Granulomatous diseases of the lung

1
Granulomatous diseases of the lung

• Dr Keith M Kerr
• Aberdeen Royal Infirmary
• and Aberdeen University School of Medicine

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Granulomatous Lung Diseases

• Pneumoconiosis (Berrylium, Aluminium, Cobalt)
• Drug reactions
• Drug abusers
• Necrotising sarcoidal granulomatosis (NSG)
• Eosinophilic pneumonia
• Bronchocentric granulomatosis (BCG)
• Churg Strauss syndrome
• Lymphoid interstitial pneumonia (LIP)
• Sjogrens disease
• Amyloidosis
• Incidental

• Infections
• Sarcoidosis
• Hypersensitivity pneumonitis (EAA)
• Wegeners granulomatosis (WG)
• Reaction to tumours
• Foreign body

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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

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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

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Granulomatous Lung Disease Making a diagnosis

• The clinical context
• The granulomas
• Location and distribution
• Accompanying features and pathology

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The granulomas

• Necrotising or non-necrotising?
• Is the necrosis
• Caseous
• Abscess-like
• Degeneration / fibrinoid necrosis
• Distinct and compact or
• Soft and diffuse?

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Location / distribution of the process

• Diffuse process or Mass lesion?
• Value of radiology
• Microanatomical relationships (if any)
• centriacinar
• bronchocentric
• septal / lymphatic
• vascular / perivascular
• random

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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?

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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

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Necrotising granulomas

• Caseous necrosis
• TB
• Histoplasmosis
• Coccidioidomycosis
• Pneumocystis

Abscess-like necrosis

• Fungi
• Candida
• Aspergillus
• Phycomycosis
• Blastomycosis
• Crypococcosis
• Bacteria
• Nocardia, Actinomyces
• Viruses

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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

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Necrotising granulomas in a Mass Lesion Lion

• Firstly Exclude infection
• That done, consider the following
• Wegeners granulomatosis
• Necrotising sarcoidal granulomatosis
• Bronchocentric granulomatosis
• Churg Strauss syndrome
• Sarcoidosis.rarely
• TB in silicosis
• Rheumatoid nodule

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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

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Non-necrotising granulomas (mostly in the context
of diffuse disease)

• Is there associated interstitial pneumonitis?
• Nature of the granulomas?
• Distribution of disease?

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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!

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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)

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References

• Kalzenstein AA ed Katzenstein and Askins
  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. Wegeners granulomatosis is not a
  granulomatous disease. Ann Diag Pathol 2002 6
  329-333