5/9/2015 Pathologic Assessment of Dry and itchy? It could be eczema or fungal infection. We don’t need to worry, the drugs aren’t Interstitial Lung Disease that dangerous. Kirk D. Jones, MD UCSF Dept. of Pathology kirk.jones@ucsf.edu 2 nd image that came up when I searched for “dermatologist” on Google. Old School • Since nothing works on UIP, let’s just start with steroids, and if it works…great! And if it doesn’t…no harm done! 1
5/9/2015 ASCEND Trial (Pirfenidone) Significance of a UIP Diagnosis • Don’t treat with the usual agents! – Prednisone and azathioprine shown to be bad – PANTHER study • Increased deaths (8 vs. 1) • Increased hospitalization (23 vs. 7) – NAC vs placebo no difference • Novel antifibrotics and TKI’s – ASCEND trial – INPULSIS trial King TE Jr et al. N Engl J Med 2014. INPULSIS 1 and 2 (Nintedanib) Overview • New Classification of IIP – Prior classification – Modifications for new classification • Diagnosis of UIP/NSIP – Clinical, radiologic, pathologic findings – Significance of diagnoses • Differentiation of mimics – Clinical and radiologic clues – Multidisciplinary discussion Richeldi L et al. N Engl J Med 2014. 2
5/9/2015 But not all cases are IIP • Connective tissue disease UIP NSIP • Hypersensitivity pneumonia RB DIP • Drug reaction OP • Aspiration DAD • Infection LIP Elastotic fibrosis Interstitial fibrosis, difficult to classify Travis WD, et al. Am J Respir Crit Care Med. 2013 Sep 15; 188(6): 733-48. PMID: 24032382. Diagnosis of Usual Interstitial Pneumonia Fibrosis - with “temporal heterogeneity” • Hey, let’s be like radiologists! • Pathologic Findings - Temporal Heterogeneity – H oneycomb fibrosis ld collagenous fibrosis – O Temporal heterogeneity – R ecent (fibroblastic) fibrosis Spatial heterogeneity – N ormal lung Raghu G, et al. Am J Respir Crit Care Med. 2011 Mar 15; 183(6): 788-824. PMID: 21471066. 3
5/9/2015 Diagnosis of UIP • Make your pathologist aware of clinical and radiologic findings – Idiopathic pulmonary fibrosis usually age 50+ • Some exceptions • If younger, consider UIP pattern in CTD, HP, familial fibrosis, drug reaction – UIP shows basilar and subpleural distribution • If prominent upper lobe disease, consider PPFE, HP • Insure classical histologic findings with spectrum from scarred to normal (HORN) Diagnosis of NSIP • Pathologic findings are: – Diffuse alveolar septal thickening by inflammation and/or fibrosis – “Variable but diffuse” • Similar fibrosis in different zones of the pulmonary lobule 4
5/9/2015 Differential Diagnosis If my pathologist tells me the biopsy shows NSIP, • Usual interstitial pneumonia pattern then my job has only just begun. – Idiopathic pulmonary fibrosis – Chronic hypersensitivity pneumonia, connective tissue disease, other rarities (asbestosis, drug reaction, PPFE) • Nonspecific interstitial pneumonia – “Other” far exceeds “idiopathic” – CTD, HP, drug most common – Rarely see other mimics of NSIP – amyloid, PVOD Talmadge E. King, Jr, MD Case 1 • 50-year-old male with chief complaint of worsening shortness of breath over 1-2 years • Travels extensively with entertainment commitments 5
5/9/2015 Case 1 - Diagnosis • Cellular interstitial pneumonia with foreign- body giant cell reaction – Aspiration – Drug injection – Toxic inhalation • Occupational hazard of rock and roll? 6
5/9/2015 Case 1 - Diagnosis Hypersensitivity Pneumonia • Hypersensitivity pneumonia • Reaction of the lung to inhaled antigen • See characteristic CT findings – Centrilobular ground glass nodules – The “head cheese” sign • GGO, normal, air-trapping = triple density HP - Histology The Four-Part Triad • Diffuse lymphoplasmacytic interstitial infiltrate – With bronchiolocentric accentuation • Poorly-formed granulomas • Foci of organizing pneumonia Courtesy of Rick Webb, MD 7
5/9/2015 Case 1 - Diagnosis Case 2 • Traveled with same pillow for 15 years • 24-year-old woman with interstitial lung – Down pillow disease. – Typical exposure • Dry cough, Raynaud’s phenomenon, possible • Other cases we have observed: feather exposure, arthralgias. – Feathers: Pets, Farm animal, Duvet, Pillow, • CT shows patchy ground glass opacities with Jacket. a peripheral predominance. – Molds: Work freezer, Man-Cave, Sleep number mattress – Mycobacteria: Indoor spa, shower – ? Central valley: Almond dust? 8
5/9/2015 Case 2 - Diagnosis Clues for CTD • Connective tissue diseases, due to their • Cellular and fibrosing interstitial pneumonia immune activation, often affect several (non-specific interstitial pneumonia pattern). compartments of the lung (i.e. alveolar septa, • Found to have a CK of 1108 (nl = 39-189) small airways, vessels, pleura). • Autoimmune myositis • Prominent lymphoid aggregates • Improved with mycophenolate • Pleuritis • UIP pattern with lack of central normal lung • In our practice, patients with clinical – UIP/NSIP overlap symptoms get a large panel of serologic studies and likely won’t be biopsied. Case 3 • 73-year-old woman with a six month history of shortness of breath. 9
5/9/2015 Case 3 - Diagnosis • Cellular nonspecific interstitial pneumonia with prominent lymphoid aggregates and organizing pneumonia – I would probably be thinking connective tissue disease, but it looked like a prior case of a man with BPH. Case 3 - Continued Case 4 – MDD Illustrated • Missing drug history. • 62-year-old man with severe pulmonary fibrosis – Medicine note: no drugs of concern. – Surgeon’s pre-op note: Nitrofurantoin. • Prior biopsy with UIP pattern • “It wasn’t me.” • Now undergoing bilateral lung transplant • On nitrofurantoin for 1-1/2 years. – Stealth drug (post-coital UTI’s) • www.pneumotox.com 10
5/9/2015 Subpleural honeycombing Fibroblast foci Normal-appearing lung Pathologic Pattern • Usual interstitial fibrosis – Marked fibrosis with honeycombing – Patchy involvement of lung – Fibroblast foci present – ?Features suggesting alternate diagnosis? Fibroblast foci 11
5/9/2015 Poorly-formed granuloma Bronchiolocentric Fibrosis Pathologic Diagnosis • Interstitial fibrosis, UIP pattern, with bronchiolocentric fibrosis and chronic inflammation, and poorly-formed granulomas. • Most consistent with chronic hypersensitivity pneumonia. 12
5/9/2015 Final Diagnosis Conclusions • Familial Interstitial Fibrosis • The diagnosis of usual interstitial pneumonia has become more important, both for – Telomerase mutation (TERT gene) reasons of not treating, and for possibilities • With superimposed hypersensitivity of treating. pneumonia • The pulmonary team can work with the pathologist to firm up a diagnosis – ruling in diagnoses other than UIP/IPF, or verifying a diagnosis of UIP/IPF. 13
Recommend
More recommend
