Nonspecific Interstitial Pneumonia

Definition

• Idiopathic interstitial lung injury demonstrating temporal uniformity and lacking diagnostic features of other diseases

Alternate/Historical Names

• NSIP

Diagnostic Criteria

• Clinical
• Insidious onset of dyspnea, cough, fatigue
• Mean age 40-50, may be seen in children
• Pulmonary function tests: restrictive with decreased diffusing capacity
• Generally less severe than UIP
• Overall 80=90% 5 year survival
  • Responds to steroids
• High resolution computed tomography (HRCT)
• Predominantly ground glass opacities
• Changes bilateral, predominantly basal and peripheral
• Reticular, linear patterns may also be seen in 50%
• Focal honeycombing only seen in occasional cases
• Histopathologic features
• Changes in a given case are temporally uniform
• Interstitial inflammation ranges from mild to moderate
• Lymphoid follicles frequently present
• Type II pneumocyte hyperplasia
• Scant to dense interstitial fibrosis
• Generally preserves lung architecture
• EVG may be useful
• Honeycomb change is seen only in occasional cases and is not predominant
• Air spaces may be enlarged
• Traction bronchiolitis may be seen
• Bronchiole surrounded by fibrosis and larger than adjacent muscular artery
• Has been separated into two types
• Cellular type
  • Changes are predominantly cellular, with scant fibrosis
• Better prognosis
• Fibrotic type
  • Changes are predominantly fibrotic, with less cellularity
• NSIP is a diagnosis of exclusion
• The following features should not be seen
  • Granulomas or giant cells
  • Bronchiolocentric distribution
  • Acute lung injury pattern / hyaline membranes
  • More than rare eosinophils
  • Evidence of infection
• Some features of other types of interstitial lung disease may be seen to a limited extent, but do not predominate
  • Bronchiolitis obliterans / organizing pneumonia
  • Desquamative interstitial pneumonia
  • Focal fibroblastic foci typical of UIP
  • Honeycomb pattern typical of UIP
• Discordant features may be seen (UIP on one biopsy, NSIP on another)
• Behaves as UIP
• Multiple biopsies are recommended, if possible
• The following must be ruled out in every case
• Collagen vascular disease
• Drug reaction
• Chronic hypersensitivity pneumonitis
  • Giant cells and or granulomas
  • Predominantly bronchiolocentric distribution
• Immunodeficiency related changes
• Infection
• Acid fast and fungal stain should be performed in every case
• Slowly resolving acute interstitial pneumonia
• Sampling error (see Discordant above)

Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Differential Diagnosis

NSIP is a diagnosis of exclusion

• Usual Interstitial Pneumonia
  • See table below
• Acute Interstitial Pneumonia
  • Both are temporally uniform and have interstitial inflammation
  • Hyaline membranes and intra-alveolar organization should not be seen in NSIP
• Desquamative Interstitial Pneumonia
  • Both are temporally uniform
  • Predominant desquamative pattern should not be seen in NSIP
• Cryptogenic Organizing Pneumonia
  • BOOP-like changes may be seen focally but do not predominate in NSIP
  • COP has less interstitial inflammation
• Lymphocytic Interstitial Pneumonia
  • Interstitial lymphoid infiltrate is more pronounced in LIP but cutoff is not well defined
• Respiratory Bronchiolitis Associated Interstitial Lung Disease
  • Bronchiolocentric distribution in RBAILD
  • Generally uniform involvement in NSIP
• Hypersensitivity Pneumonitis
  • Granulomas and peribronchiolar distribution should not be seen in NSIP

Infection must be ruled out in every case

Classification / Lists

Idiopathic Interstitial Lung Diseases

• Acute interstitial pneumonia (diffuse alveolar damage)
• Acute fibrinous and organizng pneumonia
• Cryptogenic organizing pneumonia (BOOP)
• Desquamative interstitial pneumonia
• Lymphocytic interstitial pneumonitis
• Nonspecific interstitial pneumonia
• Respiratory bronchiolitis associated interstitial lung disease
• Usual interstitial pneumonia (idiopathic pulmonary fibrosis)

Other Diffuse Parenchymal Lung Diseases

• Alveolar microlithiasis
• Alveolar proteinosis
• Eosinophilic pneumonia, acute
• Eosinophilic pneumonia, chronic
• Eosinophilic pneumonia, simple
• Follicular broncholitis/bronchitis
• Hypersensitivity pneumonitis
• Langerhans cell histiocytosis (histiocytosis X)
• Lymphangioleiomyomatosis
• Pneumoconioses
• Sarcoidosis
• Secondary to other known causes
  • Collagen vascular disease
  • Drug reactions
  • Lymphangitic carcinoma

Bibliography

• Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Müller NL, King TE Jr.  Non-neoplastic Disorders of the Lower Respiratory Tract, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 2, 2002.
• American Thoracic Society; European Respiratory Society. ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002 Jan 15;165(2):277-304
• Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun;3(4):322-9.
  
• Travis WD, Hunninghake G, King TE Jr, Lynch DA, Colby TV, Galvin JR, Brown KK, Chung MP, Cordier JF, du Bois RM, Flaherty KR, Franks TJ, Hansell DM, Hartman TE, Kazerooni EA, Kim DS, Kitaichi M, Koyama T, Martinez FJ, Nagai S, Midthun DE, Müller NL, Nicholson AG, Raghu G, Selman M, Wells A. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1338-47.
• Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol. 2000 Jan;24(1):19-33
• Monaghan H, Wells AU, Colby TV, du Bois RM, Hansell DM, Nicholson AG. Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias. Chest. 2004 Feb;125(2):522-6.