Histopathology Features

Only a subset of possible IPF cases are candidates for a lung biopsy.

Patients whose HRCT results are non-diagnostic for IPF may undergo a surgical lung biopsy to reach a definite IPF diagnosis.^1-3 Surgical lung biopsy is not indicated in patients at high risk for intra-, peri-, or postoperative complications (e.g., severe hypoxemia at rest and/or severe pulmonary hypertension with a diffusion capacity <25% after correction for hematocrit).^1-3 A multidisciplinary discussion is needed before a diagnosis of IPF is made.^1-3

The decision to pursue lung biopsy must take into account underlying comorbidities, pulmonary function, and patient preference.^1,2

Choosing the right biopsy method is crucial for making an accurate diagnosis.

A biopsy should take samples from multiple lobes, preferably via video-assisted thoracoscopic approaches to obtain adequate tissue for histologic diagnosis.^1-3

Transbronchial biopsies via fiberoptic bronchoscopy are not recommended in diagnosing IPF due to low yield.^2-4

Recommendations differ based on HRCT evidence of UIP or the potential for something other than UIP:¹

• Surgical or transbronchial lung biopsies are not recommended for patients with a pattern of UIP on HRCT^1,3
• The 2018 ATS/ERS/JRS/ALAT guidelines recommend surgical biopsy for patients with an HRCT pattern of probable UIP, indeterminate UIP, or alternative diagnosis¹
• However, the 2018 Fleischner Society White Paper suggests surgical lung biopsy is only needed in cases where HRCT patterns are indeterminate for UIP or suggest an alternative diagnosis³

THERE ARE 4 CATEGORIES OF UIP PATTERN IN HISTOPATHOLOGY.

The histopathologic features of UIP fall into 1 of 4 categories:^1,3

• UIP
• Probable UIP
• Indeterminate for UIP
• Alternative Diagnosis

UIP PATTERN^1,3

Evidence of dense fibrosis with architectural distortion (i.e., honeycombing and/or destructive scarring) in a predominantly subpleural/paraseptal distribution
AND
Predominant subpleural and/or paraseptal distribution of fibrosis
AND
Presence of patchy involvement of lung parenchyma by fibrosis
AND
Presence of fibroblast foci
AND
Absence of features to suggest an alternate diagnosis (see Alternate Diagnosis section)

The chief diagnostic criterion of UIP is patchy dense fibrosis at low magnification.¹

UIP shows alternating areas of patchy pulmonary parenchymal fibrosis with scarring and honeycomb changes and less affected or normal parenchyma.^5,6

Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.⁴

Histopathologic changes in IPF often affect the subpleural and paraseptal parenchyma most severely.^1,3

The involved areas of the lung show complete distortion of normal architecture, with sheets of dense collagen replacing normal lung tissue and occasional microscopic honeycomb cysts.⁴

At high magnification, the detailed features of definite UIP are visible.

Areas of honeycomb change are composed of cystic fibrotic airspaces that are frequently lined by bronchiolar epithelium and filled with mucus and inflammatory cells.⁶

Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw-Hill Companies, Inc. Copyright © 2007 McGraw-Hill Companies, Inc.⁴

As the region of scarred lung tissue encroaches upon the areas of normal lung tissue, the advancing edge of the young fibrosis contains specialized structures known as fibroblast foci.^4-6

Fibroblastic foci may reflect a reticulum of scar tissue.

Fibrosis may occur as a reticulum of scar tissue that extends from the pleura to the central portions of lung rather than existing as discrete areas of fibrosis.⁷

These findings, observed together, are diagnostic of UIP, assuming atypical findings are absent.^1,2

Histopathologic features of usual interstitial pneumonia. Reprinted from Fishman's Pulmonary Diseases and Disorders, 4th edition 2007. Meltzer, EB and Noble, PW: Chapter 70, Idiopathic Pulmonary Fibrosis. Used with permission from McGraw—Hill Companies, Inc. Copyright © 2007 McGraw—Hill Companies, Inc.

UIP is not limited to IPF.

The UIP pattern can be found in several other diseases, including:^3,4

• Connective tissue diseases
• Asbestosis
• Chronic hypersensitivity pneumonitis
• Hermansky-Pudlak syndrome
• Drug toxicities

Clinical history is essential for distinguishing IPF from other disorders that also produce a UIP pattern on biopsy.²

UIP may occur simultaneously with patterns of other lung diseases.

• It is important to recognize that UIP may be present along with patterns consistent with other lung diseases, such as emphysema^8,9
• In these cases, changes characteristic of each disease are expected to be present⁹

PROBABLE UIP PATTERN

The following features are suggestive of a probable UIP pattern:^1,3

Honeycomb Changes
OR
Some features of UIP, but precludes a definitive diagnosis of UIP/IPF
AND
Absence of features suggestive of an alternative diagnosis

INDETERMINATE UIP PATTERN

An indeterminate UIP pattern includes all of the following criteria:^1,3

Fibrosis with or without architectural distortion with features supporting a pattern other than UIP or UIP secondary to another cause^a
AND
Features of UIP along with features suggesting an alternative diagnosis^b

^aGranulomas, hyaline membranes (other than when associated with acute exacerbation of IPF, which may be the presenting manifestation in some patients), prominent airway-centered changes, areas of interstitial inflammation lacking associated fibrosis marked chronic fibrous pleuritis, organizing pneumonia. These features may not be easily seen to the untrained eye and often need to be specifically sought.

^bThese include: inflammatory infiltrate away from areas of honeycombing, prominent lymphoid hyperplasia including secondary germinal centers, and a distinctly bronchiolocentric distribution that could include extensive peribronchiolar metaplasia.

ALTERNATIVE DIAGNOSIS

Presence of the following features is considered indicative of an alternative diagnosis and should lead to the consideration of other diseases.^1,3

• All biopsies have features of other histologic patterns of IIPs (absence of fibroblast foci, loose fibrosis)
• Histologic findings indicative of other diseases – sarcoidosis, Langerhans cell histiocytosis, hypersensitivity pneumonitis, lymphangioleiomyomatosis (LAM)