Kirsch, Claudia; Davis, Melissa; Bousabarah, Khaled; Holler, Wolfgang; Lin, MingDe; Westerhoff, Malte; Aneja, Sanjay; Memon, Fatima; Aboian, Mariam S.; Pathology and Laboratory Medicine, School of MedicineResection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.Item A Large Open Access Dataset of Brain Metastasis 3D Segmentations with Clinical and Imaging Feature Information(Springer Nature, 2024-02-29) Ramakrishnan, Divya; Jekel, Leon; Chadha, Saahil; Janas, Anastasia; Moy, Harrison; Maleki, Nazanin; Sala, Matthew; Kaur, Manpreet; Cassinelli Petersen, Gabriel; Merkaj, Sara; von Reppert, Marc; Baid, Ujjwal; Bakas, Spyridon; Kirsch, Claudia; Davis, Melissa; Bousabarah, Khaled; Holler, Wolfgang; Lin, MingDe; Westerhoff, Malte; Aneja, Sanjay; Memon, Fatima; Aboian, Mariam S.; Pathology and Laboratory Medicine, School of MedicineResection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.Item A massive 13.5 cm sclerosing pneumocytoma in a 61-year-old female(Elsevier, 2021) Boham, Sampson K.; Kesler, Kenneth A.; Geib, Merideth E.; Wang, Xiaoyan; Pathology and Laboratory Medicine, School of MedicineSclerosing pneumocytoma (previously called pulmonary sclerosing hemangioma) is a very rare benign pulmonary neoplasm. Diagnosis of this tumor can be problematic especially on the small biopsy specimens. Here, we report a massive 13.5 cm sclerosing pneumocytoma in a 61-year-old female who presented with progressive shortness of breath and underwent lobectomy procedure. Radiological findings, gross and histological features, immunohistochemical staining profile as well as differential diagnoses are discussed in detail. The purpose of this case study is to increase awareness of this entity among physicians and to further aid in proper clinical management.