Week 2: Interstitial lung disease

Question 1

Pathology of interstitial pneumonias

Answer 1

• family of illnesses that share finding of fibrosis and/or inflammation of alveolar walls (pulmonary interstitium)
• corresponds to restrictive lung disease (reduces lung compliance)
• shares common final pathway in honeycombing fibrosis

Question 2

Classification of interstitial lung disease

Answer 2

1 .ILD of known causes

• drugs, CT disease, environment, infection
  2. Idiopathic Interstitial pneumonias
• Idiopathic pulm fibrosis
• non-specific interstitial pneumonitis (NSIP)
• cryptogenic organizing pnuemonia
• desquamative interstitial pneumonia
• respiratory bronchiolotis-ILD
• acute interstitial pneumonia (AIP)
• lymphocytic interstitial pneumonia
  3. Granulomatous sarcoidosis
  4. Specific ILD
• LAM
• histiocytosis X

Question 3

Gross pathology of IPF

Answer 3

• firm, gray, contracted lung due to fibrosis
• honeycomb cysts beneath pleura
• fibrosis predominantly in lower lobes
• may be sharp line of demarcation between gray fibrotic lung and less involved lung

Question 4

Microscopic pathology of IPF

Answer 4

• shows uip (usual interstitial pneumonia) pattern
• patchy involvement of lung by fibrosing interstitial pneumonitis (geographic heterogeneity). Fibrosis most marked beneath pleura and adjacent to lobular septa
• temporal heterogeneity: variation in age of fibrosis with areas of young fibrosis (fibroblast foci) and older fibrosis
• zones of dense fibrosis alternating with scattered foci of young myxoid fibrosis and fibroblasts
• fibroblast foci may represent advancing or progressive edge of the disease

Question 5

Other histological features of uip pattern

Answer 5

1. interstitial inflammation
   - lymphocytes, plasma cells, few eos, few PMNs, collagen
2. alveolar inflammation: macrophages, few neutrophils, rare eos
3. cellular proliferation: type 2 cells, bronchiolar cells, fibroblasts, myofibroblasts, SM
4. honeycombing cysts: caused by revised alveolar spaces

Question 6

Pathogenesis of IPF

Answer 6

• unknown etiology
• multifocal injury over months to years–>minute scars in interstitium
• increased PMNs in alveolar lavage fluid
• inflammatory mediators in lavage fluid: leukotriene B, a-TNF, TGF-b
• this uip pattern can be seen in other diseases

Question 7

Diseases that can cause a uip pattern

Answer 7

• IPF
• collagen vascular diseases
• some drug induced interstitial pneumonitides
• radiation pneumonitis
• pneumoconiosis

Question 8

Rheumatoid interstitial pneumonitis

Answer 8

• found in up to 17% of patients with
• usually men>60
• manifestations: pleural effusion, interstitial pulmonary fibrosis, rheumatoid nodules, Caplan’s syndrome, bronchiolitis obliterans, pulmonary arteritis

Question 9

Bronchiolitis Obliterans-organizing pneumonia (BOOP)

Answer 9

• is a pattern and a disease
• morphological pattern: organizing pneumonia pattern=plugs of fibrous tissue filling bronchiolar lumens and alveolar ducts and spaces

Question 10

diffuse alveolar damage (dad) pattern

Answer 10

• pathologic pattern characterized by hyaline membranes
• damage of Type 1 pneumocytes and endothelial cells leads to break down of alveolar capillary barrier and flooding of interstitium and lumen with edema
• hallmark: hyaline membranes, ropy eosinophilic material made of type 1 cell debris and proteins
• nonspecific reaction that can be caused by many things
• idiopathic condition with unknown etiology=AIP

Question 11

hypersensitivity pneumonitis

Answer 11

• inflammatory reaction in distal lung from hypersensitivity to organic proteins
• classically: farmer’s lungs, bird fancier’s lungs, air conditioner lung,

Question 12

Pathogenesis of hypersensitivity pneumonitis

Answer 12

• inhaled insoluble particulates 1-3 um reach distal lung, invoke immune response
• cellular immunity mediated by T cells and maybe humoral

Question 13

presentation of hypersensitivity pneumonitis

Answer 13

• acute: dyspnea 4-6 hors after exposure
• chronic presentation: indolent onset of dyspnea and cor pulmonale
• PFT: restrictive pattern
• bronchoalveolar lavage: CD8 lymphocytosis

Question 14

Pathologic findings in hypersensitivity pneumonitis

Answer 14

• interstitial pneumonitis w/interstitial lymphoplasmacytic infiltrate
• poorly formed interstitial and peribronchiolar granulomas (2/3s have)
• tufts of organizing fibrous tissue in terminal and respiratory bronchioles

Question 15

groupings of drug induced interstitial lung disease

Answer 15

The histology can range from chronic interstitial pneumonitis, dad, eosinophilic pneumonia, hemorrhage, edema, pulm HTN

1. chemotherapeutic agents
   - alkylating agents
   - nitrosoureas
   - cytotoxic antibiotics
2. Antimicrobials
   - nitrofurantoin
   - penicillin
3. anti-inflammatory drugs
   - gold salts
   - penicillamine
4. antiarrhythmics
   - amiodarone

Question 16

Bleomycin pulmonary toxicity: pathology

Answer 16

• most often see dad: hyaline membranes, replicating type 2 cells, interstitial adema
• later stages: scarring/interstitial fibrosis
• you’ll see: broad pink matrix, bizarre dark nuclei, type 2 hyperplasia

Question 17

Pneumoconiosis

Answer 17

• pathologic response to inhaled or injected exogenous material
• Abestosis: interstitial fiboriss occuring as a reult of inhalation of abestos fibers
• abestos assoc. with insulation, roofing tiles, brake linings, clutch pads, ship boilers

Question 18

Lung and pleura reactions to abestos

Answer 18

1. lung
   - interstitial fibrosis
   - carcinoma
2. pleura
   - hyaline pleural plaques
   - diffuse pleural fibrosis
   - pleuritis with effusion
   - malignant mesothelioma of pleura-rare

Question 19

Clinical features of abestosis

Answer 19

• dyspnea, cough
• clubbing
• small long volumes, decreased diffusion capacity
• bilateral lower lung zone reticular infiltrates with or without pleural plaques

Question 20

Microscopic features of asbestosis

Answer 20

• fibrosis around respiratory bronchioles initially. Extends into alveolar interstitium with uip pattern
• at least one ferruginous or abestos body should be seen: rigid elongated bodies with bulbous ends and long corrugated appearance

Question 21

Pathogenesis of Asbestosis

Answer 21

• fibers>3-5 micra not likely to reach lower respiratory tract
• fibers deposit preferentially at respiratory bronchioles
• fibers may be phagocytosed by alveolar macrophages or penetrate the epithelium– produce ferruginous or abestos bodies