De pathologie achter de CT Bronkhorst colloquium 2013-2014 Interstitiële longziekten De pathologie achter de CT Katrien Grünberg, klinisch patholoog K.grunberg@vumc.nl

Voorbereiding De opzet van de lezing is om u kennis te laten maken met een aantal histopathologische afwijkingen en patronen. Tijdens de cursus zal verder worden ingegaan op de vertaling van de histologie naar CT. Om de histologische afwijkingen van de longen te kunnen herkennen, is kennis van de normale microscopische anatomie essentieel. Neem de volgende dia’s door als U uw kennis wilt opfrissen. Vervolgens kunt U zelf aan de slag met 3 casus. Na enkele inleidende dia’s, vindt U de links naar gescande coupes.

Even opfrissen Om de histologische afwijkingen van de longen te kunnen herkennen, is kennis van de normale microscopische anatomie essentieel. Neem de volgende dia’s door als U uw kennis wilt opfrissen.

Lungs are for gas exchange 1.6 mL/1m2! Alveolar surface area: 143 m2 Capillary surface area: 140 m2 90% Air-blood interface surface area: 126 m2 (70 times skin: 1.8 m2) Blood content 0.2 L RBC passes through capillary bed in 0.75 seconds

The alveolar-capillary membrane CO2 0.6 m O2

The alveolar-capillary membrane CO2

Lungs Core business Gas exchange Infrastructure and Logistics Conducting airways Conducting vessels Innervation Defence

Alveolar duct – terminal bronchiole

Bronchioli alveoli airway smooth muscle epithelium lumen pulmonary artery Bronchovascular bundle

Airway epithelium 2 - 3 days

Alveoli Illustrate pores of cohn

Surfactant producing cells: Type II pneumocytes and Clara cells Figure 1. Transmission electron microscopic appearance of Clara cells in terminal bronchioles of wild-type (A) and CCSP-/- mice (B). The apex of the cell projected into the airway lumen and the nucleus (N) was located in the basal portion of the cell. Electron dense secretory granules were found near the apical cytoplasmic membrane in WT mice (arrow), but were absent among Clara cells from CCSP-/- mice (magnification: bar = 1.0 µm). Alveolar surface area: 143 m2 Barry R. Stripp et al. Am. J. Respir Cell Molec Biol. 2002;. 27: 170-8

Tracheobronchial lining Seromuc. Glands Goblet cell s surfactant

Lung vasculature Alveolar surface area: 143 m2 Capillary surface area: 140 m2 90% Air-blood interface surface area: 126 m2 Blood content 0.2 L RBC passes through capillary bed in 0.75 seconds

Arteries and veins Axial artery Interlobular septum Lymph vessel Vein Plaatjes van bronch arterie en interlob vene Vein Bronchiole

Arteries Elastic artery (> 1 mm ) Muscular artery (50-1000 m) bronchi Muscular artery (50-1000 m) bronchioli Arterioles (< 50 m) Alveolar parenchyma

Bronchus-associated lymphatic tissue (BALT)

Lymph vessels Around p. arteries In interlobular septa D-240

The secondary lobule Interlobular septum Pulm artery Vein Lymph vessel Airway

Inleiding in histopathologie van ILD

ILD is about patterns Type of lesions Distribution Fibrosis Inflammation Distribution

Fibrosis: distribution Intersitial or airspace Centrilobular or subpleural Basal fields vs upper fields Lymphatic Centrilobular distribution

Inflammation Composition Distribution lymphocytic, plasmacell, neutro/eosinophilic granulomatous Distribution Interstitial (centrilobular/diffuse) Bronchiolitis Vasculitis

Inflammation

Clues Necrosis Hyaline membranes (as in diffuse alveolar damage) Pigmentation Iron (bleeding) Inhaled stuff Funny looking cells and such

Case 1 Fibrosis? Inflammation? Clues? Descriptive diagnosis DD Distribution (centrilobular or subpleural?) Inflammation? Type? Clues? Descriptive diagnosis Summary of pattern of fibrosis and inflammation, clues DD A93 (uip pattern) centrilobular, possibly LCH Similar case A78

Case 1 pleura

Old and young fibrosis: temporal heterogeneity → fibroblast foci

Case 2 M 71 yr. History of myocardial infarction. Fibrosis? Inflammation? Distribution? Airspaces? Pattern DD A82 amiodarone Consult Spaane Ziekenhuis (S12-20), longen: Uitgebreide en gevorderde organiserende pneumonie van beide longen, met slechts een focaal en gering diffuus alveolair schade beeld. Het beeld is niet specifiek is maar kan goed passen bij Amiodarone gebruik. Verminderd beoordeelbaar t.a.v. vaatpathologie, onvoldoende argumenten voor hypoxische - of congestieve vasculopathie.

Fibrosis. Where?

Nodular fibrosis. Where? And some infiltrate. Where?

Lymphocytic infiltrate in alveolar septa (interstitial pneumonitis) Nodular fibrosis in alveolar spaces: Masson bodies

Funny looking alveolar macrophages (foamy)

Pattern Organizing pneumonia Mild pneumonitis Clue: foamy macrophages

General Differentials Infection Vasculitis Collagen vascular disease / AID / IgG4 Occupational/recreational toxic stuff (inhaled) Drugs (iv, otherwise) Idiopathic fibrosis Other (inborn)

Clue Patient used amiodarone OP, pneumonitis, foamy macrophages all fit with amiodarone-induced ILD http://www.pneumotox.com

Case 3 M 75 yr Fibrosis? (EvG this staining shows fibrosis in red, elastin in black) Specifics Inflammation? Distribution? Pattern DD A80-79 EAA Consult Kennemer Gasthuis (T12-13665), chirurgische longbiopten (I ROK, II RBK): Complex beeld van overwegend bronchiolocentrisch georiënteerde interstitiële fibrose, pneumonitis en granulomen waarbij in eerste plaats een extrinsieke allergische alveolitis overwogen wordt. Voor besprekingen verdere overwegingen zie microscopie.

Inflammation, bronchiolocentric

bronchiolocentric inflammation: lymphocytes (T cells)

Clues

Giant cells in poorly formed granulomas

Differential Dx … Pattern Minimal fibrosis Bronchiolocentric interstitial pneumonia Clue: poorly formed granulomas Differential Dx …

Clue Patient kept pigeons

EAA – hypersensitivity pneumonitis Bird fancier's lung  Also called bird breeder's lung, pigeon breeder's lung, and poultry worker's lung Bagassosis Cephalosporium HP Cheese-washer's lung Chemical worker’s lung - Isocyanate HP Chemical worker's lung[9] - Trimellitic anhydride (TMA) HP Coffee worker's lung Compost lung Detergent worker's disease Familial HP Also called Domestic HP Farmer's lung Hot tub lung Humidifier lung Japanese summer house HP Also called Japanese summer-type HP Laboratory worker's lung Lycoperdonosis Malt worker's lung Maple bark disease Metalworking fluids HP Miller's lung Mollusc shell HP Mushroom worker's lung Peat moss worker's lung Pituitary snuff taker's lung Sauna worker's lung Sequoiosis Streptomyces HP Suberosis Tap water HP Thatched roof disease Tobacco worker's lung Wine-grower's lung Woodworker's lung

How to bluff your way through interstitial lung disease EAA HP UIP NSIP SR-ILD (C)OP (BO)OP DIP RB-ILD DAD Extrinsic allergic alveolitis Hypersensitivity pneumonitis Usual interstitial pneumonia Non-specific interstitial pneumonia Smoking-related interstitial lung disease (Cryptogenic) Organizing Pneumonia (Bronchiolitis Obliterans) Organizing Pneumonia Desquamative interstitial pneumonia Respiratory bronchiolitis - ILD Diffuse alveolar damage (≈ ARDS)