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Am I Missing Something? Blindness • Dan Simons and Chris Chabris: Video Studies Created During Experimental Psychology Course

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Am I Missing Something? Blindness • Dan Simons and Chris Chabris: Video Studies Created During Experimental Psychology Course 5/24/2018 Is This Normal Lung? Looking Beyond the Interstitium Kirk D. Jones, MD UCSF Dept of Pathology [email protected] Inattentional Blindness • Ulric Neisser: Selective looking • Arien Mack and Irvin Rock: Inattentional Am I Missing Something? blindness • Dan Simons and Chris Chabris: Video studies created during Experimental Psychology course 1 5/24/2018 Inattentional Blindness • “when our attention is focused on one thing, we fail to notice other, unexpected things around us—including those we might want to see.” • In pathology of the lung, there are often two things that focus our attention: – The tumor in neoplastic disease – The alveoli in non-neoplastic disease The Neglected Compartments • Bronchioles – Inflammatory bronchiolitis – Fibrotic bronchiolitis ALVEOLI • Vessels – Pulmonary arteriopathy – Pulmonary venopathy • Pleura – Pleural inflammation or neoplasm bronchioles vessels pleura • Absence of alveoli – Cystic disease 2 5/24/2018 Overview of Talk • Bronchioles – Bronchiolitis – Diffuse panbronchiolitis – Constrictive bronchiolitis • Vessels – Pulmonary arteriopathy – Pulmonary veno-occlusive disease • Lack of alveoli – cystic disease – Lymphangioleiomyomatosis Classification of Bronchiolitis • Cellular infiltrates (inflammatory) – Intraluminal • Neutrophils: Acute bronchiolitis, bronchopneumonia • Macrophages: Respiratory bronchiolitis – Mural • Lymphocytes: Chronic/cellular bronchiolitis • Lymphoid follicles: Follicular bronchiolitis – Peribronchiolar/Interstitial • Macrophages: Diffuse panbronchiolitis 3 5/24/2018 Adenovirus CC77-111 Respiratory bronchiolitis Respiratory bronchiolitis Follicular bronchiolitis 4 5/24/2018 Illustrative Case • 46-year-old woman with hypogammaglobulinemia treated with IVIG • Profound progressive dyspnea and sinusitis • Lung transplant performed Follicular bronchiolitis 5 5/24/2018 Diffuse Panbronchiolitis • First described in the 1960’s in Japan • Named diffuse panbronchiolitis in 1969 due to involvement of terminal bronchiole (sinusitis is often also present) • Progressive inflammatory bronchiolitis with subsequent bronchiectasis Diffuse Panbronchiolitis Diffuse Panbronchiolitis Classification of Bronchiolitis • Accumulation of foamy macrophages in the • Fibrotic/Fibroplastic peribronchiolar interstitium – Intraluminal polyps: Proliferative bronchiolitis • The bronchioles usually show mixed acute • This is the old BOOP and chronic mural inflammation – Intramural scarring: Constrictive bronchiolitis • Similar lesions observed in • aka BO, OB, cicatricial bronchiolitis hypogammaglobulinemia, inflammatory – Peribronchiolar/Interstitial bowel disease, autoimmune disease • Peribronchiolar metaplasia • Often lethal without treatment, but controllable with low-dose macrolide therapy 6 5/24/2018 BOOP Granulation tissue polyp Organizing pneumonia – “Proliferative bronchiolitis” Bronchiolitis Obliterans? or Organizing Pneumonia Organizing pneumonia – “Proliferative bronchiolitis” 7 5/24/2018 Organizing Pneumonia Organizing pneumonia Organizing pneumonia 8 5/24/2018 Constrictive Bronchiolitis Transplant rejection with CB Illustrative Case • Legal case with limited history • Transplanted, worked with artificial flavoring agents at some point 9 5/24/2018 10 5/24/2018 Popcorn-worker lung • May 2000: a physician in Jasper, MO identified a group of 8 former workers from a microwave popcorn plant. • 4 of the 8 worked in the “mixing room” (of the 425 total workers at the plant, only 13 worked in the mixing room). • Soybean oil, salt, and flavorings were mixed into a large heated tank in a process that produces visible dust, aerosols, and vapors with a strong buttery odor • Analysis of the vapors identified diacetyl as the likely culprit • Although originally referred to as “Popcorn-worker lung” this is occasionally called “flavorings-related lung disease” Diacetyl-related CB CB - Associated Histologic Findings • Foamy macrophage accumulation – Often in the region immediately proximal to obstruction • Cholesterol “stasis” granuloma formation – Often in the alveolar ducts distal to obstruction • Proximal bronchiectasis and bronchiolectasis Transplant rejection with CB 11 5/24/2018 Diacetyl-related CB Transplant rejection with bronchiolectasis CB - Increasing Diagnostic Yield • Clinical context helpful – PFTs, CT with expiratory views • Obtain additional sections – step or level sections (usually 30 micron gap) • Obtain elastic stains – Verhoeff-van Gieson Stain (VVG) – Movat Pentachrome Transplant rejection with bronchiolectasis 12 5/24/2018 EVG stain reveals CB Histologic Mimic/Tissue Artifact • Ex vivo contraction of smooth muscle can result in narrowing of bronchioles • This effect is less likely to occur when fixation is performed through bronchi (as in lobectomy or pneumonectomy samples). Thunnissen E, et al. Arch Pathol Lab Med. 2016 Mar; 140(3): 212-20. PMID: 26927715. Pneumonectomy perfused through mainstem bronchus 13 5/24/2018 Causes and Associations of CB • Chronic lung transplant rejection • Graft versus host disease • Post-infectious • Connective tissue disease • Fume or toxin exposure – SO2 gas – Diacetyl (popcorn worker lung) – Sauropus androgynus tea • Drug reaction (penicillamine, gold) • Miscellaneous – Inflammatory bowel disease – DIPNECH • Idiopathic Surgical biopsy in patient with emphysema Chronic Rejection, Lung Transplant- CB Chronic Rejection, Lung Transplant- CB 14 5/24/2018 Chronic Rejection, Lung Transplant- CB Chronic Rejection, Lung Transplant- CB Penicillamine toxicity - CB Penicillamine toxicity - CB 15 5/24/2018 Constrictive Bronchiolitis Pulmonary Vascular Disease • Subepithelial (often concentric) fibrosis • Pulmonary arteries run alongside bronchioles and are approximately the same caliber • Patchy nature can make diagnosis difficult • Pulmonary veins lie in the interlobular septa, – Knowledge of clinical and radiologic features but small venules are arranged within the – Use of level sections and elastic stains lobules – Recognize “next-to” lesions • Vascular disease can manifest as changes in • Ex vivo smooth muscle contraction can mimic the vessel wall or changes within the vessel • Various causes, but overall low incidence lumen Normal Pulmonary Vessels • Pulmonary arteries have two distinct elastic tissue layers while pulmonary veins have only one. 16 5/24/2018 17 5/24/2018 Pulmonary arteriopathy Illustrative Case • Plexogenic arteriopathy • 18-year-old woman with history of systemic – Tufts of capillary-like vessels bulging from artery lupus erythematosus, treated with plaquenil with damaged elastica and steroid pulses, presenting with persistent – More common in primary pulmonary hypertension progressive dyspnea • Thrombotic arteriopathy – Re-canalized thrombi (Masson lesion) with intact vascular elastica • Isolated medial and intimal thickening – Beware of age-related changes 18 5/24/2018 Pulmonary veno-occlusive disease Diseases with Alveolar Loss (Occlusive Venopathy) • Cystic lung disease • My least favorite diagnosis – Pulmonary Langerhans cell histiocytosis • • Upper zone dominant, often with nodules or irregular Characterized by intimal obliteration of post- shapes, observed in smokers capillary venules in many cases – Lymphangioleiomyomatosis • Can see associated pathologic findings: • Diffuse involvement, observed in women, can see angiomyolipoma in kidneys – Pulmonary capillary hemangiomatosis – Lymphoid interstitial pneumonia (LIP) – Alveolar siderosis • Fewer cysts usually, associated with dense intersitial infiltrates – Encrustation of vascular elastica – Birt-Hogg-Dube • More often in lower lung zones, punched-out look 19 5/24/2018 Illustrative Case • 65-year-old woman with diffuse bilateral pulmonary cystic disease • Transbronchial biopsy with “increased muscle” • Sent for consultation 20 5/24/2018 Smooth-muscle actin Estrogen receptor Diagnosis of LAM • Patients with LAM show increases in VEGF-D (but not VEGF-A or -C) Seyama K, et al. Lymphat Res Biol. 2006;4(3):143-52. PMID: 17034294. HMB-45 Young LR, et al. N Engl J Med. 2008 Jan 10;358(2):199-200. PMID: 18184970. 21 5/24/2018 Diagnosis of LAM • Cysts on CT? TSC? If both yes – LAM • Cysts on CT? Send serum VEGF-D. If (+) – LAM • TBBx • VATS Inattentional Blindness • A key to inattentional blindness is that the event is unexpected • Knowledge of possibilities and attention to normal structures decreases the likelihood of an unexpected event Drew T, et al. Psychol Sci. 2013 Sep;24(9):1848-53. PMID: 23863753. 22.
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