P ulmonary
Aliya N. Husain, M.D.
V. Chronic Interstitial Lung Disease
A. Idiopathic pulmonary fibrosis (IPF) or usual interstitial pneumonitis (UIP)
  1. This is diagnosed when all known causes of pulmonary fibrosis are excluded.

  2. The histologic hallmark is varying degrees of interstitial fibrosis which also varies in time i.e., some areas are dense pink (mature collagen) while others are bluish myoid (early or young collagen).

  3. There are varying amounts of inflammation, type II pneumocyte hyperplasia and secondary pulmonary hypertension.

  4. Although the exact pathogenesis is unknown, the sequence of events is thought to begin with some form of alveolar wall injury which results in interstitial edema and accumulation of inflammatory cells. Subsequently, there is hyperplasia of type II pneumocytes in an attempt to regenerate the alveolar epithelial lining. Fibroblasts then proliferate, and progressive fibrosis results in obliteration of normal pulmonary architecture.
B. Hamman-Rich syndrome
  1. This diagnosis should be restricted to the rapidly progressive, fulminant form of IPF. Most of the original cases are thought to have been organizing DAD or BOOP.
C. End-stage or honeycomb lung
  1. Any fibrosing disease of the lung can lead to this picture.

  2. Honeycombing may be localized or diffuse.

  3. The lung architecture is completely destroyed and replaced by irregular nonfunctional cystic sacs with dense fibrotic walls.
D. Desquamative interstitial pneumonitis (DIP)
  1. The lung architecture is preserved with minimal to moderate interstitial fibrosis.

  2. Most air spaces are filled by macrophages with fine granular pigment.

  3. The above findings are uniform throughout the lung.

  4. Many cases of DIP progress with increasing fibrosis and eventually are indistinguishable from UIP.
E. Lymphocytic interstitial pneumonitis (LIP)
  1. There is intense infiltrate of the interstitium diffusely.

  2. The infiltrate is composed of lymphocytes, plasma cells and histiocytes, which are polyclonal.

  3. LIP may represent early low grade well-differentiated lymphoma or may be a premalignant lymphoproliferative disorder which may progress to lymphoma.

  4. LIP is associated with autoimmune diseases e.g., Sjogren syndrome, chronic active hepatitis and autoimmune hemolytic anemia and with graft-versus-host disease in bone marrow transplant patients.

  5. LIP is also a feature of pulmonary involvement in AIDS in adults and especially in children. HIV, HTLV-1 and EVB have been associated with cases of LIP.
F. Bronchiolitis obliterans organizing pneumonia (BOOP)
  1. Also known as "cryptogenic organizing pneumonia" in the British literature, this disease is characterized by granulation tissue plugs (i.e., Masson bodies) within the lumen of small airways and extending into alveolar ducts and alveoli. Masson bodies are rounded balls of myxomatous (bluish) connective tissue that form intraluminal polyps within bronchioles and air spaces.

  2. The diagnosis of idiopathic BOOP should only be made after careful consideration of clinical and radiological features since the histologic picture of BOOP can be seen in several conditions e.g., pulmonary infections, organizing DAD, bronchial obstruction, aspiration pneumonia, hypersensitivity pneumonitis, drug reaction, toxic fumes, and bone marrow, lung and heart-lung transplantation.
G. Eosinophilic pneumonia
  1. There are numerous eosinophils mixed with inflammatory cells and histiocytes in the airspaces and interstitium.

  2. Chronic eosinophilic pneumonia frequently has multinucleated giant cells. 25% have bronchiolitis obliterans.

  3. Underlying lung architecture is preserved with no significant fibrosis.
H. Sarcoidosis
  1. The histologic hallmark is lymphangitic distribution of non-caseating granulomas with Langhan's or foreign body type giant cells.

  2. Within the granulomas there may be calcified, rounded, laminated concretions known as Schumann's bodies.

  3. With the giant cells there are often star-shaped inclusions (Asteroid bodies).

  4. The above two are characteristic but not diagnostic of sarcoidosis.

  5. There is varying degree of fibrosis around granulomas and in the interstitium.

  6. Sarcoidosis is a diagnosis of exclusion.
I. Allergic alveolitis/hypersensitivity pneumonitis
  1. The pathologic features are the same regardless of etiology.

  2. Triad of findings: chronic interstitial inflammation, chronic bronchiolitis and small non-necrotizing granulomas. Between involved areas, there is usually normal lung parenchyma.
J. Pulmonary alveolar proteinosis
  1. There is diffuse intra-alveolar granular material which is PAS positive and also contains lipid.

  2. Biochemically and electron microscopically, this material resembles surfactant.

  3. There is no significant inflammation or fibrosis.

  4. Some cases may progress to chronic fibrosis.
K. Lymphangioleiomyomatosis (LAM)
  1. There is proliferation of smooth muscle initially in and around lymphatics (i.e., plural and peribronchial) which progresses to involve more of the lung.

  2. There are emphysematous spaces of varying sizes surrounded by immature, plump smooth muscle cells.

  3. On trichrome stain, the muscle is red. Strong actin positivity can be seen on immunohistochemistry.
L. Eosinophilic granuloma (histiocytosis X)
  1. This is a form of interstitial lung disease characterized by scattered nodular proliferations of Langerhans cells (grooved, angulated nuclei) mixed with varying numbers of eosinophils, lymphocytes, fibroblasts and giant cells (which are multinucleated cells with the same type of nuclei as Langerhans cells). Eventually the lesions becomes more and more fibrotic and lead to scarring and honeycomb lung. Langerhans cells can be identified by immunohistochemistry (S-100 and OKT-6 positive) or electron microscopy (Birbeck granules which are racket-shaped pentalaminar bodies).
M. Amyloidosis:
  1. The lung architecture is well-reserved with diffuse thickening of the alveolar septa by deposition of amorphous eosinophilic material. The amyloid deposits may be diffuse and uniform and consist of multiple interstitial nodules. The blood vessels, and occasionally pleura, may also contain amyloid deposits. Amyloid has apple-green birefringence when congo red stained section is polarized. On EM it has a characteristic fibrillar structure.
N. Pulmonary hemorrhage syndromes1. Goodpasture's syndrome

  1. The lungs are heavy, red and hemorrhagic.

  2. There is recent and old intraalveolar hemorrhage

  3. Direct immunofluorescent examination reveals linear staining along septal and capillary basement membranes with IgG and complement.

  4. Acute capillaritis may be seen if biopsy is large enough.

2. Idiopathic pulmonary hemosiderosis
  1. The histologic picture varies from recent to old intra-alveolar hemorrhage.

  2. There may be mild interstitial fibrosis without inflammation.

  3. IPH is a diagnosis of exclusion

3. Wegener's granulomatosis
  1. The diagnostic triad includes necrotizing granulomata in the upper and lower respiratory tract, generalized necrotizing vasculitis and glomerulonephritis.

  2. The classic nodular WG of the lung is characterized by three major histologic features: large zones of basophilic (bluish) geographic necrosis, granulomatous vasculitis and areas of granulomatous inflammation. The granulomas are small and ill-defined. Capillaritis is often seen in adjacent alveoli.

  3. The pneumonia-like WG has extensive granulomatous alveolitis with both interstitial and alveolar filling. There are numerous neutrophils, histiocytes and scattered multinucleated giant cells. Vasculitis is diffuse and widespread; small vessels show extensive fibrinoid necrosis.

  4. WG accounts for approximately one-third of all cases of diffuse alveolar hemorrhage.

  5. C-ANCA has a high degree of specificity for WG. There is a correlation of antibody titer with clinical activity of the disease.
O. Pneumoconioses1. Silicosis:

There are three basic pathologic patterns of response to silica:

  1. Fibrotic nodules are most common. They are usually less than 1 cm. in diameter, spherical, hard and gray to black. They are composed of concentric bundles of dense, acellular collagen. They may coalesce and have central necrosis. With central cavitation, tuberculosis should be suspected.

  2. Progressive massive fibrosis is a form of silicosis characterized by dense agglomeration of nodules causing massive scarring usually in the upper lobes.

  3. Alveolar proteinosis is a pattern of lung injury caused by inhalation of large amounts of silica. There is accumulation of proteinaceous material in the air spaces similar to that seen in idiopathic alveolar proteinosis. However, there is more interstitial inflammation in silicosis.

2. Coal worker's pneumoconiosis (CWP)

The pathologic lesions are of three types:

  1. Primary macules are less than 7 mm. in diameter and are composed of macrophages filled with black pigment, adjacent to a respiratory bronchiole, extending into adjacent alveoli. They are often associated with fibrosis or focal emphysema. There is only minimal impairment in lung function.

  2. Nodular lesions are up to 2.0 cm. in diameter and are composed of interlacing unoriented collagen bundles with dust-filled macrophages. They are not confined to the area around respiratory bronchioles. They often encompass more proximal bronchioles and wider zones of alveolar ducts and alveoli and other sites, particularly in subpleural and periseptal regions.

  3. Progressive massive fibrosis is a mass or nodule greater than 2.0 cm. (1 cm. on x-ray) composed of haphazardly arranged collagen with anthracotic pigment. The center contains less pigment and is often necrotic.

3. Asbestosis
  1. The histologic changes vary from bronchiolocentric fibrosis to honeycomb lung. Asbestos bodies, which are the hallmark of exposure to asbestos, are found within the fibrosis or alveolar spaces or occasionally in foreign-body giant cells. An asbestos body consists of a central core fiber of asbestos that is coated with an iron-protein-mucopolysaccharide layer forming a golden-brown, segmented, dumb bell appearance. Iron stains e.g., Prussian blue, can make detection easy.