1. Granulomatous diseases of the lung Dr Keith M Kerr Aberdeen Royal Infirmary and Aberdeen University School of Medicine

2. Granulomatous Lung Diseases Infections Sarcoidosis Hypersensitivity pneumonitis (EAA) Wegener’s granulomatosis (WG) Reaction to tumours Foreign body Pneumoconiosis (Berrylium, Aluminium, Cobalt) Drug reactions Drug abusers Necrotising sarcoidal granulomatosis (NSG) Eosinophilic pneumonia Bronchocentric granulomatosis (BCG) Churg Strauss syndrome Lymphoid interstitial pneumonia (LIP) Sjogren’s disease Amyloidosis Incidental

3. What is a granuloma? “a compact (organised) collection of mature mononuclear phagocytes (macrophages and/or epithelioid cells) which may or may not be accompanied by accessory features such as necrosis or infiltration of inflammatory leucocytes” Adams, 1983 Key features. A granuloma is: Discrete Avascular Comprises epithelioid histiocytes EJ Mark, 2004

4. Granulomas and granulomatous inflammation: synonymous or different? Granuloma is well defined (sarcoidal or tuberculoid type) Granulomatous inflammation –Diffuse process, ill-defined –Palisading histiocytes in zones

5. Granulomatous Lung Disease : Making a diagnosis The clinical context The granulomas Location and distribution Accompanying features and pathology

6. The granulomas Necrotising or non-necrotising? Is the necrosis –Caseous –Abscess-like –Degeneration / fibrinoid necrosis ‘Distinct and compact’ or ‘Soft and diffuse’?

7. Location / distribution of the process Diffuse process or Mass lesion? Value of radiology Microanatomical relationships (if any) –centriacinar –bronchocentric –septal / lymphatic –vascular / perivascular –random

8. Accompanying features and pathology Are the granulomas the main feature or are they part of a ‘bigger’ picture? Reaction to foreign body, microorganism or tumour? Is there vasculitis or tissue necrosis? Is there interstitial inflammation?

9. Necrotising granulomas Features favouring infection Microorganisms - ZN, GMS, PAS Abscess-like or caseous necrosis Mass lesion Clinical history M. tuberculosis Atypical mycobacteria Histoplasma, coccidioides cryptococcus, blastomyces pneumocystis, candida, aspergillus Actinomyces, nocardia Viruses

10. Necrotising granulomas Caseous necrosis TB Histoplasmosis Coccidioidomycosis Pneumocystis Fungi Candida Aspergillus Phycomycosis Blastomycosis Crypococcosis Bacteria Nocardia, Actinomyces Viruses Abscess-like necrosis

11. Hot tub Lung: an unusual manifestation of mycobacterial ‘infection’ Non-tuberculous organisms: MAI Diffuse infiltrative disease Culture positive but rarely ZN positive Histology like hypersensitivity pneumonitis but granulomas larger, better formed and may show necrosis Immunocompetent host Debate about pathogenesis Khoor A et al, Am J Clin Pathol 115; 755-762: 2001

12. Necrotising granulomas in a Mass Lesion Lion Firstly: Exclude infection That done, consider the following Wegener’s granulomatosis Necrotising sarcoidal granulomatosis Bronchocentric granulomatosis Churg Strauss syndrome Sarcoidosis….rarely TB in silicosis Rheumatoid nodule

13. Necrotising Sarcoidal Granulomatosis (NSG) vs Nodular Sarcoidosis: different entities or the same disease? NSG shows Conglomerate granulomatous masses ‘Geographic’ necrosis, probably of ischaemic origin Granulomatous vasculitis Lower zone distribution Less tendency to extra-pulmonary disease

14. Non-necrotising granulomas (mostly in the context of diffuse disease) Is there associated interstitial pneumonitis? Nature of the granulomas? Distribution of disease?

15. Non-necrotising granulomas: Interstitial inflammation ABSENT If there are Tight well formed granulomas Evidence of multisystem disease ‘Lymphatic’ distribution Consider Sarcoidosis Berylliosis Aluminium If not Random distribution? Airways? Vessels? Try viewing under polarised light History of inhalation or injection? Food, dust, haemosiderin, amyloid, IVDA Help!

16. Non-necrotising granulomas: Interstitial inflammation PRESENT If there are Inflammation and granulomas centriacinar Granulomas often ‘soft’ Foamy macrophages, cholesterol clefts, COP- like features Consider Hypersensitivity Pneumonitis (EAA) If not Random distribution? Check history Other pathological features Drug reaction Aspiration pneumonia Foreign material? Eosinophilic pneumonia LIP, LYG (Still consider HP/EAA)

17. References Kalzenstein AA ed: Katzenstein and Askin’s Surgical Pathology of Non-Neoplastic Lung Disease, ed. 5, Philadelphia 1997, Saunders. Ulbright TM, Katzenstein AA Solitary necrotising granulomas of the lung. Am J Surg Pathol 1980; 4: 13-28 Kerr KM. Granulomatous Lung Disease. CPD Cellular Pathology 2000; 2: 130-137 Cheung OY et al. Surgical Pathology of Granulomatous Interstitial Pneumonia. Ann Diag Pathol 2003; 7: 127-138 Mark EJ Cappilaritis and diffuse granulomatous tissue in the lung. Pathol Int 2004; 54, Suppl 1: S472-S476 Heffner DK. Wegener’s granulomatosis is not a granulomatous disease. Ann Diag Pathol 2002; 6: 329-333