Browsing by Subject "Pathology"
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Item A Case of Metastatic Basal Cell Carcinoma (BCC) With Spinal and Pulmonary Metastases Treated With Vismodegib, Sonedigib, and Radiotherapy(Springer Nature, 2022-03-17) Samia, Arthur M.; Nenow, Joseph M.; Boyer, Philip; Medicine, School of MedicineBasal cell carcinoma (BCC) is the most common malignancy worldwide and has one of the most favorable prognoses due to its tendency to remain local. Clinical presentation with rare distant metastases significantly increases morbidity and mortality. Historically, no effective therapies have existed for locally advanced or metastatic BCC. Recent research highlights the possibility of treating patients with advanced and metastatic BCC with hedgehog pathway inhibitors, such as vismodegib or sonedigib. We present the case of a 62-year-old male with a history of a large left shoulder lesion, which was diagnosed as a nodulocystic BCC following biopsy and histopathologic examination. The primary lesion was managed with surgical excision, and his ensuing metastatic disease was treated with vismodegib, sonedigib, tumor debulking, and radiation therapy. Magnetic resonance imaging and computed tomography of the chest revealed probable metastases to the apical segment of the left upper lobe and thoracic spine, leading to spinal stenosis and probable cause of the patient's ataxia and paresthesias. Due to the ability of BCCs to transform during metastasis, it is impossible to identify the nature of metastatic lesions (i.e., basaloid, squamous, or hybrid) without biopsy. In this case report, we review the etiologies, typical demographics, presentation patterns, and treatment regimens for metastatic BCC and the possibility of metastatic disease transforming to squamous or hybrid variants.Item A case report of terbinafine-induced acute generalized exanthematous pustulosis in a striking photodistributed pattern(Sage, 2024-02-14) Lange, Charles D.; Madden, Laura; Rawlings Parker, Eva; Dermatology, School of MedicineAcute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction that classically presents in intertriginous or flexural areas and subsequently spreads diffusely across the trunk and extremities. To date, few cases of acute generalized exanthematous pustulosis arising in a photodistributed pattern are documented. Herein, we describe the second known case of photodistributed generalized exanthematous pustulosis arising in association with oral terbinafine use, providing a summary of the previously documented cases along with exploration of the potential pathophysiological mechanisms for this cutaneous reaction.Item Alois Alzheimer: His Life and Times(Wiley, 2007-01) Goedert, Michel; Ghetti, Bernardino; Pathology and Laboratory Medicine, School of MedicineBetween national unification and World War I, Germany was preeminent in many areas of science and medicine. Alois Alzheimer, who lived during this period, was one of the founders of the field of neuropathology. His name will always be linked with the form of dementia that he described 100 years ago. Here we mark this anniversary by discussing Alzheimer's contributions to dementia research in the context of his life and times.Item Correction to: Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research(Springer, 2022) Jagsi, R.; Mason, G.; Overmoyer, B.A.; Woodward, W.A.; Badve, S.; Schneider, R.J.; Lang, J.E.; Alpaugh, M.; Williams, K.P.; Vaught, D.; Smith, A.; Smith, K.; Miller, K.D.; Medicine, School of MedicineErratum for: Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research. Jagsi R, Mason G, Overmoyer BA, Woodward WA, Badve S, Schneider RJ, Lang JE, Alpaugh M, Williams KP, Vaught D, Smith A, Smith K, Miller KD; Susan G. Komen-IBCRF IBC Collaborative in partnership with the Milburn Foundation. Breast Cancer Res Treat. 2022 Apr;192(2):235-243. doi: 10.1007/s10549-021-06434-x. Epub 2022 Jan 1. PMID: 34973083Item Distinct mouse models correspond to distinct AD molecular subtypes(Wiley, 2025-01-03) Pandey, Ravi S.; Carter, Gregory W.; Howell, Gareth R.; Sasner, Michael; Kotredes, Kevin P.; Oblak, Adrian L.; Lamb, Bruce T.; Pharmacology and Toxicology, School of MedicineBackground: Alzheimer’s disease (AD) is a complex, multifactorial pathology with high heterogeneity in biological alterations. Our understanding of cellular and molecular mechanisms from disease risk variants to various phenotypes is still limited. Mouse models of AD serve as indispensable platforms for comprehensively characterizing AD pathology, disease progression, and biological mechanisms. However, selection of the right model in preclinical research and translation of findings to clinical populations are intricate processes that require identification of pathophysiological resemblance between model organisms and humans. Many existing clinical trials that showed promising efficacy in one particular mouse model later do not align with human trial results, assuming that study had consisted of a heterogeneous group of participants, and individual animal models may only recapitulate features of a subgroup of human cases. To improve interspecies translation, it is necessary to comprehensively compare molecular signatures in mouse models with subgroup of human AD cases with distinct molecular signatures. Method: We performed transcriptomic and proteomics analysis on whole brain samples from mouse models carrying LOAD risk variants. To assess the human disease relevance of LOAD risk variants in mice, we determined the extent to which changes due to genetic perturbations in mice matched those observed in human AD subtypes and disease stages of AD in the ROS/MAP, Mayo and Mount Sinai Brain Bank cohorts. Genesets within these disease subtypes are highly co‐expressed and represent specific molecular pathways. Result: We have identified that distinct mouse models match to distinct human AD subtypes in age‐dependent manner. Specifically, mouse models carrying human AD risk variants such as Abca7*A1527G showed strong correlation with inflammatory AD subtypes, while mouse models carrying risk variant such as Plcg2*M28L exhibited transcriptomics changes similar to non‐inflammatory AD subtypes. Conclusion: In this study, we highlighted that mouse model of AD may match to a particular subset of human AD subtypes but not all subtypes simultaneously, and that risk for these subtypes may be influenced by distinct AD genetic factors. Additional work toward validating and better understanding the role of each subtype key regulator in its matching mouse model will provide great value and have a great impact on future studies of AD.Item Endoscopic observations as a tool to define underlying pathology in kidney stone formers(Springer, 2019-10) Pless, Maria Sloth; Williams, James Caldwell, Jr.; Andreassen, Kim Hovgaard; Jung, Helene Ulrich; Osther, Susanne Sloth; Christensen, Dorte Ravnsmed; Osther, Palle Jörn Sloth; Anatomy and Cell Biology, School of MedicinePURPOSE: Advancements in endoscopy offer the possibility of inspection of intrarenal anatomy and pathology. The aim of the study was to evaluate renal papillary appearance in kidney stone formers and to correlate papillary findings with stone type and patient metabolic data. MATERIALS AND METHODS: A consecutive cohort of 46 kidney stone formers undergoing retrograde intrarenal surgery was enrolled. During surgery, renal papillae were characterized in the domains of ductal Plugging (DP), surface Pitting, Loss of papillary contour, and Amount of Randall's plaque (RP, PPLA scoring). Stone material was analyzed using micro-CT and infrared spectroscopy, and blood and urine were collected for metabolic evaluation. RESULTS: In all patients, renal papillae had changes in at least one of the domains of the PPLA score. Examining the total population, it was evident that patients with predominantly plugging (DP > 0) all had very low RP scores. There were no significant trends between mean PPLA scores and urinary analytes for the total group. CONCLUSION: Efforts to prevent renal stone formation have so far been insufficient in majority of patients. Digital endoscopy reveals that kidney stone formers have different and distinct papillary morphologies that seem to be linked to specific stone-forming pathways. Since renal papillary abnormalities may be easily identified during endoscopy, this may in the future prove to be an important method for tailoring prevention strategies in kidney stone patients.Item Glycogenosis is common in nonalcoholic fatty liver disease and is independently associated with ballooning, but lower steatosis and lower fibrosis(Wiley, 2021-05) Allende, Daniela S.; Gawrieh, Samer; Cummings, Oscar W.; Belt, Patricia; Wilson, Laura; Van Natta, Mark; Behling, Cynthia A.; Carpenter, Danielle; Gill, Ryan M.; Kleiner, David E.; Yeh, Mathew M.; Chalasani, Naga; Guy, Cynthia D.; Medicine, School of MedicineBackground/aims: Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD). Methods: Glycogenosis in NAFLD liver biopsies was graded as "none", "focal" (in <50% of hepatocytes), or "diffuse" (in ≥50% of hepatocytes). Clinical and pathological variables associated with glycogenosis were assessed. 2047 liver biopsies were prospectively analysed. Results: In adults and children, any glycogenosis was present in 54% of cases; diffuse glycogenosis was noted in approximately 1/3 of cases. On multiple logistic regression analysis, adults with glycogenosis tended to be older (P = .003), female (P = .04), have higher serum glucose (P = .01), and use insulin (P = .02). Adults tended to have lower steatosis scores (P = .006) and lower fibrosis stages (P = .005); however, unexpectedly, they also tended to have more hepatocyte injury including ballooning (P = .003). On multiple logistic regression analysis, paediatric patients with glycogenosis were more likely to be Hispanic (P = .03), have lower body weight (P = .002), elevated triglycerides (P = .001), and a higher fasting glucose (P = .007). Paediatric patients with glycogenosis also had less steatosis (P < .001) than those without. Conclusions: Glycogenosis is common in adult and paediatric NAFLD, and is associated with clinical features of insulin resistance. Glycogenosis is important to recognize histologically because it may be misinterpreted as ballooning, and when diffuse, confusion with glycogen storage disorders or glycogenic hepatopathy must be avoided. The newly observed dichotomous relationship between glycogenosis and increased liver cell injury but decreased steatosis and fibrosis requires further study.Item Implementation of a Quality and Patient Safety Curriculum for Pathology Residency Training(Elsevier, 2021-03-18) Sapatnekar, Suneeti; Demkowicz, Ryan; Chute, Deborah J.; Pathology and Laboratory Medicine, School of MedicineQuality and Patient Safety education for resident physicians is necessary to prepare them for independent practice and to meet accreditation requirements. Integrating such education into the residents' routine work can provide them with valuable practical experience, while advancing the institution's quality priorities. We committed to Quality and Patient Safety education for our pathology residents but found no published program that met their specific needs. To fill this gap in pathology residency education, we designed and implemented a new curriculum that spans the 4-year duration of residency training. Curriculum content was drawn from the pathology milestones, and educational strategies were based on the principles of adult learning. The curriculum was implemented in the 2018 to 19 academic year, and residents were assessed before and after their participation. The residents engaged in several Quality and Patient Safety activities and projects under faculty supervision, and improved their scores on objective assessments (Quality and Patient Safety quiz and in-service examination). Implementation was facilitated by a Quality and Patient Safety chief resident, and the recruitment of faculty with demonstrated Quality and Patient Safety interest. Our comprehensive Quality and Patient Safety curriculum is feasible to implement and can help pathology residents develop the knowledge and skills needed to lead quality initiatives. We believe that the curriculum framework is readily adaptable to other residency programs.Item Incidence and Importance of Calcium Deposition in Kidney Biopsy Specimens(Karger, 2022) Gaddy, Anna; Schwantes-An, Tae-Hwi; Moorthi, Ranjani N.; Phillips, Carrie L.; Eadon, Michael T.; Moe, Sharon M.; Medical and Molecular Genetics, School of MedicineIntroduction: Calcification on native kidney biopsy specimens is often noted by pathologists, but the consequence is unknown. Methods: We searched the pathology reports in the Biopsy Biobank Cohort of Indiana for native biopsy specimens with calcification. Results: Of the 4,364 specimens, 416 (9.8%) had calcification. We compared clinical and histopathology findings in those with calcification (n = 429) compared to those without calcification (n = 3,936). Patients with calcification were older, had more comorbidities, lower estimated glomerular filtration rates (eGFR), were more likely to have hyaline arteriosclerosis, interstitial fibrosis/tubular atrophy, and a primary pathologic diagnosis of acute tubular injury or acute tubular necrosis when compared to patients without calcification. Patients with calcium oxalate deposition alone, compared to calcium phosphate or mixed calcifications, had fewer comorbidities but were more likely to have a history of gastric bypass surgery or malabsorption and take vitamin D. In patients with two or more years of follow-up, multivariate analyses showed the presence of calcification (HR 0.59, 0.38-0.92, p = 0.02) and higher eGFR (HR 0.76, 0.73-0.79, p < 0.001), was associated with decreased likelihood of progressing to end-stage renal disease. The presence of calcification was also associated with a reduced slope/decline in eGFR compared to known biopsy and clinical risk factors for decline in kidney function. We hypothesized this was due to more recoverable acute kidney injury (AKI) and found more severe acute kidney injury network stage in patients with kidney calcification but also greater improvement over time. Discussion/conclusion: In summary, we demonstrated that calcification on kidney biopsy specimens was associated with a better prognosis than those without calcification due to the association with recoverable AKI.